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Huang XY, Zhou XX, Yang H, Xu T, Dao JW, Bian L, Wei DX. Directed osteogenic differentiation of human bone marrow mesenchymal stem cells via sustained release of BMP4 from PBVHx-based nanoparticles. Int J Biol Macromol 2024; 265:130649. [PMID: 38453121 DOI: 10.1016/j.ijbiomac.2024.130649] [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: 01/21/2024] [Revised: 02/29/2024] [Accepted: 03/04/2024] [Indexed: 03/09/2024]
Abstract
Bone Morphogenetic Protein 4 (BMP4) is crucial for bone and cartilage tissue regeneration, essential in medical tissue engineering, cosmetology, and aerospace. However, its cost and degradation susceptibility pose significant clinical challenges. To enhance its osteogenic activity while reducing dosage and administration frequency, we developed a novel long-acting BMP4 delivery system using poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PBVHx) nanoparticles with soybean lecithin-modified BMP4 (sBP-NPs). These nanoparticles promote directed osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) through sustained BMP4 release. sBP-NPs exhibited uniform size (100-200 nm) and surface charges, with higher BMP4 entrapment efficiency (82.63 %) compared to controls. After an initial burst release within 24 h, sBP-NPs achieved 80 % cumulative BMP4 release within 20 days, maintaining levels better than control BP-NPs with unmodified BMP4. Co-incubation and nanoparticle uptake experiments confirmed excellent biocompatibility of sBP-NPs, promoting hBMSC differentiation towards osteogenic lineage with increased expression of type I collagen, calcium deposition, and ALP activity (> 20,000 U/g protein) compared to controls. Moreover, hBMSCs treated with sBP-NPs exhibited heightened expression of osteogenic genetic markers, surpassing control groups. Hence, this innovative strategy of sustained BMP4 release from sBP-NPs holds potential to revolutionize bone regeneration in minimally invasive surgery, medical cosmetology or space environments.
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Affiliation(s)
- Xiao-Yun Huang
- School of Clinical Medicine, Qujing Medical College, Qujing 655000, China; Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
| | - Xiao-Xiang Zhou
- School of Clinical Medicine, Qujing Medical College, Qujing 655000, China
| | - Hui Yang
- School of Clinical Medicine, Qujing Medical College, Qujing 655000, China
| | - Tao Xu
- School of Clinical Medicine, Qujing Medical College, Qujing 655000, China
| | - Jin-Wei Dao
- Zigong Affiliated Hospital of Southwest Medical University, Zigong Psychiatric Research Center, Zigong Institute of Brain Science, Zigong 643002, China
| | - Li Bian
- Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
| | - Dai-Xu Wei
- School of Clinical Medicine, Qujing Medical College, Qujing 655000, China; School of Clinical Medicine, Chengdu University, Chengdu, China; Zigong Affiliated Hospital of Southwest Medical University, Zigong Psychiatric Research Center, Zigong Institute of Brain Science, Zigong 643002, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Department of Life Sciences and Medicine, Northwest University, Xi'an 710069, China.
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2
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Shang J, Zhou C, Jiang C, Huang X, Liu Z, Zhang H, Zhao J, Liang W, Zeng B. Recent developments in nanomaterials for upgrading treatment of orthopedics diseases. Front Bioeng Biotechnol 2023; 11:1221365. [PMID: 37621999 PMCID: PMC10446844 DOI: 10.3389/fbioe.2023.1221365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 07/11/2023] [Indexed: 08/26/2023] Open
Abstract
Nanotechnology has changed science in the last three decades. Recent applications of nanotechnology in the disciplines of medicine and biology have enhanced medical diagnostics, manufacturing, and drug delivery. The latest studies have demonstrated this modern technology's potential for developing novel methods of disease detection and treatment, particularly in orthopedics. According to recent developments in bone tissue engineering, implantable substances, diagnostics and treatment, and surface adhesives, nanomedicine has revolutionized orthopedics. Numerous nanomaterials with distinctive chemical, physical, and biological properties have been engineered to generate innovative medication delivery methods for the local, sustained, and targeted delivery of drugs with enhanced therapeutic efficacy and minimal or no toxicity, indicating a very promising strategy for effectively controlling illnesses. Extensive study has been carried out on the applications of nanotechnology, particularly in orthopedics. Nanotechnology can revolutionize orthopedics cure, diagnosis, and research. Drug delivery precision employing nanotechnology using gold and liposome nanoparticles has shown especially encouraging results. Moreover, the delivery of drugs and biologics for osteosarcoma is actively investigated. Different kind of biosensors and nanoparticles has been used in the diagnosis of bone disorders, for example, renal osteodystrophy, Paget's disease, and osteoporosis. The major hurdles to the commercialization of nanotechnology-based composite are eventually examined, thus helping in eliminating the limits in connection to some pre-existing biomaterials for orthopedics, important variables like implant life, quality, cure cost, and pain and relief from pain. The potential for nanotechnology in orthopedics is tremendous, and most of it looks to remain unexplored, but not without challenges. This review aims to highlight the up tp date developments in nanotechnology for boosting the treatment modalities for orthopedic ailments. Moreover, we also highlighted unmet requirements and present barriers to the practical adoption of biomimetic nanotechnology-based orthopedic treatments.
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Affiliation(s)
- Jinxiang Shang
- Department of Orthopedics, Affiliated Hospital of Shaoxing University, Shaoxing, China
| | - Chao Zhou
- Department of Orthopedics, Zhoushan Guanghua Hospital, Zhoushan, China
| | - Chanyi Jiang
- Department of Pharmacy, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, China
| | - Xiaogang Huang
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, China
| | - Zunyong Liu
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, China
| | - Hengjian Zhang
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, China
| | - Jiayi Zhao
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, China
| | - Wenqing Liang
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, China
| | - Bin Zeng
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, China
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Pan Y, Jiang Z, Ye Y, Zhu D, Li N, Yang G, Wang Y. Role and Mechanism of BMP4 in Regenerative Medicine and Tissue Engineering. Ann Biomed Eng 2023:10.1007/s10439-023-03173-6. [PMID: 37014581 DOI: 10.1007/s10439-023-03173-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 02/21/2023] [Indexed: 04/05/2023]
Abstract
Bone morphogenetic protein 4 (BMP4) is emerging as a promising cytokine for regenerative medicine and tissue engineering. BMP4 has been shown to promote the regeneration of teeth, periodontal tissue, bone, cartilage, the thymus, hair, neurons, nucleus pulposus, and adipose tissue, as well as the formation of skeletal myotubes and vessels. BMP4 can also contribute to the formation of tissues in the heart, lung, and kidney. However, there are certain deficiencies, including the insufficiency of the mechanism of BMP4 in some fields and an appropriate carrier of BMP4 for clinical use. There has also been a lack of in vivo experiments and orthotopic transplantation studies in some fields. BMP4 has great distance from the clinical application. Therefore, there are many BMP4-related studies waiting to be explored. This review mainly discusses the effects, mechanisms, and applications of BMP4 in regenerative medicine and tissue engineering over the last 10 years in various domains and possible improvements. BMP4 has shown great potential in regenerative medicine and tissue engineering. The research of BMP4 has broad development space and great value.
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Affiliation(s)
- Yiqi Pan
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China
| | - Zhiwei Jiang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China
| | - Yuer Ye
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China
| | - Danji Zhu
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China
| | - Na Li
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China
| | - Guoli Yang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China
| | - Ying Wang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China.
