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Bosch-Rué E, Zhang Q, Truskey GA, Olmos Buitrago J, M Bosch B, Pérez RA. Development of small tissue engineered blood vessels and their clinical and research applications. Biofabrication 2025; 17:032005. [PMID: 40341214 DOI: 10.1088/1758-5090/add626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 05/08/2025] [Indexed: 05/10/2025]
Abstract
Since the first tissue engineered blood vessel (TEBV) was developed, different approaches, biomaterial scaffolds and cell sources have been used to obtain an engineered vessel as much similar as native vessels in terms of structure, functionality and mechanical properties. At the same time, diverse needs to obtain a functional TEBV have emerged, such as for blood vessel replacement for cardiovascular diseases (CVDs) to be used as artery bypass, to vascularize tissue engineered constructs, or even to model vascular diseases or drug testing. In this review, after briefly describing the native structure and function of arteries, we will give an overview of different biomaterials, cells and methods that have been used during the last years for the development of small TEBV (1-6 mm diameter). The importance of perfusing the TEBV to acquire functionality and maturation will be also discussed. Finally, we will center the review on TEBV applications beyond their use as vascular graft for CVDs.
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Affiliation(s)
- Elia Bosch-Rué
- Bioengineering Institute of Technology (BIT), Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
- Bioengineering Department, Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
| | - Qiao Zhang
- Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States of America
| | - George A Truskey
- Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States of America
| | - Jenifer Olmos Buitrago
- Bioengineering Institute of Technology (BIT), Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
- Bioengineering Department, Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
| | - Begoña M Bosch
- Bioengineering Institute of Technology (BIT), Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
- Bioengineering Department, Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
| | - Román A Pérez
- Bioengineering Institute of Technology (BIT), Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
- Bioengineering Department, Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08195 Barcelona, Spain
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Zhang Y, Lin S, Xu X, Yao Y, Feng S, Jiang S, Wang Y, He W, Mo R. Programmable hierarchical hydrogel dressing for sequential release of growth factor and DNase to accelerate diabetic wound healing. J Control Release 2025; 383:113825. [PMID: 40339657 DOI: 10.1016/j.jconrel.2025.113825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 04/30/2025] [Accepted: 05/05/2025] [Indexed: 05/10/2025]
Abstract
Dysregulation of growth factor expression causes impaired healing of diabetic foot ulcer (DFU). Platelet-derived growth factor (PDGF)-containing gel has been clinically applied for topical treatment of DFU. Recruitment of neutrophils stimulated by PDGF favors the wound healing of DFU. However, overactivation of neutrophils induced by hyperglycemia causes massive generation and long-term persistence of neutrophil extracellular traps (NETs), ultimately leading to unexpected skin damage and delayed wound repair. Here, we engineer a hierarchically-assembled hydrogel to achieve local release of the growth factor, PDGF-BB and the NET scavenger, deoxyribonuclease (DNase) I with distinct kinetics for enhanced healing of DFU. The hydrogel is constructed by crosslinking of anti-bacterial quaternized chitosan and hypochlorite-degradable nanogel via a copper-free click reaction, in which PDGF-BB is loaded in the hydrogel matrix while DNase I is encapsulated in the inner nanogel. Programmable release of combinatorial therapeutics is implemented by the hydrogel in response to the wound microenvironment. We show that the hierarchical hydrogel co-loaded with PDGF-BB and DNase I promotes neutrophil recruitment, increases endothelial cell migration, degrades excess NETs, and prevents wound infection for accelerating the wound closure in the diabetic mouse wound models.
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Affiliation(s)
- Ying Zhang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
| | - Shiqi Lin
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
| | - Xiao Xu
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
| | - Yufan Yao
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
| | - Shufan Feng
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
| | - Sida Jiang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
| | - Yuqian Wang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
| | - Wei He
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
| | - Ran Mo
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China; State Key Laboratory of Advanced Drug Delivery and Release Systems, Shandong Luye Pharmaceutical Co., Ltd., Yantai 264003, China.
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Wu M, Sapin-Minet A, Gaucher C. Heparin, an active excipient to carry biosignal molecules: Applications in tissue engineering - A review. Int J Biol Macromol 2025; 312:143959. [PMID: 40334894 DOI: 10.1016/j.ijbiomac.2025.143959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 04/29/2025] [Accepted: 05/04/2025] [Indexed: 05/09/2025]
Abstract
Drug repositioning refers to new medical application exploration for existing drugs. Heparins, beyond their well-known anticoagulant properties widely used in clinics, present the capacity to carry biosignal molecules that is responsible for other properties such as anti-inflammatory, angiogenesis. Thus, heparins interaction with different biosignal molecules such as cytokines and growth factors have recently drawn attention and have promoted heparin repositioning as an active excipient with useful applications as drug-delivery systems and biomaterial-based tissue engineering scaffolds. Indeed, biomaterial heparinization can further help in their formulation such as in self-assembled heparin-based hydrogels or nanoparticles, and improve their biocompatibility. Moreover, the capacity of heparin to carry biosignal molecules enables the direct functionalization of heparinized biomaterial for tissue engineering. Both heparin characteristics namely the biosignal molecule carrying and biomaterial heparinization are reviewed here along their combination for biomaterial functionalization in tissue engineering applications.
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Affiliation(s)
- Meiling Wu
- Université de Lorraine, CITHEFOR, F-54000 Nancy, France
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Fukunaga T, Pearson JJ, Miller RC, Zhang C, Lakrat M, Haglund L, Diaz-Hernandez ME, Temenoff JS, Drissi H. PDGF-Releasing Hydrogels for Enhanced Proliferation of Human Nucleus Pulposus Cells. J Biomed Mater Res A 2025; 113:e37918. [PMID: 40344482 DOI: 10.1002/jbm.a.37918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 03/12/2025] [Accepted: 04/11/2025] [Indexed: 05/11/2025]
Abstract
Hydrogels offer a promising solution for sustained and controlled drug delivery and cell-tissue biocompatibility. In the intervertebral disc (IVD), delivering growth factors faces challenges due to the antagonistic inflammatory environment and continuous mechanical stress, which can degrade biological agents and may reduce their local activity. To address this, we investigated the prolonged release of platelet-derived growth factor isoforms BB (PDGF-BB) and AB (PDGF-AB) by using N-desulfated heparin methacrylamide (Hep-N) crosslinked within matrix-metalloproteinase sensitive poly(ethylene glycol) (PEG) hydrogels. Using electrostatic interactions between the heparin derivative and PDGF, we optimized a sustained release dose of PDGF-BB from the hydrogel in the presence of collagenase to mimic the in vivo environment. We then assessed the effects of PDGF released from PEG-hydrogel on human nucleus pulposus (NP) Cells. The MTT assay confirmed that 100 and 200 ng doses significantly increased cell viability by 2.52-fold and 2.46-fold on Day 3, respectively. RT-qPCR analysis revealed that PDGF-AB and PDGF-BB upregulated the expression of proliferation marker Ki-67 (MKI67) on both Day 3 and Day 5. Additionally, collagen type II alpha 1 chain (COL2A1) was significantly upregulated in the PDGF-AB group on Day 5, indicating potential anabolic effects. These findings could pave the way for long-term in vivo studies on sustainable PDGF treatment for IVD degeneration.
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Affiliation(s)
- Takanori Fukunaga
- Musculoskeletal Institute, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Joseph J Pearson
- Coulter Department of Biomedical Engineering, Georgia Tech/Emory University, Atlanta, Georgia, USA
| | - Ryan Cree Miller
- Coulter Department of Biomedical Engineering, Georgia Tech/Emory University, Atlanta, Georgia, USA
| | - Changli Zhang
- Musculoskeletal Institute, Emory University School of Medicine, Atlanta, Georgia, USA
- Atlanta VA Medical Center, Decatur, Georgia, USA
| | - Mohammed Lakrat
- Musculoskeletal Institute, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Lisbet Haglund
- Department of Surgery, McGill University, Montreal, Quebec, Canada
| | - Martha Elena Diaz-Hernandez
- Musculoskeletal Institute, Emory University School of Medicine, Atlanta, Georgia, USA
- Atlanta VA Medical Center, Decatur, Georgia, USA
| | - Johnna S Temenoff
- Coulter Department of Biomedical Engineering, Georgia Tech/Emory University, Atlanta, Georgia, USA
- Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA
| | - Hicham Drissi
- Musculoskeletal Institute, Emory University School of Medicine, Atlanta, Georgia, USA
- Atlanta VA Medical Center, Decatur, Georgia, USA
- Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA
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Pearson JJ, Mao J, Temenoff JS. Effects of Release of TSG-6 from Heparin Hydrogels on Supraspinatus Muscle Regeneration. Tissue Eng Part A 2025; 31:195-207. [PMID: 39556321 DOI: 10.1089/ten.tea.2024.0241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2024] Open
Abstract
Muscle degeneration after rotator cuff tendon tear is a significant clinical problem. In these experiments, we developed a poly(ethylene glycol)-based injectable granular hydrogel containing two heparin derivatives (fully sulfated [Hep] and fully desulfated [Hep-]) as well as a matrix metalloproteinase-sensitive peptide to promote sustained release of tumor necrosis factor-stimulated gene 6 (TSG-6) over 14+ days in vivo in a rat model of rotator cuff muscle injury. The hydrogel formulations demonstrated similar release profiles in vivo, thus facilitating comparisons between delivery from heparin derivatives on the level of tissue repair in two different areas of muscle (near the myotendious junction [MTJ] and in the muscle belly [MB]) that have been shown previously to have differing responses to rotator cuff tendon injury. We hypothesized that sustained delivery of TSG-6 would enhance the anti-inflammatory response following rotator cuff injury through macrophage polarization and that release from Hep would potentiate this effect throughout the muscle. Inflammatory/immune cells, satellite cells, and fibroadipogenic progenitor cells were analyzed by flow cytometry 3 and 7 days after injury and hydrogel injection, while metrics of muscle healing were examined via immunohistochemistry up to day 14. Results showed controlled delivery of TSG-6 from Hep caused heightened macrophage response (day 7 macrophages, 4.00 ± 1.85% single cells, M2a, 3.27 ± 1.95% single cells) and increased markers of early muscle regeneration (embryonic heavy chain staining) by day 7, particularly in the MTJ region of the muscle. This work provides a novel strategy for localized, controlled delivery of TSG-6 to enhance muscle healing after rotator cuff tear.
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Affiliation(s)
- Joseph J Pearson
- Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech, Emory University, Atlanta, Georgia, USA
| | - Jiahui Mao
- Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech, Emory University, Atlanta, Georgia, USA
| | - Johnna S Temenoff
- Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech, Emory University, Atlanta, Georgia, USA
- Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA
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Hao ZW, Zhang ZY, Wang ZP, Wang Y, Chen JY, Chen TH, Shi G, Li HK, Wang JW, Dong MC, Hong L, Li JF. Bioactive peptides and proteins for tissue repair: microenvironment modulation, rational delivery, and clinical potential. Mil Med Res 2024; 11:75. [PMID: 39639374 PMCID: PMC11619216 DOI: 10.1186/s40779-024-00576-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 10/25/2024] [Indexed: 12/07/2024] Open
Abstract
Bioactive peptides and proteins (BAPPs) are promising therapeutic agents for tissue repair with considerable advantages, including multifunctionality, specificity, biocompatibility, and biodegradability. However, the high complexity of tissue microenvironments and their inherent deficiencies such as short half-live and susceptibility to enzymatic degradation, adversely affect their therapeutic efficacy and clinical applications. Investigating the fundamental mechanisms by which BAPPs modulate the microenvironment and developing rational delivery strategies are essential for optimizing their administration in distinct tissue repairs and facilitating clinical translation. This review initially focuses on the mechanisms through which BAPPs influence the microenvironment for tissue repair via reactive oxygen species, blood and lymphatic vessels, immune cells, and repair cells. Then, a variety of delivery platforms, including scaffolds and hydrogels, electrospun fibers, surface coatings, assisted particles, nanotubes, two-dimensional nanomaterials, and nanoparticles engineered cells, are summarized to incorporate BAPPs for effective tissue repair, modification strategies aimed at enhancing loading efficiencies and release kinetics are also reviewed. Additionally, the delivery of BAPPs can be precisely regulated by endogenous stimuli (glucose, reactive oxygen species, enzymes, pH) or exogenous stimuli (ultrasound, heat, light, magnetic field, and electric field) to achieve on-demand release tailored for specific tissue repair needs. Furthermore, this review focuses on the clinical potential of BAPPs in facilitating tissue repair across various types, including bone, cartilage, intervertebral discs, muscle, tendons, periodontal tissues, skin, myocardium, nervous system (encompassing brain, spinal cord, and peripheral nerve), endometrium, as well as ear and ocular tissue. Finally, current challenges and prospects are discussed.
