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An B, Cui H, Wang M, Li Z, Li J. Hydrogel tissue adhesive: Adhesion strategy and application. Colloids Surf B Biointerfaces 2025; 253:114755. [PMID: 40344744 DOI: 10.1016/j.colsurfb.2025.114755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2025] [Revised: 04/23/2025] [Accepted: 04/29/2025] [Indexed: 05/11/2025]
Abstract
Hydrogel tissue adhesives have emerged as a promising alternative to conventional wound closure methods such as sutures and staples due to their operational simplicity demonstrated biocompatibility and capacity for multifunctional integration. However, complex and variable tissue microenvironments and dynamic adhesion surfaces still challenge the actual adhesion performance of adhesives, especially natural polymer-based adhesives. In addition, to expand the application of adhesives in biomedical fields, there is an urgent need to further improve tissue adhesion performance through composition design, adhesion mechanism research and bioeffect development. This review focuses on the adhesive properties of adhesives and their applications in biomedical fields. Adhesion-cohesion equilibria, forms of adhesion failure, methods for improving cohesion and various interfacial adhesion mechanisms are presented. Moreover, practical biomedical applications of tissue adhesives are reviewed, focusing on skin, heart, stomach, liver, and cornea. Finally, this review looks ahead to a new generation of multi-functional, strong adhesion tissue adhesives, in the hope of providing inspiration to those working in the field.
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Affiliation(s)
- Boyuan An
- Henan Eye Hospital, Henan Provincial People's Hospital of Zhengzhou University, Zhengzhou 450003, China; School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, China
| | - Haohao Cui
- Henan Eye Hospital, Henan Provincial People's Hospital of Zhengzhou University, Zhengzhou 450003, China; School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, China
| | - Mengke Wang
- Henan Eye Hospital, Henan Provincial People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Zhanrong Li
- Henan Eye Hospital, Henan Provincial People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Jingguo Li
- Henan Eye Hospital, Henan Provincial People's Hospital of Zhengzhou University, Zhengzhou 450003, China; School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, China.
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Romo-Valera C, Appel EA, Etxebarria J, Arluzea J, Andollo N. In Vitro Evaluation of Gelatin-Based Hydrogels as Potential Fillers for Corneal Wounds. Biomacromolecules 2025. [PMID: 40079491 DOI: 10.1021/acs.biomac.4c01759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/15/2025]
Abstract
Corneal persistent epithelial defects are common ophthalmic injuries that can cause significant visual and structural damage. While diagnosis is straightforward, treatment remains challenging. Noninvasive therapies like eye drops are preferred, but severe neurotrophic keratopathy may require surgical interventions. This study explores gelatin-based hydrogels as noninvasive alternatives for corneal repair. Four photo-cross-linkable hydrogels with gelatin and riboflavin phosphate (RFP) were evaluated: a control and variants incorporating 2.5% dextran (D), 0.4% hyaluronic acid (HA), or 1% methylcellulose (MC). In vitro assessments included physicochemical properties, biocompatibility, and release kinetics alongside ex vivo wound healing assays. The gelatin-RFP hydrogel maintained corneal transparency, while additives reduced it. Dextran slowed compound release, and HA and MC reduced the release rate of larger molecules. All hydrogels showed excellent biocompatibility, and ex vivo models confirmed re-epithelialization, though slower than controls. The unmodified gelatin-RFP hydrogel demonstrated the best potential for corneal tissue engineering, supporting its future clinical translation.
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Affiliation(s)
- Cristina Romo-Valera
- Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country UPV/EHU, Sarriena s/n, Leioa 48940, Spain
- BEGIKER Ophthalmology Research Group, Biobizkaia Health Research Institute, Plaza Cruces S/N, Barakaldo 48903, Spain
| | - Eric A Appel
- Department of Bioengineering and Department of Pediatrics (Endocrinology), Stanford University, Stanford, California 94305, United States
- Department of Materials Science & Engineering, Stanford University, Stanford, California 94305, United States
- Sarafan ChEM-H, Stanford University, Stanford, California 94305, United States
- Wood Institute for the Environment, Stanford University, Stanford, California 94305, United States
| | - Jaime Etxebarria
- Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country UPV/EHU, Sarriena s/n, Leioa 48940, Spain
- BEGIKER Ophthalmology Research Group, Biobizkaia Health Research Institute, Plaza Cruces S/N, Barakaldo 48903, Spain
- Department of Ophthalmology, University Hospital of Cruces, Plaza Cruces S/N, Barakaldo 48903, Spain
| | - Jon Arluzea
- Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country UPV/EHU, Sarriena s/n, Leioa 48940, Spain
- BEGIKER Ophthalmology Research Group, Biobizkaia Health Research Institute, Plaza Cruces S/N, Barakaldo 48903, Spain
| | - Noelia Andollo
- Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country UPV/EHU, Sarriena s/n, Leioa 48940, Spain
- BEGIKER Ophthalmology Research Group, Biobizkaia Health Research Institute, Plaza Cruces S/N, Barakaldo 48903, Spain
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3
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Al Monla R, Daien V, Michon F. Advanced bioengineering strategies broaden the therapeutic landscape for corneal failure. Front Bioeng Biotechnol 2024; 12:1480772. [PMID: 39605752 PMCID: PMC11598527 DOI: 10.3389/fbioe.2024.1480772] [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: 08/14/2024] [Accepted: 10/30/2024] [Indexed: 11/29/2024] Open
Abstract
The cornea acts as the eye foremost protective layer and is essential for its focusing power. Corneal blindness may arise from physical trauma or conditions like dystrophies, keratitis, keratoconus, or ulceration. While conventional treatments involve medical therapies and donor allografts-sometimes supplemented with keratoprostheses-these options are not suitable for all corneal defects. Consequently, the development of bioartificial corneal tissue has emerged as a critical research area, aiming to address the global shortage of human cornea donors. Bioengineered corneas hold considerable promise as substitutes, with the potential to replace either specific layers or the entire thickness of damaged corneas. This review first delves into the structural anatomy of the human cornea, identifying key attributes necessary for successful corneal tissue bioengineering. It then examines various corneal pathologies, current treatments, and their limitations. Finally, the review outlines the primary approaches in corneal tissue engineering, exploring cell-free, cell-based, and scaffold-based options as three emerging strategies to address corneal failure.
