关键词: Cartilage repair RADA-16 Self-assembled peptides TGF-β1 hBMSCs

Mesh : Transforming Growth Factor beta1 / metabolism pharmacology Regeneration / drug effects Tissue Scaffolds / chemistry Hydrogels / chemistry pharmacology Humans Chondrocytes / drug effects cytology metabolism Cell Differentiation / drug effects Cartilage / drug effects physiology metabolism Cell Proliferation / drug effects Tissue Engineering / methods Cells, Cultured Mesenchymal Stem Cells / drug effects cytology Animals Chondrogenesis / drug effects Peptides

来  源:   DOI:10.1016/j.colsurfb.2024.113959

Abstract:
Cartilage repair remains a major challenge in clinical trials. These current cartilage repair materials can not effectively promote chondrocyte generation, limiting their practical application in cartilage repair. In this work, we develop an implantable scaffold of RADA-16 peptide hydrogel incorporated with TGF-β1 to provide a microenvironment for stem cell-directed differentiation and chondrocyte adhesion growth. The longest release of growth factor TGF-β1 release can reach up to 600 h under physiological conditions. TGF-β1/RADA-16 hydrogel was demonstrated to be a lamellar porous structure. Based on the cell culture with hBMSCs, TGF-β1/RADA-16 hydrogel showed excellent ability to promote cell proliferation, directed differentiation into chondrocytes, and functional protein secretion. Within 14 days, 80% of hBMSCs were observed to be directed to differentiate into vigorous chondrocytes in the co-culture of TGF-β1/RADA-16 hydrogels with hBMSCs. Specifically, these newly generated chondrocytes can secrete and accumulate large amounts of collagen II within 28 days, which can effectively promote the formation of cartilage tissue. Finally, the exploration of RADA-16 hydrogel-based scaffolds incorporated with TGF-β1 bioactive species would further greatly promote the practical clinical trials of cartilage remediation, which might have excellent potential to promote cartilage regeneration in areas of cartilage damage.
摘要:
软骨修复仍然是临床试验中的主要挑战。目前这些软骨修复材料不能有效促进软骨细胞的生成,限制了它们在软骨修复中的实际应用。在这项工作中,我们开发了一种与TGF-β1结合的RADA-16肽水凝胶可植入支架,为干细胞定向分化和软骨细胞粘附生长提供微环境.在生理条件下,生长因子TGF-β1释放的最长释放可达600h。TGF-β1/RADA-16水凝胶被证明是层状多孔结构。基于hBMSCs的细胞培养,TGF-β1/RADA-16水凝胶显示出优异的促进细胞增殖的能力,定向分化为软骨细胞,和功能性蛋白质分泌。14天内,在TGF-β1/RADA-16水凝胶与hBMSC的共培养中,观察到80%的hBMSC被定向分化为有活力的软骨细胞。具体来说,这些新生成的软骨细胞可以在28天内分泌和积累大量的胶原蛋白II,能有效促进软骨组织的形成。最后,结合TGF-β1生物活性物质的RADA-16水凝胶支架的探索将进一步极大地促进软骨修复的实际临床试验,这可能具有促进软骨损伤区域软骨再生的极好潜力。
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