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Affiliation(s)
- Zhuo-Wen Hao
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Zhe-Yuan Zhang
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Ze-Pu Wang
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Ying Wang
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Jia-Yao Chen
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Tian-Hong Chen
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Guang Shi
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Han-Ke Li
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Jun-Wu Wang
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Min-Chao Dong
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Li Hong
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
| | - Jing-Feng Li
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
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Li R, Zhang K, Dong C, Wang K, Gu X, Qin Y. Osteoinductivity enhancement by tailoring the surface chemical bond status: A strategy to mobilize host bone growth factors for in situ bone regeneration. Mater Today Bio 2024; 29:101256. [PMID: 39381265 PMCID: PMC11460471 DOI: 10.1016/j.mtbio.2024.101256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 08/21/2024] [Accepted: 09/15/2024] [Indexed: 10/10/2024] Open
Abstract
The incorporation of growth factors and biomaterials is a promising strategy for improving osseointegration. However, current strategies to develop biomaterials with exogenous growth factors present disadvantages like inefficiency, difficult deployment, and potential off-target activation, making their translation into clinical practice challenging. This study reveals a bioactive N-doped tantalum carbide (TaC) solid solution film that can be used to construct a TaCN film via bionic interface engineering to recruit host bone growth factors to the wounded site and improve bone regeneration. X-ray photoelectron spectroscopy (XPS) and protein absorption analysis reveal that the performance of TaCN is related to the surface chemical bonds of films. The introduction of N to TaC causes a cascade effect wherein negative charges enrich on the TaCN surface, and the recruitment of positively charged bone growth factors around the TaCN film is facilitated. Under these circumstances, the endogenous bone growth factors enhance bone healing. The TaCN film shows an outstanding performance for in vivo osteogenic differentiation along with a superior in vitro cytocompatibility. Incorporation of N atoms into TaC provides a new clinically translatable strategy to mobilize host bone growth factors for in situ bone regeneration without the need for incorporation of exogenous growth factors.
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Affiliation(s)
- Ruiyan Li
- Department of Orthopaedics, and Joint International Research Laboratory of Ageing Active Strategy and Bionic Health in Northeast Asia of Ministry of Education, The Second Hospital of Jilin University, Changchun, 130041, China
| | - Kan Zhang
- State Key Laboratory of Super Hard Materials, Key Laboratory of Mobile Materials, MOE, School of Materials Science and Engineering, Jilin University, Changchun, 130012, China
| | - Chuanyao Dong
- State Key Laboratory of Super Hard Materials, Key Laboratory of Mobile Materials, MOE, School of Materials Science and Engineering, Jilin University, Changchun, 130012, China
| | - Kaiwen Wang
- State Key Laboratory of Super Hard Materials, Key Laboratory of Mobile Materials, MOE, School of Materials Science and Engineering, Jilin University, Changchun, 130012, China
| | - Xinlei Gu
- State Key Laboratory of Super Hard Materials, Key Laboratory of Mobile Materials, MOE, School of Materials Science and Engineering, Jilin University, Changchun, 130012, China
| | - Yanguo Qin
- Department of Orthopaedics, and Joint International Research Laboratory of Ageing Active Strategy and Bionic Health in Northeast Asia of Ministry of Education, The Second Hospital of Jilin University, Changchun, 130041, China
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Pearson JJ, Mao J, Temenoff JS. Effects of Release of TSG-6 from Heparin Hydrogels on Supraspinatus Muscle Regeneration. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.08.20.608812. [PMID: 39229126 PMCID: PMC11370378 DOI: 10.1101/2024.08.20.608812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/05/2024]
Abstract
Muscle degeneration after rotator cuff tendon tear is a significant clinical problem. In these experiments, we developed a poly(ethylene glycol)-based injectable granular hydrogel containing two heparin derivatives (fully sulfated (Hep) and fully desulfated (Hep-)) as well as a matrix metalloproteinase-sensitive peptide to promote sustained release of Tumor Necrosis Factor Stimulated Gene 6 (TSG-6) over 14+ days in vivo in a rat model of rotator cuff muscle injury. The hydrogel formulations demonstrated similar release profiles in vivo , thus facilitating comparisons between delivery from heparin derivatives on level of tissue repair in two different areas of muscle (near the myotendious junction (MTJ) and in the muscle belly (MB)) that have been shown previously to have differing responses to rotator cuff tendon injury. We hypothesized that sustained delivery of TSG-6 would enhance the anti-inflammatory response following rotator cuff injury through macrophage polarization, and that release from a fully sulfated heparin derivative (Hep) would potentiate this effect throughout the muscle. Inflammatory/immune cells, satellite cells, and fibroadipogenic progenitor cells, were analyzed by flow cytometery 3 and 7 days after injury and hydrogel injection, while metrics of muscle healing were examined via immunohistochemistry up to Day 14. Results showed controlled delivery of TSG-6 from Hep caused heightened macrophage response (Day 14 macrophages, 4.00 ± 1.85% single cells, M2a, 3.27 ± 1.95% single cells) and increased markers of early muscle regeneration (embryonic heavy chain staining) by Day 7, particularly in the MTJ region of the muscle, compared to release from desulfated heparin hydrogels. This work provides a novel strategy for localized, controlled delivery of TSG-6 to enhance muscle healing after rotator cuff tear. IMPACT STATEMENT Rotator cuff tear is a significant problem that can cause muscle degeneration. In this study, a hydrogel particle system was developed for sustained release of an anti-inflammatory protein, Tumor Necrosis Factor Stimulated Gene 6 (TSG-6), to injured muscle. Release of the protein from a fully sulfated heparin hydrogel-based carrier demonstrated greater changes in amount inflammatory cells and more early regenerative effects than a less-sulfated carrier. Thus, this work provides a novel strategy for localized, controlled delivery of an anti-inflammatory protein to enhance muscle healing after rotator cuff tear.
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Beheshtizadeh N, Mohammadzadeh M, Mostafavi M, Seraji AA, Esmaeili Ranjbar F, Tabatabaei SZ, Ghafelehbashi R, Afzali M, Lolasi F. Improving hemocompatibility in tissue-engineered products employing heparin-loaded nanoplatforms. Pharmacol Res 2024; 206:107260. [PMID: 38906204 DOI: 10.1016/j.phrs.2024.107260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 05/21/2024] [Accepted: 06/10/2024] [Indexed: 06/23/2024]
Abstract
The enhancement of hemocompatibility through the use of nanoplatforms loaded with heparin represents a highly desirable characteristic in the context of emerging tissue engineering applications. The significance of employing heparin in biological processes is unquestionable, owing to its ability to interact with a diverse range of proteins. It plays a crucial role in numerous biological processes by engaging in interactions with diverse proteins and hydrogels. This review provides a summary of recent endeavors focused on augmenting the hemocompatibility of tissue engineering methods through the utilization of nanoplatforms loaded with heparin. This study also provides a comprehensive review of the various applications of heparin-loaded nanofibers and nanoparticles, as well as the techniques employed for encapsulating heparin within these nanoplatforms. The biological and physical effects resulting from the encapsulation of heparin in nanoplatforms are examined. The potential applications of heparin-based materials in tissue engineering are also discussed, along with future perspectives in this field.
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Affiliation(s)
- Nima Beheshtizadeh
- Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | - Mahsa Mohammadzadeh
- Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran; Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mehrnaz Mostafavi
- Faculty of Allied Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Abbas Seraji
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Canada; Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, Tehran, Iran
| | - Faezeh Esmaeili Ranjbar
- Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Seyedeh Zoha Tabatabaei
- Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Robabehbeygom Ghafelehbashi
- Dental Materials Research Center, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran; Department of Materials and Textile Engineering, College of Engineering, Razi University, Kermanshah, Iran; Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Maede Afzali
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Farshad Lolasi
- Department of pharmaceutical biotechnology, Faculty of Pharmacy And Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran; Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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Wanniarachchi CT, Arjunan A, Baroutaji A, Singh M, Robinson J, Vance A, Appiah M, Arafat A. 3D printed CoCrMo personalised load-bearing meta-scaffold for critical size tibial reconstruction. ANNALS OF 3D PRINTED MEDICINE 2024; 15:100163. [DOI: 10.1016/j.stlm.2024.100163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025] Open
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11
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Esmaeili J, Jalise SZ, Pisani S, Rochefort GY, Ghobadinezhad F, Mirzaei Z, Mohammed RUR, Fathi M, Tebyani A, Nejad ZM. Development and characterization of Polycaprolactone/chitosan-based scaffolds for tissue engineering of various organs: A review. Int J Biol Macromol 2024; 272:132941. [PMID: 38848842 DOI: 10.1016/j.ijbiomac.2024.132941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 05/27/2024] [Accepted: 06/04/2024] [Indexed: 06/09/2024]
Abstract
Research in creating 3D structures mirroring the extracellular matrix (ECM) with accurate environmental cues holds paramount significance in biological applications.Biomaterials that replicate ECM properties-mechanical, physicochemical, and biological-emerge as pivotal tools in mimicking ECM behavior.Incorporating synthetic and natural biomaterials is widely used to produce scaffolds suitable for the intended organs.Polycaprolactone (PCL), a synthetic biomaterial, boasts commendable mechanical properties, albeit with relatively modest biological attributes due to its hydrophobic nature.Chitosan (CTS) exhibits strong biological traits but lacks mechanical resilience for complex tissue regeneration.Notably, both PCL and CTS have demonstrated their application in tissue engineering for diverse types of tissues.Their combination across varying PCL:CTS ratios has increased the likelihood of fabricating scaffolds to address defects in sturdy and pliable tissues.This comprehensive analysis aspires to accentuate their distinct attributes within tissue engineering across different organs.The central focus resides in the role of PCL:CTS-based scaffolds, elucidating their contribution to the evolution of advanced functional 3D frameworks tailored for tissue engineering across diverse organs.Moreover, this discourse delves into the considerations pertinent to each organ.
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Affiliation(s)
- Javad Esmaeili
- Department of Chemical Engineering, Faculty of Engineering, Arak University, Arak 38156-88349, Iran; Department of Tissue Engineering, TISSUEHUB Co., Tehran, Iran; Tissue Engineering Hub (TEHUB), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | - Saeedeh Zare Jalise
- Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Qom University of Medical Sciences, Qom, Iran
| | - Silvia Pisani
- Department of Drug Sciences, University of Pavia, Via Taramelli 12,27100 Pavia, Italy
| | - Gaël Y Rochefort
- Bioengineering Biomodulation and Imaging of the Orofacial Sphere, 2BIOS, faculty of dentistry, tours university, France; UMR 1253, iBrain, Tours University, France
| | | | - Zeynab Mirzaei
- Institute for Nanotechnology and Correlative Microscopy e.V.INAM, Forchheim, Germany
| | | | - Mehdi Fathi
- Department of Esthetic and Restorative Dentistry, School of Dentistry, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Amir Tebyani
- Department of Chemical Engineering, Faculty of Engineering, Tehran University, Tehran, Iran
| | - Zohreh Mousavi Nejad
- School of Mechanical and Manufacturing Engineering, Dublin City University, D09 Y074 Dublin, Ireland; Centre for medical engineering research, school of mechanical and manufacturing engineering, Dublin city university, D09 Y074 Dublin, Ireland
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12
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Hazrati R, Alizadeh E, Soltani S, Keyhanvar P, Davaran S. Development of a Composite Hydrogel Containing Statistically Optimized PDGF-Loaded Polymeric Nanospheres for Skin Regeneration: In Vitro Evaluation and Stem Cell Differentiation Studies. ACS OMEGA 2024; 9:15114-15133. [PMID: 38585049 PMCID: PMC10993260 DOI: 10.1021/acsomega.3c09391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 02/21/2024] [Accepted: 03/05/2024] [Indexed: 04/09/2024]
Abstract
Platelet-derived growth factor-BB (PDGF-BB) is a polypeptide growth factor generated by platelet granules faced to cytokines. It plays a role in forming and remodeling various tissue types, including epithelial tissue, through interaction with cell-surface receptors on most mesenchymal origin cells. However, it breaks down quickly in biological fluids, emphasizing the importance of preserving them from biodegradation. To address this challenge, we formulated and evaluated PDGF-encapsulated nanospheres (PD@PCEC) using polycaprolactone-polyethylene glycol-polycaprolactone. PD@PCECs were fabricated through the triple emulsion methodology and optimized by using the Box-Behnken design. The encapsulation efficiency (EE) of nanoencapsulated PDGF-BB was investigated concerning four variables: stirring rate (X1), stirring duration (X2), poly(vinyl alcohol) concentration (X3), and PDGF-BB concentration (X4). The selected optimized nanospheres were integrated into a gelatin-collagen scaffold (PD@PCEC@GC) and assessed for morphology, biocompatibility, in vitro release, and differentiation-inducing activity in human adipose-derived stem cells (hADSCs). The optimized PD@PCEC nanospheres exhibited a particle size of 177.9 ± 91 nm, a zeta potential of 5.2 mV, and an EE of 87.7 ± 0.44%. The release profile demonstrated approximately 85% of loaded PDGF-BB released during the first 360 h, with a sustained release over the entire 504 h period, maintaining bioactivity of 87.3%. The study also included an evaluation of the physicochemical properties of the scaffolds and an assessment of hADSC adhesion to the scaffold's surface. Additionally, hADSCs cultivated within the scaffold effectively differentiated into keratinocyte-like cells (KLCs) over 21 days, evidenced by morphological changes and upregulation of keratinocyte-specific genes, including cytokeratin 18, cytokeratin 19, and involucrin, at both transcriptional and protein levels.
