Long term outcomes of biomaterial-mediated repair of focal cartilage defects in a large animal model

• Type of Material: Article
• Authors: M.L. Sennett, CMC VA Medical Center; J.M. Friedman, CMC VA Medical Center; B.S. Ashley, CMC VA Medical Center; B.D. Stoeckl, CMC VA Medical Center; Jay Patel, Emory University; M. Alini, Acute Cartilage Injury Consortium; M. Cucchiarini, Acute Cartilage Injury Consortium; D. Eglin, Acute Cartilage Injury Consortium; H. Madry, Acute Cartilage Injury Consortium; A. Mata, Acute Cartilage Injury Consortium; C. Semino, Acute Cartilage Injury Consortium; M.J. Stoddart, Acute Cartilage Injury Consortium; B. Johnstone, Oregon Health and Science University; F.T. Moutos, Cytex Therapeut; B.T. Estes, Cytex Therapeut; F. Guilak, Acute Cartilage Injury Consortium; R.L. Mauck, Acute Cartilage Injury Consortium; George R. Dodge, Acute Cartilage Injury Consortium
• Language: English
• Date: 2021-01-01
• Publisher: AO RESEARCH INSTITUTE DAVOS-ARI
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 The Author(s)
• License: Creative Commons Attribution-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.22203/eCM.v041a04
• Title of Journal or Parent Work: EUROPEAN CELLS & MATERIALS
• Volume: 41
• Start Page: 40
• End Page: 51
• Grant/Funding Information: This study was supported by the AO Foundation Acute Cartilage Injury Consortium. Additional support was provided by the Department of Veteran’s Affairs (I01 RX001213) and the NIH through the Penn Center for Musculoskeletal Diseases Histology and Biomechanics Cores (P30 AR069619) and the Washington University Musculoskeletal Research Center (P30 AR074992)
• Keywords: MESENCHYMAL STEM-CELLS; Technology; HYDROGELS; Engineering, Biomedical; LESIONS; Materials Science; Cartilage defects; DIFFERENTIATION; Science & Technology; articular cartilage repair; orthopaedics; Life Sciences & Biomedicine; tissue engineering; MICROFRACTURE; Orthopedics; Materials Science, Biomaterials; KNEE; scaffolds; long-term outcomes; Cell Biology; Cell & Tissue Engineering; QUALITY; MATRIX-INDUCED CHONDROGENESIS; cartilage biomechanics; large animal models; biomaterials; POLY(EPSILON-CAPROLACTONE) SCAFFOLDS; COMPOSITE SCAFFOLD; Engineering

Abstract

The repair of focal cartilage defects remains one of the foremost issues in the field of orthopaedics. Chondral defects may arise from a variety of joint pathologies and left untreated, will likely progress to osteoarthritis. Current repair techniques, such as microfracture, result in short-term clinical improvements but have poor long-term outcomes. Emerging scaffold-based repair strategies have reported superior outcomes compared to microfracture and motivate the development of new biomaterials for this purpose. In this study, unique composite implants consisting of a base porous reinforcing component (woven poly(ε-caprolactone)) infiltrated with 1 of 2 hydrogels (self-assembling peptide or thermo-gelling hyaluronan) or bone marrow aspirate were evaluated. The objective was to evaluate cartilage repair with composite scaffold treatment compared to the current standard of care (microfracture) in a translationally relevant large animal model, the Yucatan minipig. While many cartilage-repair studies have shown some success in vivo, most are short term and not clinically relevant. Informed by promising 6-week findings, a 12-month study was carried out and those results are presented here. To aid in comparisons across platforms, several structural and functionally relevant outcome measures were performed. Despite positive early findings, the long-term results indicated less than optimal structural and mechanical results with respect to cartilage repair, with all treatment groups performing worse than the standard of care. This study is important in that it brings much needed attention to the importance of performing translationally relevant long-term studies in an appropriate animal model when developing new clinical cartilage repair approaches.