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Affiliation(s)
- Reem Al Monla
- Institute for Neurosciences of Montpellier, INSERM, University of Montpellier, Montpellier, France
| | - Vincent Daien
- Department of Ophthalmology, Gui de Chauliac Hospital, Montpellier, France
- Sydney Medical School, The Save Sight Institute, The University of Sydney, Sydney, NSW, Australia
| | - Frederic Michon
- Institute for Neurosciences of Montpellier, INSERM, University of Montpellier, Montpellier, France
- Department of Ophthalmology, Gui de Chauliac Hospital, Montpellier, France
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4
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Robbins BT, Montreuil KA, Kundu N, Kumar P, Agrahari V. Corneal Treatment, Repair, and Regeneration: Exosomes at Rescue. Pharmaceutics 2024; 16:1424. [PMID: 39598547 PMCID: PMC11597686 DOI: 10.3390/pharmaceutics16111424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 10/30/2024] [Accepted: 11/01/2024] [Indexed: 11/29/2024] Open
Abstract
Exosomes are extracellular vesicles within the nanosized range that play roles in intercellular communication and thus have certain biological activities. The secretory signaling communication mechanism is an efficient way of exchanging information between cells and has been investigated as nature's therapeutic drug carriers. This review will summarize the potential of exosomes as therapeutic tools and drug delivery vehicles for corneal pathologies. The cornea is an avascular ocular tissue, and its healing is a complex process including cell death and migration, cell proliferation and differentiation, and extracellular matrix remodeling. Here, we discussed the structure, barrier, phases, and healing cascade of cornea. We briefly reviewed the immunogenicity and toxicity of exosomes and role of exosomes in preserving cornea. Additionally, we provided combining exosome strategies with hydrogels, gene and stem cells therapy focused on corneal treatment, repair, and regeneration.
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Affiliation(s)
- Brooke T. Robbins
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA
| | - Kate A. Montreuil
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA
| | - Neloy Kundu
- Graduate College, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA
| | - Prashant Kumar
- Vaccine Analytics and Formulation Center, Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, USA;
| | - Vibhuti Agrahari
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA
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Wang Y, Geng X, Sun X, Cui H, Guo Z, Chu D, Li J, Li Z. Celastrol alleviates subconjunctival fibrosis induced by silicone implants mimicking glaucoma surgery. Eur J Pharm Biopharm 2024; 201:114352. [PMID: 38851459 DOI: 10.1016/j.ejpb.2024.114352] [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: 02/05/2024] [Revised: 05/29/2024] [Accepted: 06/06/2024] [Indexed: 06/10/2024]
Abstract
Subconjunctival fibrosis is critical to the outcomes of several ophthalmic conditions or procedures, such as glaucoma filtering surgery. This study aimed to investigate the anti-fibrotic effect of celastrol on subconjunctival fibrosis and to further reveal the underlying mechanisms. We used celastrol-loaded nanomicelles hydrogel hybrid as a sustained-release drug. A rabbit model of subconjunctival fibrosis following silicone implantation was used for in vivo study, and TGF-β1-induced human pterygium fibroblast (HPF) activation as an in vitro model. The effects of celastrol on inhibiting TGF-β1-induced migration and proliferation of HPFs were evaluated by scratch wound assay and CCK-8, respectively. Immunofluorescence and western blotting were used to examine the effect of celastrol on the expression of α-SMA, collagen I, fibronectin, and the targets of the Hippo signaling pathway. We found that in vivo celastrol treatment reduced the expression of YAP and TAZ in subconjunctival tissue. Moreover, celastrol alleviated collagen deposition and subconjunctival fibrosis at 8 weeks. No obvious tissue toxicity was observed in the rabbit models. Mechanistically, celastrol significantly inhibited TGF-β1-induced proliferation and migration of HPFs. Pretreatment of HPFs with celastrol also suppressed the TGF-β1-induced protein expression of α-SMA, collagen I, fibronectin, TGF-βRII, phosphorylated Smad2/3, YAP, TAZ, and TEAD1. In conclusion, celastrol effectively prevented subconjunctival fibrosis through inhibiting TGF-β1/Smad2/3-YAP/TAZ pathway. Celastrol could serve as a promising therapy for subconjunctival fibrosis.
