Meng Haoye, Liu Xuejian, Liu Ronghui, Zheng Yudong, Hou Angyang, Liu Shuyun, He Wei, Wang Yu, Wang Aiyuan, Guo Quanyi, Peng Jiang
School of Material Science and Engineering, University of Science and Technology Beijing, Beijing, China.
Institute of Orthopaedics, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
J Orthop Translat. 2024 May 10;46:18-32. doi: 10.1016/j.jot.2024.04.005. eCollection 2024 May.
Osteochondral regeneration has long been recognized as a complex and challenging project in the field of tissue engineering. In particular, reconstructing the osteochondral interface is crucial for determining the effectiveness of the repair. Although several artificial layered or gradient scaffolds have been developed recently to simulate the natural interface, the functions of this unique structure have still not been fully replicated. In this paper, we utilized laser micro-patterning technology (LMPT) to modify the natural osteochondral "plugs" for use as grafts and aimed to directly apply the functional interface unit to repair osteochondral defects in a goat model.
For in vitro evaluations, the optimal combination of LMPT parameters was confirmed through mechanical testing, finite element analysis, and comparing decellularization efficiency. The structural and biological properties of the laser micro-patterned osteochondral implants (LMP-OI) were verified by measuring the permeability of the interface and assessing the recellularization processes. In the goat model for osteochondral regeneration, a conical frustum-shaped defect was specifically created in the weight-bearing area of femoral condyles using a customized trephine with a variable diameter. This unreported defect shape enabled the implant to properly self-fix as expected.
The micro-patterning with the suitable pore density and morphology increased the permeability of the LMP-OIs, accelerated decellularization, maintained mechanical stability, and provided two relative independent microenvironments for subsequent recellularization. The LMP-OIs with goat's autologous bone marrow stromal cells in the cartilage layer have securely integrated into the osteochondral defects. At 6 and 12 months after implantation, both imaging and histological assessments showed a significant improvement in the healing of the cartilage and subchondral bone.
With the natural interface unit and zonal recellularization, the LMP-OI is an ideal scaffold to repair osteochondral defects especially in large animals.
These findings suggest that such a modified xenogeneic osteochondral implant could potentially be explored in clinical translation for treatment of osteochondral injuries. Furthermore, trimming a conical frustum shape to the defect region, especially for large-sized defects, may be an effective way to achieve self-fixing for the implant.
骨软骨再生长期以来一直被认为是组织工程领域中一个复杂且具有挑战性的项目。特别是,重建骨软骨界面对于确定修复效果至关重要。尽管最近已经开发了几种人工分层或梯度支架来模拟天然界面,但这种独特结构的功能仍未得到充分复制。在本文中,我们利用激光微图案化技术(LMPT)对天然骨软骨“栓子”进行改性以用作移植物,并旨在直接应用功能性界面单元修复山羊模型中的骨软骨缺损。
对于体外评估,通过力学测试、有限元分析和比较脱细胞效率来确定LMPT参数的最佳组合。通过测量界面的渗透性和评估再细胞化过程来验证激光微图案化骨软骨植入物(LMP-OI)的结构和生物学特性。在骨软骨再生的山羊模型中,使用定制的可变直径环锯在股骨髁的负重区域专门制造一个截头圆锥形缺损。这种未报道过的缺损形状使植入物能够如预期那样正确地自我固定。
具有合适孔隙密度和形态的微图案化增加了LMP-OI的渗透性,加速了脱细胞过程,保持了机械稳定性,并为随后的再细胞化提供了两个相对独立的微环境。软骨层中含有山羊自体骨髓基质细胞的LMP-OI已牢固地整合到骨软骨缺损中。植入后6个月和12个月,影像学和组织学评估均显示软骨和软骨下骨的愈合有显著改善。
凭借天然界面单元和区域再细胞化,LMP-OI是修复骨软骨缺损的理想支架,尤其是在大型动物中。
这些发现表明,这种改性的异种骨软骨植入物有可能在临床转化中用于治疗骨软骨损伤。此外,将缺损区域修整成截头圆锥形,特别是对于大型缺损,可能是实现植入物自我固定的有效方法。