Preclinical biological and physicochemical evaluation of two-photon engineered 3D biomimetic copolymer scaffolds for bone healing

Kampleitner, Carina; Changi, Katayoon; Felfel, Reda M.; Scotchford, Colin A.; Sottile, Virginie; Kluger, Rainer; Hoffmann, Oskar; Grant, David M.; Epstein, Michelle M.

Abstract

A major challenge in orthopedics is the repair of large non-union bone fractures. A promising therapy for this indication is the use of biodegradable bioinspired biomaterials that stabilize the fracture site, relieve pain and initiate bone formation and healing. This study uses a multidisciplinary evaluation strategy to assess immunogenicity, allergenicity, bone responses and physicochemical properties of a novel biomaterial scaffold. Two-photon stereolithography generated personalized custom-built scaffolds with a repeating 3D structure of Schwarz Primitive minimal surface unit cell with a specific pore size of ∼400 μm from three different methacrylated poly(D,L-lactide-co-ε-caprolactone) copolymers with lactide to caprolactone monomer ratios of 16 : 4, 18 : 2 and 9 : 1. Using in vitro and in vivo assays for bone responses, immunological reactions and degradation dynamics, we found that copolymer composition influenced the scaffold physicochemical and biological properties. The scaffolds with the fastest degradation rate correlated with adverse cellular effects and mechanical stiffness correlated with in vitro osteoblast mineralization. The physicochemical properties also correlated with in vivo bone healing and immune responses. Overall these observations provide compelling support for these scaffolds for bone repair and illustrate the effectiveness of a promising multidisciplinary strategy with great potential for the preclinical evaluation of biomaterials.

Citation

Kampleitner, C., Changi, K., Felfel, R. M., Scotchford, C. A., Sottile, V., Kluger, R., Hoffmann, O., Grant, D. M., & Epstein, M. M. (2020). Preclinical biological and physicochemical evaluation of two-photon engineered 3D biomimetic copolymer scaffolds for bone healing. Biomaterials Science, 8(6), 1683-1694. https://doi.org/10.1039/c9bm01827a

• Journal Article Type: Article
• Acceptance Date: Jan 17, 2020
• Online Publication Date: Jan 27, 2020
• Publication Date: Jan 27, 2020
• Deposit Date: Jan 29, 2020
• Publicly Available Date: Jan 28, 2021
• Journal: Biomaterials Science
• Electronic ISSN: 2047-4849
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 6
• Pages: 1683-1694
• DOI: https://doi.org/10.1039/c9bm01827a
• Keywords: General Materials Science; Biomedical Engineering
• Public URL: https://nottingham-repository.worktribe.com/output/3813737
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2020/BM/C9BM01827A
• Additional Information: : This document is Similarity Check deposited; : Virginie Sottile (ORCID); : Michelle M. Epstein (ORCID); : Single-blind; : Received 12 November 2019; Accepted 17 January 2020; Advance Article published 27 January 2020