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Affiliation(s)
- Yiwei Wang
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Xingchen Geng
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Xue Sun
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Haohao Cui
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Zhihua Guo
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Dandan Chu
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Jingguo Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
| | - Zhanrong Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
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6
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Wu X, Xin Y, Zhang H, Quan L, Ao Q. Biopolymer-Based Nanomedicine for Cancer Therapy: Opportunities and Challenges. Int J Nanomedicine 2024; 19:7415-7471. [PMID: 39071502 PMCID: PMC11278852 DOI: 10.2147/ijn.s460047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 05/18/2024] [Indexed: 07/30/2024] Open
Abstract
Cancer, as the foremost challenge among human diseases, has plagued medical professionals for many years. While there have been numerous treatment approaches in clinical practice, they often cause additional harm to patients. The emergence of nanotechnology has brought new directions for cancer treatment, which can deliver anticancer drugs specifically to tumor areas. This article first introduces the application scenarios of nanotherapies and treatment strategies of nanomedicine. Then, the noteworthy characteristics exhibited by biopolymer materials were described, which make biopolymers stand out in polymeric nanomedicine delivery. Next, we focus on summarizing the state-of-art studies of five categories of proteins (Albumin, Gelatin, Silk fibroin, Zein, Ferritin), nine varieties of polysaccharides (Chitosan, Starch, Hyaluronic acid, Dextran, cellulose, Fucoidan, Carrageenan, Lignin, Pectin) and liposomes in the field of anticancer drug delivery. Finally, we also provide a summary of the advantages and limitations of these biopolymers, discuss the prevailing impediments to their application, and discuss in detail the prospective research directions. This review not only helps readers understand the current development status of nano anticancer drug delivery systems based on biopolymers, but also is helpful for readers to understand the properties of various biopolymers and find suitable solutions in this field through comparative reading.
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Affiliation(s)
- Xixi Wu
- NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial, & Institute of Regulatory Science for Medical Device, & National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, People’s Republic of China
| | - Yuan Xin
- NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial, & Institute of Regulatory Science for Medical Device, & National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, People’s Republic of China
| | - Hengtong Zhang
- NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial, & Institute of Regulatory Science for Medical Device, & National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, People’s Republic of China
| | - Liang Quan
- NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial, & Institute of Regulatory Science for Medical Device, & National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, People’s Republic of China
| | - Qiang Ao
- NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial, & Institute of Regulatory Science for Medical Device, & National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, People’s Republic of China
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7
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Yew PYM, Chee PL, Lin Q, Owh C, Li J, Dou QQ, Loh XJ, Kai D, Zhang Y. Hydrogel for light delivery in biomedical applications. Bioact Mater 2024; 37:407-423. [PMID: 38689660 PMCID: PMC11059474 DOI: 10.1016/j.bioactmat.2024.03.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 03/06/2024] [Accepted: 03/26/2024] [Indexed: 05/02/2024] Open
Abstract
Traditional optical waveguides or mediums are often silica-based materials, but their applications in biomedicine and healthcare are limited due to the poor biocompatibility and unsuitable mechanical properties. In term of the applications in human body, a biocompatible hydrogel system with excellent optical transparency and mechanical flexibility could be beneficial. In this review, we explore the different designs of hydrogel-based optical waveguides derived from natural and synthetic sources. We highlighted key developments such as light emitting contact lenses, implantable optical fibres, biosensing systems, luminating and fluorescent materials. Finally, we expand further on the challenges and perspectives for hydrogel waveguides to achieve clinical applications.
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Affiliation(s)
- Pek Yin Michelle Yew
- Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 1 Pesek Road, 627833, Singapore
- Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, 117583, Singapore
| | - Pei Lin Chee
- Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 1 Pesek Road, 627833, Singapore
| | - Qianyu Lin
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, Innovis #08-03, Singapore, 138634, Singapore
| | - Cally Owh
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, Innovis #08-03, Singapore, 138634, Singapore
| | - Jiayi Li
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore
| | - Qing Qing Dou
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China
| | - Xian Jun Loh
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, Innovis #08-03, Singapore, 138634, Singapore
| | - Dan Kai
- Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 1 Pesek Road, 627833, Singapore
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, Innovis #08-03, Singapore, 138634, Singapore
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371, Singapore
| | - Yong Zhang
- Department of Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China
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Xu P, Chen P, Sun Y, Nuliqiman M, Zhou Y, Cao J, Yu S, Huang J, Ye J. A novel injectable thermo/photo dual-crosslinking hydrogel based on modified chitosan for fast sealing open globe injury. Carbohydr Polym 2024; 331:121854. [PMID: 38388052 DOI: 10.1016/j.carbpol.2024.121854] [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: 10/20/2023] [Revised: 01/18/2024] [Accepted: 01/20/2024] [Indexed: 02/24/2024]
Abstract
Open globe injuries (OGIs) demand immediate attention to prevent further complications and improve vision prognosis. Herein, we developed a thermo/photo dual-crosslinking injectable hydrogel, HBC_m_Arg, for rapidly sealing OGIs in emergency ophthalmic cases. HBC_m_Arg was prepared with arginine and methacrylic anhydride modified hydroxybutyl chitosan (HBC). HBC_m_Arg was initially in liquid form at 25 °C, enabling easy injection at the injury site. After reaching the ocular surface temperature, it underwent reversible heat-induced gelation to achieve in situ transformation. Further, HBC_m_Arg was capable of rapid photocrosslinking under UV light, forming a dual network structure to bolster mechanical strength, thereby facilitating effective OGI closure. Biocompatibility assessments, including in vitro studies with three ocular cell types and in vivo experiments on rabbit eyes, confirmed the safety profile of HBC_m_Arg. Ex vivo and in vivo burst pressure tests demonstrated the hydrogel's ability to promptly restore intraocular pressure and withstand elevated pressures, underscoring its potential for OGI stabilization. Additionally, the suitable degradation of HBC_m_Arg within ocular tissues, coupled with its stability in ex vivo assessments, presented a delicate balance between stability and biodegradability. In conclusion, HBC_m_Arg holds promise for improving emergency ophthalmic care by providing a rapid, effective, and safe way to seal OGIs in critical situations.
