Regenerative Biomaterials最新文献

{"title":"Microvascular network based on the Hilbert curve for nutrient transport in thick tissue.","authors":"Zhenxing Wang, Xuemin Liu, Xuetao Shi, Yingjun Wang","doi":"10.1093/rb/rbae094","DOIUrl":"10.1093/rb/rbae094","url":null,"abstract":"<p><p>To address the uneven nutrient distribution within three-dimensional (3D) tissue models and organoids currently used in medical research, this study introduces a microvascular network based on the Hilbert curve. Our aim was to develop innovative solutions for enhancing nutrient supply in thick tissue models <i>in vitro</i>. By using 3D bioprinting, we engineered microvascular networks of varying Hilbert orders and validated their efficacy in enhancing nutrient uniformity through numerical simulations and experiments. These networks facilitated broader and more uniform nutrient distribution throughout the thick tissue models, particularly the 2° Hilbert microvascular structure, which occupies less space and significantly reduces regions of cellular death. Furthermore, we explored the potential of assembling larger tissue constructs using the 2° Hilbert microvascular network, showcasing its applicability in constructing large-scale biological models. The findings suggest that the 2° Hilbert microvascular structure is particularly effective in ensuring adequate nutrient delivery, thus enhancing the viability and functionality of large-volume tissue models. These innovations hold significant promise for advancing the fields of tissue engineering and regenerative medicine by improving nutrient delivery to <i>in vitro</i> thick tissue block models. This provides a robust foundation for future <i>in vitro</i> research and clinical applications, potentially leading to more effective treatments and interventions in the medical field. The development of these microvascular networks represents a crucial step forward in overcoming the limitations of current 3D tissue models and organoids, paving the way for more sophisticated and reliable biomedical research tools.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae094"},"PeriodicalIF":5.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balancing functions of antifouling, nitric oxide release and vascular cell selectivity for enhanced endothelialization of assembled multilayers.","authors":"Sulei Zhang, Jun Sun, Shuaihang Guo, Yichen Wang, Yuheng Zhang, Jiao Lei, Xiaoli Liu, Hong Chen","doi":"10.1093/rb/rbae096","DOIUrl":"https://doi.org/10.1093/rb/rbae096","url":null,"abstract":"<p><p>Surface endothelialization is a promising way to improve the hemocompatibility of biomaterials. However, current surface endothelialization strategies have limitations. For example, various surface functions are not well balanced, leading to undesirable results, especially when multiple functional components are introduced. In this work, a multifunctional surface was constructed by balancing the functions of antifouling, nitric oxide (NO) release and endothelial cell promotion via layer-by-layer (LBL) self-assembly. Poly(sodium <i>p</i>-styrenesulfonate-<i>co-</i>oligo(ethylene glycol) methacrylate) (negatively charged) and polyethyleneimine (positively charged) were deposited on silicon substrates to construct multilayers by LBL self-assembly. Then, organic selenium, which has a NO-releasing function, and the cell-adhesive peptide Gly-Arg-Glu-Asp-Val-Tyr, which selectively promotes endothelial cells, were introduced on the assembled multilayers. Poly(oligo(ethylene glycol) methacrylate) is a hydrophilic component for antifouling properties, and poly(sodium <i>p</i>-styrenesulfonate) is a heparin analog that provides negative charges. By modulating the contents of poly(oligo(ethylene glycol) methacrylate) and poly(sodium <i>p-</i>styrenesulfonate) in the copolymers, the NO release rates catalyzed by the modified surfaces were regulated. Moreover, the behaviors of endothelial cells and smooth muscle cells on modified surfaces were well controlled. The optimized surface strongly promoted endothelial cells and inhibited smooth muscle cells to achieve endothelialization effectively.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae096"},"PeriodicalIF":5.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constructing a highly efficient multifunctional carbon quantum dot platform for the treatment of infectious wounds.","authors":"Hangzhen Zhang, Jiafan Bai, Xiangli Chen, Linyu Wang, Wenzhen Peng, Yuancong Zhao, Jie Weng, Wei Zhi, Jianxin Wang, Kai Zhang, Xingdong Zhang","doi":"10.1093/rb/rbae105","DOIUrl":"10.1093/rb/rbae105","url":null,"abstract":"<p><p>Antibiotic resistance poses a huge threat to public health, which has increased the difficulty and transmission of disease treatment, as well as the burden and cost of medical institutions. In response to the current problems and challenges in inflammation control and treatment of bacterial infected wounds, inspired by antibacterial mechanisms based on active elements such as N, S, Cu and tannic acid (TA), a highly efficient multifunctional carbon quantum dot platform was proposed in this study and constructed through their special assembly in a solvothermal reaction system for the treatment of infected wounds. By