Advances in viscosupplementation and tribosupplementation for early-stage osteoarthritis therapy.

Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degeneration, synovial fluid lubricity decreases in OA owing to a reduction in the concentration and molecular weight of hyaluronic acid and surface-active mucinous glycoproteins that form a lubricating film over the articulating joint surfaces. Minimizing friction between articulating joint surfaces by lubrication is fundamental for decreasing hyaline cartilage wear and for maintaining the function of synovial joints. Augmentation with highly viscous supplements (that is, viscosupplementation) offers one approach to re-establishing the rheological and tribological properties of synovial fluid in OA. However, this approach has varied clinical outcomes owing to limited intra-articular residence time and ineffective mechanisms of chondroprotection. This Review discusses normal hyaline cartilage function and lubrication and examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. These strategies include contemporary viscosupplements that contain antioxidants, anti-inflammatory drugs or platelet-rich plasma and new synthetic synovial fluid additives and cartilage matrix enhancers. Advanced biomimetic tribosupplements offer promise for mitigating cartilage wear, restoring joint function and, ultimately, improving patient care.

A polymer network architecture provides superior cushioning and lubrication of soft tissue compared to a linear architecture.

We report the relationships between linear vs. network polymer architecture and biomechanical outcomes including lubrication and cushioning when the polymers are applied to the surface of articulating knee cartilage. Aqueous formulations of the bioinspired polymer poly(2-methacryloyloxylethyl phosphorylcholine) (pMPC) exhibit tuneable rheological properties, with network pMPC exhibiting increased elasticity and viscosity compared to linear pMPC. Application of a polymer network, compared to a linear one, to articulating tissue surfaces reduces friction, lessens tissue strain, minimizes wear, and protects tissue - thereby improving overall tissue performance. Administration of the network pMPC to the middle carpal joint of skeletally mature horses elicits a safe response similar to saline as monitored over a 70 day period.

Single Cell Sequencing Analysis of Lizard Phagocytic Cell Populations and Their Role in Tail Regeneration.

Lizards are the closest relatives of mammals capable of tail regeneration, but the specific determinants of amniote regenerative capabilities are currently unknown. Macrophages are phagocytic immune cells that play a critical role in wound healing and tissue regeneration in a wide range of species. We hypothesize that macrophages regulate the process of lizard tail regeneration, and that comparisons with mammalian cell populations will yield insight into the role phagocytes play in determining an organism's regenerative potential. Single cell RNA sequencing (scRNAseq) was used to profile lizard immune cells and compare with mouse counterparts to contrast cell types between the two species. Treatment with clodronate liposomes effectively inhibited lizard tail stump tissue ablation and subsequent regeneration, and scRNAseq was used to profile changes in lizard immune cell populations resulting from tail amputation as well as identifying specific cell types affected by clodronate treatment. ScRNAseq analysis of lizard bone marrow, peripheral blood, and tissue-resident phagocyte cell populations was used to trace marker progression during macrophage differentiation and activation. These results indicated that lizard macrophages are recruited to tail amputation injuries faster than mouse populations and express high levels of matrix metalloproteinases (MMPs). In turn, treatment with MMP inhibitors inhibited lizard tail regeneration. These results provide single cell sequencing data sets for evaluating and comparing lizard and mammalian immune cell populations, and identifying macrophage populations that are critical regulators of lizard tail regrowth.