Eduardo Anitua Foundation for Biomedical Research, 01007 Vitoria, Spain.
Regenerative Medicine Laboratory, BTI-Biotechnology Institute IMASD, 01007 Vitoria, Spain.
Int J Mol Sci. 2023 Jul 18;24(14):11581. doi: 10.3390/ijms241411581.
The treatment of chondral and osteochondral defects is challenging. These types of lesions are painful and progress to osteoarthritis over time. Tissue engineering offers tools to address this unmet medical need. The use of an autologous cartilage construct consisting of hyaline cartilage chips embedded in plasma rich in growth factors (PRGF) has been proposed as a therapeutic alternative. The purpose of this study was to dig into the potential mechanisms behind the in vitro remodelling process that might explain the clinical success of this technique and facilitate its optimisation. Chondrocyte viability and cellular behaviour over eight weeks of in vitro culture, type II collagen synthesis, the dual delivery of growth factors by hyaline cartilage and PRGF matrix, and the ultrastructure of the construct and its remodelling were characterised. The main finding of this research is that the cartilage fragments embedded in the three-dimensional PRGF scaffold contain viable chondrocytes that are able to migrate into the fibrin network, proliferate and synthesise extracellular matrix after the second week of in vitro culture. The characterization of this three-dimensional matrix is key to unravelling the molecular kinetics responsible for its efficacy.
软骨和骨软骨缺损的治疗具有挑战性。这些类型的病变会引起疼痛,并随着时间的推移进展为骨关节炎。组织工程提供了满足这一未满足医疗需求的工具。使用由富含生长因子的富血浆(PRGF)嵌入的透明软骨片组成的自体软骨构建体已被提议作为一种治疗替代方法。本研究的目的是深入研究体外重塑过程背后的潜在机制,这些机制可能解释该技术的临床成功,并促进其优化。研究了体外培养 8 周内的软骨细胞活力和细胞行为、II 型胶原合成、透明软骨和 PRGF 基质的双重生长因子传递,以及构建体的超微结构及其重塑。这项研究的主要发现是,嵌入在三维 PRGF 支架中的软骨碎片含有存活的软骨细胞,这些细胞能够在体外培养的第二周迁移到纤维蛋白网络中,并增殖和合成细胞外基质。这种三维基质的特性是揭示其功效的分子动力学的关键。