introducing active elements such as N, S and Cu, this carbon quantum dot platform is endowed with antibacterial properties, while also achieving good angiogenesis promoting performance through the use of ion Cu. Meanwhile, the good antioxidant activity of TA (one of the precursors used) enables this platform to have better immunomodulatory performance <i>in vivo</i>. The research results on the treatment of bacterial infection models indicate that the multifunctional carbon quantum dots obtained can accelerate the healing of infected wounds by inhibiting bacterial infection, regulating immunoreaction, accelerating collagen deposition and promoting angiogenesis. This multifunctional carbon quantum dot platform shows good clinical application prospects in treating bacterial infected wounds. Additionally, the fluorescence characteristics of such carbon dots can be expected to realize visual therapy in the future.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae105"},"PeriodicalIF":5.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing tumor photodynamic synergistic therapy efficacy through generation of carbon radicals by Prussian blue nanomedicine.","authors":"Jun Zhong, Mingzhi Zhu, Jiaqi Guo, Xinyu Chen, Ruimin Long, Fabian Körte, Shibin Wang, Hao Chen, Xin Xiong, Yuangang Liu","doi":"10.1093/rb/rbae103","DOIUrl":"https://doi.org/10.1093/rb/rbae103","url":null,"abstract":"<p><p>Significant progress has been achieved in tumor therapies utilizing nano-enzymes which could convert hydrogen peroxide into reactive oxygen species (ROS). However, the ROS generated by these enzymes possess a short half-life and exhibit limited diffusion within cells, making it challenging to inflict substantial damage on major organelles for effective tumor therapy. Therefore, it becomes crucial to develop a novel nanoplatform that could extend radicals half-life. Artesunate (ATS) is a Fe (II)-dependent drug, while the limited availability of iron (II), coupled with the poor aqueous solubility of ATS, limits its application. Here, Prussian blue (PB) was selected as a nano-carrier to release Fe (II), thus constructing a hollow Prussian blue/artesunate/methylene blue (HPB/ATS/MB) nanoplatform. HPB degraded and released iron(III), ATS and MB, under the combined effects of NIR irradiation and the unique tumor microenvironment. Moreover, Fe (III) exploited GSH to formation of Fe (II), disturbing the redox homeostasis of tumor cells and Fe (II) reacted with H₂O₂ and ATS to generate carbon radicals with a long half-life <i>in situ</i>. Furthermore, MB generates ¹O₂ under laser irradiation conditions. <i>In vitro</i> and <i>in vivo</i> experiments have demonstrated that the HPB/ATS/MB NPs exhibit a synergistic therapeutic effect through photothermal therapy, photodynamic therapy and radical therapy.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae103"},"PeriodicalIF":5.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assembled peptide hydrogel loaded with functional peptide Dentonin accelerates vascularized bone tissue regeneration in critical-size bone defects.","authors":"Yijuan Liu,Li Li,Mengjiao He,Yanmei Xu,Zekai Wu,Xiongcheng Xu,Kai Luo,Hongbing Lv","doi":"10.1093/rb/rbae106","DOIUrl":"https://doi.org/10.1093/rb/rbae106","url":null,"abstract":"Regeneration of oral craniofacial bone defects is a complex process, and reconstruction of large bone defects without the use of exogenous cells or bioactive substances remains a major challenge. Hydrogels are highly hydrophilic polymer networks with the potential to promote bone tissue regeneration. In this study, functional peptide Dentonin was loaded onto self-assembled peptide hydrogels (RAD) to constitute functionally self-assembling peptide RAD/Dentonin hydrogel scaffolds with a view that RAD/Dentonin hydrogel could facilitate vascularized bone regeneration in critical-size calvarial defects. The functionalized peptide RAD/Dentonin forms highly ordered β-sheet supramolecular structures via non-covalent interactions like hydrogen bonding, ultimately assembling into nano-fiber network. RAD/Dentonin hydrogels exhibited desirable porosity and swelling properties, and appropriate biodegradability. RAD/Dentonin hydrogel supported the adhesion, proliferation and three-dimensional migration of bone marrow mesenchymal stem cells (BMSCs) and has the potential to induce differentiation of BMSCs towards osteogenesis through activation of the Wnt/β-catenin pathway. Moreover, RAD/Dentonin hydrogel modulated paracrine secretion of BMSCs and increased the migration, tube formation and angiogenic gene expression of human umbilical vein endothelial cells (HUVECs), which boosted the angiogenic capacity of HUVECs. In vivo, RAD/Dentonin hydrogel significantly strengthened vascularized bone formation in rat calvarial defect. Taken together, these results indicated that the functionalized self-assembling peptide RAD/Dentonin hydrogel effectively enhance osteogenic differentiation of BMSCs, indirectly induce angiogenic effects in HUVECs, and facilitate vascularized bone regeneration in vivo. Thus, it is a promising bioactive material for oral and maxillofacial regeneration.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"42 1","pages":"rbae106"},"PeriodicalIF":6.