A Multifunctional Scaffold for Bone Infection Treatment by Delivery of microRNA Therapeutics Combined With Antimicrobial Nanoparticles.

Treating bone infections and ensuring bone repair is one of the greatest global challenges of modern orthopedics, made complex by antimicrobial resistance (AMR) risks due to long-term antibiotic treatment and debilitating large bone defects following infected tissue removal. An ideal multi-faceted solution would will eradicate bacterial infection without long-term antibiotic use, simultaneously stimulating osteogenesis and angiogenesis. Here, a multifunctional collagen-based scaffold that addresses these needs by leveraging the potential of antibiotic-free antimicrobial nanoparticles (copper-doped bioactive glass, CuBG) to combat infection without contributing to AMR in conjunction with microRNA-based gene therapy (utilizing an inhibitor of microRNA-138) to stimulate both osteogenesis and angiogenesis, is developed.

Development of miR-26a-activated scaffold to promote healing of critical-sized bone defects through angiogenic and osteogenic mechanisms.

Very large bone defects significantly diminish the vascular, blood, and nutrient supply to the injured site, reducing the bone's ability to self-regenerate and complicating treatment. Delivering nanomedicines from biomaterial scaffolds that induce host cells to produce bone-healing proteins is emerging as an appealing solution for treating these challenging defects. In this context, microRNA-26a mimics (miR-26a) are particularly interesting as they target the two most relevant processes in bone regeneration-angiogenesis and osteogenesis.

The role of synovial fluid constituents in the lubrication of collagen-glycosaminoglycan scaffolds for cartilage repair.

Extracellular matrix (ECM)-derived scaffolds have shown promise as tissue-engineered grafts for promoting cartilage repair. However, there has been a lack of focus on fine-tuning the frictional properties of scaffolds for cartilage tissue engineering as well as understanding their interactions with synovial fluid constituents. Proteoglycan-4 (PRG4) and hyaluronan (HA) are macromolecules within synovial fluid that play key roles as boundary mode lubricants during cartilage surface interactions.

Investigating the Synergistic Interactions of Surface Immobilized and Free Natural Ocular Lubricants for Contact Lens Applications: A Comparative Study between Hyaluronic Acid and Proteoglycan 4 (Lubricin).

The main reasons for the discontinuation of contact lens wear are ocular dryness and discomfort. Proteoglycan 4 (PRG4), a mucinous glycoprotein, and hyaluronic acid (HA), a nonsulfated linear glycosaminoglycan, are naturally present in the eye and contribute to ocular hydration and lubrication. This study aimed to investigate the impact of the structure of the recombinant human PRG4 (rhPRG4)/HA complex on contact lens properties, when one agent is grafted and the counterpart is physisorbed on the surface of model conventional or silicone contact lens materials.

The Effect of Intense Exercise on Equine Serum Proteoglycan-4/Lubricin.

Local biological and biomechanical-stimuli modulate proteoglycan-4 secretion within synovial joints. For the horse, changes to proteoglycan-4 concentration and function are notable in acute joint injury and osteoarthritis. Proteoglycan-4 (also known as Lubricin) is present in the blood, however the effect of exercise on equine serum levels is unknown.

Proteoglycan-4 and hyaluronan composition in synovial fluid and serum from clinical equine subjects: relationship to cartilage boundary lubrication and viscosity of synovial fluid.

: In experimental models of equine joint-injury and osteoarthritis synovial fluid (SF) composition (proteoglycan-4, hyaluronan) can vary, along with changes to SF mechanical function (lubrication, viscosity). The study hypotheses were a) clinical equine joint-injury and disease results in altered SF composition and diminished mechanical function, and b) serum composition (proteoglycan-4 or hyaluronan) changes concurrently. The objectives were to characterize composition (proteoglycan-4, hyaluronan), and function of SF and serum from normal horses compared to clinical groups: osteoarthritis, acute-joint-injury, and osteochondrosis.

A Physicochemically Optimized and Neuroconductive Biphasic Nerve Guidance Conduit for Peripheral Nerve Repair.

Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid-based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates.