Department of Orthopedics, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China; Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Capital Medical University, No.31 Xinjiekou East Street, Xicheng District, Beijing 100035, China; Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
Department of Orthopedics, Eighth Medical Center, General Hospital of Chinese PLA, Beijing 100853, China.
Acta Biomater. 2024 Oct 1;187:66-81. doi: 10.1016/j.actbio.2024.08.014. Epub 2024 Aug 19.
Tissue engineering presents a promising approach for the treatment of meniscal injuries, yet the development of meniscal scaffolds that exhibit both superior biomechanical properties and biocompatibility remains a considerable challenge. In this study, decellularized skin matrix (DSM) scaffolds were first prepared using porcine skin through decellularization and freeze-drying techniques. The DSM scaffold has favorable porosity, hydrophilicity, and biocompatibility. Importantly, the collagen content and tensile modulus of the scaffold are comparable to those of native meniscus (44.13 ± 2.396 mg/g vs. 42.41 ± 2.40 mg/g and 103.30 ± 2.98 MPa vs. 128.80 ± 9.115 MPa). Subsequently, the peptide PFSSTKT (PFS) with mesenchymal stem cells (MSCs) recruitment capability was used to modify DSM to construct DSM-PFS scaffolds. Compared to the DSM scaffold, the optimized DSM-PFS scaffold enhanced in vitro collagen and glycosaminoglycan (GAG) production and upregulated the expression of cartilage-specific genes. Furthermore, the DSM-PFS scaffold was more effective in recruiting MSCs in vitro. In vivo studies in rabbit models showed that the DSM-PFS scaffold successfully promoted meniscus tissue regeneration. Three months post-implantation, meniscus tissue formation can be observable, and after six months, the neo-meniscus exhibited tissue structure and tensile properties similar to the native meniscus. Notably, the DSM-PFS scaffold exhibited significant chondroprotective effects, slowing osteoarthritis (OA) progression. In conclusion, the DSM-PFS scaffold may represent a promising candidate for future applications in meniscus tissue engineering. STATEMENT OF SIGNIFICANCE: We developed a decellularized skin matrix (DSM) meniscus scaffold using whole-layer porcine skin, demonstrating superior biomechanical strength and biocompatibility. Following modification with the stem cell-recruiting peptide PFS, the optimized DSM-PFS scaffold outperformed the DSM scaffold in cell attraction, collagen and glycosaminoglycan production, and cartilage-specific gene expression. Implanted into rabbit knee joints, the cell-free DSM-PFS scaffold induced meniscal tissue formation within three months, achieving the histological structure and tensile strength of the native meniscus by six months. Moreover, it significantly protected the cartilage. Our findings provide new insights into the fabrication of scaffolds for meniscal tissue engineering, with the DSM-PFS scaffold emerging as an ideal candidate for future applications.
组织工程为治疗半月板损伤提供了一种很有前途的方法，但开发出具有优异生物力学性能和生物相容性的半月板支架仍然是一个相当大的挑战。在这项研究中，首先通过脱细胞和冻干技术从猪皮中制备脱细胞皮肤基质（DSM）支架。DSM 支架具有良好的孔隙率、亲水性和生物相容性。重要的是，支架的胶原含量和拉伸模量与天然半月板相当（44.13±2.396mg/g 与 42.41±2.40mg/g 和 103.30±2.98MPa 与 128.80±9.115MPa）。随后，使用具有间充质干细胞（MSCs）募集能力的肽 PFSSTKT（PFS）修饰 DSM 以构建 DSM-PFS 支架。与 DSM 支架相比，优化后的 DSM-PFS 支架增强了体外胶原蛋白和糖胺聚糖（GAG）的产生，并上调了软骨特异性基因的表达。此外，DSM-PFS 支架在体外更有效地募集 MSCs。在兔模型中的体内研究表明，DSM-PFS 支架成功促进了半月板组织再生。植入后 3 个月，可以观察到半月板组织的形成，6 个月后，新的半月板表现出与天然半月板相似的组织结构和拉伸性能。值得注意的是，DSM-PFS 支架具有显著的软骨保护作用，减缓了骨关节炎（OA）的进展。总之，DSM-PFS 支架可能成为未来半月板组织工程应用的有前途的候选物。
我们使用全层猪皮开发了脱细胞皮肤基质（DSM）半月板支架，表现出优异的生物力学强度和生物相容性。用募集干细胞的肽 PFS 修饰后，优化后的 DSM-PFS 支架在细胞吸引力、胶原蛋白和糖胺聚糖产生以及软骨特异性基因表达方面优于 DSM 支架。植入兔膝关节后，无细胞的 DSM-PFS 支架在 3 个月内诱导半月板组织形成，6 个月时达到天然半月板的组织结构和拉伸强度。此外，它还能显著保护软骨。我们的研究结果为半月板组织工程支架的制备提供了新的见解，DSM-PFS 支架作为未来应用的理想候选物脱颖而出。
