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- Title
Injectable mechanical pillows for attenuation of load-induced post-traumatic osteoarthritis.
- Authors
Holyoak, Derek T; Wheeler, Tibra A; Meulen, Marjolein C H van der; Singh, Ankur
- Abstract
Osteoarthritis (OA) of the knee joint is a degenerative disease initiated by mechanical stress that affects millions of individuals. The disease manifests as joint damage and synovial inflammation. Post-traumatic osteoarthritis (PTOA) is a specific form of OA caused by mechanical trauma to the joint. The progression of PTOA is prevented by immediate post-injury therapeutic intervention. Intra-articular injection of anti-inflammatory therapeutics (e.g. corticosteroids) is a common treatment option for OA before end-stage surgical intervention. However, the efficacy of intra-articular injection is limited due to poor drug retention time in the joint space and the variable efficacy of corticosteroids. Here, we endeavored to characterize a four-arm maleimide-functionalized polyethylene glycol (PEG-4MAL) hydrogel system as a 'mechanical pillow' to cushion the load-bearing joint, withstand repetitive loading and improve the efficacy of intra-articular injections of nanoparticles containing dexamethasone, an anti-inflammatory agent. PEG-4MAL hydrogels maintained their mechanical properties after physiologically relevant cyclic compression and released therapeutic payload in an on-demand manner under in vitro inflammatory conditions. Importantly, the on-demand hydrogels did not release nanoparticles under repetitive mechanical loading as experienced by daily walking. Although dexamethasone had minimal protective effects on OA-like pathology in our studies, the PEG-4MAL hydrogel functioned as a mechanical pillow to protect the knee joint from cartilage degradation and inhibit osteophyte formation in an in vivo load-induced OA mouse model.
- Subjects
OSTEOARTHRITIS; DEGENERATION (Pathology); POST-traumatic stress disorder; ADRENOCORTICAL hormones; DRUG efficacy; DEXAMETHASONE
- Publication
Regenerative Biomaterials, 2019, Vol 6, Issue 4, p211
- ISSN
2056-3418
- Publication type
Article
- DOI
10.1093/rb/rbz013