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Affiliation(s)
- Raheleh Hazrati
- Department
of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz 51664-14766, Iran
- Research
Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz 51664, Iran
| | - Effat Alizadeh
- Department
of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz 51664-15731, Iran
| | - Somaieh Soltani
- Department
of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz 51664-14766, Iran
| | - Peyman Keyhanvar
- Department
of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz 51664-15731, Iran
| | - Soodabeh Davaran
- Department
of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz 51664-14766, Iran
- Research
Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz 51664, Iran
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13
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Huang Y, He S, Yu S, Johnson HM, Chan YK, Jiao Z, Wang S, Wu Z, Deng Y. MXene-Decorated Nanofibrous Membrane with Programmed Antibacterial and Anti-Inflammatory Effects via Steering NF-κB Pathway for Infectious Cutaneous Regeneration. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2304119. [PMID: 37759420 DOI: 10.1002/smll.202304119] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 07/08/2023] [Indexed: 09/29/2023]
Abstract
Although antibiotic is still the main choice for antibacteria both in hospital and community, phototherapy has become a possibly one of the alternative approaches in the treatment of microbe-associated infections nowadays because of its considerable potential in effective eradication of pathogenic bacteria. However, overwhelming reactive oxygen species (ROS) generated from phototherapy inevitably provoke an inflammatory response, complicating the healing process. To address this outstanding issue, a MXene-decorated nanofibrious is devised that not only yield localized heat but also elevate ROS levels under near-infrared laser exposure ascribed to the synergistic photothermal/photodynamic effect, for potent bacterial inactivation. After being further loaded with aspirin, the nanofibrous membranes exhibit benign cytocompatibility, boosting cell growth and suppressing the (nuclear factor kappa-B ( NF-κB) signaling pathways through RNA sequencing analysis, indicating an excellent anti-inflammatory effect. Interestingly, in vivo investigations also corroborate that the nanofibrous membranes accelerate infectious cutaneous regeneration by efficiently killing pathogenic bacteria, promoting collagen deposition, boosting angiogenesis, and dampening inflammatory reaction via steering NF-κB pathway. As envisaged, this work furnishes a decorated nanofibrous membrane with programmed antibacterial and anti-inflammatory effects for remedy of refractory bacteria-invaded wound regeneration.
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Affiliation(s)
- Yixuan Huang
- School of Chemical Engineering, Sichuan University, Chengdu, 610065, China
| | - Shuai He
- School of Chemical Engineering, Sichuan University, Chengdu, 610065, China
| | - Sheng Yu
- Department of Chemistry, Washington State University, Pullman, WA, 99164, USA
| | - Hannah M Johnson
- Department of Chemistry, Washington State University, Pullman, WA, 99164, USA
| | - Yau Kei Chan
- Department of Ophthalmology, The University of Hong Kong, Hong Kong, 999077, China
| | - Zheng Jiao
- Sichuan University-Pittsburgh Institute, Sichuan University, Chengdu, 610207, China
| | - Shouteng Wang
- School of Chemical Engineering, Sichuan University, Chengdu, 610065, China
| | - Zixiang Wu
- School of Chemical Engineering, Sichuan University, Chengdu, 610065, China
| | - Yi Deng
- School of Chemical Engineering, Sichuan University, Chengdu, 610065, China
- State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China
- Department of Mechanical Engineering, The University of Hong Kong, Hong Kong, 999077, China
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14
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West-Livingston L, Lim JW, Lee SJ. Translational tissue-engineered vascular grafts: From bench to bedside. Biomaterials 2023; 302:122322. [PMID: 37713761 DOI: 10.1016/j.biomaterials.2023.122322] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 09/01/2023] [Accepted: 09/09/2023] [Indexed: 09/17/2023]
Abstract
Cardiovascular disease is a primary cause of mortality worldwide, and patients often require bypass surgery that utilizes autologous vessels as conduits. However, the limited availability of suitable vessels and the risk of failure and complications have driven the need for alternative solutions. Tissue-engineered vascular grafts (TEVGs) offer a promising solution to these challenges. TEVGs are artificial vascular grafts made of biomaterials and/or vascular cells that can mimic the structure and function of natural blood vessels. The ideal TEVG should possess biocompatibility, biomechanical mechanical properties, and durability for long-term success in vivo. Achieving these characteristics requires a multi-disciplinary approach involving material science, engineering, biology, and clinical translation. Recent advancements in scaffold fabrication have led to the development of TEVGs with improved functional and biomechanical properties. Innovative techniques such as electrospinning, 3D bioprinting, and multi-part microfluidic channel systems have allowed the creation of intricate and customized tubular scaffolds. Nevertheless, multiple obstacles must be overcome to apply these innovations effectively in clinical practice, including the need for standardized preclinical models and cost-effective and scalable manufacturing methods. This review highlights the fundamental approaches required to successfully fabricate functional vascular grafts and the necessary translational methodologies to advance their use in clinical practice.
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Affiliation(s)
- Lauren West-Livingston
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA; Department of Vascular and Endovascular Surgery, Duke University, Durham, NC, 27712, USA
| | - Jae Woong Lim
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA; Department of Thoracic and Cardiovascular Surgery, Soonchunhyang University Hospital, Bucheon-Si, Gyeonggi-do, 420-767, Republic of Korea
| | - Sang Jin Lee
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
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15
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Pei B, Hu M, Wu X, Lu D, Zhang S, Zhang L, Wu S. Investigations into the effects of scaffold microstructure on slow-release system with bioactive factors for bone repair. Front Bioeng Biotechnol 2023; 11:1230682. [PMID: 37781533 PMCID: PMC10537235 DOI: 10.3389/fbioe.2023.1230682] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 09/01/2023] [Indexed: 10/03/2023] Open
Abstract
In recent years, bone tissue engineering (BTE) has played an essential role in the repair of bone tissue defects. Although bioactive factors as one component of BTE have great potential to effectively promote cell differentiation and bone regeneration, they are usually not used alone due to their short effective half-lives, high concentrations, etc. The release rate of bioactive factors could be controlled by loading them into scaffolds, and the scaffold microstructure has been shown to significantly influence release rates of bioactive factors. Therefore, this review attempted to investigate how the scaffold microstructure affected the release rate of bioactive factors, in which the variables included pore size, pore shape and porosity. The loading nature and the releasing mechanism of bioactive factors were also summarized. The main conclusions were achieved as follows: i) The pore shapes in the scaffold may have had no apparent effect on the release of bioactive factors but significantly affected mechanical properties of the scaffolds; ii) The pore size of about 400 μm in the scaffold may be more conducive to controlling the release of bioactive factors to promote bone formation; iii) The porosity of scaffolds may be positively correlated with the release rate, and the porosity of 70%-80% may be better to control the release rate. This review indicates that a slow-release system with proper scaffold microstructure control could be a tremendous inspiration for developing new treatment strategies for bone disease. It is anticipated to eventually be developed into clinical applications to tackle treatment-related issues effectively.
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Affiliation(s)
- Baoqing Pei
- Beijing Key Laboratory for Design and Evaluation Technology of Advanced Implantable and Interventional Medical Devices, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Mengyuan Hu
- Beijing Key Laboratory for Design and Evaluation Technology of Advanced Implantable and Interventional Medical Devices, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Xueqing Wu
- Beijing Key Laboratory for Design and Evaluation Technology of Advanced Implantable and Interventional Medical Devices, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Da Lu
- Beijing Key Laboratory for Design and Evaluation Technology of Advanced Implantable and Interventional Medical Devices, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Shijia Zhang
- Beijing Key Laboratory for Design and Evaluation Technology of Advanced Implantable and Interventional Medical Devices, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Le Zhang
- Beijing Key Laboratory for Design and Evaluation Technology of Advanced Implantable and Interventional Medical Devices, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Shuqin Wu
- School of Big Data and Information, Shanxi College of Technology, Taiyuan, Shanxi, China
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16
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Westwood L, Emmerson E, Callanan A. Fabrication of polycaprolactone electrospun fibres with retinyl acetate for antioxidant delivery in a ROS-mimicking environment. Front Bioeng Biotechnol 2023; 11:1233801. [PMID: 37650040 PMCID: PMC10463743 DOI: 10.3389/fbioe.2023.1233801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 07/31/2023] [Indexed: 09/01/2023] Open
Abstract
Background: Increased cancer rates denote that one in two people will be diagnosed with cancer in their lifetime. Over 60% of cancer patients receive radiotherapy, either as a stand-alone treatment or in combination with other treatments such as chemotherapy and surgery. Whilst radiotherapy is effective in destroying cancer cells, it also causes subsequent damage to healthy cells and surrounding tissue due to alterations in the tumor microenvironment and an increase in reactive oxygen species (ROS). This can cause extensive damage that impairs tissue function, and the likelihood of tissue regeneration and restoration of function is significantly reduced as new healthy cells cannot survive in the damaged environment. In the treatment of head and neck cancers, radiotherapy can cause salivary gland dysfunction. This significantly impairs the patient's quality of life and there is currently no cure, only palliative treatment options. Tissue engineering approaches are used to mimic the microenvironment of the tissue and can mediate the damaged microenvironment via bioactive compounds, to support the delivery, survival, and proliferation of new, healthy cells into the damaged environment. Methods: In this study, retinyl acetate, a derivative of vitamin A, was successfully incorporated into electrospun polycaprolactone fibres. Results: SEM images and characterization analyses showed that all scaffolds produced had similar characteristics, including fiber morphology and scaffold wettability. The vitamin scaffolds were shown to exert an antioxidant effect through scavenging activity of both DPPH and hydroxyl radicals in vitro. Critically, the antioxidant scaffolds supported the growth of human submandibular gland cells and significantly upregulated the expression of GPx1, an antioxidant enzyme, when cultured under both normal conditions and under a simulated oxidative stress environment. Discussion: These results suggest that incorporation of retinyl acetate into electrospun fibres has may mediate the damaged microenvironment post cancer radiation therapy.
