In vitro and in vivo investigation of a zonal microstructured scaffold for osteochondral defect repair

Joseph A M Steele; Axel C Moore; Jean-Philippe St-Pierre; Seth D McCullen; Adam J Gormley; Conor C Horgan; Cameron Rm Black; Christoph Meinert; Travis Klein; Siamak Saifzadeh; Roland Steck; Jiongyu Ren; Maria A Woodruff; Molly M Stevens

doi:10.1016/j.biomaterials.2022.121548

In vitro and in vivo investigation of a zonal microstructured scaffold for osteochondral defect repair

Biomaterials. 2022 Jul:286:121548. doi: 10.1016/j.biomaterials.2022.121548. Epub 2022 May 2.

Authors

Affiliations

¹ Department of Materials, Imperial College London, SW7 2AZ, UK; Department of Bioengineering, Imperial College London, SW7 2AZ, UK; Institute of Biomedical Engineering, Imperial College London, SW7 2AZ, UK; Division of Biomaterials and Regenerative Medicine, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, SE 171 77, Sweden.
² Department of Materials, Imperial College London, SW7 2AZ, UK; Department of Bioengineering, Imperial College London, SW7 2AZ, UK; Institute of Biomedical Engineering, Imperial College London, SW7 2AZ, UK.
³ Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Developmental Origins of Health and Disease, Institute of Developmental Sciences, University of Southampton Medical School, Southampton, SO16 6YD, UK; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Australia.
⁴ Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
⁵ Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; ARC Training Centre in Additive Biomanufacturing, Brisbane, Australia.
⁶ Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Australia.
⁷ Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; ARC Training Centre in Additive Biomanufacturing, Brisbane, Australia. Electronic address: mia.woodruff@qut.edu.au.
⁸ Department of Materials, Imperial College London, SW7 2AZ, UK; Department of Bioengineering, Imperial College London, SW7 2AZ, UK; Institute of Biomedical Engineering, Imperial College London, SW7 2AZ, UK; Division of Biomaterials and Regenerative Medicine, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, SE 171 77, Sweden. Electronic address: m.stevens@imperial.ac.uk.

Abstract

Articular cartilage is comprised of zones that vary in architecture, extracellular matrix composition, and mechanical properties. Here, we designed and engineered a porous zonal microstructured scaffold from a single biocompatible polymer (poly [ϵ-caprolactone]) using multiple fabrication strategies: electrospinning, spherical porogen leaching, directional freezing, and melt electrowriting. With this approach we mimicked the zonal structure of articular cartilage and produced a stiffness gradient through the scaffold which aligns with the mechanics of the native tissue. Chondrocyte-seeded scaffolds accumulated extracellular matrix including glycosaminoglycans and collagen II over four weeks in vitro. This prompted us to further study the repair efficacy in a skeletally mature porcine model. Two osteochondral lesions were produced in the trochlear groove of 12 animals and repaired using four treatment conditions: (1) microstructured scaffold, (2) chondrocyte seeded microstructured scaffold, (3) MaioRegen™, and (4) empty defect. After 6 months the defect sites were harvested and analyzed using histology, micro computed tomography, and Raman microspectroscopy mapping. Overall, the scaffolds were retained in the defect space, repair quality was repeatable, and there was clear evidence of osteointegration. The repair quality of the microstructured scaffolds was not superior to the control based on histological scoring; however, the lower score was biased by the lack of histological staining due to the limited degradation of the implant at 6 months. Longer follow up studies (e.g., 1 yr) will be required to fully evaluate the efficacy of the microstructured scaffold. In conclusion, we found consistent scaffold retention, osteointegration, and prolonged degradation of the microstructured scaffold, which we propose may have beneficial effects for the long-term repair of osteochondral defects.

Keywords: Cartilage tissue engineering; MaioRegen™; Microstructured scaffold; Osteochondral defect repair; Polycaprolactone; Zonal articular cartilage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cartilage, Articular*
Chondrocytes
Swine
Tissue Engineering / methods
Tissue Scaffolds* / chemistry
X-Ray Microtomography

Abstract

Publication types

MeSH terms

Grants and funding