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Wang Y, Ren C, Bi F, Li P, Tian K. The hydroxyapatite modified 3D printed poly L-lactic acid porous screw in reconstruction of anterior cruciate ligament of rabbit knee joint: a histological and biomechanical study. BMC Musculoskelet Disord 2023; 24:151. [PMID: 36849968 PMCID: PMC9969685 DOI: 10.1186/s12891-023-06245-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 02/15/2023] [Indexed: 03/01/2023] Open
Abstract
BACKGROUND 3D printing technology has become a research hotspot in the field of scientific research because of its personalized customization, maneuverability and the ability to achieve multiple material fabrications. The focus of this study is to use 3D printing technology to customize personalized poly L-lactic acid (PLLA) porous screws in orthopedic plants and to explore its effect on tendon-bone healing after anterior cruciate ligament (ACL) reconstruction. METHODS Preparation of PLLA porous screws with good orthogonal pore structure by 3D printer. The hydroxyapatite (HA) was adsorbed on porous screws by electrostatic layer-by-layer self-assembly (ELSA) technology, and PLLA-HA porous screws were prepared. The surface and spatial morphology of the modified screws were observed by scanning electron microscopy (SEM). The porosity of porous screw was measured by liquid displacement method. Thirty New Zealand male white rabbits were divided into two groups according to simple randomization. Autologous tendon was used for right ACL reconstruction, and porous screws were inserted into the femoral tunnel to fix the transplanted tendon. PLLA group was fixed with porous screws, PLLA-HA group was fixed with HA modified porous screws. At 6 weeks and 12 weeks after surgery, 5 animals in each group were sacrificed randomly for histological examination. The remaining 5 animals in each group underwent Micro-CT and biomechanical tests. RESULTS The pores of PLLA porous screws prepared by 3D printer were uniformly distributed and connected with each other, which meet the experimental requirements. HA was evenly distributed in the porous screw by ELSA technique. Histology showed that compared with PLLA group, mature bone trabeculae were integrated with grafted tendons in PLLA-HA group. Micro-CT showed that the bone formation index of PLLA-HA group was better than that of PLLA group. The new bone was uniformly distributed in the bone tunnel along the screw channel. Biomechanical experiments showed that the failure load and stiffness of PLLA-HA group were significantly higher than those of PLLA group. CONCLUSIONS The 3D printed PLLA porous screw modified by HA can not only fix the grafted tendons, but also increase the inductivity of bone, promote bone growth in the bone tunnel and promote bone integration at the tendon-bone interface. The PLLA-HA porous screw is likely to be used in clinic in the future.
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Affiliation(s)
- Yafei Wang
- Department of Orthopedic Surgery, the First Affiliated Hospital of Zhengzhou University, NO.1 Jianshe East Road, Zhengzhou, China
| | - Chengzhen Ren
- Department of Orthopedic Surgery, the First Affiliated Hospital of Zhengzhou University, NO.1 Jianshe East Road, Zhengzhou, China
| | - Fanggang Bi
- Department of Orthopedic Surgery, the First Affiliated Hospital of Zhengzhou University, NO.1 Jianshe East Road, Zhengzhou, China
| | - Pengju Li
- Department of Orthopedic Surgery, the Honghui Hospital of Xi'an, No. 76 Nanguo road, Nan Xiaomen, Xi'an, 710054, China
| | - Ke Tian
- Department of Orthopedic Surgery, the First Affiliated Hospital of Zhengzhou University, NO.1 Jianshe East Road, Zhengzhou, China.
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Ragni E, Perucca Orfei C, Valli F, Zagra L, de Girolamo L. Molecular Characterization of Secreted Factors and Extracellular Vesicles-Embedded miRNAs from Bone Marrow-Derived Mesenchymal Stromal Cells in Presence of Synovial Fluid from Osteoarthritis Patients. BIOLOGY 2022; 11:1632. [PMID: 36358333 PMCID: PMC9687557 DOI: 10.3390/biology11111632] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 11/02/2022] [Accepted: 11/04/2022] [Indexed: 02/07/2024]
Abstract
Bone marrow-derived mesenchymal stromal cells (BMSCs)-based therapies show a great potential to manage inflammation and tissue degeneration in osteoarthritis (OA) patients. Clinical trials showed the ability to manage pain and activation of immune cells and allowed restoration of damaged cartilage. To date, a molecular fingerprint of BMSC-secreted molecules in OA joint conditions able to support clinical outcomes is missing; the lack of that molecular bridge between BMSC activity and clinical results hampers clinical awareness and translation into practice. In this study, BMSCs were cultured in synovial fluid (SF) obtained from OA patients and, for the first time, a thorough characterization of soluble factors and extracellular vesicles (EVs)-embedded miRNAs was performed in this condition. Molecular data were sifted through the sieve of molecules and pathways characterizing the OA phenotype in immune cells and joint tissues. One-hundred and twenty-five secreted factors and one-hundred and ninety-two miRNAs were identified. The combined action of both types of molecules was shown to, first, foster BMSCs interaction with the most important OA immune cells, such as macrophages and T cells, driving their switch towards an anti-inflammatory phenotype and, second, promote cartilage homeostasis assisting chondrocyte proliferation and attenuating the imbalance between destructive and protective extracellular matrix-related players. Overall, molecular data give an understanding of the clinical results observed in OA patients and can enable a faster translation of BMSC-based products into everyday clinical practice.
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Affiliation(s)
- Enrico Ragni
- Laboratorio di Biotecnologie applicate all’Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, I-20161 Milan, Italy
| | - Carlotta Perucca Orfei
- Laboratorio di Biotecnologie applicate all’Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, I-20161 Milan, Italy
| | - Federico Valli
- Chirurgia Articolare Sostitutiva e Chirurgia Ortopedica (CASCO), IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, I-20161 Milan, Italy
| | - Luigi Zagra
- Hip Department, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, I-20161 Milan, Italy
| | - Laura de Girolamo
- Laboratorio di Biotecnologie applicate all’Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, I-20161 Milan, Italy
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Advances in Biomaterial-Mediated Gene Therapy for Articular Cartilage Repair. Bioengineering (Basel) 2022; 9:bioengineering9100502. [PMID: 36290470 PMCID: PMC9598732 DOI: 10.3390/bioengineering9100502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/16/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022] Open
Abstract
Articular cartilage defects caused by various reasons are relatively common in clinical practice, but the lack of efficient therapeutic methods remains a substantial challenge due to limitations in the chondrocytes’ repair abilities. In the search for scientific cartilage repair methods, gene therapy appears to be more effective and promising, especially with acellular biomaterial-assisted procedures. Biomaterial-mediated gene therapy has mainly been divided into non-viral vector and viral vector strategies, where the controlled delivery of gene vectors is contained using biocompatible materials. This review will introduce the common clinical methods of cartilage repair used, the strategies of gene therapy for cartilage injuries, and the latest progress.
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Siefen T, Bjerregaard S, Borglin C, Lamprecht A. Assessment of joint pharmacokinetics and consequences for the intraarticular delivery of biologics. J Control Release 2022; 348:745-759. [PMID: 35714731 DOI: 10.1016/j.jconrel.2022.06.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 06/08/2022] [Accepted: 06/09/2022] [Indexed: 01/15/2023]
Abstract
Intraarticular (IA) injections provide the opportunity to deliver biologics directly to their site of action for a local and efficient treatment of osteoarthritis. However, the synovial joint is a challenging site of administration since the drug is rapidly eliminated across the synovial membrane and has limited distribution into cartilage, resulting in unsatisfactory therapeutic efficacy. In order to rationally develop appropriate drug delivery systems, it is essential to thoroughly understand the unique biopharmaceutical environments and kinetics in the joint to adequately simulate them in relevant experimental models. This review presents a detailed view on articular kinetics and drug-tissue interplay of IA administered drugs and summarizes how these can be translated into reasonable formulation strategies by identification of key factors through which the joint residence time can be prolonged and specific structures can be targeted. In this way, pros and cons of the delivery approaches for biologics will be evaluated and the extent to which biorelevant models are applicable to gain mechanistic insights and ameliorate formulation design is discussed.
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Affiliation(s)
- Tobias Siefen
- Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany
| | | | | | - Alf Lamprecht
- Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany; PEPITE (EA4267), University of Burgundy/Franche-Comté, Besançon, France.
