IMDEA Materials Institute, 28906 Getafe, Madrid, Spain; Department of Materials Science, Polytechnic University of Madrid/Universidad Politécnica de Madrid, 28040, Madrid, Spain.
Tissue Engineering Research Group, Department of Anatomy & Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland; Trinity Centre for Biomedical Engineering, Trinity College Dublin (TCD), Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI and TCD, Dublin, Ireland.
Int J Biol Macromol. 2024 Nov;280(Pt 2):135827. doi: 10.1016/j.ijbiomac.2024.135827. Epub 2024 Sep 19.
Cartilage defect repair with optimal efficiency remains a significant challenge due to the limited self-repair capability of native tissues. The development of bioactive scaffolds with biomimicking mechanical properties and degradation rates matched with cartilage regeneration while simultaneously driving chondrogenesis, plays a crucial role in enhancing cartilage defect repair. To this end, a novel composite scaffold with hierarchical porosity was manufactured by incorporating a pro-chondrogenic collagen type I/II-hyaluronic acid (CI/II-HyA) matrix to a 3D-printed poly(glycerol sebacate) (PGS) framework. Based on the mechanical enforcement of PGS framework, the composite scaffold exhibited a compressive modulus of 167.0 kPa, similar to that of native cartilage, as well as excellent fatigue resistance, similar to that of native joint tissue. In vitro degradation tests demonstrated that the composite scaffold maintained structural, mass, and mechanical stability during the initial cartilage regeneration period of 4 weeks, while degraded linearly over time. In vitro biological tests with rat-derived mesenchymal stem cell (MSC) revealed that, the composite scaffold displayed increased cell loading efficiency and improved overall cell viability due to the incorporation of CI/II-HyA matrix. Additionally, it also sustained an effective and high-quality MSC chondrogenesis and abundant de-novo cartilage-like matrix deposition up to day 28. Overall, the biomimetic composite scaffold with sufficient mechanical support, matched degradation rate with cartilage regeneration, and effective chondrogenesis stimulation shows great potential to be an ideal candidate for enhancing cartilage defect repair.
由于天然组织的自我修复能力有限，因此以最佳效率修复软骨缺损仍然是一个重大挑战。开发具有仿生机械性能和降解率的生物活性支架，与软骨再生相匹配，同时促进软骨生成，对于增强软骨缺损修复至关重要。为此，通过将具有促软骨生成特性的胶原 I/II-透明质酸（CI/II-HyA）基质纳入 3D 打印的聚甘油癸二酸酯（PGS）框架中，制造了一种具有分级多孔结构的新型复合支架。基于 PGS 框架的机械增强作用，复合支架的压缩模量为 167.0kPa，与天然软骨相似，并且具有出色的耐疲劳性，与天然关节组织相当。体外降解测试表明，在最初的 4 周软骨再生期间，复合支架保持了结构、质量和机械稳定性，同时随时间呈线性降解。体外大鼠来源间充质干细胞（MSC）试验表明，由于 CI/II-HyA 基质的加入，复合支架提高了细胞负载效率和整体细胞活力。此外，它还能持续有效地促进 MSC 软骨生成，并在第 28 天之前大量生成新的软骨样基质。总体而言，这种具有足够机械支撑、与软骨再生相匹配的降解率以及有效软骨生成刺激作用的仿生复合支架，有望成为增强软骨缺损修复的理想候选材料。