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Affiliation(s)
- Peifang Xu
- Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang, China
| | - Pengjie Chen
- Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang, China
| | - Yiming Sun
- Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang, China
| | - Maimaiti Nuliqiman
- Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang, China
| | - Yifan Zhou
- Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang, China
| | - Jing Cao
- Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang, China
| | - Shan Yu
- Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou, China
| | - Jun Huang
- Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou, China.
| | - Juan Ye
- Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang, China.
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9
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Li Z, Liu R, Zhang X, Guo Z, Geng X, Chu D, Cui H, Zhang A, Li W, Zhu L, Li J. An injectable thermoresponsive-hydrogel for lamellar keratoplasty: In-situ releases celastrol and hampers corneal scars. J Control Release 2024; 369:604-616. [PMID: 38582337 DOI: 10.1016/j.jconrel.2024.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 04/01/2024] [Accepted: 04/03/2024] [Indexed: 04/08/2024]
Abstract
Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers. In situ delivery offers a unique alternative to improve efficacy and minimize systemic toxicity. Herein, a drug delivery platform based on thermoresponsive injectable hydrogel/nano-micelles composite with in situ drug-controlled release and long-acting features is developed to prevent corneal scarring and reduce corneal stromal fibrosis in lamellar keratoplasty. The in-situ gelation hydrogels enabled direct delivery of celastrol to the corneal stroma. In vivo evaluation with a rabbit anterior lamellar keratoplasty model showed that hydrogel/micelles platform could effectively inhibit corneal stromal fibrosis. This strategy achieves controlled and prolonged release of celastrol in the corneal stroma of rabbit. Following a single corneal interlamellar injection, celastrol effectively alleviated fibrosis via mTORC1 signal promoting autophagy and inhibiting TGF-β1/Smad2/3 signaling pathway. Overall, this strategy demonstrates promise for the clinical application of celastrol in preventing corneal scarring and reducing corneal stromal fibrosis post-lamellar keratoplasty, highlighting the potential benefits of targeted drug delivery systems in ocular therapeutics.
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Affiliation(s)
- Zhanrong Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Ruixing Liu
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Xiacong Zhang
- International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Shanghai 200444, China
| | - Zhihua Guo
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Xingchen Geng
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Dandan Chu
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Haohao Cui
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Afang Zhang
- International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Shanghai 200444, China
| | - Wen Li
- International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Shanghai 200444, China.
| | - Lei Zhu
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
| | - Jingguo Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
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10
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Yao Y, Shi X, Zhao Z, Zhang A, Li W. Dendronization of chitosan to afford unprecedent thermoresponsiveness and tunable microconfinement. J Mater Chem B 2023; 11:11024-11034. [PMID: 37975703 DOI: 10.1039/d3tb01803b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2023]
Abstract
Convenient chemical modification of biomacromolecules to create novel biocompatible functional materials satisfies the current requirements of sustainable chemistry. Dendronization of chitosan with dendritic oligoethylene glycols (OEGs) paves a strategy for the preparation of functional dendronized chitosans (DCSs) with unprecedent thermoresponsive behavior, which inherit biological features from polysaccharides and the topological features from dendritic OEGs. In addition, densely packed dendritic OEG chains around the backbone provide efficient cooperative interactions and form an intriguing confined microenvironment based on the degradable biopolymers. In this perspective, we describe the principle for the preparation of the thermoresponsive DCSs, and focus on the molecular envelop effect from the hydrophobic microconfinement to the encapsulated guest molecules or moieties. Particular attention is put on their capacity to regulate behavior and the functions of the encapsulated guests through thermally-mediated dehydration and collapse of the densely packed dendritic OEGs. We believe that the methodology described here may provide prospects for the fabrication of functional materials from biomacromolecules, especially when used as environmentally friendly nanomaterials or in accurate diagnosis and therapy.
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Affiliation(s)
- Yi Yao
- International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Nanchen Street 333, Shanghai 200444, China.
| | - Xiaoxin Shi
- International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Nanchen Street 333, Shanghai 200444, China.
| | - Zihong Zhao
- International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Nanchen Street 333, Shanghai 200444, China.
| | - Afang Zhang
- International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Nanchen Street 333, Shanghai 200444, China.
| | - Wen Li
- International Joint Laboratory of Biomimetic and Smart Polymers, School of Materials Science and Engineering, Shanghai University, Nanchen Street 333, Shanghai 200444, China.
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11
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Wang X, Luan F, Yue H, Song C, Wang S, Feng J, Zhang X, Yang W, Li Y, Wei W, Tao Y. Recent advances of smart materials for ocular drug delivery. Adv Drug Deliv Rev 2023; 200:115006. [PMID: 37451500 DOI: 10.1016/j.addr.2023.115006] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 07/04/2023] [Accepted: 07/06/2023] [Indexed: 07/18/2023]
Abstract
Owing to the variety and complexity of ocular diseases and the natural ocular barriers, drug therapy for ocular diseases has significant limitations, such as poor drug targeting to the site of the disease, poor drug penetration, and short drug retention time in the vitreous body. With the development of biotechnology, biomedical materials have reached the "smart" stage. To date, despite their inability to overcome all the aforementioned drawbacks, a variety of smart materials have been widely tested to treat various ocular diseases. This review analyses the most recent developments in multiple smart materials (inorganic particles, polymeric particles, lipid-based particles, hydrogels, and devices) to treat common ocular diseases and discusses the future directions and perspectives regarding clinical translation issues. This review can help researchers rationally design more smart materials for specific ocular applications.
