Sustained delivery of the bone morphogenetic proteins BMP-2 and BMP-7 for cartilage repair and regeneration in osteoarthritis

Ciara Whitty; Christian Pernstich; Charlotte Marris; Andrew McCaskie; Michael Jones; Frances Henson

doi:10.1016/j.ocarto.2022.100240

Sustained delivery of the bone morphogenetic proteins BMP-2 and BMP-7 for cartilage repair and regeneration in osteoarthritis

Osteoarthr Cartil Open. 2022 Feb 8;4(1):100240. doi: 10.1016/j.ocarto.2022.100240. eCollection 2022 Mar.

Authors

Ciara Whitty¹, Christian Pernstich¹, Charlotte Marris¹, Andrew McCaskie², Michael Jones¹, Frances Henson²

Affiliations

¹ Cell Guidance Systems, Maia Building, Babraham Research Campus, Cambridge, CB22 3AT, UK.
² Division of Trauma & Orthopaedic Surgery, University of Cambridge, Addenbrooke's Hospital, Box 180, Hills Road, Cambridge, CB2 0QQ, UK.

Abstract

Objective: Attempts to utilise growth factors (GF) such as bone morphogenic proteins (BMPs) to treat osteoarthritis (OA) in the clinic have not secured widespread adoption. However, the novel crystalline GF formulation called PODS offers new perspectives. This study investigated the hypothesis that Polyhedrin Delivery System (PODS) BMP-2 and PODS BMP-7, compared with conventional BMP-2 and BMP-7 increase capacity for cartilage repair.

Design: Sustained release from PODS BMP-2 and PODS BMP-7 and their effects on OA patient-derived cells as well as a chondrocyte cell line were first assessed in vitro. Here, extra cellular matrix (ECM) protein gene expression and actual ECM deposition were measured and compared to the effect achieved with conventional, soluble BMPs. Subsequently, in an established murine model of cartilage regeneration of the knee joint, changes were traced over 8 weeks and scored with two metrics, modified Pineda and Mankin.

Results: Both crystalline PODS BMP formulations strongly induced proliferation in primary as well as immortal cell line chondrocytes, outperforming conventional soluble BMP-2 and BMP-7. Furthermore, ECM-producing genes were upregulated and the production of ECM could be demonstrated. In the murine cartilage regeneration model, both PODS BMP-2 and PODS-BMP-7 improved cartilage repair assessed with both histological scoring methods.

Conclusions: This study showed that the sustained release of GF from PODS BMPs is effective in promoting chondrogenesis in vitro. The small animal data suggests that this novel approach of delivering therapeutic proteins sustainably and locally to the knee has promise for developing future disease-modifying therapies of OA.

Keywords: BMP, Bone morphogenic protein; BMP-2; BMP-7; Cartilage regeneration; Joint osteoarthritis; PODS; PODS, Polyhedrin delivery system; Sustained release.