Photopolymerizable Injectable Cartilage Mimetic Hydrogel for the Treatment of Focal Chondral Lesions: A Proof of Concept Study in a Rabbit Animal Model

• Published in: The American journal of sports medicine 2019-01, Vol.47 (1), p.212-221
• Main Authors: Pascual-Garrido, Cecilia, Aisenbrey, Elizabeth A., Rodriguez-Fontan, Francisco, Payne, Karin A., Bryant, Stephanie J., Goodrich, Laurie R.
• Format: Article
• Language: English
• Subjects: Animals; Biocompatible Materials - administration & dosage; Cartilage; Cartilage Diseases - physiopathology; Cartilage Diseases - therapy; Cell Differentiation; Cells, Cultured; Chondrogenesis; Defects; Disease Models, Animal; Extracellular Matrix; Humans; Hydrogels; Hydrogels - administration & dosage; Knee; Male; Mesenchymal Stem Cell Transplantation - methods; Proof of Concept Study; Rabbits; Random Allocation; Sports medicine; Studies; Tissue Engineering; Wound Healing
• ISSN: 0363-5465; 1552-3365
• DOI: 10.1177/0363546518808012

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.