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Affiliation(s)
- Lorna Westwood
- School of Engineering, Institute for Bioengineering, University of Edinburgh, Edinburgh, United Kingdom
- The Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom
| | - Elaine Emmerson
- The Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom
| | - Anthony Callanan
- School of Engineering, Institute for Bioengineering, University of Edinburgh, Edinburgh, United Kingdom
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17
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Puiggalí-Jou A, Asadikorayem M, Maniura-Weber K, Zenobi-Wong M. Growth factor-loaded sulfated microislands in granular hydrogels promote hMSCs migration and chondrogenic differentiation. Acta Biomater 2023; 166:69-84. [PMID: 37030622 DOI: 10.1016/j.actbio.2023.03.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 03/30/2023] [Accepted: 03/31/2023] [Indexed: 04/10/2023]
Abstract
Cell-based therapies for articular cartilage lesions are expensive and time-consuming; clearly, a one-step procedure to induce endogenous repair would have significant clinical benefits. Acellular heterogeneous granular hydrogels were explored for their injectability, cell-friendly cross-linking, and ability to promote migration, as well as to serve as a scaffold for depositing cartilage extracellular matrix. The hydrogels were prepared by mechanical sizing of bulk methacrylated hyaluronic acid (HAMA) and bulk HAMA incorporating sulfated HAMA (SHAMA). SHAMA's negative charges allowed for the retention of positively charged growth factors (GFs) (e.g., TGFB3 and PDGF-BB). Mixtures of HAMA and GF-loaded SHAMA microgels were annealed by enzymatic cross-linking, forming heterogeneous granular hydrogels with GF deposits. The addition of GF loaded sulfated microislands guided cell migration and enhanced chondrogenesis. Granular heterogeneous hydrogels showed increased matrix deposition and cartilage tissue maturation compared to bulk or homogeneous granular hydrogels. This advanced material provides an ideal 3D environment for guiding cell migration and differentiation into cartilage. STATEMENT OF SIGNIFICANCE: Acellular materials which promote regeneration are of great interest for repair of cartilage defects, and they are more cost- and time-effective compared to current cell-based therapies. Here we develop an injectable, granular hydrogel system which promotes cell migration from the surrounding tissue, facilitating endogenous repair. The hydrogel architecture and chemistry were optimized to increase cell migration and extracellular matrix deposition. The present study provides quantitative data on the effect of microgel size and chemical modification on cell migration, growth factor retention and tissue maturation.
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Affiliation(s)
- Anna Puiggalí-Jou
- Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences & Technology, ETH Zürich, Otto-Stern-Weg 7, 8093 Zürich, Switzerland
| | - Maryam Asadikorayem
- Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences & Technology, ETH Zürich, Otto-Stern-Weg 7, 8093 Zürich, Switzerland
| | - Katharina Maniura-Weber
- Laboratory for Biointerfaces, Empa, Swiss Federal Laboratories for Materials Science and Technology, 9014 St. Gallen, Switzerland
| | - Marcy Zenobi-Wong
- Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences & Technology, ETH Zürich, Otto-Stern-Weg 7, 8093 Zürich, Switzerland.
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18
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Snyder Y, Jana S. Fibrin gel enhanced trilayer structure in cell-cultured constructs. Biotechnol Bioeng 2023; 120:1678-1693. [PMID: 36891782 PMCID: PMC10182258 DOI: 10.1002/bit.28371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 12/12/2022] [Accepted: 03/04/2023] [Indexed: 03/10/2023]
Abstract
Efficient cell seeding and subsequent support from a substrate ensure optimal cell growth and neotissue development during tissue engineering, including heart valve tissue engineering. Fibrin gel as a cell carrier may provide high cell seeding efficiency and adhesion property, improved cellular interaction, and structural support to enhance cellular growth in trilayer polycaprolactone (PCL) substrates that mimic the structure of native heart valve leaflets. This cell carrier gel coupled with a trilayer PCL substrate may enable the production of native-like cell-cultured leaflet constructs suitable for heart valve tissue engineering. In this study, we seeded valvular interstitial cells onto trilayer PCL substrates with fibrin gel as a cell carrier and cultured them for 1 month in vitro to determine if this gel can improve cell proliferation and production of extracellular matrix within the trilayer cell-cultured constructs. We observed that the fibrin gel enhanced cellular proliferation, their vimentin expression, and collagen and glycosaminoglycan production, leading to improved structure and mechanical properties of the developing PCL cell-cultured constructs. Fibrin gel as a cell carrier significantly improved the orientations of the cells and their produced tissue materials within trilayer PCL substrates that mimic the structure of native heart valve leaflets and, thus, may be highly beneficial for developing functional tissue-engineered leaflet constructs.
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Affiliation(s)
- Yuriy Snyder
- Department of Bioengineering, University of Missouri, Columbia, MO 65211, USA
| | - Soumen Jana
- Department of Bioengineering, University of Missouri, Columbia, MO 65211, USA
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19
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El-Seedi HR, Said NS, Yosri N, Hawash HB, El-Sherif DM, Abouzid M, Abdel-Daim MM, Yaseen M, Omar H, Shou Q, Attia NF, Zou X, Guo Z, Khalifa SA. Gelatin nanofibers: Recent insights in synthesis, bio-medical applications and limitations. Heliyon 2023; 9:e16228. [PMID: 37234631 PMCID: PMC10205520 DOI: 10.1016/j.heliyon.2023.e16228] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 05/05/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
The use of gelatin and gelatin-blend polymers as environmentally safe polymers to synthesis electrospun nanofibers, has caused a revolution in the biomedical field. The development of efficient nanofibers has played a significant role in drug delivery, and for use in advanced scaffolds in regenerative medicine. Gelatin is an exceptional biopolymer, which is highly versatile, despite variations in the processing technology. The electrospinning process is an efficient technique for the manufacture of gelatin electrospun nanofibers (GNFs), as it is simple, efficient, and cost-effective. GNFs have higher porosity with large surface area and biocompatibility, despite that there are some drawbacks. These drawbacks include rapid degradation, poor mechanical strength, and complete dissolution, which limits the use of gelatin electrospun nanofibers in this form for biomedicine. Thus, these fibers need to be cross-linked, in order to control its solubility. This modification caused an improvement in the biological properties of GNFs, which made them suitable candidates for various biomedical applications, such as wound healing, drug delivery, bone regeneration, tubular scaffolding, skin, nerve, kidney, and cardiac tissue engineering. In this review an outline of electrospinning is shown with critical summary of literature evaluated with respect to the various applications of nanofibers-derived gelatin.
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Affiliation(s)
- Hesham R. El-Seedi
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, 212013, China
- International Joint Research Laboratory of Intelligent Agriculture and Agri-products Processing, Jiangsu Education Department, Zhenjiang 212013, China
- Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom 32512, Egypt
| | - Noha S. Said
- Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom 32512, Egypt
| | - Nermeen Yosri
- Chemistry Department of Medicinal and Aromatic Plants, Research Institute of Medicinal and Aromatic Plants (RIMAP), Beni-Suef University, Beni-Suef 62514, Egypt
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
| | - Hamada B. Hawash
- Environmental Division, National Institute of Oceanography and Fisheries, NIOF, Cairo, Egypt
| | - Dina M. El-Sherif
- National Institute of Oceanography and Fisheries, NIOF, Cairo, Egypt
| | - Mohamed Abouzid
- Department of Physical Pharmacy and Pharmacokinetics, Faculty of Pharmacy, Poznan University of Medical Sciences, Poznan, Poland
| | - Mohamed M. Abdel-Daim
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231 Jeddah 21442, Saudi Arabia
- Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
| | - Mohammed Yaseen
- School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK
| | - Hany Omar
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Qiyang Shou
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Nour F. Attia
- Gas Analysis and Fire Safety Laboratory, Chemistry Division, National Institute of Standards, 136, Giza 12211, Egypt
| | - Xiaobo Zou
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
| | - Zhiming Guo
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
| | - Shaden A.M. Khalifa
- Psychiatry and Psychology Department, Capio Saint Göran's Hospital, Sankt Göransplan 1, 112 19 Stockholm, Sweden
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20
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Wu W, Jia S, Xu H, Gao Z, Wang Z, Lu B, Ai Y, Liu Y, Liu R, Yang T, Luo R, Hu C, Kong L, Huang D, Yan L, Yang Z, Zhu L, Hao D. Supramolecular Hydrogel Microspheres of Platelet-Derived Growth Factor Mimetic Peptide Promote Recovery from Spinal Cord Injury. ACS NANO 2023; 17:3818-3837. [PMID: 36787636 DOI: 10.1021/acsnano.2c12017] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and neuronal differentiation of NSCs are strongly affected by the unfavorable microenvironment induced by SCI, which critically impairs their therapeutic ability to treat SCI. Herein, a strategy to fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead of bulk hydrogels is proposed to dramatically enhance the efficiency of platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated by a piezoelectric ceramic-driven thermal electrospray device, had an average size of 9 μm, and also had the ability to activate the PDGFRβ of NSCs more effectively than PDGF-MPH. In vitro, PDGF-MPHM exerted strong neuroprotective effects by maintaining the proliferation and inhibiting the apoptosis of NSCs in the presence of myelin extracts. In vivo, PDGF-MPHM inhibited M1 macrophage infiltration and extrinsic or intrinsic cells apoptosis on the seventh day after SCI. Eight weeks after SCI, the T10 SCI treatment results showed that PDGF-MPHM + NSCs significantly promoted the survival of NSCs and neuronal differentiation, reduced lesion size, and considerably improved motor function recovery in SCI rats by stimulating axonal regeneration, synapse formation, and angiogenesis in comparison with the NSCs graft group. Therefore, our findings provide insights into the ability of PDGF-MPHM to be a promising therapeutic agent for SCI repair.
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Affiliation(s)
- Weidong Wu
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Shuaijun Jia
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Hailiang Xu
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Ziheng Gao
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Zhiyuan Wang
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Botao Lu
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Yixiang Ai
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Youjun Liu
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Renfeng Liu
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Tong Yang
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Rongjin Luo
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Chunping Hu
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Lingbo Kong
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Dageng Huang
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Liang Yan
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Zhimou Yang
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education and College of Life Sciences, Nankai University, Tianjin 300071, China
| | - Lei Zhu
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
| | - Dingjun Hao
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi 710054, China
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21
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Meissner S, Raos B, Svirskis D. Hydrogels can control the presentation of growth factors and thereby improve their efficacy in tissue engineering. Eur J Pharm Biopharm 2022. [DOI: 10.1016/j.ejpb.2022.10.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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22
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Huber L, Gvaramia D, Kern J, Jakob Y, Zoellner FG, Hirsch D, Breiter R, Brenner RE, Rotter N. In situ regeneration of nasal septal defects using acellular cartilage enhanced with platelet-derived growth factor. J Tissue Eng 2022; 13:20417314221114423. [PMID: 36158899 PMCID: PMC9493673 DOI: 10.1177/20417314221114423] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 07/02/2022] [Indexed: 11/30/2022] Open
Abstract
Nasal septum defects can currently only be reconstructed using autologous cartilage grafts. In this study, we examine the reconstruction of septal cartilage defects in a rabbit model using porcine decellularized nasal septal cartilage (DNSC) functionalized with recombinant platelet-derived growth factor-BB (PDFG-BB). The supportive function of the transplanted DNSC was estimated by the degree of septum deviation and shrinkage using magnetic resonance imaging (MRI). The biocompatibility of the transplanted scaffolds was evaluated by histology according to international standards. A study group with an autologous septal transplant was used as a reference. In situ regeneration of cartilage defects was assessed by histological evaluation 4 and 16 weeks following DNSC transplantation. A study group with non-functionalized DNSC was introduced for estimation of the effects of PDFG-BB functionalization. DNSC scaffolds provided sufficient structural support to the nasal septum, with no significant shrinkage or septal deviations as evaluated by the MRI. Biocompatibility analysis after 4 weeks revealed an increased inflammatory reaction of the surrounding tissue in response to DNSC as compared to the autologous transplants. The inflammatory reaction was, however, significantly attenuated after 16 weeks in the PDGF-BB group whereas only a slight improvement of the biocompatibility score was observed in the untreated group. In situ regeneration of septal cartilage, as evidenced by the degradation of the DNSC matrix and production of neocartilage, was observed in both experimental groups after 16 weeks but was more pronounced in the PDFG-BB group. Overall, DNSC provided structural support to the nasal septum and stimulated in situ regeneration of the cartilage tissue. Furthermore, PDFG-BB augmented the regenerative potential of DNSC and enhanced the healing process, as demonstrated by reduced inflammation after 16 weeks.
