Wei Chuanzhi, Lin Mingyue, Bo Qitao, Dai Wufei, Ding Jinghao, Chen Ru
Department of Breast Surgery, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou, 570311, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Regen Biomater. 2025 May 8;12:rbaf037. doi: 10.1093/rb/rbaf037. eCollection 2025.
The immature state of engineered cartilage (IVEC) hinders its clinical translation, highlighting the need for optimized scaffold platforms and cultivation models. Our previous work demonstrated that Wharton's jelly (WJ) contains an extracellular matrix (ECM) whose composition closely resembles that of native cartilage and includes several bioactive factors that promote chondrogenic induction. Furthermore, earlier studies have shown that photo-crosslinkable hydrogels are ideal carrier scaffolds for cartilage tissue engineering and that bioreactors improve nutrient and waste exchange between scaffolds and the culture medium. Based on these findings, we employed a dynamic bioreactor in combination with a WJ-derived photo-crosslinkable hydrogel to enhance IVEC maturity. Our results indicate that the decellularized WJ matrix (DWJM) effectively retains its native chondrogenic ECM components and bioactive factors. The photo-crosslinkable ADWJM hydrogel-produced by modifying DWJM with methacrylate anhydride-demonstrated excellent gelation capacity as well as tunable rheological properties, swelling ratios and degradation rates across different DWJM concentrations. In addition, the ADWJM hydrogel exhibited outstanding biocompatibility by providing a favorable 3D microenvironment for chondrocyte survival and proliferation. Most importantly, the dynamic bioreactor markedly promoted IVEC maturation. Constructs cultured under dynamic conditions displayed increased thickness, wet weight and volume; enhanced mechanical strength; more typical lacunae structures; and uniform deposition of cartilage-specific ECM compared to constructs maintained in static conditions or within a static bioreactor. Moreover, in vivo subcutaneous implantation of IVEC in goats further validated these findings, as the implanted constructs exhibited cartilage components and mechanical properties closely resembling those of natural cartilage. These results offer a promising approach for enhancing IVEC maturity and support its future clinical translation.
工程化软骨（IVEC）的不成熟状态阻碍了其临床转化，这凸显了优化支架平台和培养模型的必要性。我们之前的研究表明，脐带华通氏胶（WJ）含有一种细胞外基质（ECM），其组成与天然软骨的组成非常相似，并且包含几种促进软骨形成诱导的生物活性因子。此外，早期研究表明，可光交联水凝胶是软骨组织工程的理想载体支架，生物反应器可改善支架与培养基之间的营养物质和废物交换。基于这些发现，我们采用了动态生物反应器与源自WJ的可光交联水凝胶相结合的方法来提高IVEC的成熟度。我们的结果表明，脱细胞WJ基质（DWJM）有效地保留了其天然的软骨形成ECM成分和生物活性因子。通过用甲基丙烯酸酐修饰DWJM制备的可光交联ADWJM水凝胶，在不同DWJM浓度下表现出优异的凝胶化能力以及可调节的流变学性质、溶胀率和降解率。此外，ADWJM水凝胶通过为软骨细胞的存活和增殖提供有利的三维微环境，表现出出色的生物相容性。最重要的是，动态生物反应器显著促进了IVEC的成熟。与在静态条件下或静态生物反应器中培养的构建体相比，在动态条件下培养的构建体显示出厚度、湿重和体积增加；机械强度增强；更典型的陷窝结构；以及软骨特异性ECM的均匀沉积。此外，在山羊体内皮下植入IVEC进一步验证了这些发现，因为植入的构建体表现出与天然软骨非常相似的软骨成分和力学性能。这些结果为提高IVEC的成熟度提供了一种有前景的方法，并支持其未来的临床转化。