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Affiliation(s)
- Xiaojun Wang
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China
| | - Fuxiao Luan
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China
| | - Hua Yue
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China
| | - Cui Song
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China
| | - Shuang Wang
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China
| | - Jing Feng
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China
| | - Xiao Zhang
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China
| | - Wei Yang
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China
| | - Yuxin Li
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China
| | - Wei Wei
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
| | - Yong Tao
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China.
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12
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Geng X, Wang Y, Cui H, Li C, Cheng B, Cui B, Liu R, Zhang J, Zhu L, Li J, Shen J, Li Z. Carboxymethyl chitosan regulates macrophages polarization to inhibit early subconjunctival inflammation in conjunctival injury. Int J Biol Macromol 2023:125159. [PMID: 37268068 DOI: 10.1016/j.ijbiomac.2023.125159] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 05/24/2023] [Accepted: 05/28/2023] [Indexed: 06/04/2023]
Abstract
Persistent subconjunctival inflammation leads to subconjunctival fibrosis and eventual visual impairment. There is an unmet need for how to effectively inhibit subconjunctival inflammation. Herein, the effect of carboxymethyl chitosan (CMCS) on subconjunctival inflammation was investigated and the mechanism was involved. The evaluation of cytocompatibility demonstrated that CMCS had good biocompatibility. The in vitro results showed that CMCS inhibited secretions of pro-inflammatory cytokines (IL-6, TNF-α, IL-8 and IFN-γ) and chemokines (MCP-1), and downregulated TLR4/MyD88/NF-κB pathway in M1. The in vivo results displayed that CMCS alleviated conjunctival edema and congestion, and improved conjunctival epithelial reconstruction significantly. Both in vitro and in vivo results demonstrated that CMCS inhibited the infiltration of macrophages and reduced the expressions of iNOS, IL-6, IL-8 and TNF-α in the conjunctiva. Given that CMCS indicated the activities of inhibiting M1 polarization, NF-κB pathway, and subconjunctival inflammation, which may be employed as a potent treatment for subconjunctival inflammation.
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Affiliation(s)
- Xingchen Geng
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Yiwei Wang
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Haohao Cui
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Chengcheng Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Boyuan Cheng
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Bingbing Cui
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Ruixing Liu
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Junjie Zhang
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Lei Zhu
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China
| | - Jingguo Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
| | - Jianliang Shen
- School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China.
| | - Zhanrong Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
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13
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Desai N, Rana D, Salave S, Gupta R, Patel P, Karunakaran B, Sharma A, Giri J, Benival D, Kommineni N. Chitosan: A Potential Biopolymer in Drug Delivery and Biomedical Applications. Pharmaceutics 2023; 15:pharmaceutics15041313. [PMID: 37111795 PMCID: PMC10144389 DOI: 10.3390/pharmaceutics15041313] [Citation(s) in RCA: 152] [Impact Index Per Article: 76.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 04/11/2023] [Accepted: 04/19/2023] [Indexed: 04/29/2023] Open
Abstract
Chitosan, a biocompatible and biodegradable polysaccharide derived from chitin, has surfaced as a material of promise for drug delivery and biomedical applications. Different chitin and chitosan extraction techniques can produce materials with unique properties, which can be further modified to enhance their bioactivities. Chitosan-based drug delivery systems have been developed for various routes of administration, including oral, ophthalmic, transdermal, nasal, and vaginal, allowing for targeted and sustained release of drugs. Additionally, chitosan has been used in numerous biomedical applications, such as bone regeneration, cartilage tissue regeneration, cardiac tissue regeneration, corneal regeneration, periodontal tissue regeneration, and wound healing. Moreover, chitosan has also been utilized in gene delivery, bioimaging, vaccination, and cosmeceutical applications. Modified chitosan derivatives have been developed to improve their biocompatibility and enhance their properties, resulting in innovative materials with promising potentials in various biomedical applications. This article summarizes the recent findings on chitosan and its application in drug delivery and biomedical science.
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Affiliation(s)
- Nimeet Desai
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi 502285, India
| | - Dhwani Rana
- National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad 382355, India
| | - Sagar Salave
- National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad 382355, India
| | - Raghav Gupta
- National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad 382355, India
| | - Pranav Patel
- National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad 382355, India
| | - Bharathi Karunakaran
- National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad 382355, India
| | - Amit Sharma
- National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad 382355, India
| | - Jyotsnendu Giri
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi 502285, India
| | - Derajram Benival
- National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad 382355, India
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14
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Tang W, Wang J, Hou H, Li Y, Wang J, Fu J, Lu L, Gao D, Liu Z, Zhao F, Gao X, Ling P, Wang F, Sun F, Tan H. Review: Application of chitosan and its derivatives in medical materials. Int J Biol Macromol 2023; 240:124398. [PMID: 37059277 DOI: 10.1016/j.ijbiomac.2023.124398] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 04/03/2023] [Accepted: 04/06/2023] [Indexed: 04/16/2023]
Abstract
Chitin is a natural polymeric polysaccharide extracted from marine crustaceans, and chitosan is obtained by removing part of the acetyl group (usually more than 60 %) in chitin's structure. Chitosan has attracted wide attention from researchers worldwide due to its good biodegradability, biocompatibility, hypoallergenic and biological activities (antibacterial, immune and antitumor activities). However, research has shown that chitosan does not melt or dissolve in water, alkaline solutions and general organic solvents, which greatly limits its application range. Therefore, researchers have carried out extensive and in-depth chemical modification of chitosan and prepared a variety of chitosan derivatives, which have expanded the application field of chitosan. Among them, the most extensive research has been conducted in the pharmaceutical field. This paper summarizes the application of chitosan and chitosan derivatives in medical materials over the past five years.
