Positive effects of cell-free porous PLGA implants and early loading exercise on hyaline cartilage regeneration in rabbits
Positive effects of cell-free porous PLGA implants and early loading exercise on hyaline cartilage regeneration in rabbits
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DOI：
10.1016/j.actbio.2015.09.026
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发表时间：
2015-12-01
影响因子：
9.7
通讯作者：
Chu, Chih-Jou
中科院分区：
文献类型：
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作者：
Chang, Nai-Jen;Lin, Chih-Chan;Chu, Chih-Jou
透明软骨的再生在临床上仍然具有挑战性。在这里，我们评估了使用无细胞多孔聚（乳酸-乙醇酸共聚物）（PLGA）移植植入物（PGI）沿着早期负荷运动来修复全层骨软骨缺损的治疗效果。将家兔随机分为平板运动（TRE）组和安静（SED）组，并制备PGI模型和空缺损（艾德）模型。TRE是作为短期负荷运动进行的; SED是在自由笼中进行身体活动。在术后6周和12周对膝关节进行评价。在测试结束时，没有膝关节出现滑膜炎、骨赘形成或感染。大体上，PGI-TRE组再生了光滑的关节面，透明的新透明样组织与邻近的软骨完全整合，但其他组在边缘处仍有纤维或不透明组织。在显微CT分析中，PGI-TRE组的合成骨体积/组织体积（BV/TV）显著更高，其在再生部位也具有整合结构。从6到12周，所有组的松质骨（软骨下）厚度均有所改善。组织学上，软骨再生的显著差异是可见的。在第6周，与SED组相比，TRE组表现出适度的具有促炎细胞因子的炎性细胞（即，TNF-α和IL-6），改善胶原排列和更高的糖胺聚糖（GAG）含量，特别是在PGI-TRE组。在第12周，PGI-TRE组具有最好的再生结果，显示透明样软骨的形成，柱状圆形软骨细胞的发育，其表达丰富水平的II型胶原和GAG，以及骨细胞的功能化骨小梁。综上所述，植入无细胞PLGA和进行早期负荷运动的组合可以显著促进兔膝关节模型中的全层骨软骨再生。显著性声明促进有效的透明软骨再生而不是纤维软骨瘢痕组织仍然具有临床挑战性。为了解决这一问题，我们制作了一种海绵状无细胞PLGA支架，并设计了合理的运动计划，以产生联合治疗效果。首先，植入支架产生负担得起的机械结构，以承受负载力并与宿主桥接，为兔膝关节全层骨软骨再生提供空间。植入后，兔进行早期跑步机运动15分钟/天，5天/周，持续2周，直接发挥原位内源性生长因子和抗炎作用的修复部位。先进的治疗策略表明，新的透明软骨形成，富含II型胶原，更高的糖胺聚糖，整合软骨下骨形成和适度的炎症。(C)2015 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
The regeneration of hyaline cartilage remains clinically challenging. Here, we evaluated the therapeutic effects of using cell-free porous poly(lactic-co-glycolic acid) (PLGA) graft implants (PGIs) along with early loading exercise to repair a full-thickness osteochondral defect. Rabbits were randomly allocated to a treadmill exercise (TRE) group or a sedentary (SED) group and were prepared as either a PGI model or an empty defect (ED) model. TRE was performed as a short-term loading exercise; SED was physical inactivity in a free cage. The knees were evaluated at 6 and 12 weeks after surgery. At the end of testing, none of the knees developed synovitis, formed osteophytes, or became infected. Macroscopically, the PGI-TRE group regenerated a smooth articular surface, with transparent new hyaline-like tissue soundly integrated with the neighboring cartilage, but the other groups remained distinct at the margins with fibrous or opaque tissues. In a micro-CT analysis, the synthesized bone volume/tissue volume (BV/TV) was significantly higher in the PGI-TRE group, which also had integrating architecture in the regeneration site. The thickness of the trabecular (subchondral) bone was improved in all groups from 6 to 12 weeks. Histologically, remarkable differences in the cartilage regeneration were visible. At week 6, compared with SED groups, the TRE groups manifested modest inflammatory cells with pro-inflammatory cytokines (i.e., TNF-alpha and IL-6), improved collagen alignment and higher glycosaminoglycan (GAG) content, particularly in the PGI-TRE group. At week 12, the PGI-TRE group had the best regeneration outcomes, showing the formation of hyaline-like cartilage, the development of columnar rounded chondrocytes that expressed enriched levels of collagen type II and GAG, and functionalized trabecular bone with osteocytes. In summary, the combination of implanting cell-free PLGA and performing an early loading exercise can significantly promote the full-thickness osteochondral regeneration in rabbit knee joint models.Statement of significancePromoting effective hyaline cartilage regeneration rather than fibrocartilage scar tissue remains clinically challenging. To address the obstacle, we fabricated a spongy cell-free PLGA scaffold, and designed a reasonable exercise program to generate combined therapeutic effects. First, the implanting scaffold generates an affordable mechanical structure to bear the loading forces and bridge with the host to offer a space in the full-thickness osteochondral regeneration in rabbit knee joint. After implantation, rabbits were performed by an early treadmill exercise 15 min/day, 5 days/week for 2 weeks that directly exerts in situ endogenous growth factor and anti-inflammatory effects in the reparative site. The advanced therapeutic strategy showed that neo-hyaline cartilage formation with enriched collagen type II, higher glycosaminoglycan, integrating subchondral bone formation and modest inflammation. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.