Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Chemical & Biological Engineering, University of Colorado Boulder, Boulder, Colorado, USA.
Am J Sports Med. 2019 Jan;47(1):212-221. doi: 10.1177/0363546518808012. Epub 2018 Nov 27.
BACKGROUND: In this study, we investigate the in vitro and in vivo chondrogenic capacity of a novel photopolymerizable cartilage mimetic hydrogel, enhanced with extracellular matrix analogs, for cartilage regeneration. PURPOSE: To (1) determine whether mesenchymal stem cells (MSCs) embedded in a novel cartilage mimetic hydrogel support in vitro chondrogenesis, (2) demonstrate that the proposed hydrogel can be delivered in situ in a critical chondral defect in a rabbit model, and (3) determine whether the hydrogel with or without MSCs supports in vivo chondrogenesis in a critical chondral defect. STUDY DESIGN: Controlled laboratory study. METHODS: Rabbit bone marrow-derived MSCs were isolated, expanded, encapsulated in the hydrogel, and cultured in chondrogenic differentiation medium for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6, and 9. Chondrogenic differentiation was investigated via quantitative polymerase reaction, safranin-O staining, and immunofluorescence. In vivo, a 3 mm-wide × 2-mm-deep chondral defect was created bilaterally on the knee trochlea of 10 rabbits. Each animal had 1 defect randomly assigned to be treated with hydrogel with or without MSCs, and the contralateral knee was left untreated. Hence, each rabbit served as its own matched control. Three groups were established: group A, hydrogel (n = 5); group B, hydrogel with MSCs (n = 5); and group C, control (n = 10). Repair tissue was evaluated at 6 months after intervention. RESULTS: In vitro, chondrogenesis and the degradable behavior of the hydrogel by MSCs were confirmed. In vivo, the hydrogel could be delivered intraoperatively in a sterile manner. Overall, the hydrogel group had the highest scores on the modified O'Driscoll scoring system (group A, 17.4 ± 4.7; group B, 13 ± 3; group C, 16.7 ± 2.9) ( P = .11) and showed higher safranin-O staining (group A, 49.4% ± 20%; group B, 25.8% ± 16.4%; group C, 36.9% ± 25.2%) ( P = .27), although significance was not detected for either parameter. CONCLUSION: This study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a small animal model. In vitro chondrogenesis was evident when MSCs were encapsulated in the hydrogel. CLINICAL RELEVANCE: Cartilage mimetic hydrogel may offer a tissue engineering approach for the treatment of osteochondral lesions.
背景：本研究旨在探讨一种新型光聚合软骨仿生水凝胶的体外和体内软骨生成能力，该水凝胶通过添加细胞外基质类似物增强。 目的：（1）确定嵌入新型软骨仿生水凝胶中的间充质干细胞（MSCs）是否支持体外软骨生成，（2）证明拟议的水凝胶可在兔模型中的临界软骨缺损部位原位递送，（3）确定含有或不含有 MSC 的水凝胶是否支持临界软骨缺损中的体内软骨生成。 研究设计：对照实验室研究。 方法：分离、扩增兔骨髓来源的 MSC，将其包埋于水凝胶中，并在软骨分化培养基中培养 9 周。在第 1 天和第 3、6、9 周评估压缩模量。通过定量聚合酶链反应、番红 O 染色和免疫荧光检测软骨分化情况。在体内，在 10 只兔子的膝关节滑车双侧创建 3mm 宽×2mm 深的软骨缺损。每个动物的 1 个缺损随机分配接受水凝胶治疗或不接受 MSC 治疗，而对侧膝关节不做任何处理。因此，每只兔子都作为自己的配对对照。建立了 3 组：A 组，水凝胶（n=5）；B 组，含 MSC 的水凝胶（n=5）；C 组，对照组（n=10）。干预后 6 个月评估修复组织。 结果：体外证实了 MSC 诱导的软骨生成和水凝胶的可降解行为。体内，水凝胶可以在无菌条件下进行手术递送。总体而言，水凝胶组在改良 O'Driscoll 评分系统上的评分最高（A 组，17.4±4.7；B 组，13±3；C 组，16.7±2.9）（P=0.11），且番红 O 染色更高（A 组，49.4%±20%；B 组，25.8%±16.4%；C 组，36.9%±25.2%）（P=0.27），尽管两个参数均未达到统计学意义。 结论：本研究首次提供了在原位光聚合这种新型水凝胶并评估其在小动物模型中为软骨修复提供软骨形成线索的能力的证据。当 MSCs 被包埋在水凝胶中时，体外软骨生成是明显的。 临床相关性：软骨仿生水凝胶可能为治疗骨软骨病变提供组织工程方法。
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