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Affiliation(s)
- Wen Tang
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China
| | - Juan Wang
- Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan 250001, Shandong, China
| | - Huiwen Hou
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China
| | - Yan Li
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China
| | - Jie Wang
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China
| | - Jiaai Fu
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China
| | - Lu Lu
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China
| | - Didi Gao
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China
| | - Zengmei Liu
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China
| | - Feiyan Zhao
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China
| | - Xinqing Gao
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China
| | - Peixue Ling
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; School of Pharmaceutical sciences, Shandong University, Jinan 250012, Shandong, China
| | - Fengshan Wang
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China; School of Pharmaceutical sciences, Shandong University, Jinan 250012, Shandong, China
| | - Feng Sun
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China
| | - Haining Tan
- National Glycoengineering Research Center, Shandong University, Qingdao 266237, Shandong, China; NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, Qingdao 266237, Shandong, China; Shandong Provincial Technology Innovation Center of Carbohydrate, Shandong University, Qingdao 266237, Shandong, China; School of Pharmaceutical sciences, Shandong University, Jinan 250012, Shandong, China.
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15
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Das A, Pal S, Jewrajka SK. Physical, Electrochemical, and Solvent Permeation Properties of Amphiphilic Conetwork Membranes Formed through Interlinking of Poly(vinylidene fluoride)- Graft-Poly[(2-dimethylamino)ethyl Methacrylate] with Telechelic Poly(ethylene glycol) and Small Molecular Weight Cross-Linkers. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2022; 38:15340-15352. [PMID: 36459173 DOI: 10.1021/acs.langmuir.2c02553] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
We report the preparation of dense and porous amphiphilic conetwork (APCN) membranes through the covalent interconnection of poly(vinylidene fluoride)-graft-poly[(2-dimethylamino)ethyl methacrylate] (PVDF-g-PDMAEMA) copolymers with telechelic poly(ethylene glycol) (PEG) or α,α-dichloro-p-xylene (XDC). The dense APCN membranes exhibit varying solvent swelling and mechanical properties depending on the compositions and overall crystallinity. The crystallinity of both PVDF (20-47%) and PEG (9-17%) is significantly suppressed in the dense APCNs prepared through the interconnection of PVDF-g-PDMAEMA with reactive PEG as compared to the APCN membranes (48-53%) prepared with XDC as well as mechanical blend of PVDF-g-PDMAEMA plus nonreactive PEG. The dense APCN membranes exhibit a good transport number of monovalent ions and ionic conductivity. The APCN membrane interconnected with PEG and containing binary ionic liquids exhibits a room-temperature lithium ion conductivity of 0.52 mS/cm. On the other hand, APCN ultrafiltration (UF) membranes exhibit organic solvent-resistant behavior. The UF membrane obtained by interconnecting PVDF-g-PDMAEMA with telechelic PEG shows low protein fouling propensity, higher hydrophilicity, and water flux as compared to membranes prepared using XDC as the interconnecting agent. The significant effect of the covalent interconnection of the amphiphilic graft copolymers with telechelic PEG or XDC on the overall properties provides a good opportunity to modulate the properties and performance of APCN membranes.
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Affiliation(s)
- Anupam Das
- School of Chemistry, University of Hyderabad, Hyderabad, Telangana500046, India
| | - Sandip Pal
- Membrane Science and Separation Technology Division, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), G. B. Marg, Bhavnagar, Gujarat364002, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh201002, India
| | - Suresh K Jewrajka
- Membrane Science and Separation Technology Division, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), G. B. Marg, Bhavnagar, Gujarat364002, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh201002, India
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16
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Thermogelling materials and their important role in biomedical engineering applications. CURRENT OPINION IN BIOMEDICAL ENGINEERING 2022. [DOI: 10.1016/j.cobme.2022.100412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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17
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Yao Y, Cao S, Yang Q, Zhang A, Li W. Thermo-Gelling Dendronized Chitosans for Modulating Protein Activity. ACS APPLIED BIO MATERIALS 2022; 5:5377-5385. [PMID: 36343279 DOI: 10.1021/acsabm.2c00755] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Regulation of protein activity is important in their applications for biomedicine and therapeutics. Here, an approach for the regulation of protein bioactivity through molecular confinement provided by oligoethylene glycol (OEG)-based dendronized chitosan (DCS) hydrogels is reported. Structural effects on their thermoresponsiveness are investigated. The highly transparent hydrogels are formed from thermoresponsive DCSs through their thermal dehydration and exhibit an intriguing reversible sol-gel transition property when triggered at physiological temperatures. The thermo-gelling behavior and mechanical strength of these hydrogels are investigated, and possible effects from hydrophobicity of the OEG dendrons, grafting rates of the dendrons on the chitosan main chain, and solid content of polymers are examined. These DCS hydrogels are found to have lamellar morphologies and can provide characteristic hydrophobicity microenvironments formed through the crowded OEG dendrons, which show a higher level of confinement to guest proteins. This allows the DCS hydrogels remarkable activity protection capability to proteins. Furthermore, these DCS hydrogels inherit the degradability from chitosan, allowing protein release from these hydrogels through the controllable ways without impairing their activities.
