Pot Michiel W, Gonzales Veronica K, Buma Pieter, IntHout Joanna, van Kuppevelt Toin H, de Vries Rob B M, Daamen Willeke F
Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
Department of Orthopedics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
PeerJ. 2016 Sep 8;4:e2243. doi: 10.7717/peerj.2243. eCollection 2016.
Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of mechanically inferior fibrocartilage. As a result, this technique offers only temporary clinical improvement. Tissue engineering and regenerative medicine may improve the outcome of microfracture surgery. Filling the subchondral defect with a biomaterial may provide a template for the formation of new hyaline cartilage tissue. In this study, a systematic review and meta-analysis were performed to assess the current evidence for the efficacy of cartilage regeneration in preclinical models using acellular biomaterials implanted after marrow stimulating techniques (microfracturing and subchondral drilling) compared to the natural healing response of defects. The review aims to provide new insights into the most effective biomaterials, to provide an overview of currently existing knowledge, and to identify potential lacunae in current studies to direct future research. A comprehensive search was systematically performed in PubMed and EMBASE (via OvidSP) using search terms related to tissue engineering, cartilage and animals. Primary studies in which acellular biomaterials were implanted in osteochondral defects in the knee or ankle joint in healthy animals were included and study characteristics tabulated (283 studies out of 6,688 studies found). For studies comparing non-treated empty defects to defects containing implanted biomaterials and using semi-quantitative histology as outcome measure, the risk of bias (135 studies) was assessed and outcome data were collected for meta-analysis (151 studies). Random-effects meta-analyses were performed, using cartilage regeneration as outcome measure on an absolute 0-100% scale. Implantation of acellular biomaterials significantly improved cartilage regeneration by 15.6% compared to non-treated empty defect controls. The addition of biologics to biomaterials significantly improved cartilage regeneration by 7.6% compared to control biomaterials. No significant differences were found between biomaterials from natural or synthetic origin or between scaffolds, hydrogels and blends. No noticeable differences were found in outcome between animal models. The risk of bias assessment indicated poor reporting for the majority of studies, impeding an assessment of the actual risk of bias. In conclusion, implantation of biomaterials in osteochondral defects improves cartilage regeneration compared to natural healing, which is further improved by the incorporation of biologics.
微骨折手术可用于治疗软骨缺损。在手术过程中，软骨下骨被穿透，使骨髓来源的间充质干细胞向缺损部位迁移并形成新的软骨组织。微骨折手术通常会形成机械性能较差的纤维软骨。因此，该技术仅能带来暂时的临床改善。组织工程和再生医学可能会改善微骨折手术的效果。用生物材料填充软骨下缺损可为新的透明软骨组织形成提供模板。在本研究中，进行了一项系统评价和荟萃分析，以评估与缺损的自然愈合反应相比，在骨髓刺激技术（微骨折和软骨下钻孔）后植入脱细胞生物材料的临床前模型中软骨再生疗效的现有证据。该评价旨在为最有效的生物材料提供新见解，概述现有知识，并识别当前研究中的潜在空白以指导未来研究。在PubMed和EMBASE（通过OvidSP）中使用与组织工程、软骨和动物相关的检索词进行了系统全面的检索。纳入了在健康动物的膝关节或踝关节骨软骨缺损中植入脱细胞生物材料的主要研究，并将研究特征制成表格（在6688项研究中找到283项研究）。对于比较未处理的空白缺损与含有植入生物材料的缺损并使用半定量组织学作为结局指标的研究，评估了偏倚风险（135项研究），并收集结局数据进行荟萃分析（151项研究）。进行随机效应荟萃分析，将软骨再生作为绝对0 - 100%尺度的结局指标。与未处理的空白缺损对照组相比，植入脱细胞生物材料显著提高了15.6%的软骨再生。与对照生物材料相比，向生物材料中添加生物制剂显著提高了7.6%的软骨再生。天然或合成来源的生物材料之间或支架、水凝胶和混合物之间未发现显著差异。动物模型之间的结局未发现明显差异。偏倚风险评估表明大多数研究报告质量较差，妨碍了对实际偏倚风险的评估。总之，与自然愈合相比，在骨软骨缺损中植入生物材料可改善软骨再生，而加入生物制剂可进一步改善。
