Kimura Yuta, Hokugo Akishige, Takamoto Tomoaki, Tabata Yasuhiko, Kurosawa Hisashi
Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Tissue Eng Part C Methods. 2008 Mar;14(1):47-57. doi: 10.1089/tec.2007.0286.
The objective of this study was to increase the therapeutic efficacy of anterior cruciate ligament (ACL) surgery using an artificial ligament material developed through a combination of tissue engineering technologies. A poly-L-lactic acid (PLLA) scaffold of plain-woven braid was incorporated with a gelatin hydrogel for controlled release of basic fibroblast growth factor (bFGF) and wrapped with a collagen membrane to allow space for ligament regeneration. For the ACL reconstruction surgery, the PLLA braid scaffold combined with the gelatin hydrogel incorporating bFGF and the collagen wrapping was applied to a tunnel prepared in the femur and tibia of rabbits. The hydrogel was placed in the bone, whereas the portion of the braid inside the joint cavity was wrapped with the membrane. As controls, the PLLA scaffold was applied with the hydrogel or the membrane, or without either material. Bone regeneration in the tunnel and ACL tissue regeneration in the joint cavity were histologically evaluated, and the mechanical strength and collagen content of the regenerated ACL were assessed. When the PLLA scaffold was integrated with both the hydrogel and the membrane, bone and ACL tissues were regenerated in the corresponding sites, in marked contrast to the control groups. Combination of bFGF-controlled release resulted in enhanced mechanical strength of the regenerated ACL tissue. In the joint cavity, it is possible that the local bFGF release inside the membrane enhanced the cell migration and collagen production, and that the surrounding PLLA scaffold results in the biological regeneration of ligament-like tissue. Additionally, significant bone regeneration around the scaffold was observed in the bone tunnel. It is therefore possible that the local controlled release of bFGF near the PLLA braid induced both osseointegration and intrascaffold cell migration in the bone tunnel and joint cavity, respectively, resulting in an overall increase in the mechanical strength of the regenerated ACL.
本研究的目的是通过结合组织工程技术开发的人工韧带材料来提高前交叉韧带（ACL）手术的治疗效果。将平纹编织的聚-L-乳酸（PLLA）支架与明胶水凝胶结合，用于碱性成纤维细胞生长因子（bFGF）的控释，并包裹胶原膜以留出韧带再生的空间。对于ACL重建手术，将结合了含bFGF的明胶水凝胶和胶原包裹的PLLA编织支架应用于兔股骨和胫骨制备的隧道中。水凝胶置于骨内，而关节腔内编织物的部分则用膜包裹。作为对照，PLLA支架单独应用水凝胶或膜，或不应用任何一种材料。对隧道内的骨再生和关节腔内的ACL组织再生进行组织学评估，并评估再生ACL的机械强度和胶原含量。当PLLA支架与水凝胶和膜两者结合时，相应部位再生出骨和ACL组织，这与对照组形成明显对比。bFGF控释的联合应用导致再生ACL组织的机械强度增强。在关节腔内，膜内局部bFGF释放可能增强了细胞迁移和胶原产生，并且周围的PLLA支架导致韧带样组织的生物再生。此外，在骨隧道中观察到支架周围有明显的骨再生。因此，PLLA编织物附近bFGF的局部控释可能分别在骨隧道和关节腔内诱导了骨整合和支架内细胞迁移，从而导致再生ACL的机械强度总体增加。
