Intra-articular augmentation of lubrication with silk microspheres

Abstract

Purpose: Osteoarthritis of the knee represents a large unmet clinical need. Deficits in synovial lubrication have been reported in osteoarthritis, and several strategies to augment lubrication have shown preclinical benefit. We hypothesized that augmentation of the boundary lubrication of synovial fluid by intra-articular administration of long-residence non-inflammatory lubricating silk microspheres could reduce mechanical injury and pain in an osteoarthritis animal model. Methods: Silk microspheres with phospholipid coatings were prepared by a modified version of previously published methods. Osteoarthritis was induced in rats using the surgical instability model consisting of MCL tear and meniscectomy. One week following injury, affected knees were intra-articularly administered saline vehicle or silk microspheres (2.5mg). Serial body weights, knee effusion, gait analysis on Day 14, and Von Frey secondary allodynia testing on Days -1, 6, and 13 were measured. Severity of osteoarthritis was assessed by histopathologic analysis by a trained pathologist on Day 28 after injury. Results: Silk microspheres with varying size distributions were synthesized and achieved coefficients of friction approaching 0.05 to 0.02. Intra-articular injection of silk microspheres was well tolerated in rats with no adverse reactions. Von Frey testing of secondary allodynia 6 days after injection indicated a trend towards a modest but sustained reduction of osteoarthritic pain. Conclusions: Intra-articular silk microspheres offer a novel, biologically inert, non-inflammatory, and well tolerated potential therapy for osteoarthritis. These results motivate further formulation optimization of silk microsphere composition to tune synovial residence, degradation profile, lubrication properties, and potentially to provide prolonged delivery of active therapeutics. Augmentation of joint lubrication with silk microspheres merits further preclinical exploration as a novel therapy to address the unmet need in osteoarthritis.