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Affiliation(s)
- Lena Huber
- Department of Otorhinolaryngology, Head
and Neck Surgery, University Medical Center Mannheim, Heidelberg University,
Mannheim, Germany
| | - David Gvaramia
- Department of Otorhinolaryngology, Head
and Neck Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim,
Germany
| | - Johann Kern
- Department of Otorhinolaryngology, Head
and Neck Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim,
Germany
| | - Yvonne Jakob
- Department of Otorhinolaryngology, Head
and Neck Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim,
Germany
| | - Frank G Zoellner
- Computer Assisted Clinical Medicine,
Mannheim Institute for Intelligent System, Medical Faculty Mannheim, Heidelberg
University, Mannheim, Germany
| | - Daniela Hirsch
- Institute of Pathology, University
Medical Center Mannheim, Heidelberg University, Mannheim, Germany
| | - Roman Breiter
- Institute of Bioprocess Engineering,
University of Erlangen, Erlangen, Germany
| | - Rolf E Brenner
- Division for Biochemistry of Joint and
Connective Tissue Diseases, Department of Orthopedics, University of Ulm, Ulm,
Germany
| | - Nicole Rotter
- Department of Otorhinolaryngology, Head
and Neck Surgery, University Medical Center Mannheim, Heidelberg University,
Mannheim, Germany,Department of Otorhinolaryngology, Head
and Neck Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim,
Germany,Nicole Rotter, Department of
Otorhinolaryngology, Head and Neck Surgery, University Medical Center Mannheim,
University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
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23
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Prospects and Challenges of Electrospun Cell and Drug Delivery Vehicles to Correct Urethral Stricture. Int J Mol Sci 2022; 23:ijms231810519. [PMID: 36142432 PMCID: PMC9502833 DOI: 10.3390/ijms231810519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 08/30/2022] [Accepted: 09/01/2022] [Indexed: 11/17/2022] Open
Abstract
Current therapeutic modalities to treat urethral strictures are associated with several challenges and shortcomings. Therefore, significant strides have been made to develop strategies with minimal side effects and the highest therapeutic potential. In this framework, electrospun scaffolds incorporated with various cells or bioactive agents have provided promising vistas to repair urethral defects. Due to the biomimetic nature of these constructs, they can efficiently mimic the native cells’ niches and provide essential microenvironmental cues for the safe transplantation of multiple cell types. Furthermore, these scaffolds are versatile platforms for delivering various drug molecules, growth factors, and nucleic acids. This review discusses the recent progress, applications, and challenges of electrospun scaffolds to deliver cells or bioactive agents during the urethral defect repair process. First, the current status of electrospinning in urethral tissue engineering is presented. Then, the principles of electrospinning in drug and cell delivery applications are reviewed. Finally, the recent preclinical studies are summarized and the current challenges are discussed.
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24
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Zhu Y, Dai B, Li X, Liu W, Wang J, Xu J, Xu S, He X, Zhang S, Li Q, Qin L, Ngai T. Periosteum-Inspired Membranes Integrated with Bioactive Magnesium Oxychloride Ceramic Nanoneedles for Guided Bone Regeneration. ACS APPLIED MATERIALS & INTERFACES 2022; 14:39830-39842. [PMID: 36026585 DOI: 10.1021/acsami.2c10615] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Guided bone regeneration (GBR) technique using a barrier membrane holds great potential to allow the single-stage reconstruction of critical-sized bone defects. Here, bioactive nanoneedle-like magnesium oxychloride ceramics (MOCs) are synthesized and recruited as an osteoinductive factor within a polycaprolactone-gelatin A (PCL-GelA) membranous matrix to generate a periosteum-mimicking biphasic GBR membrane (PCL-GelA/MOC) to accelerate calvarial defect repair. The PCL-GelA/MOC membrane acts as a shield for defect areas and a reservoir of osteoinductive molecules, which provides a favorable microenvironment for supporting cell proliferation, infiltration, and differentiation. This membrane leads to accelerated osteogenesis and angiogenesis, effectual defect bridging, and significantly enhanced bone regeneration when applied to a 5 mm sized rat calvarial defect. This makes this innovative and multifunctional GBR membrane a suitable candidate for clinical applications with promising curative efficacy.
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Affiliation(s)
- Yuwei Zhu
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
| | - Bingyang Dai
- Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
| | - Xu Li
- Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
| | - Wei Liu
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
| | - Jiangpeng Wang
- Department of Physics, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
| | - Jiankun Xu
- Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
| | - Shunxiang Xu
- Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
| | - Xuan He
- Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
| | - Shian Zhang
- Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
| | - Quan Li
- Department of Physics, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
| | - Ling Qin
- Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
| | - To Ngai
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, P. R. China
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25
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Capuani S, Malgir G, Chua CYX, Grattoni A. Advanced strategies to thwart foreign body response to implantable devices. Bioeng Transl Med 2022; 7:e10300. [PMID: 36176611 PMCID: PMC9472022 DOI: 10.1002/btm2.10300] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/21/2022] [Accepted: 01/24/2022] [Indexed: 11/10/2022] Open
Abstract
Mitigating the foreign body response (FBR) to implantable medical devices (IMDs) is critical for successful long-term clinical deployment. The FBR is an inevitable immunological reaction to IMDs, resulting in inflammation and subsequent fibrotic encapsulation. Excessive fibrosis may impair IMDs function, eventually necessitating retrieval or replacement for continued therapy. Therefore, understanding the implant design parameters and their degree of influence on FBR is pivotal to effective and long lasting IMDs. This review gives an overview of FBR as well as anti-FBR strategies. Furthermore, we highlight recent advances in biomimetic approaches to resist FBR, focusing on their characteristics and potential biomedical applications.
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Affiliation(s)
- Simone Capuani
- Department of NanomedicineHouston Methodist Research InstituteHoustonTexasUSA
- University of Chinese Academy of Science (UCAS)BeijingChina
| | - Gulsah Malgir
- Department of NanomedicineHouston Methodist Research InstituteHoustonTexasUSA
- Department of Biomedical EngineeringUniversity of HoustonHoustonTexasUSA
| | | | - Alessandro Grattoni
- Department of NanomedicineHouston Methodist Research InstituteHoustonTexasUSA
- Department of SurgeryHouston Methodist HospitalHoustonTexasUSA
- Department of Radiation OncologyHouston Methodist HospitalHoustonTexasUSA
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26
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Zhu Y, Zhou J, Dai B, Liu W, Wang J, Li Q, Wang J, Zhao L, Ngai T. A Bilayer Membrane Doped with Struvite Nanowires for Guided Bone Regeneration. Adv Healthc Mater 2022; 11:e2201679. [PMID: 36026579 DOI: 10.1002/adhm.202201679] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 08/11/2022] [Indexed: 01/27/2023]
Abstract
Guided bone regeneration (GBR) therapy demonstrates a prominent curative effect on the management of craniomaxillofacial (CMF) bone defects. In this study, a GBR membrane consisting of a microporous layer and a struvite-nanowire-doped fibrous layer is constructed via non-solvent induced phase separation, followed by an electrospinning procedure to treat critical-sized calvarial defects. The microporous layer shows selective permeability for excluding the rapid-growing non-osteogenic tissues and potential wound stabilization. The nanowire-like struvite is synthesized as the deliverable therapeutic agent within the fibrous layer to facilitate bone regeneration. Such a membrane displays a well-developed heterogeneous architecture, satisfactory mechanical performance, and long-lasting characteristics. The in vitro biological evaluation reveals that apart from being a strong barrier, the bilayer struvite-laden membrane can actively promote cellular adhesion, proliferation, and osteogenic differentiation. Consequently, the multifunctional struvite-doped membranes are applied to treat 5 mm-sized bilateral calvarial defects in rats, resulting in overall improved healing outcomes compared with the untreated or the struvite-free membrane-treated group, which is characterized by enhanced osteogenesis and significantly increased new bone formation. The encouraging preclinical results reveal the great potential of the bilayer struvite-doped membrane as a clinical GBR device for augmenting large-area CMF bone reconstruction.
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Affiliation(s)
- Yuwei Zhu
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong
| | - Jianpeng Zhou
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Bingyang Dai
- Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong
| | - Wei Liu
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong
| | - Jiangpeng Wang
- Department of Physics, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong
| | - Quan Li
- Department of Physics, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong
| | - Jun Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Lei Zhao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - To Ngai
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong
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27
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Gao C, Jiang J, Wang J, Wang Y, Zhang Y, Rao C, Cheng Y, Chen Z, Yang R, Zhao G. Recent progress of mechanism of mineralization process induced by
Ta
2
O
5
/
PCL
scaffolds. J Appl Polym Sci 2022. [DOI: 10.1002/app.52649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Chen Gao
- College of Life Sciences Anhui Medical University Hefei China
| | - Junbo Jiang
- School of Biomedical Engineering Anhui Medical University Hefei China
| | - Juan Wang
- Chaohu Clinical Medical College Anhui Medical University Hefei China
| | - Yutong Wang
- School of Biomedical Engineering Anhui Medical University Hefei China
| | - Yangyang Zhang
- School of Biomedical Engineering Anhui Medical University Hefei China
| | - Caihua Rao
- Department of Ophthalmology The First Affiliated Hospital of Anhui Medical University Hefei China
| | - Yue Cheng
- School of Biomedical Engineering Anhui Medical University Hefei China
| | - Zhongrong Chen
- School of Biomedical Engineering Anhui Medical University Hefei China
| | - Runhuai Yang
- School of Biomedical Engineering Anhui Medical University Hefei China
| | - Gang Zhao
- School of Biomedical Engineering Anhui Medical University Hefei China
- Department of Electronic Science and Technology University of Science and Technology of China Hefei China
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28
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Wang J, Xiao L, Wang W, Zhang D, Ma Y, Zhang Y, Wang X. The Auxiliary Role of Heparin in Bone Regeneration and its Application in Bone Substitute Materials. Front Bioeng Biotechnol 2022; 10:837172. [PMID: 35646879 PMCID: PMC9133562 DOI: 10.3389/fbioe.2022.837172] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 04/13/2022] [Indexed: 11/18/2022] Open
Abstract
Bone regeneration in large segmental defects depends on the action of osteoblasts and the ingrowth of new blood vessels. Therefore, it is important to promote the release of osteogenic/angiogenic growth factors. Since the discovery of heparin, its anticoagulant, anti-inflammatory, and anticancer functions have been extensively studied for over a century. Although the application of heparin is widely used in the orthopedic field, its auxiliary effect on bone regeneration is yet to be unveiled. Specifically, approximately one-third of the transforming growth factor (TGF) superfamily is bound to heparin and heparan sulfate, among which TGF-β1, TGF-β2, and bone morphogenetic protein (BMP) are the most common growth factors used. In addition, heparin can also improve the delivery and retention of BMP-2 in vivo promoting the healing of large bone defects at hyper physiological doses. In blood vessel formation, heparin still plays an integral part of fracture healing by cooperating with the platelet-derived growth factor (PDGF). Importantly, since heparin binds to growth factors and release components in nanomaterials, it can significantly facilitate the controlled release and retention of growth factors [such as fibroblast growth factor (FGF), BMP, and PDGF] in vivo. Consequently, the knowledge of scaffolds or delivery systems composed of heparin and different biomaterials (including organic, inorganic, metal, and natural polymers) is vital for material-guided bone regeneration research. This study systematically reviews the structural properties and auxiliary functions of heparin, with an emphasis on bone regeneration and its application in biomaterials under physiological conditions.
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Affiliation(s)
- Jing Wang
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Lan Xiao
- Centre for Biomedical Technologies, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, Australia
- Australia−China Centre for Tissue Engineering and Regenerative Medicine, Brisbane, Australia
| | - Weiqun Wang
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Dingmei Zhang
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yaping Ma
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yi Zhang
- Department of Hygiene Toxicology, School of Public Health, Zunyi Medical University, Zunyi, China
| | - Xin Wang
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Centre for Biomedical Technologies, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, Australia
- Australia−China Centre for Tissue Engineering and Regenerative Medicine, Brisbane, Australia
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29
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Liu G, Zhang B, Wan T, Zhou C, Fan Y, Tian W, Jing W. A 3D-printed biphasic calcium phosphate scaffold loaded with platelet lysate/gelatin methacrylate to promote vascularization. J Mater Chem B 2022; 10:3138-3151. [PMID: 35352743 DOI: 10.1039/d2tb00006g] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
3D-printed biphasic calcium phosphate (BCP) scaffolds show great clinical application potential in bone tissue engineering; however, vascularization of the scaffold is a crucial step for bone regeneration and is still difficult to be controlled. To enhance scaffold vascularization, a novel bioactive scaffold loaded with platelet lysate/gelatin methacrylate (PL/GelMA) in a BCP scaffold was proposed for promoting vascularization. The PL/GelMA/BCP scaffold was successfully prepared via digital light processing (DLP) printing and filled with PL/GelMA to promote the vascularization effect. In vitro evaluation indicated that human umbilical vein endothelial cells (HUVECs) adhered well on the PL/GelMA/BCP scaffold, and cell proliferation was significantly promoted by coculture with the scaffold. Moreover, a variety of growth factors (GFs) in the PL were detected which were slowly released from the scaffold to modulate the cell behaviour and promote the formation of blood vessel-like structures. Co-culturing with the PL/GelMA/BCP scaffold upregulated the expression of angiogenesis-related genes in cells. In vitro results showed that a higher capillary formation was also observed in PL/GelMA/BCP scaffolds implanted subcutaneously on the back of the rats. These results indicated that the vascularization ability of BCP was enhanced by filling it with PL/GelMA. The PL/GelMA/BCP scaffold has the potential to promote vascularization in tissue engineering.