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Affiliation(s)
- Yi Yao
- International Joint Laboratory of Biomimetic & Smart Polymers, School of Materials Science and Engineering, Shanghai University, Shanghai200444, China
| | - Shijie Cao
- International Joint Laboratory of Biomimetic & Smart Polymers, School of Materials Science and Engineering, Shanghai University, Shanghai200444, China
| | - Qingcen Yang
- International Joint Laboratory of Biomimetic & Smart Polymers, School of Materials Science and Engineering, Shanghai University, Shanghai200444, China
| | - Afang Zhang
- International Joint Laboratory of Biomimetic & Smart Polymers, School of Materials Science and Engineering, Shanghai University, Shanghai200444, China
| | - Wen Li
- International Joint Laboratory of Biomimetic & Smart Polymers, School of Materials Science and Engineering, Shanghai University, Shanghai200444, China
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18
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Xia D, Chen J, Zhang Z, Dong M. Emerging polymeric biomaterials and manufacturing techniques in regenerative medicine. AGGREGATE 2022; 3. [DOI: 10.1002/agt2.176] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
AbstractThe current demand for patients’ organ and tissue repair and regeneration is continually increasing, where autologous or allograft is the golden standard treatment in the clinic. However, due to the shortage of donors, mismatched size and modality, functional loss of the donor region, possible immune rejection, and so forth, the application of auto‐/allo‐grafts is frequently hindered in many cases. In order to solve these problems, artificial constructs structurally and functionally imitating the extracellular matrix have been developed as substitutes to promoting cell attachment, proliferation, and differentiation, and ultimately forming functional tissues or organs for better tissue regeneration. Particularly, polymeric materials have been widely utilized in regenerative medicine because of their ease of manufacturing, flexibility, biocompatibility, as well as good mechanical, chemical, and thermal properties. This review presents a comprehensive overview of a variety of polymeric materials, their fabrication methods as well applications in regenerative medicine. Finally, we discussed the future challenges and perspectives in the development and clinical transformation of polymeric biomaterials.
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Affiliation(s)
- Dan Xia
- Tianjin Key Laboratory of Materials Laminating Fabrication and Interface Control Technology, School of Materials Science and Engineering Hebei University of Technology Tianjin China
| | - Jiatian Chen
- Tianjin Key Laboratory of Materials Laminating Fabrication and Interface Control Technology, School of Materials Science and Engineering Hebei University of Technology Tianjin China
| | - Zhongyang Zhang
- Interdisciplinary Nanoscience Center (iNANO) Aarhus University Aarhus Denmark
| | - Mingdong Dong
- Interdisciplinary Nanoscience Center (iNANO) Aarhus University Aarhus Denmark
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19
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Recent Advances of Chitosan Formulations in Biomedical Applications. Int J Mol Sci 2022; 23:ijms231810975. [PMID: 36142887 PMCID: PMC9504745 DOI: 10.3390/ijms231810975] [Citation(s) in RCA: 104] [Impact Index Per Article: 34.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/12/2022] [Accepted: 09/13/2022] [Indexed: 02/07/2023] Open
Abstract
Chitosan, a naturally abundant cationic polymer, is chemically composed of cellulose-based biopolymers derived by deacetylating chitin. It offers several attractive characteristics such as renewability, hydrophilicity, biodegradability, biocompatibility, non-toxicity, and a broad spectrum of antimicrobial activity towards gram-positive and gram-negative bacteria as well as fungi, etc., because of which it is receiving immense attention as a biopolymer for a plethora of applications including drug delivery, protective coating materials, food packaging films, wastewater treatment, and so on. Additionally, its structure carries reactive functional groups that enable several reactions and electrochemical interactions at the biomolecular level and improves the chitosan’s physicochemical properties and functionality. This review article highlights the extensive research about the properties, extraction techniques, and recent developments of chitosan-based composites for drug, gene, protein, and vaccine delivery applications. Its versatile applications in tissue engineering and wound healing are also discussed. Finally, the challenges and future perspectives for chitosan in biomedical applications are elucidated.