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Li Q, Sun L, Huang X, Liu S, Yong H, Wang C, Li J, Zhou D. Genetic Engineering of Adipose-Derived Stem Cells Using Biodegradable and Lipid-Like Highly Branched Poly(β-amino ester)s. ACS Macro Lett 2022; 11:636-642. [PMID: 35570814 DOI: 10.1021/acsmacrolett.2c00095] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Biodegradable and lipid-like highly branched poly(β-amino ester)s, HPAESA, were developed to enhance the biological functions of adipose-derived stem cells by gene transfection. Biodegradability reduces the cytotoxicity of HPAESA and enables controlled DNA release. Lipid mimicry enhances cellular uptake and endosomal escape of HPAESA/DNA polyplexes. HPAESA are able to transfect rat adipose-derived stem cells (rADSs) and human ADSCs (hADSCs) with orders of magnitude higher efficiency than commercial gene transfection reagents, with cell viability exceeding 90%. Most importantly, HPAESA can effectively transfer the nerve growth factor (NGF)-encoding plasmid to rADSCs and induce high NGF secretion, which significantly promotes neurite outgrowth of PC12 cells.
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Affiliation(s)
- Qiuxia Li
- School of Chemical Engineering and Technology, Xi’an Jiaotong University, Xi’an 710049, China
| | - Litao Sun
- School of Chemical Engineering and Technology, Xi’an Jiaotong University, Xi’an 710049, China
| | - Xiaobei Huang
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China
| | - Shuai Liu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Haiyang Yong
- School of Chemical Engineering and Technology, Xi’an Jiaotong University, Xi’an 710049, China
| | - Chenfei Wang
- School of Chemical Engineering and Technology, Xi’an Jiaotong University, Xi’an 710049, China
| | - Jianzhong Li
- Department of Thoracic Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
| | - Dezhong Zhou
- School of Chemical Engineering and Technology, Xi’an Jiaotong University, Xi’an 710049, China
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Nabizadeh Z, Nasrollahzadeh M, Daemi H, Baghaban Eslaminejad M, Shabani AA, Dadashpour M, Mirmohammadkhani M, Nasrabadi D. Micro- and nanotechnology in biomedical engineering for cartilage tissue regeneration in osteoarthritis. BEILSTEIN JOURNAL OF NANOTECHNOLOGY 2022; 13:363-389. [PMID: 35529803 PMCID: PMC9039523 DOI: 10.3762/bjnano.13.31] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 03/24/2022] [Indexed: 05/12/2023]
Abstract
Osteoarthritis, which typically arises from aging, traumatic injury, or obesity, is the most common form of arthritis, which usually leads to malfunction of the joints and requires medical interventions due to the poor self-healing capacity of articular cartilage. However, currently used medical treatment modalities have reported, at least in part, disappointing and frustrating results for patients with osteoarthritis. Recent progress in the design and fabrication of tissue-engineered microscale/nanoscale platforms, which arises from the convergence of stem cell research and nanotechnology methods, has shown promising results in the administration of new and efficient options for treating osteochondral lesions. This paper presents an overview of the recent advances in osteochondral tissue engineering resulting from the application of micro- and nanotechnology approaches in the structure of biomaterials, including biological and microscale/nanoscale topographical cues, microspheres, nanoparticles, nanofibers, and nanotubes.
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Affiliation(s)
- Zahra Nabizadeh
- Department of Medical Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
- Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | | | - Hamed Daemi
- Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Mohamadreza Baghaban Eslaminejad
- Department of Stem Cell and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Ali Akbar Shabani
- Department of Medical Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
- Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Mehdi Dadashpour
- Department of Medical Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
- Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Majid Mirmohammadkhani
- Department of Epidemiology and Biostatistics, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Davood Nasrabadi
- Department of Medical Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
- Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran
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Qiao K, Xu L, Tang J, Wang Q, Lim KS, Hooper G, Woodfield TBF, Liu G, Tian K, Zhang W, Cui X. The advances in nanomedicine for bone and cartilage repair. J Nanobiotechnology 2022; 20:141. [PMID: 35303876 PMCID: PMC8932118 DOI: 10.1186/s12951-022-01342-8] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 03/01/2022] [Indexed: 12/24/2022] Open
Abstract
With the gradual demographic shift toward an aging and obese society, an increasing number of patients are suffering from bone and cartilage injuries. However, conventional therapies are hindered by the defects of materials, failing to adequately stimulate the necessary cellular response to promote sufficient cartilage regeneration, bone remodeling and osseointegration. In recent years, the rapid development of nanomedicine has initiated a revolution in orthopedics, especially in tissue engineering and regenerative medicine, due to their capacity to effectively stimulate cellular responses on a nanoscale with enhanced drug loading efficiency, targeted capability, increased mechanical properties and improved uptake rate, resulting in an improved therapeutic effect. Therefore, a comprehensive review of advancements in nanomedicine for bone and cartilage diseases is timely and beneficial. This review firstly summarized the wide range of existing nanotechnology applications in the medical field. The progressive development of nano delivery systems in nanomedicine, including nanoparticles and biomimetic techniques, which are lacking in the current literature, is further described. More importantly, we also highlighted the research advancements of nanomedicine in bone and cartilage repair using the latest preclinical and clinical examples, and further discussed the research directions of nano-therapies in future clinical practice.
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Affiliation(s)
- Kai Qiao
- Department of Bone & Joint, the First Affiliated Hospital of Dalian Medical University, Dalian, 116000, Liaoning, China
| | - Lu Xu
- Department of Bone & Joint, the First Affiliated Hospital of Dalian Medical University, Dalian, 116000, Liaoning, China
- Department of Dermatology, the Second Affiliated Hospital of Dalian Medical University, Dalian, 116000, Liaoning, China
| | - Junnan Tang
- Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Qiguang Wang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 61004, Sichuan, China
| | - Khoon S Lim
- Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, Department of Orthopaedic Surgery & Musculoskeletal Medicine, University of Otago, Christchurch, 8011, New Zealand
| | - Gary Hooper
- Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, Department of Orthopaedic Surgery & Musculoskeletal Medicine, University of Otago, Christchurch, 8011, New Zealand
| | - Tim B F Woodfield
- Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, Department of Orthopaedic Surgery & Musculoskeletal Medicine, University of Otago, Christchurch, 8011, New Zealand
| | - Guozhen Liu
- School of Life and Health Sciences, The Chinese University of Hong Kong (Shenzhen), Shenzhen, 518172, Guangdong, China
| | - Kang Tian
- Department of Bone & Joint, the First Affiliated Hospital of Dalian Medical University, Dalian, 116000, Liaoning, China.
| | - Weiguo Zhang
- Department of Bone & Joint, the First Affiliated Hospital of Dalian Medical University, Dalian, 116000, Liaoning, China.
| | - Xiaolin Cui
- Department of Bone & Joint, the First Affiliated Hospital of Dalian Medical University, Dalian, 116000, Liaoning, China.
- Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, Department of Orthopaedic Surgery & Musculoskeletal Medicine, University of Otago, Christchurch, 8011, New Zealand.
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Li X, Dai B, Guo J, Zheng L, Guo Q, Peng J, Xu J, Qin L. Nanoparticle-Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy. NANO-MICRO LETTERS 2021; 13:149. [PMID: 34160733 PMCID: PMC8222488 DOI: 10.1007/s40820-021-00670-y] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 05/19/2021] [Indexed: 05/03/2023]
Abstract
Osteoarthritis is the most prevalent chronic and debilitating joint disease, resulting in huge medical and socioeconomic burdens. Intra-articular administration of agents is clinically used for pain management. However, the effectiveness is inapparent caused by the rapid clearance of agents. To overcome this issue, nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic agents. Given the therapeutic programs are inseparable from pathological progress of osteoarthritis, an ideal delivery system should allow the release of therapeutic agents upon specific features of disorders. In this review, we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug release. Then, we review the interactions of nanoparticles with cartilage microenvironment and the rational design. Furthermore, we highlight advances in the therapeutic schemes according to the pathology signals. Finally, armed with an updated understanding of the pathological mechanisms, we place an emphasis on the development of "smart" bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological signals. We anticipate that the exploration of nanoparticles by balancing the efficacy, safety, and complexity will lay down a solid foundation tangible for clinical translation.