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Affiliation(s)
- Gang Liu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. .,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 14, 3Rd Section of Ren Min Nan Rd., Chengdu, Sichuan 610041, China
| | - Boqing Zhang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Ting Wan
- Affiliated Hospital of Sichuan Nursing Vocational College (The Third People's Hospital of Sichuan Province), Chengdu 610071, China
| | - Changchun Zhou
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Yujiang Fan
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
| | - Weidong Tian
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. .,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 14, 3Rd Section of Ren Min Nan Rd., Chengdu, Sichuan 610041, China
| | - Wei Jing
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. .,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 14, 3Rd Section of Ren Min Nan Rd., Chengdu, Sichuan 610041, China
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30
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Xu L, Liu Y, Zhou W, Yu D. Electrospun Medical Sutures for Wound Healing: A Review. Polymers (Basel) 2022; 14:1637. [PMID: 35566807 PMCID: PMC9105379 DOI: 10.3390/polym14091637] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/16/2022] [Accepted: 04/17/2022] [Indexed: 02/01/2023] Open
Abstract
With the increasing demand for wound healing around the world, the level of medical equipment is also increasing, but sutures are still the preferred medical equipment for medical personnel to solve wound closures. Compared with the traditional sutures, the nanofiber sutures produced by combining the preparation technology of drug-eluting sutures have greatly improved both mechanical properties and biological properties. Electrospinning technology has attracted more attention as one of the most convenient and simple methods for preparing functional nanofibers and the related sutures. This review firstly discusses the structural classification of sutures and the performance analysis affecting the manufacture and use of sutures, followed by the discussion and classification of electrospinning technology, and then summarizes the relevant research on absorbable and non-absorbable sutures. Finally, several common polymers and biologically active substances used in creating sutures are concluded, the related applications of sutures are discussed, and the future prospects of electrospinning sutures are suggested.
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Affiliation(s)
- Lin Xu
- School of Materials and Chemistry, University of Shanghai for Science and Technology, Shanghai 200093, China; (L.X.); (W.Z.)
| | - Yanan Liu
- School of Materials and Chemistry, University of Shanghai for Science and Technology, Shanghai 200093, China; (L.X.); (W.Z.)
| | - Wenhui Zhou
- School of Materials and Chemistry, University of Shanghai for Science and Technology, Shanghai 200093, China; (L.X.); (W.Z.)
| | - Dengguang Yu
- School of Materials and Chemistry, University of Shanghai for Science and Technology, Shanghai 200093, China; (L.X.); (W.Z.)
- Shanghai Engineering Technology Research Center for High-Performance Medical Device Materials, Shanghai 200093, China
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31
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Wu S, Ma J, Liu J, Liu C, Ni S, Dai T, Wang Y, Weng Y, Zhao H, Zhou D, Zhao X. Immunomodulation of Telmisartan-Loaded PCL/PVP Scaffolds on Macrophages Promotes Endogenous Bone Regeneration. ACS APPLIED MATERIALS & INTERFACES 2022; 14:15942-15955. [PMID: 35353482 DOI: 10.1021/acsami.1c24748] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Biomaterial-immune system interactions play an important role in postimplantation osseointegration to retain the functionality of healthy and intact bones. Therefore, appropriate osteoimmunomodulation of implants has been considered and validated as an efficient strategy to alleviate inflammation and enhance new bone formation. Here, we fabricated a nanostructured PCL/PVP (polycaprolactone/polyvinylpyrrolidone) electrospinning scaffold for cell adhesion, tissue ingrowth, and bone defect padding. In addition, telmisartan, an angiotensin 2 receptor blocker with distinct immune bioactivity, was doped into PCL-/PVP-electrospun scaffolds at different proportions [1% (TPP-1), 5% (TPP-5), and 10% (TPP-10)] to investigate its immunomodulatory effects and osteoinductivity/conductivity. Telmisartan-loaded scaffolds displayed in vitro anti-inflammatory bioactivity on lipopolysaccharide-induced M1 macrophages by polarizing them to an M2-like phenotype and exhibited pro-osteogenic properties on bone marrow-derived mesenchymal stem cells (BMSCs). Histological analysis and micro-CT results of a rat skull defect model also showed that the telmisartan-loaded scaffolds induced a higher M2/M1 ratio, less inflammatory infiltration, and better bone regenerative patterns. Furthermore, activation of the BMP2 (bone morphogenetic protein-2)-Smad signaling pathway was found to be dominant in telmisartan-loaded scaffold-mediated macrophage-BMSC interactions. These findings indicate that telmisartan incorporation with PCL/PVP nanofibrous scaffolds is a potential therapeutic strategy for promoting bone healing by modulating M1 macrophages to a more M2 phenotype at early stages of postimplantation.
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Affiliation(s)
- Siyu Wu
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213164, China
- Dalian Medical University, Dalian 116044, China
| | - Jiayi Ma
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213164, China
- Dalian Medical University, Dalian 116044, China
| | - Jun Liu
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213164, China
- Dalian Medical University, Dalian 116044, China
| | - Chun Liu
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213164, China
| | - Su Ni
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213164, China
| | - Ting Dai
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213164, China
| | - Yan Wang
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213164, China
| | - Yiping Weng
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213164, China
| | - Hongbin Zhao
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213164, China
| | - Dong Zhou
- The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou 213164, China
| | - Xiubo Zhao
- School of Pharmacy, Changzhou University, Changzhou 213164, China
- Department of Chemical and Biological Engineering, University of Sheffield, Sheffield S1 3JD, U.K
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ABSTRACTS (BY NUMBER). Tissue Eng Part A 2022. [DOI: 10.1089/ten.tea.2022.29025.abstracts] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Surface engineering of 3D-printed scaffolds with minerals and a pro-angiogenic factor for vascularized bone regeneration. Acta Biomater 2022; 140:730-744. [PMID: 34896633 DOI: 10.1016/j.actbio.2021.12.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 11/19/2021] [Accepted: 12/05/2021] [Indexed: 11/22/2022]
Abstract
Scaffolds functionalized with biomolecules have been developed for bone regeneration but inducing the regeneration of complex structured bone with neovessels remains a challenge. For this study, we developed three-dimensional printed scaffolds with bioactive surfaces coated with minerals and platelet-derived growth factor. The minerals were homogeneously deposited on the surface of the scaffold using 0.01 M NaHCO3 with epigallocatechin gallate in simulated body fluid solution (M2). The M2 scaffold demonstrated enhanced mineral coating amount per scaffold with a greater compressive modulus than the others which used different concentration of NaHCO3. Then, we immobilized PDGF on the mineralized scaffold (M2/P), which enhanced the osteogenic differentiation of human adipose derived stem cells in vitro and promoted the secretion of pro-angiogenic factors. Cells cultured in M2/P showed remarkable ratio of osteocalcin- and osteopontin-positive nuclei, and M2/P-derived medium induced endothelial cells to form tubule structures. Finally, the implanted M2/P scaffolds onto mouse calvarial defects had regenerated bone in 80.8 ± 9.8% of the defect area with the arterioles were formed, after 8 weeks. In summary, our scaffold, which composed of minerals and pro-angiogenic growth factor, could be used therapeutically to improve the regeneration of bone with a highly vascularized structure. STATEMENT OF SIGNIFICANCE: Surface engineered scaffolds have been developed for bone regeneration but inducing the volumetric regeneration of bone with neovessels remains a challenge. In here, we developed 3D printed scaffolds with bioactive surfaces coated with bio-minerals and platelet-derived growth factors. We proved that the 0.01 M NaHCO3 with polyphenol in simulated body fluid solution enhanced the deposition of bio-minerals and even distribution on the surface of scaffold. The in vitro studies demonstrated that the attached cells on the bioactive surface showed the enhanced osteogenic differentiation and secretion of pro-angiogenic factors. Finally, the scaffold with bioactive surface not only improved the regenerated volume of bone tissues but also increased neovessel formation after in vivo implantation onto mouse calvarial defect.
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Baek J, Lee KI, Ra HJ, Lotz MK, D'Lima DD. Collagen fibrous scaffolds for sustained delivery of growth factors for meniscal tissue engineering. Nanomedicine (Lond) 2022; 17:77-93. [PMID: 34991339 PMCID: PMC8765117 DOI: 10.2217/nnm-2021-0313] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Aim: To mimic the ultrastructural morphology of the meniscus with nanofiber scaffolds coupled with controlled growth factor delivery to modulate cellular performance for tissue engineering of menisci. Methods: The authors functionalized collagen nanofibers by conjugating heparin to the following growth factors for sustained release: PDGF-BB, TGF-β1 and CTGF. Results: Incorporating growth factors increased human meniscal and synovial cell viability, proliferation and infiltration in vitro, ex vivo and in vivo; upregulated key genes involved in meniscal extracellular matrix synthesis and enhanced generation of meniscus-like tissue. Conclusion: The authors' results indicate that functionalizing collagen nanofibers can create a cell-favorable micro- and nanoenvironment and can serve as a system for sustained release of bioactive factors.
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Affiliation(s)
- Jihye Baek
- Shiley Center for Orthopaedic Research and Education at Scripps Clinic, 10666 North Torrey Pines Road, MS126, La Jolla, CA 92037, USA,Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, MB-102, La Jolla, CA 92037, USA
| | - Kwang Il Lee
- Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, MB-102, La Jolla, CA 92037, USA
| | - Ho Jong Ra
- Shiley Center for Orthopaedic Research and Education at Scripps Clinic, 10666 North Torrey Pines Road, MS126, La Jolla, CA 92037, USA,Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, MB-102, La Jolla, CA 92037, USA
| | - Martin K Lotz
- Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, MB-102, La Jolla, CA 92037, USA
| | - Darryl D D'Lima
- Shiley Center for Orthopaedic Research and Education at Scripps Clinic, 10666 North Torrey Pines Road, MS126, La Jolla, CA 92037, USA,Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, MB-102, La Jolla, CA 92037, USA,Author for correspondence: Tel.: +1 858 784 7816;
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Zhang Y, Luo J, Zhang Q, Deng T. Growth factors, as biological macromolecules in bioactivity enhancing of electrospun wound dressings for diabetic wound healing: A review. Int J Biol Macromol 2021; 193:205-218. [PMID: 34627847 DOI: 10.1016/j.ijbiomac.2021.09.210] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/30/2021] [Accepted: 09/30/2021] [Indexed: 01/07/2023]
Abstract
Impaired wound healing is of the most conspicuous characteristics of diabetic mellitus. Reduced blood flow, chronic inflammatory reactions, infection, endothelial dysfunction, elevated levels of reactive oxygen species, and metabolic disorders cause wounds to heal more slowly in these patients. Previous studies have reported useful impacts of growth factors in management of such wounds. However, due to their short half-life and low stability, a suitable delivery platform with sustained release profile may boost their healing potential. Controlled and localized delivery of growth factors via electrospun fibers have been extensively explored in previous studies. The electrospinning method; although not new, has turned out to be extremely effective for the preparation of delivery carriers for growth factors. Due to their structural resemblance to native tissues' extracellular matrix, high encapsulation efficacy, tunability, and high surface to volume ratio, electrospun scaffolds have gained significant attention in drug delivery and tissue engineering. In the current review, careful integration of current research regarding the applications of growth factors' delivery through electrospun fibers in diabetic wounds healing has been done. This review will not only give an insight into the current updates, but will also highlights the future perspectives and challenges.