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A promising strategy for combating bacterial infections through the use of light-triggered ROS in Ce6-immobilized hydrogels.","authors":"Seung Hee Hong, Mi Hee Lee, Eun Jeong Go, Jong-Chul Park","doi":"10.1093/rb/rbae101","DOIUrl":"https://doi.org/10.1093/rb/rbae101","url":null,"abstract":"<p><p>The reactive oxygen species (ROS) are composed of highly reactive molecules, including superoxide anions ( <math> <mrow> <msubsup><mrow><mi>O</mi></mrow> <mrow><mn>2</mn></mrow> <mrow><mo>•</mo> <mo>-</mo></mrow> </msubsup> </mrow> </math> ), hydrogen peroxide (H₂O₂) and hydroxyl radicals. Researchers have explored the potential benefits of using hydrogel dressings that incorporate active substances to accelerate wound healing. The present investigation involved the development of a hyaluronic acid (HA) hydrogel capable of producing ROS using LED irradiation. The process of creating a composite hydrogel was created by chemically bonding Ce6 to an amide group. Our analysis revealed that the synthesized hydrogel had a well-structured amide bond, and the degree of cross-linking was assessed through swelling, enzyme stability and cytotoxicity tests. ROS production was found to be influenced by both the intensity and duration of light exposure. Furthermore, in situations where cell toxicity resulting from ROS generation in the hydrogel surpassed 70%, no detectable genotoxic consequences were evident, and antibacterial activity was confirmed to be directly caused by the destruction of bacterial membranes as a result of ROS damage. Furthermore, the utilization of the generated ROS influences the polarization of macrophages, resulting in the secretion of pro-inflammatory cytokines, which is a characteristic feature of M1 polarization. Subsequently, we validated the efficacy of a HA hydrogel that produces ROS to directly eradicate microorganisms. Furthermore, this hydrogel facilitated indirect antibacterial activity by stimulating macrophages to release pro-inflammatory cytokines. These cytokines are crucial for coordinating cell-mediated immune responses and for modulating the overall effectiveness of the immune system. Therefore, the Ce6-HA hydrogel has the potential to serve as an effective wound dressing solution for infected wounds because of its ability to produce substantial levels or a consistent supply.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae101"},"PeriodicalIF":5.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium silicate cements endowing bioactivity and sustaining mechanical strength of low-heat-releasing and fast-curing magnesium phosphate cements.","authors":"Lijun Xie, Yan Zhang, Binji Cao, Xiaoyi Jiao, Xusong Yue, Yan Xu, Xianyan Yang, Guojing Yang, Yingjie Wang, Jian Shen, Cong Wang, Xisheng Weng, Zhongru Gou","doi":"10.1093/rb/rbae100","DOIUrl":"10.1093/rb/rbae100","url":null,"abstract":"<p><p>It is known that magnesium phosphate cements (MPCs) show appreciable mechanical strength and biocompatibility, but the hydration reaction processes often lead to intense heat release while the hydration products present weak resistance to mechanical decay and low bioactivity. Herein we developed an MPC-based system, which was low-heat-releasing and fast-curing in this study, by compounding with self-curing calcium silicate cements (CSCs). The MPC composed of magnesium oxide (MgO), potassium dihydrogen phosphate (KH₂PO₄), disodium hydrogen phosphate (Na₂HPO₄), magnesium hydrogen phosphate trihydrate (MgHPO₄·3H₂O) and chitosan were weakly basic, which would be more stable <i>in vivo</i>. The physicochemical properties indicated that the addition of CSCs could increase the final setting time while decrease the heat release. Meanwhile, the CSCs could endow MPC substrate with apatite re-mineralization reactivity, especially, which add 25 wt.% CSCs showed the most significant apatite deposition. What's more, the mechanical evolution in buffer demonstrated CSCs could enhance and sustain the mechanical strength during degradation, and the internal constructs of cement implants could still be reconstructed by μCT analysis in rabbit femoral bone defect model <i>in vivo</i>. Particularly, appropriate CSCs adjusted the biodegradation and promoted new bone tissue regeneration <i>in vivo</i>. Totally, the MPC/CSCs composite system endows bioactivity and sustains mechanical strength of the MPC, which may be promising for expending the clinical applications of MPC-based bone cements.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae100"},"PeriodicalIF":5.