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Affiliation(s)
- Xu Li
- Musculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
- Joint Laboratory of Chinese Academic of Science and Hong Kong for Biomaterials, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
- Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
| | - Bingyang Dai
- Musculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
- Joint Laboratory of Chinese Academic of Science and Hong Kong for Biomaterials, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
- Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
| | - Jiaxin Guo
- Musculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
- Joint Laboratory of Chinese Academic of Science and Hong Kong for Biomaterials, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
- Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
| | - Lizhen Zheng
- Musculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
- Joint Laboratory of Chinese Academic of Science and Hong Kong for Biomaterials, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
- Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China
| | - Quanyi Guo
- Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, Institute of Orthopedics, Chinese PLA General Hospital, Beijing, People's Republic of China
| | - Jiang Peng
- Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, Institute of Orthopedics, Chinese PLA General Hospital, Beijing, People's Republic of China
| | - Jiankun Xu
- Musculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China.
- Joint Laboratory of Chinese Academic of Science and Hong Kong for Biomaterials, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China.
- Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China.
| | - Ling Qin
- Musculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China.
- Joint Laboratory of Chinese Academic of Science and Hong Kong for Biomaterials, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China.
- Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, People's Republic of China.
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12
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Lawson TB, Mäkelä JTA, Klein T, Snyder BD, Grinstaff MW. Nanotechnology and Osteoarthritis. Part 2: Opportunities for advanced devices and therapeutics. J Orthop Res 2021; 39:473-484. [PMID: 32860444 DOI: 10.1002/jor.24842] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 08/27/2020] [Indexed: 02/04/2023]
Abstract
Osteoarthritis (OA) is a multifactorial disease of the entire joint which afflicts 140 million individuals worldwide regardless of economic or social status. Current clinical treatments for OA primarily center on reducing pain and increasing mobility, and there are limited therapeutic interventions to restore degraded cartilage or slow disease pathogenesis. This second installment of a two-part review on nanotechnology and OA focuses on novel treatment strategies. Specifically, Part 2 first discusses current surgical and nonsurgical treatments for OA and then summarizes recent advancements in nanotechnology-based treatments, while Part 1 (10.1002/jor.24817) described advances in imaging and diagnostics. We review nano delivery systems for small molecule drugs, nucleic acids, and proteins followed by nano-based scaffolds for neocartilage formation and osteochondral regeneration, and lastly nanoparticle lubricants. We conclude by identifying opportunities for nanomedicine advances, and prospects for OA treatments.
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Affiliation(s)
- Taylor B Lawson
- Departments of Biomedical Engineering, Mechanical Engineering, Chemistry, and Medicine Boston University, Boston, Massachusetts, USA
- Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Janne T A Mäkelä
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland
| | - Travis Klein
- Center for Biomedical Technologies, Queensland University of Technology, Brisbane, Australia
| | - Brian D Snyder
- Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Mark W Grinstaff
- Departments of Biomedical Engineering, Mechanical Engineering, Chemistry, and Medicine Boston University, Boston, Massachusetts, USA
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13
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Sharma V, Srinivasan A, Nikolajeff F, Kumar S. Biomineralization process in hard tissues: The interaction complexity within protein and inorganic counterparts. Acta Biomater 2021; 120:20-37. [PMID: 32413577 DOI: 10.1016/j.actbio.2020.04.049] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 04/17/2020] [Accepted: 04/26/2020] [Indexed: 02/07/2023]
Abstract
Biomineralization can be considered as nature's strategy to produce and sustain biominerals, primarily via creation of hard tissues for protection and support. This review examines the biomineralization process within the hard tissues of the human body with special emphasis on the mechanisms and principles of bone and teeth mineralization. We describe the detailed role of proteins and inorganic ions in mediating the mineralization process. Furthermore, we highlight the various available models for studying bone physiology and mineralization starting from the historical static cell line-based methods to the most advanced 3D culture systems, elucidating the pros and cons of each one of these methods. With respect to the mineralization process in teeth, enamel and dentin mineralization is discussed in detail. The key role of intrinsically disordered proteins in modulating the process of mineralization in enamel and dentine is given attention. Finally, nanotechnological interventions in the area of bone and teeth mineralization, diseases and tissue regeneration is also discussed. STATEMENT OF SIGNIFICANCE: This article provides an overview of the biomineralization process within hard tissues of the human body, which encompasses the detailed mechanism innvolved in the formation of structures like teeth and bone. Moreover, we have discussed various available models used for studying biomineralization and also explored the nanotechnological applications in the field of bone regeneration and dentistry.
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Affiliation(s)
- Vaibhav Sharma
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
| | | | | | - Saroj Kumar
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
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14
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Hakamivala A, Shuxin li, Robinson K, Huang Y, Yu S, Yuan B, Borrelli J, Tang L. Recruitment of endogenous progenitor cells by erythropoietin loaded particles for in situ cartilage regeneration. Bioact Mater 2020; 5:142-152. [PMID: 32072078 PMCID: PMC7011041 DOI: 10.1016/j.bioactmat.2020.01.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 11/12/2019] [Accepted: 01/12/2020] [Indexed: 12/21/2022] Open
Abstract
Cartilage injury affects millions of people throughout the world, and at this time there is no cure. While transplantation of stem cells has shown some success in the treatment of injured cartilage, such treatment is limited by limited cell sources and safety concerns. To overcome these drawbacks, a microscaffolds system was developed capable of targeting, reducing the inflammatory response and recruiting endogenous progenitor cells to cartilage-defect. Erythropoietin (EPO)-loaded-hyaluronic acid (HA) microscaffolds (HA + EPO) were fabricated and characterized. HA-microscaffolds showed good cell-compatibility and could target chondrocytes via CD44 receptors. HA + EPO was designed to slowly release EPO while recruiting progenitor cells. Finally, the ability of HA + EPO to repair cartilage-defects was assessed using a rabbit model of full-thickness cartilage-defect. Our results showed that the intra-articular administration of EPO, HA, and EPO + HA reduced the number of inflammatory cells inside the synovial-fluid, while EPO + HA had the greatest anti-inflammatory effects. Furthermore, among all groups, EPO + HA achieved the greatest progenitor cell recruitment and subsequent chondrogenesis. The results of this work support that, by targeting and localizing the release of growth-factors, HA + EPO can reduce inflammatory responses and promote progenitor cells responses. This new platform represents an alternative treatment to stem-cell transplantation for the treatment of cartilage injury.
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Affiliation(s)
- Amirhossein Hakamivala
- Bioengineering Department, University of Texas Southwestern Medical Center, The University of Texas at Arlington, Arlington, TX, 76019, USA
| | - Shuxin li
- Bioengineering Department, University of Texas Southwestern Medical Center, The University of Texas at Arlington, Arlington, TX, 76019, USA
| | - Kayti Robinson
- Department of Biology, The University of Texas at Arlington, Arlington, TX, 76019, USA
| | - YiHui Huang
- Bioengineering Department, University of Texas Southwestern Medical Center, The University of Texas at Arlington, Arlington, TX, 76019, USA
| | - Shuai Yu
- Bioengineering Department, University of Texas Southwestern Medical Center, The University of Texas at Arlington, Arlington, TX, 76019, USA
| | - Baohong Yuan
- Bioengineering Department, University of Texas Southwestern Medical Center, The University of Texas at Arlington, Arlington, TX, 76019, USA
| | - Joseph Borrelli
- Bioengineering Department, University of Texas Southwestern Medical Center, The University of Texas at Arlington, Arlington, TX, 76019, USA
| | - Liping Tang
- Bioengineering Department, University of Texas Southwestern Medical Center, The University of Texas at Arlington, Arlington, TX, 76019, USA
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15
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Filippi M, Born G, Felder-Flesch D, Scherberich A. Use of nanoparticles in skeletal tissue regeneration and engineering. Histol Histopathol 2019; 35:331-350. [PMID: 31721139 DOI: 10.14670/hh-18-184] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Bone and osteochondral defects represent one of the major causes of disabilities in the world. Derived from traumas and degenerative pathologies, these lesions cause severe pain, joint deformity, and loss of joint motion. The standard treatments in clinical practice present several limitations. By producing functional substitutes for damaged tissues, tissue engineering has emerged as an alternative in the treatment of defects in the skeletal system. Despite promising preliminary clinical outcomes, several limitations remain. Nanotechnologies could offer new solutions to overcome those limitations, generating materials more closely mimicking the structures present in naturally occurring systems. Nanostructures comparable in size to those appearing in natural bone and cartilage have thus become relevant in skeletal tissue engineering. In particular, nanoparticles allow for a unique combination of approaches (e.g. cell labelling, scaffold modification or drug and gene delivery) inside single integrated systems for optimized tissue regeneration. In the present review, the main types of nanoparticles and the current strategies for their application to skeletal tissue engineering are described. The collection of studies herein considered confirms that advanced nanomaterials will be determinant in the design of regenerative therapeutic protocols for skeletal lesions in the future.
