Kim Iris L, Pfeifer Christian G, Fisher Matthew B, Saxena Vishal, Meloni Gregory R, Kwon Mi Y, Kim Minwook, Steinberg David R, Mauck Robert L, Burdick Jason A
1 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.
2 Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania.
Tissue Eng Part A. 2015 Nov;21(21-22):2680-90. doi: 10.1089/ten.tea.2015.0150. Epub 2015 Sep 24.
Current clinically approved methods for cartilage repair are generally based on either endogenous cell recruitment (e.g., microfracture) or chondrocyte delivery (e.g., autologous chondrocyte implantation). However, both methods culminate in repair tissue with inferior mechanical properties and the addition of biomaterials to these clinical interventions may improve their efficacy. To this end, the objective of this study was to investigate the ability of multipolymer acellular fibrous scaffolds to improve cartilage repair when combined with microfracture in a large animal (i.e., minipig) model. Composite scaffolds were formulated from a combination of hyaluronic acid (HA) fibers and poly(ɛ-caprolactone) (PCL) fibers, either with or without transforming growth factor-β3 (TGFβ3). After 12 weeks in vivo, material choice and TGFβ3 delivery had a significant impact on outcomes; specifically, PCL scaffolds without TGFβ3 had inferior gross appearance and reduced mechanical properties, whereas HA scaffolds that released TGFβ3 resulted in improved histological scores and increased type 2 collagen content. Importantly, analysis of the overall dataset revealed that histology, but not gross appearance, was a better predictor of mechanical properties. This study highlights the importance of scaffold properties on in vivo cartilage repair as well as the need for numerous quantitative outcome measures to fully evaluate treatment methods.
目前临床上批准的软骨修复方法通常基于内源性细胞募集(如微骨折)或软骨细胞递送(如自体软骨细胞植入)。然而,这两种方法最终形成的修复组织机械性能较差,在这些临床干预措施中添加生物材料可能会提高其疗效。为此,本研究的目的是在大型动物(即小型猪)模型中,研究多聚物无细胞纤维支架与微骨折联合使用时改善软骨修复的能力。复合支架由透明质酸(HA)纤维和聚己内酯(PCL)纤维组合而成,添加或不添加转化生长因子-β3(TGFβ3)。体内实验12周后,材料选择和TGFβ3递送对结果有显著影响;具体而言,不含TGFβ3的PCL支架外观较差且机械性能降低,而释放TGFβ3的HA支架则导致组织学评分提高和Ⅱ型胶原蛋白含量增加。重要的是,对整个数据集的分析表明,组织学而非外观是机械性能的更好预测指标。本研究强调了支架特性对体内软骨修复的重要性,以及需要众多定量结果指标来全面评估治疗方法。