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In situ</i> MgO nanoparticle-doped Janus electrospun dressing against bacterial invasion and immune imbalance for irregular wound healing.","authors":"Tao Zhou, Yedan Chen, Liangmin Fu, Shan Wang, Haihu Ding, Qiaosheng Bai, Jingjing Guan, Yingji Mao","doi":"10.1093/rb/rbae107","DOIUrl":"10.1093/rb/rbae107","url":null,"abstract":"<p><p>Owing to the unpredictable size of wounds and irregular edges formed by trauma, nanofibers' highly customizable and adherent <i>in situ</i> deposition can contribute to intervention in the healing process. However, electrospinning is limited by the constraints of conventional polymeric materials despite its potential for anti-inflammatory and antimicrobial properties. Here, inspired by the Janus structure and biochemistry of nanometal ions, we developed an <i>in situ</i> sprayed electrospinning method to overcome bacterial infections and immune imbalances during wound healing. The bilayer fiber scaffold has a hydrophobic outer layer composed of polycaprolactone (PCL) and a hydrophilic inner layer composed of gelatin, poly(L-lactic acid) (PLLA), and magnesium oxide nanoparticles, constituting the PCL/PLLA-gelatin-MgO (PPGM) electrospun scaffold. This electrospun scaffold blocked the colonization and growth of bacteria and remained stable on the wound for continuous anti-inflammatory properties to promote wound healing. Furthermore, PPGM electrospinning modulated collagen deposition and the inflammatory microenvironment in the full-thickness skin model, significantly accelerating vascularization and epithelialization progression. This personalized Janus electrospun scaffold has excellent potential as a new type of wound dressing for first aid and wound healthcare.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae107"},"PeriodicalIF":5.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyzwitterion-grafted decellularized bovine intercostal arteries as new substitutes of small-diameter arteries for vascular regeneration.","authors":"Yuan Xia, Zilong Rao, Simin Wu, Jiayao Huang, Haiyun Zhou, Hanzhao Li, Hui Zheng, Daxin Guo, Daping Quan, Jing-Song Ou, Ying Bai, Yunqi Liu","doi":"10.1093/rb/rbae098","DOIUrl":"10.1093/rb/rbae098","url":null,"abstract":"<p><p>Coronary artery bypass grafting is acknowledged as a major clinical approach for treatment of severe coronary artery atherosclerotic heart disease. This procedure typically requires autologous small-diameter vascular grafts. However, the limited availability of the donor vessels and associated trauma during tissue harvest underscore the necessity for artificial arterial alternatives. Herein, decellularized bovine intercostal arteries were successfully fabricated with lengths ranging from 15 to 30 cm, which also closely match the inner diameters of human coronary arteries. These decellularized arterial grafts exhibited great promise following poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) grafting from the inner surface. Such surface modification endowed the decellularized arteries with superior mechanical strength, enhanced anticoagulant properties and improved biocompatibility, compared to the decellularized bovine intercostal arteries alone, or even those decellularized grafts modified with both heparin and vascular endothelial growth factor. After replacement of the carotid arteries in rabbits, all surface-modified vascular grafts have shown good patency within 30 days post-implantation. Notably, strong signal was observed after α-SMA immunofluorescence staining on the PMPC-grafted vessels, indicating significant potential for regenerating the vascular smooth muscle layer and thereby restoring full structures of the artery. Consequently, the decellularized bovine intercostal arteries surface modified by PMPC can emerge as a potent candidate for small-diameter artificial blood vessels, and have shown great promise to serve as viable substitutes of arterial autografts.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae098"},"PeriodicalIF":5.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of ECM protein-coated surfaces on the generation of retinal pigment epithelium cells differentiated from human pluripotent stem cells.","authors":"Zeyu Tian, Qian Liu, Hui-Yu Lin, Yu-Ru Zhu, Ling Ling, Tzu-Cheng Sung, Ting Wang, Wanqi Li, Min Gao, Sitian Cheng, Remya Rajan Renuka, Suresh Kumar Subbiah, Guoping Fan, Gwo-Jang Wu, Akon Higuchi","doi":"10.1093/rb/rbae091","DOIUrl":"10.1093/rb/rbae091","url":null,"abstract":"<p><p>Retinal degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), initially manifest as dysfunction or death of the retinal pigment epithelium (RPE). Subretinal transplantation of human pluripotent stem cell (hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration. However, RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials. The development of hPSC-derived RPE cell differentiation protocols using xeno-free biomaterials is urgently needed for clinical applications. In this study, two protocols (the activin A and NIC84 protocols) were selected for modification and use in the differentiation of hiPSCs into RPE cells; the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells. The xeno-free extracellular matrix (ECM) proteins, laminin-511, laminin-521 and recombinant vitronectin, were selected as plate-coating substrates, and a Matrigel (xeno-containing ECM)-coated surface was used as a positive control. Healthy, mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons (RCS) rats, a model of retinal degeneration disease. The visual function of RCS rats was evaluated by optomotor response (qOMR) and electroretinography after transplantation of hPSC-derived RPE cells. Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 protocol, and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae091"},"PeriodicalIF":5.6,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}