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Affiliation(s)
- Yunwu Zhang
- Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China
| | - Jingsong Luo
- Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Qi Zhang
- School of Nursing, Peking University, Beijing 100191, China
| | - Tingting Deng
- Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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Cationic, anionic and neutral polysaccharides for skin tissue engineering and wound healing applications. Int J Biol Macromol 2021; 192:298-322. [PMID: 34634326 DOI: 10.1016/j.ijbiomac.2021.10.013] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 09/25/2021] [Accepted: 10/03/2021] [Indexed: 12/17/2022]
Abstract
Today, chronic wound care and management can be regarded as a clinically critical issue. However, the limitations of current approaches for wound healing have encouraged researchers and physicians to develop more efficient alternative approaches. Advances in tissue engineering and regenerative medicine have resulted in the development of promising approaches that can accelerate wound healing and improve the skin regeneration rate and quality. The design and fabrication of scaffolds that can address the multifactorial nature of chronic wound occurrence and provide support for the healing process can be considered an important area requiring improvement. In this regard, polysaccharide-based scaffolds have distinctive properties such as biocompatibility, biodegradability, high water retention capacity and nontoxicity, making them ideal for wound healing applications. Their tunable structure and networked morphology could facilitate a number of functions, such as controlling their diffusion, maintaining wound moisture, absorbing a large amount of exudates and facilitating gas exchange. In this review, the wound healing process and the influential factors, structure and properties of carbohydrate polymers, physical and chemical crosslinking of polysaccharides, scaffold fabrication techniques, and the use of polysaccharide-based scaffolds in skin tissue engineering and wound healing applications are discussed.
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Laner-Plamberger S, Oeller M, Rohde E, Schallmoser K, Strunk D. Heparin and Derivatives for Advanced Cell Therapies. Int J Mol Sci 2021; 22:12041. [PMID: 34769471 PMCID: PMC8584295 DOI: 10.3390/ijms222112041] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/03/2021] [Accepted: 11/05/2021] [Indexed: 12/27/2022] Open
Abstract
Heparin and its derivatives are saving thousands of human lives annually, by successfully preventing and treating thromboembolic events. Although the mode of action during anticoagulation is well studied, their influence on cell behavior is not fully understood as is the risk of bleeding and other side effects. New applications in regenerative medicine have evolved supporting production of cell-based therapeutics or as a substrate for creating functionalized matrices in biotechnology. The currently resurgent interest in heparins is related to the expected combined anti-inflammatory, anti-thrombotic and anti-viral action against COVID-19. Based on a concise summary of key biochemical and clinical data, this review summarizes the impact for manufacturing and application of cell therapeutics and highlights the need for discriminating the different heparins.
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Affiliation(s)
- Sandra Laner-Plamberger
- Department of Transfusion Medicine, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria; (S.L.-P.); (M.O.); (E.R.)
- Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria;
| | - Michaela Oeller
- Department of Transfusion Medicine, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria; (S.L.-P.); (M.O.); (E.R.)
- Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria;
| | - Eva Rohde
- Department of Transfusion Medicine, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria; (S.L.-P.); (M.O.); (E.R.)
- Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria;
| | - Katharina Schallmoser
- Department of Transfusion Medicine, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria; (S.L.-P.); (M.O.); (E.R.)
- Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria;
| | - Dirk Strunk
- Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria;
- Cell Therapy Institute, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria
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38
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Lee KI, Gamini R, Olmer M, Ikuta Y, Hasei J, Baek J, Alvarez-Garcia O, Grogan SP, D'Lima DD, Asahara H, Su AI, Lotz MK. Mohawk is a transcription factor that promotes meniscus cell phenotype and tissue repair and reduces osteoarthritis severity. Sci Transl Med 2021; 12:12/567/eaan7967. [PMID: 33115953 DOI: 10.1126/scitranslmed.aan7967] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 02/06/2020] [Accepted: 09/21/2020] [Indexed: 12/13/2022]
Abstract
Meniscus tears are common knee injuries and a major osteoarthritis (OA) risk factor. Knowledge gaps that limit the development of therapies for meniscus injury and degeneration concern transcription factors that control the meniscus cell phenotype. Analysis of RNA sequencing data from 37 human tissues in the Genotype-Tissue Expression database and RNA sequencing data from meniscus and articular cartilage showed that transcription factor Mohawk (MKX) is highly enriched in meniscus. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2). In mesenchymal stem cells (MSCs), the combination of adenoviral MKX (Ad-MKX) and transforming growth factor-β3 (TGF-β3) induced a meniscus cell phenotype. When Ad-MKX-transduced MSCs were seeded on TGF-β3-conjugated decellularized meniscus scaffold (DMS) and inserted into experimental tears in meniscus explants, they increased glycosaminoglycan content, extracellular matrix interconnectivity, cell infiltration into the DMS, and improved biomechanical properties. Ad-MKX injection into mouse knee joints with experimental OA induced by surgical destabilization of the meniscus suppressed meniscus and cartilage damage, reducing OA severity. Ad-MKX injection into human OA meniscus tissue explants corrected pathogenic gene expression. These results identify MKX as a previously unidentified key transcription factor that regulates the meniscus cell phenotype. The combination of Ad-MKX with TGF-β3 is effective for differentiation of MSCs to a meniscus cell phenotype and useful for meniscus repair. MKX is a promising therapeutic target for meniscus tissue engineering, repair, and prevention of OA.
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Affiliation(s)
- Kwang Il Lee
- Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA
| | - Ramya Gamini
- Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA
| | - Merissa Olmer
- Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA
| | - Yasunari Ikuta
- Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA
| | - Joe Hasei
- Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA
| | - Jihye Baek
- Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA.,Shiley Center for Orthopaedic Research and Education at Scripps Clinic, La Jolla, CA 92037, USA
| | | | - Shawn P Grogan
- Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA.,Shiley Center for Orthopaedic Research and Education at Scripps Clinic, La Jolla, CA 92037, USA
| | - Darryl D D'Lima
- Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA.,Shiley Center for Orthopaedic Research and Education at Scripps Clinic, La Jolla, CA 92037, USA
| | - Hiroshi Asahara
- Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA
| | - Andrew I Su
- Department of Integrative, Structural and Computational Biology, Scripps Research, La Jolla, CA 92037, USA
| | - Martin K Lotz
- Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA.
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Ding Z, Cheng W, Mia MS, Lu Q. Silk Biomaterials for Bone Tissue Engineering. Macromol Biosci 2021; 21:e2100153. [PMID: 34117836 DOI: 10.1002/mabi.202100153] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/17/2021] [Indexed: 12/14/2022]
Abstract
Silk is a natural fibrous polymer with application potential in regenerative medicine. Increasing interest remains for silk materials in bone tissue engineering due to their characteristics in biocompatibility, biodegradability and mechanical properties. Plenty of the in vitro and in vivo studies confirmed the advantages of silk in accelerating bone regeneration. Silk is processed into scaffolds, hydrogels, and films to facilitate different bone regenerative applications. Bioactive factors such as growth factors and drugs, and stem cells are introduced to silk-based matrices to create friendly and osteogenic microenvironments, directing cell behaviors and bone regeneration. The recent progress in silk-based bone biomaterials is discussed and focused on different fabrication and functionalization methods related to osteogenesis. The challenges and potential targets of silk bone materials are highlighted to evaluate the future development of silk-based bone materials.
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Affiliation(s)
- Zhaozhao Ding
- National Engineering Laboratory for Modern Silk and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123, P. R. China
| | - Weinan Cheng
- Department of Orthopedics, The First Affiliated Hospital of Xiamen University, Xiamen, 361000, P. R. China
| | - Md Shipan Mia
- National Engineering Laboratory for Modern Silk and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123, P. R. China
| | - Qiang Lu
- National Engineering Laboratory for Modern Silk and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123, P. R. China
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40
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Active agents loaded extracellular matrix mimetic electrospun membranes for wound healing applications. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2021.102500] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Bhutada SS, Sriram M, Katti DS. Sulfated carboxymethylcellulose conjugated electrospun fibers as a growth factor presenting system for tissue engineering. Carbohydr Polym 2021; 268:118256. [PMID: 34127227 DOI: 10.1016/j.carbpol.2021.118256] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 05/08/2021] [Accepted: 05/21/2021] [Indexed: 01/08/2023]
Abstract
Inspired by the natural electrostatic interaction of cationic growth factors with anionic sulfated glycosaminoglycans in the extracellular matrix, we developed electrospun poly(hydroxybutyrate)/gelatin (PG) fibers conjugated with anionic sulfated carboxymethylcellulose (sCMC) to enable growth factor immobilization via electrostatic interaction for tissue engineering. The fibrous scaffold bound cationic molecules, was cytocompatible and exhibited a remarkable morphological and functional stability. Transforming growth factor-β1 immobilized on the sCMC conjugated fibers was retained for at least 4 weeks with negligible release (3%). Immobilized fibroblast growth factor-2 and connective tissue growth factor were bioactive and induced proliferation and fibrogenic differentiation of infrapatellar fat pad derived mesenchymal stem cells respectively with efficiency similar to or better than free growth factors. Taken together, our studies demonstrate that sCMC conjugated PG fibers can immobilize and retain function of cationic growth factors and hence show potential for use in various tissue engineering applications.
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Affiliation(s)
- Sarang S Bhutada
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India; Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
| | - M Sriram
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India; Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
| | - Dhirendra S Katti
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India; Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
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Xing Z, Zhao C, Wu S, Zhang C, Liu H, Fan Y. Hydrogel-based therapeutic angiogenesis: An alternative treatment strategy for critical limb ischemia. Biomaterials 2021; 274:120872. [PMID: 33991951 DOI: 10.1016/j.biomaterials.2021.120872] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 04/24/2021] [Accepted: 05/02/2021] [Indexed: 02/08/2023]
Abstract
Critical limb ischemia (CLI) is the most severe clinical manifestation of peripheral arterial disease (PAD), resulting in the total or partial loss of limb function. Although the conventional treatment strategy of CLI (e.g., medical treatment and surgery) can improve blood perfusion and restore limb function, many patients are unsuitable for these strategies and they still face the threats of amputation or death. Therapeutic angiogenesis, as a potential solution for these problems, attempts to manipulate blood vessel growth in vivo for augment perfusion without the help of extra pharmaceutics and surgery. With the rise of interdisciplinary research, regenerative medicine strategies provide new possibilities for treating many clinical diseases. Hydrogel, as an excellent biocompatibility material, is an ideal candidate for delivering bioactive molecules and cells for therapeutic angiogenesis. Besides, hydrogel could precisely deliver, control release, and keep the bioactivity of cargos, making hydrogel-based therapeutic angiogenesis a new strategy for CLI therapy. In this review, we comprehensively discuss the approaches of hydrogel-based strategy for CLI treatment as well as their challenges, and future directions.
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Affiliation(s)
- Zheng Xing
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, PR China
| | - Chen Zhao
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, PR China
| | - Siwen Wu
- State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, PR China
| | - Chunchen Zhang
- Key Laboratory for Biomedical Engineering of Education Ministry of China, Zhejiang University, Hangzhou, 310027, PR China; Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, 310027, PR China
| | - Haifeng Liu
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, PR China.
| | - Yubo Fan
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, PR China.
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Tang Q, Lim T, Shen LY, Zheng G, Wei XJ, Zhang CQ, Zhu ZZ. Well-dispersed platelet lysate entrapped nanoparticles incorporate with injectable PDLLA-PEG-PDLLA triblock for preferable cartilage engineering application. Biomaterials 2020; 268:120605. [PMID: 33360073 DOI: 10.1016/j.biomaterials.2020.120605] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 12/08/2020] [Accepted: 12/11/2020] [Indexed: 01/02/2023]
Abstract
Platelet lysate (PL) as a cost-effective cocktail of growth factors is an emerging ingredient in regenerative medicine, especially in cartilage tissue engineering. However, most studies fail to pay attention to PL's intrinsic characteristics and incorporate it directly with scaffolds or hydrogels by simple mixture. Currently, the particle size distribution of PL was determined to be scattered. Directly introducing PL into a thermosensitive poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PLEL) hydrogel disturbed its sol-gel transition. Electrostatic self-assembly heparin (Hep) and ε-poly-l-lysine (EPL) nanoparticles (NPs) were fabricated to improve the dispersity of PL. Such PL-NPs-incorporated PLEL gels retained the initial gelling capacity and showed a long-term PL-releasing ability. Moreover, the PL-loaded composite hydrogels inhibited the inflammatory response and dedifferentiation of IL-1β-induced chondrocytes. For in vivo applications, the PLEL@PL-NPs system ameliorated the early cartilage degeneration and promoted cartilage repair in the late stage of osteoarthritis. RNA sequencing analysis indicated that PL's protective effects might be associated with modulating hyaluronan synthase 1 (HAS-1) expression. Taken together, these results suggest that well-dispersed PL by Hep/EPL NPs is a preferable approach for its incorporation into hydrogels and the constructed PLEL@PL-NPs system is a promising cell-free and stepwise treatment option for cartilage tissue engineering.