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Affiliation(s)
- Miriam Filippi
- Department of Biomedical Engineering, University of Basel, Allschwil, Basel, Switzerland.,Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Gordian Born
- Department of Biomedical Engineering, University of Basel, Allschwil, Basel, Switzerland.,Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Delphine Felder-Flesch
- Institut de Physique et Chimie des Matériaux Strasbourg, UMR CNRS-Université de Strasbourg, Strasbourg, France
| | - Arnaud Scherberich
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.,Department of Biomedical Engineering, University of Basel, Allschwil, Basel, Switzerland.
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16
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García-Couce J, Almirall A, Fuentes G, Kaijzel E, Chan A, Cruz LJ. Targeting Polymeric Nanobiomaterials as a Platform for Cartilage Tissue Engineering. Curr Pharm Des 2019; 25:1915-1932. [DOI: 10.2174/1381612825666190708184745] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 06/26/2019] [Indexed: 01/05/2023]
Abstract
Articular cartilage is a connective tissue structure that is found in anatomical areas that are important for the movement of the human body. Osteoarthritis is the ailment that most often affects the articular cartilage. Due to its poor intrinsic healing capacity, damage to the articular cartilage is highly detrimental and at present the reconstructive options for its repair are limited. Tissue engineering and the science of nanobiomaterials are two lines of research that together can contribute to the restoration of damaged tissue. The science of nanobiomaterials focuses on the development of different nanoscale structures that can be used as carriers of drugs / cells to treat and repair damaged tissues such as articular cartilage. This review article is an overview of the composition of articular cartilage, the causes and treatments of osteoarthritis, with a special emphasis on nanomaterials as carriers of drugs and cells, which reduce inflammation, promote the activation of biochemical factors and ultimately contribute to the total restoration of articular cartilage.
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Affiliation(s)
- Jomarien García-Couce
- Translational Nanobiomaterials and Imaging (TNI) group, Radiology department, Leiden University Medical Centrum, Leiden, Netherlands
| | - Amisel Almirall
- Translational Nanobiomaterials and Imaging (TNI) group, Radiology department, Leiden University Medical Centrum, Leiden, Netherlands
| | - Gastón Fuentes
- Translational Nanobiomaterials and Imaging (TNI) group, Radiology department, Leiden University Medical Centrum, Leiden, Netherlands
| | - Eric Kaijzel
- Translational Nanobiomaterials and Imaging (TNI) group, Radiology department, Leiden University Medical Centrum, Leiden, Netherlands
| | - Alan Chan
- Percuros B.V., Zernikedreef 8, 2333 CL Leiden, Netherlands
| | - Luis J. Cruz
- Translational Nanobiomaterials and Imaging (TNI) group, Radiology department, Leiden University Medical Centrum, Leiden, Netherlands
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17
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Biomaterial-guided delivery of gene vectors for targeted articular cartilage repair. Nat Rev Rheumatol 2018; 15:18-29. [DOI: 10.1038/s41584-018-0125-2] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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18
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Smane L, Pilmane M. Evaluation of the presence of MMP-2, TIMP-2, BMP2/4, and TGFβ3 in the facial tissue of children with cleft lip and palate. Acta Med Litu 2018; 25:86-94. [PMID: 30210242 PMCID: PMC6130923 DOI: 10.6001/actamedica.v25i2.3761] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Cleft lip and palate (CLP) is the most common defect affecting the face. The treatment consists of surgical reconstruction of the anatomical structures of the cleft. Part of the surgical treatment is reconstruction of the alveolar bone by means of autogenic bone grafting (osteoplasty). This study aimed to evaluate the levels of expression of extracellular matrix remodeling factors in the facial tissue of children with a complete unilateral (CU) and a complete bilateral (CB) CLP to assess whether the wound healing process is adequate. Twenty-two CLP patients were enrolled in this study. Tissue samples were collected during alveolar osteoplasty for unilateral (n = 12) or bilateral (n = 10) cleft palate, (age range from 6 years 8 months to 12 years 2 months). Control material was obtained in the case of tooth extraction (age range from 6 years 9 months to 14 years 5 months). Immunohistochemistry was used to assess the levels of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), bone morphogenetic proteins 2 and 4 (BMP2/4), and transforming growth factor β3 (TGFβ3). Numbers of positively stained cells were graded semi-quantitatively. Data were analysed using the Kraskel-Wallis rank test and the Bonferroni correction. The total number of MMP2-positive cells was significantly lower in the CBCLP and in the control group than in the CUCLP (p < 0.001 after the Bonferroni correction). The total number of TIMP2-positive cells was significantly higher in the CUCLP than in the CBCLP and in the control group (p < 0.001; p < 0.003 after the Bonferroni correction). The overall number of BMP2/4, TGFβ3-positive cells was significantly higher in the CUCLP than in the CBCLP and in the control group (p < 0.001 after the Bonferroni correction). The decrease of the relative amount of statistically significant BMP2/4, TGFβ3, MMP-2, TIMP-2 containing bone cells in CBCLP patients identifies affected alveolar bone regeneration and remodeling process.
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Affiliation(s)
- Liene Smane
- Department of Pediatrics, Children's Clinical University Hospital, Riga, Latvia
| | - Mara Pilmane
- Institute of Anatomy and Anthropology, Department of Morphology, Riga Stradiņš University, Riga, Latvia
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19
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Deng ZH, Li YS, Gao X, Lei GH, Huard J. Bone morphogenetic proteins for articular cartilage regeneration. Osteoarthritis Cartilage 2018; 26:1153-1161. [PMID: 29580979 DOI: 10.1016/j.joca.2018.03.007] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Revised: 02/18/2018] [Accepted: 03/19/2018] [Indexed: 02/02/2023]
Abstract
Degeneration of articular cartilage (AC) tissue is the most common cause of osteoarthritis (OA) and rheumatoid arthritis. Bone morphogenetic proteins (BMPs) play important roles in bone and cartilage formation. This article reviews the experimental and clinical applications of BMPs in cartilage regeneration. Experimental evidence indicates that BMPs play an important role in protection against cartilage damage caused by inflammation or trauma, by binding to different receptor combinations and, consequently, activating different intracellular signaling pathways. Loss of function of BMP-related receptors contributes to the decreased intrinsic repair capacity of damaged cartilage and, thus, the multifunctional effects of BMPs make them attractive tools for the treatment of cartilage damage in patients with degenerative diseases. However, the development of BMP therapy as a treatment modality for cartilage regeneration has been hampered by certain factors, such as the eligibility of participants in clinical trials, financial support, drug delivery carrier safety, availabilities of effective scaffolds, appropriate selection of optimal dose and timing of administration, and side effects. Further research is needed to overcome these issues for future routine clinical applications. Research and development leading to the successful application of BMPs can initiate a new era in the treatment of cartilage degenerative diseases like OA.
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Affiliation(s)
- Z H Deng
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; Department of Orthopaedic Surgery, Center for Tissue Engineering and Aging Research, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Orthopedics, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University), Shenzhen, Guangdong Province, China
| | - Y S Li
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - X Gao
- Department of Orthopaedic Surgery, Center for Tissue Engineering and Aging Research, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA; The Steadman Philippon Research Institute, Vail, CO, USA
| | - G H Lei
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
| | - J Huard
- Department of Orthopaedic Surgery, Center for Tissue Engineering and Aging Research, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA; The Steadman Philippon Research Institute, Vail, CO, USA.
