Valot Laurine, Maumus Marie, Brunel Luc, Martinez Jean, Amblard Muriel, Noël Danièle, Mehdi Ahmad, Subra Gilles
IBMM, University Montpellier, CNRS, ENSCM, 34095 Montpellier, France.
ICGM, University Montpellier, CNRS, ENSCM, 34095 Montpellier, France.
Gels. 2021 Jun 15;7(2):73. doi: 10.3390/gels7020073.
Promising strategies for cartilage regeneration rely on the encapsulation of mesenchymal stromal cells (MSCs) in a hydrogel followed by an injection into the injured joint. Preclinical and clinical data using MSCs embedded in a collagen gel have demonstrated improvements in patients with focal lesions and osteoarthritis. However, an improvement is often observed in the short or medium term due to the loss of the chondrocyte capacity to produce the correct extracellular matrix and to respond to mechanical stimulation. Developing novel biomimetic materials with better chondroconductive and mechanical properties is still a challenge for cartilage engineering. Herein, we have designed a biomimetic chemical hydrogel based on silylated collagen-mimetic synthetic peptides having the ability to encapsulate MSCs using a biorthogonal sol-gel cross-linking reaction. By tuning the hydrogel composition using both mono- and bi-functional peptides, we succeeded in improving its mechanical properties, yielding a more elastic scaffold and achieving the survival of embedded MSCs for 21 days as well as the up-regulation of chondrocyte markers. This biomimetic long-standing hybrid hydrogel is of interest as a synthetic and modular scaffold for cartilage tissue engineering.
软骨再生的有前景策略依赖于将间充质基质细胞(MSCs)包裹在水凝胶中,然后注射到受损关节。使用嵌入胶原蛋白凝胶中的MSCs的临床前和临床数据已证明,局灶性病变和骨关节炎患者的病情有所改善。然而,由于软骨细胞产生正确细胞外基质和响应机械刺激的能力丧失,通常在短期或中期观察到病情改善。开发具有更好软骨传导性和机械性能的新型仿生材料仍然是软骨工程面临的挑战。在此,我们基于具有使用生物正交溶胶-凝胶交联反应包裹MSCs能力的硅烷化胶原蛋白模拟合成肽设计了一种仿生化学水凝胶。通过使用单功能和双功能肽调节水凝胶组成,我们成功改善了其机械性能,产生了更具弹性的支架,并使嵌入的MSCs存活21天以及上调软骨细胞标志物。这种仿生长效混合水凝胶作为软骨组织工程的合成和模块化支架具有重要意义。