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Affiliation(s)
- Qian Tang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
| | - Thou Lim
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
| | - Li-Yan Shen
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109, Xueyuanxi Road, 325027 Wenzhou, China
| | - Gang Zheng
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109, Xueyuanxi Road, 325027 Wenzhou, China
| | - Xiao-Juan Wei
- Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
| | - Chang-Qing Zhang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
| | - Zhen-Zhong Zhu
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
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Hamedani Y, Teixeira RB, Karbasiafshar C, Wipf P, Bhowmick S, Abid MR. Delivery of a mitochondria-targeted antioxidant from biocompatible, polymeric nanofibrous scaffolds. FEBS Open Bio 2020; 11:35-47. [PMID: 33179452 PMCID: PMC7780095 DOI: 10.1002/2211-5463.13032] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 10/23/2020] [Accepted: 11/09/2020] [Indexed: 12/31/2022] Open
Abstract
Cardiovascular disease has been associated with increased levels of reactive oxygen species (ROS). Recently, we have shown that a critical balance between cytosolic ROS and mitochondrial ROS is crucial in cardiovascular health and that modulation of mitochondrial ROS helps prevent detrimental effects of cytosolic ROS on endothelial cells (EC) in transgenic animals. Here, we report the development of a controlled delivery system for a mitochondria‐targeted antioxidant, JP4‐039, from an electrospun scaffold made of FDA‐approved biocompatible polymeric nanofibers. We demonstrate that the active antioxidant moiety was preserved in released JP4‐039 for over 72 h using electron paramagnetic resonance. We also show that both the initial burst release of the drug within the first 20 min and the ensuing slow and sustained release that occurred over the next 24 h improved tube formation in human coronary artery ECs (HCAEC) in vitro. Taken together, these findings suggest that electrospinning methods can be used to upload mitochondrial antioxidant (JP4‐039) onto a biocompatible nanofibrous PLGA scaffold, and the uploaded drug (JP4‐039) retains nitroxide antioxidant properties upon release from the scaffold, which in turn can reduce mitochondrial ROS and improve EC function in vitro.
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Affiliation(s)
- Yasaman Hamedani
- Department of Mechanical Engineering, University of Massachusetts Dartmouth, North Dartmouth, MA, USA
| | - Rayane Brinck Teixeira
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Catherine Karbasiafshar
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Peter Wipf
- Department of Chemistry, University of Pittsburgh, PA, USA.,Department of Pharmaceutical Sciences, University of Pittsburgh, PA, USA.,Department of Bioengineering, University of Pittsburgh, PA, USA
| | - Sankha Bhowmick
- Department of Mechanical Engineering, University of Massachusetts Dartmouth, North Dartmouth, MA, USA
| | - M Ruhul Abid
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA
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Tang Q, Lim T, Wei XJ, Wang QY, Xu JC, Shen LY, Zhu ZZ, Zhang CQ. A free-standing multilayer film as a novel delivery carrier of platelet lysates for potential wound-dressing applications. Biomaterials 2020; 255:120138. [DOI: 10.1016/j.biomaterials.2020.120138] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Revised: 05/03/2020] [Accepted: 05/19/2020] [Indexed: 12/16/2022]
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Grogan SP, Baek J, D'Lima DD. Meniscal tissue repair with nanofibers: future perspectives. Nanomedicine (Lond) 2020; 15:2517-2538. [PMID: 32975146 DOI: 10.2217/nnm-2020-0183] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The knee menisci are critical to the long-term health of the knee joint. Because of the high incidence of injury and degeneration, replacing damaged or lost meniscal tissue is extremely clinically relevant. The multiscale architecture of the meniscus results in unique biomechanical properties. Nanofibrous scaffolds are extremely attractive to replicate the biochemical composition and ultrastructural features in engineered meniscus tissue. We review recent advances in electrospinning to generate nanofibrous scaffolds and the current state-of-the-art of electrospun materials for meniscal regeneration. We discuss the importance of cellular function for meniscal tissue engineering and the application of cells derived from multiple sources. We compare experimental models necessary for proof of concept and to support translation. Finally, we discuss future directions and potential for technological innovations.
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Affiliation(s)
- Shawn P Grogan
- Shiley Center for Orthopedic Research & Education at Scripps Clinic 10666 North Torrey Pines Road, MS126, La Jolla, CA 92037, USA.,Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, MB-102, La Jolla, CA 92037, USA
| | - Jihye Baek
- Shiley Center for Orthopedic Research & Education at Scripps Clinic 10666 North Torrey Pines Road, MS126, La Jolla, CA 92037, USA.,Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, MB-102, La Jolla, CA 92037, USA
| | - Darryl D D'Lima
- Shiley Center for Orthopedic Research & Education at Scripps Clinic 10666 North Torrey Pines Road, MS126, La Jolla, CA 92037, USA.,Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, MB-102, La Jolla, CA 92037, USA
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Lyons JG, Plantz MA, Hsu WK, Hsu EL, Minardi S. Nanostructured Biomaterials for Bone Regeneration. Front Bioeng Biotechnol 2020; 8:922. [PMID: 32974298 PMCID: PMC7471872 DOI: 10.3389/fbioe.2020.00922] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 07/17/2020] [Indexed: 12/13/2022] Open
Abstract
This review article addresses the various aspects of nano-biomaterials used in or being pursued for the purpose of promoting bone regeneration. In the last decade, significant growth in the fields of polymer sciences, nanotechnology, and biotechnology has resulted in the development of new nano-biomaterials. These are extensively explored as drug delivery carriers and as implantable devices. At the interface of nanomaterials and biological systems, the organic and synthetic worlds have merged over the past two decades, forming a new scientific field incorporating nano-material design for biological applications. For this field to evolve, there is a need to understand the dynamic forces and molecular components that shape these interactions and influence function, while also considering safety. While there is still much to learn about the bio-physicochemical interactions at the interface, we are at a point where pockets of accumulated knowledge can provide a conceptual framework to guide further exploration and inform future product development. This review is intended as a resource for academics, scientists, and physicians working in the field of orthopedics and bone repair.
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Affiliation(s)
- Joseph G. Lyons
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
- Simpson Querrey Institute, Northwestern University, Chicago, IL, United States
| | - Mark A. Plantz
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
- Simpson Querrey Institute, Northwestern University, Chicago, IL, United States
| | - Wellington K. Hsu
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
- Simpson Querrey Institute, Northwestern University, Chicago, IL, United States
| | - Erin L. Hsu
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
- Simpson Querrey Institute, Northwestern University, Chicago, IL, United States
| | - Silvia Minardi
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
- Simpson Querrey Institute, Northwestern University, Chicago, IL, United States
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West-Livingston L, Ju YM, Lee H, Geary RL, Atala A, Lee SJ. Antibody-Conjugated Electrospun Vascular Scaffolds to Enhance In Situ Endothelialization. ACS APPLIED BIO MATERIALS 2020; 3:4486-4494. [PMID: 35025447 DOI: 10.1021/acsabm.0c00449] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Tissue-engineered vascular grafts (TEVGs) are promising alternatives to small-diameter prosthetic grafts. Previous methods of seeding tubular scaffolds with autologous vascular cells have been successful; however, these methods require significant preparation time. Endothelial cell (EC) growth on the luminal surface of vascular scaffolds may be critical for the integration of a TEVG to the host environment. An alternative approach for TEVGs includes the in situ endothelialization of acellular scaffolds by capturing circulating endothelial progenitor cells (EPCs) and ECs from the bloodstream through the biofunctionalization of the vascular scaffolds. In this study, fibrous scaffolds were electrospun with a 1:1 poly(ε-caprolactone) (PCL)/collagen blend solution. The electrospun fibrous scaffolds were surface-modified by immobilizing EC-specific antibodies: CD31, vascular endothelial cadherin (VE-CAD), vascular endothelial growth factor receptor 2 (VEGFR2), and von Willebrand factor (vWF). Antibodies most efficacious at capturing ECs were then paired to examine their potential synergistic cell-capturing capabilities. The study demonstrated that vascular scaffolds bioconjugated with dual antibodies demonstrated synergistic capture efficacy compared to bioconjugation with a single antibody. The capture of circulating EPCs and ECs can be optimized with bioconjugation of one or more antibodies on the luminal surface of TEVGs.
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Affiliation(s)
- Lauren West-Livingston
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, United States
| | - Young Min Ju
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, United States
| | - Hyeongjin Lee
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, United States
| | - Randolph L Geary
- Department of Vascular and Endovascular Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, United States
| | - Anthony Atala
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, United States
| | - Sang Jin Lee
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, United States
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Inoo K, Yamamoto M, Tabata Y. Preparation of cell aggregates incorporating gelatin hydrogel microspheres of sugar-responsive water solubilization. J Tissue Eng Regen Med 2020; 14:1050-1062. [PMID: 32478475 DOI: 10.1002/term.3076] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 05/01/2020] [Accepted: 05/11/2020] [Indexed: 12/18/2022]
Abstract
The objective of this study is to design hydrogel microspheres of a cell scaffold, which not only function as a scaffold to form cell aggregates of three-dimensional culture but also can disappear to release growth factors in the well-controlled manner by noncytotoxic stimulation in any timing. The hydrogel microspheres were prepared by a water-in-oil emulsion method from m-aminophenylboronic acid (APBA)-introduced gelatin (APBA-gelatin) with or without poly(vinyl alcohol) (PVA) mixing. Irrespective of the PVA concentration, the microspheres with the same diameter were prepared. The microspheres were water solubilized only by adding sorbitol of a sugar although the solubilization extent depended on the PVA concentration. When cocultured with the microspheres, mesenchymal stem cells formed cell aggregates homogeneously incorporating the microspheres. Upon adding sorbitol in the culture medium, mixed APBA-gelatin-PVA hydrogel microspheres disappeared with time in the cell aggregates. The microspheres containing basic fibroblast growth factor or bone morphogenetic protein-2 released the respective growth factor accompanied with the microspheres disappearance. It is concluded that the present microspheres of sugar-responsive water solubilization are promising scaffold of cell aggregates and have an ability to allow growth factors to be released in the cell aggregates when it is required.
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Affiliation(s)
- Kanako Inoo
- Laboratory of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
| | - Masaya Yamamoto
- Laboratory of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
| | - Yasuhiko Tabata
- Laboratory of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
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Buie T, McCune J, Cosgriff-Hernandez E. Gelatin Matrices for Growth Factor Sequestration. Trends Biotechnol 2020; 38:546-557. [PMID: 31954527 PMCID: PMC11577444 DOI: 10.1016/j.tibtech.2019.12.005] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 11/15/2019] [Accepted: 12/06/2019] [Indexed: 01/07/2023]
Abstract
Gelatin is used in a broad range of tissue engineering applications because of its bioactivity, mild processing conditions, and ease of modification, which have increased interest in its use as a growth factor delivery vehicle. Traditional methods to control growth factor sequestration and delivery have relied on controlling hydrogel mesh size via chemical crosslinking with corollary changes to the physical properties of the hydrogel. To decouple growth factor release from scaffold properties, affinity sequestration modalities have been developed to preserve the bioactivity of the growth factor through interactions with the modified gelatin. This review provides a summary of these mechanisms, highlights current gelatin growth factor delivery systems, and addresses the future perspective of gelatin matrices for growth factor delivery in tissue engineering.
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Affiliation(s)
- Taneidra Buie
- Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA
| | - Joshua McCune
- Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA
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