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20
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Rathod S. Interpenetrating polymeric network (IPNs) in ophthalmic drug delivery: Breaking the barriers. Int Ophthalmol 2022; 43:1063-1074. [PMID: 36053474 DOI: 10.1007/s10792-022-02482-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 08/20/2022] [Indexed: 10/14/2022]
Abstract
To maintain the therapeutic drug concentration for a prolonged period of time in aqueous and vitreous humor is primary challenge for ophthalmic drug delivery. Majority of the locally administered drug into the eye is lost as to natural reflexes like blinking and lacrimation resulting in the short span of drug residence. Consequently, less than 5% of the applied drug penetrate through the cornea and reaches the intraocular tissues. The major targets for optimal ophthalmic drug delivery are increasing drug residence time in cul-de-sac of the eye, prolonging intraocular exposure, modulating drug release from the delivery system, and minimizing pre-corneal drug loss. Development of in situ gel, contact lens, intraocular lens, inserts, artificial cornea, scaffold, etc., for ophthalmic drug delivery are few approaches to achieve these major targeted objectives for delivering the drug optimally. Interpenetrating polymeric network (IPN) or smart hydrogels or stimuli sensitive hydrogels are the class of polymers that can help to achieve the targets in ophthalmic drug delivery due to their versatility, biocompatibility and biodegradability. These novel ''smart" materials can alter their molecular configuration and result in volume phase transition in response to environmental stimuli, such as temperature, pH, ionic strength, electric and magnetic field. Hydrogel and tissue interaction, mechanical/tensile properties, pore size and surface chemistry of IPNs can also be modulated for tuning the drug release kinetics. Stimuli sensitive IPNs has been widely exploited to prepare in situ gelling formulations for ophthalmic drug delivery. Low refractive index hydrogel biomaterials with high water content, soft tissue-like physical properties, wettability, oxygen, glucose permeability and desired biocompatibility makes IPNs versatile candidate for contact lenses and corneal implants. This review article focuses on the exploration of these smart polymeric networks/IPNs for therapeutically improved ophthalmic drug delivery that has unfastened novel arenas in ophthalmic drug delivery.
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Affiliation(s)
- Sachin Rathod
- Maliba Pharmacy College, UKA Tarsadia University, Gopal-Vidyanagar Campus, Surat, 394350, India. .,Parul Institute of Pharmacy and Research, Parul University, Waghodia, Vadodara, 391760, India.
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21
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Zhang Y, Liu R, Li C, Shi L, Guo Z, Zhu L, Li W, Li J, Li Z. Celastrol-based nanomedicine hydrogels eliminate posterior capsule opacification. Nanomedicine (Lond) 2022; 17:1449-1461. [PMID: 36205091 DOI: 10.2217/nnm-2022-0191] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Aim: To formulate an injectable thermosensitive micelle-hydrogel hybrid system loaded with celastrol (celastrol-loaded micelle hydrogel: CMG) to prevent posterior capsule opacification (PCO). Materials & methods: Celastrol-loaded micelles were embedded in a thermosensitive hydrogel matrix to enable controlled on-demand celastrol delivery into the residual capsule. The efficacy and mechanisms of the system for eliminating PCO were evaluated in rabbits. Results: Celastrol-loaded micelles inhibited the migration and proliferation of lens epithelial cells induced by TGF-β1. Celastrol prevents epithelial-mesenchymal transition in lens epithelial cells induced by TGF-β1 through the TGF-β1/Smad2/3/TEAD1 signaling pathway. In vivo efficiency evaluations showed that CMG demonstrated an excellent inhibitory effect on PCO in rabbits and had no obvious tissue toxicity. Conclusion: Injectable CMG may represent a promising ophthalmic platform for preventing PCO. This versatile injectable micelle-hydrogel hybrid represents a clinically relevant platform to achieve localized therapy and controlled release of drugs in other disease therapies.
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Affiliation(s)
- Ying Zhang
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, PR China
| | - Ruixing Liu
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, PR China
| | - Chengcheng Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, PR China
| | - Liuqi Shi
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, PR China
| | - Zhihua Guo
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, PR China
| | - Lei Zhu
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, PR China
| | - Wen Li
- School of Materials Science & Engineering, Shanghai University, Shanghai, 200444, PR China
| | - Jingguo Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, PR China
| | - Zhanrong Li
- Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, PR China
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Notario-Pérez F, Martín-Illana A, Cazorla-Luna R, Ruiz-Caro R, Veiga MD. Applications of Chitosan in Surgical and Post-Surgical Materials. Mar Drugs 2022; 20:md20060396. [PMID: 35736199 PMCID: PMC9228111 DOI: 10.3390/md20060396] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 06/13/2022] [Accepted: 06/14/2022] [Indexed: 02/06/2023] Open
Abstract
The continuous advances in surgical procedures require continuous research regarding materials with surgical applications. Biopolymers are widely studied since they usually provide a biocompatible, biodegradable, and non-toxic material. Among them, chitosan is a promising material for the development of formulations and devices with surgical applications due to its intrinsic bacteriostatic, fungistatic, hemostatic, and analgesic properties. A wide range of products has been manufactured with this polymer, including scaffolds, sponges, hydrogels, meshes, membranes, sutures, fibers, and nanoparticles. The growing interest of researchers in the use of chitosan-based materials for tissue regeneration is obvious due to extensive research in the application of chitosan for the regeneration of bone, nervous tissue, cartilage, and soft tissues. Chitosan can serve as a substance for the administration of cell-growth promoters, as well as a support for cellular growth. Another interesting application of chitosan is hemostasis control, with remarkable results in studies comparing the use of chitosan-based dressings with traditional cotton gauzes. In addition, chitosan-based or chitosan-coated surgical materials provide the formulation with antimicrobial activity that has been highly appreciated not only in dressings but also for surgical sutures or meshes.
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Ding Y, Zhang X, Xu B, Li W. Dendronized Gelatins Showing Both LCST and UCST-type Thermoresponsive Behavior. Polym Chem 2022. [DOI: 10.1039/d2py00118g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Modification of natural polymers with stimuli-responsive synthetic moieties witnesses convergences of superior properties from natural polymers and stimuli-responsiveness to generate new intelligent materials. This was usally performed through synthetic polymers...
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