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20
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Controlled Non-Viral Gene Delivery in Cartilage and Bone Repair: Current Strategies and Future Directions. ADVANCED THERAPEUTICS 2018. [DOI: 10.1002/adtp.201800038] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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21
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Comparative efficacy of stem cells and secretome in articular cartilage regeneration: a systematic review and meta-analysis. Cell Tissue Res 2018; 375:329-344. [PMID: 30084022 DOI: 10.1007/s00441-018-2884-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 07/04/2018] [Indexed: 12/17/2022]
Abstract
Articular cartilage defect remains the most challenging joint disease due to limited intrinsic healing capacity of the cartilage that most often progresses to osteoarthritis. In recent years, stem cell therapy has evolved as therapeutic strategies for articular cartilage regeneration. However, a number of studies have shown that therapeutic efficacy of stem cell transplantation is attributed to multiple secreted factors that modulate the surrounding milieu to evoke reparative processes. This systematic review and meta-analysis aim to evaluate and compare the therapeutic efficacy of stem cell and secretome in articular cartilage regeneration in animal models. We systematically searched the PubMed, CINAHL, Cochrane Library, Ovid Medline and Scopus databases until August 2017 using search terms related to stem cells, cartilage regeneration and animals. A random effect meta-analysis of the included studies was performed to assess the treatment effects on new cartilage formation on an absolute score of 0-100% scale. Subgroup analyses were also performed by sorting studies independently based on similar characteristics. The pooled analysis of 59 studies that utilized stem cells significantly improved new cartilage formation by 25.99% as compared with control. Similarly, the secretome also significantly increased cartilage regeneration by 26.08% in comparison to the control. Subgroup analyses revealed no significant difference in the effect of stem cells in new cartilage formation. However, there was a significant decline in the effect of stem cells in articular cartilage regeneration during long-term follow-up, suggesting that the duration of follow-up is a predictor of new cartilage formation. Secretome has shown a similar effect to stem cells in new cartilage formation. The risk of bias assessment showed poor reporting for most studies thereby limiting the actual risk of bias assessment. The present study suggests that both stem cells and secretome interventions improve cartilage regeneration in animal trials. Graphical abstract ᅟ.
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22
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Grol MW, Stone A, Ruan MZ, Guse K, Lee BH. Prospects of Gene Therapy for Skeletal Diseases. GENETICS OF BONE BIOLOGY AND SKELETAL DISEASE 2018:119-137. [DOI: 10.1016/b978-0-12-804182-6.00008-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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23
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Paschos NK, Sennett ML. Update on mesenchymal stem cell therapies for cartilage disorders. World J Orthop 2017; 8:853-860. [PMID: 29312843 PMCID: PMC5745427 DOI: 10.5312/wjo.v8.i12.853] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Revised: 09/23/2017] [Accepted: 10/17/2017] [Indexed: 02/06/2023] Open
Abstract
Cartilage disorders, including focal cartilage lesions, are among the most common clinical problems in orthopedic practice. Left untreated, large focal lesions may result in progression to osteoarthritis, with tremendous impact on the quality of life of affected individuals. Current management strategies have shown only a modest degree of success, while several upcoming interventions signify better outcomes in the future. Among these, stem cell therapies have been suggested as a promising new era for cartilage disorders. Certain characteristics of the stem cells, such as their potential to differentiate but also to support healing made them a fruitful candidate for lesions in cartilage, a tissue with poor healing capacity. The aim of this editorial is to provide an update on the recent advancements in the field of stem cell therapy for the management of focal cartilage defects. Our goal is to present recent basic science advances and to present the potential of the use of stem cells in novel clinical interventions towards enhancement of the treatment armamentarium for cartilage lesions. Furthermore, we highlight some thoughts for the future of cartilage regeneration and repair and to explore future perspectives for the next steps in the field.
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Affiliation(s)
- Nikolaos K Paschos
- Department of Orthopaedic Surgery, Division of Sports Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, United States
- Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA 19107, United States
| | - Mackenzie L Sennett
- Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA 19107, United States
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Madrigal JL, Stilhano R, Silva EA. Biomaterial-Guided Gene Delivery for Musculoskeletal Tissue Repair. TISSUE ENGINEERING. PART B, REVIEWS 2017; 23:347-361. [PMID: 28166711 PMCID: PMC5749599 DOI: 10.1089/ten.teb.2016.0462] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Accepted: 01/11/2017] [Indexed: 02/07/2023]
Abstract
Gene therapy is a promising strategy for musculoskeletal tissue repair and regeneration where local and sustained expression of proteins and/or therapeutic nucleic acids can be achieved. However, the musculoskeletal tissues present unique engineering and biological challenges as recipients of genetic vectors. Targeting specific cell populations, regulating expression in vivo, and overcoming the harsh environment of damaged tissue accompany the general concerns of safety and efficacy common to all applications of gene therapy. In this review, we will first summarize these challenges and then discuss how biomaterial carriers for genetic vectors can address these issues. Second, we will review how limitations specific to given vectors further motivate the utility of biomaterial carriers. Finally, we will discuss how these concepts have been combined with tissue engineering strategies and approaches to improve the delivery of these vectors for musculoskeletal tissue regeneration.
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Affiliation(s)
- Justin L Madrigal
- Department of Biomedical Engineering, University of California , Davis, Davis, California
| | - Roberta Stilhano
- Department of Biomedical Engineering, University of California , Davis, Davis, California
| | - Eduardo A Silva
- Department of Biomedical Engineering, University of California , Davis, Davis, California
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25
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Garrison P, Yue S, Hanson J, Baron J, Lui JC. Spatial regulation of bone morphogenetic proteins (BMPs) in postnatal articular and growth plate cartilage. PLoS One 2017; 12:e0176752. [PMID: 28467498 PMCID: PMC5414995 DOI: 10.1371/journal.pone.0176752] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Accepted: 04/17/2017] [Indexed: 11/18/2022] Open
Abstract
Articular and growth plate cartilage both arise from condensations of mesenchymal cells, but ultimately develop important histological and functional differences. Each is composed of three layers—the superficial, mid and deep zones of articular cartilage and the resting, proliferative and hypertrophic zones of growth plate cartilage. The bone morphogenetic protein (BMP) system plays an important role in cartilage development. A gradient in expression of BMP-related genes has been observed across growth plate cartilage, likely playing a role in zonal differentiation. To investigate the presence of a similar expression gradient in articular cartilage, we used laser capture microdissection (LCM) to separate murine growth plate and articular cartilage from the proximal tibia into their six constituent zones, and used a solution hybridization assay with color-coded probes (nCounter) to quantify mRNAs for 30 different BMP-related genes in each zone. In situ hybridization and immunohistochemistry were then used to confirm spatial expression patterns. Expression gradients for Bmp2 and 6 were observed across growth plate cartilage with highest expression in hypertrophic zone. However, intracellular BMP signaling, assessed by phospho-Smad1/5/8 immunohistochemical staining, appeared to be higher in the proliferative zone and prehypertrophic area than in hypertrophic zone, possibly due to high expression of Smad7, an inhibitory Smad, in the hypertrophic zone. We also found BMP expression gradients across the articular cartilage with BMP agonists primarily expressed in the superficial zone and BMP functional antagonists primarily expressed in the deep zone. Phospho-Smad1/5/8 immunohistochemical staining showed a similar gradient. In combination with previous evidence that BMPs regulate chondrocyte proliferation and differentiation, the current findings suggest that BMP signaling gradients exist across both growth plate and articular cartilage and that these gradients may contribute to the spatial differentiation of chondrocytes in the postnatal endochondral skeleton.
