骨形态发生蛋白、碱性成纤维细胞生长因子生物材料在关节软骨缺损修复中的生物性能

Biological properties of bone morphogenetic proteins and basic fibroblast growth factor in biological materials for repair of articular cartilage defect

背景:众多的实验中发现了多种细胞因子通过自分泌和旁分泌等不同方式调节软骨和骨的生成。目的:分析骨形态发生蛋白、碱性成纤维细胞生长因子生物材料在关节软骨缺损修复中的生物性能。方法:选取40只新西兰家兔,随机分为4组,纤维蛋白组、碱性成纤维细胞生长因子组、骨形态发生蛋白组、复合组(骨形态发生蛋白+碱性成纤维细胞生长因子),每组10只。建立兔关节软骨缺损模型,止血彻底后将纤维蛋白、碱性成纤维细胞生长因子、骨形态发生蛋白以及骨形态发生蛋白、碱性成纤维细胞生长因子复合等材料组成的支架分别植入缺损部位。比较不同注射材料在家兔关节软骨缺损中的效果及复合材料的生物性能。结果与结论:(1)关节软骨缺损修复情况:纤维蛋白组2只家兔出现跛行;碱性成纤维细胞生长因子组1只家兔活动受限;骨形态发生蛋白组出现1只跛行,1只活动受限;复合组兔恢复良好,膝关节和手术前相比差异无显著性意义(P<0.05)。(2)大体观察:复合组家兔软解软骨缺损消失,内有新生血管,软骨和正常组织十分接近;骨形态发生蛋白组关节软骨边际存在裂隙,未能与正常的软骨组织紧密结合,光镜下能够看见缺损区周缘存在软骨细胞;纤维蛋白组缺损部位和周围组织基本愈合;碱性成纤维细胞生长因子组缺损部位有所修复,但不光滑。(3)苏木精-伊红染色结果:纤维蛋白组兔缺损部位未被修复,表面存在明显凹陷;碱性成纤维细胞生长因子组缺损部位被明显修复,缺损部位存在大量软骨细胞;骨形态发生蛋白组被修复,出现软骨细胞,但排列不规则;复合组修复良好,出现大量软骨细胞。(4)结果提示,骨形态发生蛋白、碱性成纤维细胞生长因子生物材料是关节软骨缺损中比较理想的修复材料,能够发挥骨形态发生蛋白诱导形成软骨的活性,能够发挥碱性成纤维细胞生长因子提高软骨细胞增生作用,可以达到优势互补,促进关节软骨缺损的恢复。

BACKGROUND： Articular cartilage regeneration can be regulated by autocrine or paracrine secretion of various cytokines. OBJECTIVE： To analyze biological properties of bone morphogenetic proteins and basic fibroblast growth factor in biological materials for repair of articular cartilage defect. METHODS： Forty New Zealand white rabbits were used and equally randomized into four groups： fibrin, basic fibroblast growth factor, bone morphogenetic protein, and combined treatment（basic fibroblast growth factor combined with bone morphogenetic protein） groups, respectively. Bioactive scaffolds with fibrin, basic fibroblast growth factor, bone morphogenetic protein, and basic fibroblast growth factor combined with bone morphogenetic protein were injected to repair the articular cartilage defect. Therapeutic effect and biological properties of biological materials were compared. RESULTS AND CONCLUSION：（1） In the fibrin group, two rabbits appeared to have limps. In the basic fibroblast growth factor group hand function was limited in one rabbit. In the bone morphogenetic protein group, one had a limp and one was in a limitation of activity. In the combined treatment group, rabbits recovered well and showed no differences in the knee joint before and after surgery（P〈0.05）.（2） General observation： In the combined treatment group, soft solution cartilage defects disappeared, and angiogenesis and cartilage were similar with normal tissues. In the bone morphogenetic protein group, fractured cartilage marginal existed and could not be closely integrated with normal cartilage. The presence of chondrocytes in the periphery of the defect was seen under light microscope. In the fibrin group, defect site and surrounding tissues healed. In the basic fibroblast growth factor group, defect was repaired, but not smooth.（3） Results of hematoxylin and eosin staining： In the fibrin group, the bone defect was not repaired, obvious depression surface was seen. In basic fibroblast growth factor group, repair of cartilage defect was obvious. There were a lot of chondrocytes. In the bone morphogenetic protein group, the bone defect was repaired; chondrocytes appeared, but irregular arrangement. In the combined treatment group, good bone defect repair and a large number of cartilage cells were seen. Taken together, biological materials with fibrin and basic fibroblast growth factor are ideal for repair of articular cartilage defect by promoting formation of cartilage by bone morphogenetic protein and enhancing chondrocyte proliferation by basic fibroblast growth factor.