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Affiliation(s)
- Presley Garrison
- Section on Growth and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Shanna Yue
- Section on Growth and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Jeffrey Hanson
- Laser Capture Microdissection Core Facility, Laboratory of Pathology, National Cancer Institute (NCI), NIH, Bethesda, Maryland, United States of America
| | - Jeffrey Baron
- Section on Growth and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Julian C. Lui
- Section on Growth and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America
- * E-mail:
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Frisch J, Cucchiarini M. Gene- and Stem Cell-Based Approaches to Regulate Hypertrophic Differentiation in Articular Cartilage Disorders. Stem Cells Dev 2016; 25:1495-1512. [DOI: 10.1089/scd.2016.0106] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Janina Frisch
- Center of Experimental Orthopaedics, Saarland University and Saarland University Medical Center, Homburg, Germany
| | - Magali Cucchiarini
- Center of Experimental Orthopaedics, Saarland University and Saarland University Medical Center, Homburg, Germany
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Trumbull A, Subramanian G, Yildirim-Ayan E. Mechanoresponsive musculoskeletal tissue differentiation of adipose-derived stem cells. Biomed Eng Online 2016; 15:43. [PMID: 27103394 PMCID: PMC4840975 DOI: 10.1186/s12938-016-0150-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Accepted: 03/24/2016] [Indexed: 02/06/2023] Open
Abstract
Musculoskeletal tissues are constantly under mechanical strains within their microenvironment. Yet, little is understood about the effect of in vivo mechanical milieu strains on cell development and function. Thus, this review article outlines the in vivo mechanical environment of bone, muscle, cartilage, tendon, and ligaments, and tabulates the mechanical strain and stress in these tissues during physiological condition, vigorous, and moderate activities. This review article further discusses the principles of mechanical loading platforms to create physiologically relevant mechanical milieu in vitro for musculoskeletal tissue regeneration. A special emphasis is placed on adipose-derived stem cells (ADSCs) as an emerging valuable tool for regenerative musculoskeletal tissue engineering, as they are easily isolated, expanded, and able to differentiate into any musculoskeletal tissue. Finally, it highlights the current state-of-the art in ADSCs-guided musculoskeletal tissue regeneration under mechanical loading.
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Affiliation(s)
- Andrew Trumbull
- Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH, 43606, USA
| | - Gayathri Subramanian
- Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH, 43606, USA
| | - Eda Yildirim-Ayan
- Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH, 43606, USA. .,Department of Orthopaedic Surgery, University of Toledo Medical Center, Toledo, OH, 43614, USA.
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Im GI. Regeneration of articular cartilage using adipose stem cells. J Biomed Mater Res A 2016; 104:1830-44. [PMID: 26990234 DOI: 10.1002/jbm.a.35705] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Accepted: 03/02/2016] [Indexed: 12/16/2022]
Abstract
Articular cartilage (AC) has limited potential for self-regeneration and damage to AC eventually leads to the development and progression of osteoarthritis (OA). Cell implantation strategies have emerged as a new treatment modality to regenerate AC. Adipose stem cells/adipose-derived stromal cells (ASCs) have gained attention due to their abundance, excellent proliferative potential, and minimal morbidity during harvest. These advantages lower the cost of cell therapy by circumventing time-consuming procedure of culture expansion. ASCs have drawn attention as a potential source for cartilage regeneration since the feasibility of chondrogenesis from ASCs was first reported. After several groups reported inferior chondrogenesis from ASCs, numerous methods were devised to overcome the intrinsic properties. Most in vivo animal studies have reported good results using predifferentiated or undifferentiated, autologous or allogeneic ASCs to regenerate cartilage in osteochondral defects or surgically-induced OA. In this review, we summarize literature on the isolation and in vitro differentiation processes of ASCs, in vivo studies to regenerate AC in osteochondral defects and OA using ASCs, and clinical applications of ASCs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1830-1844, 2016.
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Affiliation(s)
- Gun-Il Im
- Department of Orthopedics, Dongguk University Ilsan Hospital, Goyang, Korea
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29
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Controlled release of drugs in electrosprayed nanoparticles for bone tissue engineering. Adv Drug Deliv Rev 2015; 94:77-95. [PMID: 26415888 DOI: 10.1016/j.addr.2015.09.007] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2015] [Revised: 08/28/2015] [Accepted: 09/18/2015] [Indexed: 12/17/2022]
Abstract
Generating porous topographic substrates, by mimicking the native extracellular matrix (ECM) to promote the regeneration of damaged bone tissues, is a challenging process. Generally, scaffolds developed for bone tissue regeneration support bone cell growth and induce bone-forming cells by natural proteins and growth factors. Limitations are often associated with these approaches such as improper scaffold stability, and insufficient cell adhesion, proliferation, differentiation, and mineralization with less growth factor expression. Therefore, the use of engineered nanoparticles has been rapidly increasing in bone tissue engineering (BTE) applications. The electrospray technique is advantageous over other conventional methods as it generates nanomaterials of particle sizes in the micro/nanoscale range. The size and charge of the particles are controlled by regulating the polymer solution flow rate and electric voltage. The unique properties of nanoparticles such as large surface area-to-volume ratio, small size, and higher reactivity make them promising candidates in the field of biomedical engineering. These nanomaterials are extensively used as therapeutic agents and for drug delivery, mimicking ECM, and restoring and improving the functions of damaged organs. The controlled and sustained release of encapsulated drugs, proteins, vaccines, growth factors, cells, and nucleotides from nanoparticles has been well developed in nanomedicine. This review provides an insight into the preparation of nanoparticles by electrospraying technique and illustrates the use of nanoparticles in drug delivery for promoting bone tissue regeneration.
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Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence. Stem Cells Int 2015; 2015:597652. [PMID: 26240572 PMCID: PMC4512635 DOI: 10.1155/2015/597652] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2014] [Revised: 12/29/2014] [Accepted: 01/28/2015] [Indexed: 12/14/2022] Open
Abstract
Among the current therapeutic approaches for the regeneration of damaged articular cartilage, none has yet proven to offer results comparable to those of native hyaline cartilage. Recently, it has been claimed that the use of mesenchymal stem cells (MSCs) provides greater regenerative potential than differentiated cells, such as chondrocytes. Among the different kinds of MSCs available, adipose-derived mesenchymal stem cells (ADSCs) are emerging due to their abundancy and easiness to harvest. However, their mechanism of action and potential for cartilage regeneration are still under investigation, and many other aspects still need to be clarified. The aim of this systematic review is to give an overview of in vivo studies dealing with ADSCs, by summarizing the main evidence for the treatment of cartilage disease of the knee.
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Walmsley GG, McArdle A, Tevlin R, Momeni A, Atashroo D, Hu MS, Feroze AH, Wong VW, Lorenz PH, Longaker MT, Wan DC. Nanotechnology in bone tissue engineering. NANOMEDICINE : NANOTECHNOLOGY, BIOLOGY, AND MEDICINE 2015; 11:1253-63. [PMID: 25791811 PMCID: PMC4476906 DOI: 10.1016/j.nano.2015.02.013] [Citation(s) in RCA: 150] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Revised: 11/23/2014] [Accepted: 02/21/2015] [Indexed: 02/04/2023]
Abstract
Nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering. Current limitations in regenerative strategies include impaired cellular proliferation and differentiation, insufficient mechanical strength of scaffolds, and inadequate production of extrinsic factors necessary for efficient osteogenesis. Here we review several major areas of research in nanotechnology with potential implications in bone regeneration: 1) nanoparticle-based methods for delivery of bioactive molecules, growth factors, and genetic material, 2) nanoparticle-mediated cell labeling and targeting, and 3) nano-based scaffold construction and modification to enhance physicochemical interactions, biocompatibility, mechanical stability, and cellular attachment/survival. As these technologies continue to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases. FROM THE CLINICAL EDITOR Traditionally, the reconstruction of bony defects has relied on the use of bone grafts. With advances in nanotechnology, there has been significant development of synthetic biomaterials. In this article, the authors provided a comprehensive review on current research in nanoparticle-based therapies for bone tissue engineering, which should be useful reading for clinicians as well as researchers in this field.
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Affiliation(s)
- Graham G Walmsley
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Adrian McArdle
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Ruth Tevlin
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Arash Momeni
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - David Atashroo
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Michael S Hu
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Abdullah H Feroze
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Victor W Wong
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Peter H Lorenz
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Michael T Longaker
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Derrick C Wan
- Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
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Monteiro N, Martins A, Reis RL, Neves NM. Nanoparticle-based bioactive agent release systems for bone and cartilage tissue engineering. Regen Ther 2015; 1:109-118. [PMID: 31245450 PMCID: PMC6581799 DOI: 10.1016/j.reth.2015.05.004] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 04/07/2015] [Accepted: 05/25/2015] [Indexed: 11/22/2022] Open
Abstract
The inability to deliver bioactive agents locally in a transient but sustained manner is one of the challenges on the development of bio-functionalized scaffolds for tissue engineering (TE) and regenerative medicine. The mode of release is especially relevant when the bioactive agent is a growth factor (GF), because the dose and the spatiotemporal release of such agents at the site of injury are crucial to achieve a successful outcome. Strategies that combine scaffolds and drug delivery systems have the potential to provide more effective tissue regeneration relative to current therapies. Nanoparticles (NPs) can protect the bioactive agents, control its profile, decrease the occurrence and severity of side effects and deliver the bioactive agent to the target cells maximizing its effect. Scaffolds containing NPs loaded with bioactive agents can be used for their local delivery, enabling site-specific pharmacological effects such as the induction of cell proliferation and differentiation, and, consequently, neo-tissue formation. This review aims to describe the concept of combining NPs with scaffolds, and the current efforts aiming to develop highly multi-functional bioactive agent release systems, with the emphasis on their application in TE of connective tissues.
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Affiliation(s)
- Nelson Monteiro
- 3B's Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909 Caldas das Taipas, Guimarães, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Albino Martins
- 3B's Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909 Caldas das Taipas, Guimarães, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rui L. Reis
- 3B's Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909 Caldas das Taipas, Guimarães, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Nuno M. Neves
- 3B's Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909 Caldas das Taipas, Guimarães, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
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Biomimetic approaches in bone tissue engineering: Integrating biological and physicomechanical strategies. Adv Drug Deliv Rev 2015; 84:1-29. [PMID: 25236302 DOI: 10.1016/j.addr.2014.09.005] [Citation(s) in RCA: 301] [Impact Index Per Article: 30.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2014] [Revised: 09/01/2014] [Accepted: 09/05/2014] [Indexed: 02/06/2023]
Abstract
The development of responsive biomaterials capable of demonstrating modulated function in response to dynamic physiological and mechanical changes in vivo remains an important challenge in bone tissue engineering. To achieve long-term repair and good clinical outcomes, biologically responsive approaches that focus on repair and reconstitution of tissue structure and function through drug release, receptor recognition, environmental responsiveness and tuned biodegradability are required. Traditional orthopedic materials lack biomimicry, and mismatches in tissue morphology, or chemical and mechanical properties ultimately accelerate device failure. Multiple stimuli have been proposed as principal contributors or mediators of cell activity and bone tissue formation, including physical (substrate topography, stiffness, shear stress and electrical forces) and biochemical factors (growth factors, genes or proteins). However, optimal solutions to bone regeneration remain elusive. This review will focus on biological and physicomechanical considerations currently being explored in bone tissue engineering.
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Caldwell KL, Wang J. Cell-based articular cartilage repair: the link between development and regeneration. Osteoarthritis Cartilage 2015; 23:351-62. [PMID: 25450846 PMCID: PMC4339504 DOI: 10.1016/j.joca.2014.11.004] [Citation(s) in RCA: 113] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Revised: 10/02/2014] [Accepted: 11/01/2014] [Indexed: 02/02/2023]
Abstract
Clinical efforts to repair damaged articular cartilage (AC) currently face major obstacles due to limited intrinsic repair capacity of the tissue and unsuccessful biological interventions. This highlights a need for better therapeutic strategies. This review summarizes the recent advances in the field of cell-based AC repair. In both animals and humans, AC defects that penetrate into the subchondral bone marrow are mainly filled with fibrocartilaginous tissue through the differentiation of bone marrow mesenchymal stem cells (MSCs), followed by degeneration of repaired cartilage and osteoarthritis (OA). Cell therapy and tissue engineering techniques using culture-expanded chondrocytes, bone marrow MSCs, or pluripotent stem cells with chondroinductive growth factors may generate cartilaginous tissue in AC defects but do not form hyaline cartilage-based articular surface because repair cells often lose chondrogenic activity or result in chondrocyte hypertrophy. The new evidence that AC and synovium develop from the same pool of precursors with similar gene profiles and that synovium-derived chondrocytes have stable chondrogenic activity has promoted use of synovium as a new cell source for AC repair. The recent finding that NFAT1 and NFAT2 transcription factors (TFs) inhibit chondrocyte hypertrophy and maintain metabolic balance in AC is a significant advance in the field of AC repair. The use of synovial MSCs and discovery of upstream transcriptional regulators that help maintain the AC phenotype have opened new avenues to improve the outcome of AC regeneration.
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Affiliation(s)
| | - Jinxi Wang
- Corresponding Author: Jinxi Wang, Address: University of Kansas Medical Center, Department of Orthopedic Surgery, 3901 Rainbow Blvd., Mail Stop 3017, Kansas City, KS 66160, USA, Phone: +1 913-588-0870, Fax: +1 913-945-7773,
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Zhao R, Peng X, Li Q, Song W. Effects of phosphorylatable short peptide-conjugated chitosan-mediated IL-1Ra and igf-1 gene transfer on articular cartilage defects in rabbits. PLoS One 2014; 9:e112284. [PMID: 25390659 PMCID: PMC4229204 DOI: 10.1371/journal.pone.0112284] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Accepted: 10/10/2014] [Indexed: 11/25/2022] Open
Abstract
Previously, we reported an improvement in the transfection efficiency of the plasmid DNA-chitosan (pDNA/CS) complex by the utilization of phosphorylatable short peptide-conjugated chitosan (pSP-CS). In this study, we investigated the effects of pSP-CS-mediated gene transfection of interleukin-1 receptor antagonist protein (IL-1Ra) combined with insulin-like growth factor-1 (IGF-1) in rabbit chondrocytes and in a rabbit model of cartilage defects. pBudCE4.1-IL-1Ra+igf-1, pBudCE4.1-IL-1Ra and pBudCE4.1-igf-1 were constructed and combined with pSP-CS to form pDNA/pSP-CS complexes. These complexes were transfected into rabbit primary chondrocytes or injected into the joint cavity. Seven weeks after treatment, all rabbits were sacrificed and analyzed. High levels of IL-1Ra and igf-1 expression were detected both in the cell culture supernatant and in the synovial fluid. In vitro, the transgenic complexes caused significant proliferation of chondrocytes, promotion of glycosaminoglycan (GAG) and collagen II synthesis, and inhibition of chondrocyte apoptosis and nitric oxide (NO) synthesis. In vivo, the exogenous genes resulted in increased collagen II synthesis and reduced NO and GAG concentrations in the synovial fluid; histological studies revealed that pDNA/pSP-CS treatment resulted in varying degrees of hyaline-like cartilage repair and Mankin score decrease. The co-expression of both genes produced greater effects than each single gene alone both in vitro and in vivo. The results suggest that pSP-CS is a good candidate for use in gene therapy for the treatment of cartilage defects and that igf-1 and IL-1Ra co-expression produces promising biologic effects on cartilage defects.
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Affiliation(s)
- Ronglan Zhao
- Department of Medical Laboratory, Shandong Provincial Key Laboratory of Clinical Laboratory Diagnostics, Weifang Medical University, Weifang, Shandong, China
| | - Xiaoxiang Peng
- Department of Medical Laboratory, Shandong Provincial Key Laboratory of Clinical Laboratory Diagnostics, Weifang Medical University, Weifang, Shandong, China
- * E-mail:
| | - Qian Li
- Department of Medical Laboratory, Shandong Provincial Key Laboratory of Clinical Laboratory Diagnostics, Weifang Medical University, Weifang, Shandong, China
| | - Wei Song
- Department of Medical Laboratory, Shandong Provincial Key Laboratory of Clinical Laboratory Diagnostics, Weifang Medical University, Weifang, Shandong, China
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Hui JHP, Goyal D, Nakamura N, Ochi M. Cartilage repair in Asia: selected reports on research and clinical trials. Arthroscopy 2013; 29:1991. [PMID: 24286797 DOI: 10.1016/j.arthro.2013.06.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Accepted: 06/11/2013] [Indexed: 02/02/2023]
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