Background

Osteoarthritis (OA) is a leading cause of physical disability in older adults and there is currently no cure. There is a clinical need for improved treatments for cartilage defects in early-stage OA, including traumatic defects which are known to be a strong risk factor in OA development. Particularly, there is a need for regenerative therapies, especially for full thickness chondral and osteochondral defects, as alternatives to autografts, allografts, and autologous chondrocyte implantation procedures. Such treatments will help to extend the pain-free, functional life of joints and delay or prevent the need for total joint replacement.

Effective cartilage regeneration relies on the action of mesenchymal stem cells (MSCs). Researchers at The University of Sheffield present a scaffold coating technology which exploits the regenerative potential of native MSCs to promote the regeneration of cartilage tissue.

Technology Overview

The University of Sheffield researchers have developed a coating procedure which has the potential to enhance the regeneration capabilities of cartilage scaffolds and actively promote the repair of cartilage lesions. They have demonstrated this in the creation of cell-free, chondral and osteochondral scaffolds with the ability to recruit MSCs and promote chondrogenic differentiation and cartilage formation.

This scaffold-coating technology utilises plasma polymerisation and layer-by-layer ionic interactions, to bind a synergistic combination of bioactive factors (BFs) to the surface of the scaffold. This method mimics the mechanism via which BFs are stored in native cartilage to maintain chondrocyte phenotype and tissue integrity.

The BFs bound to the scaffold aid the migration of native MSCs (released during surgical microfracture) into the scaffold and promote differentiation into mature chondrocytes, leading to enhanced tissue regeneration.

Stage of Development

The team have successfully demonstrated in vitro and preliminary in vivo proof of concept with their functionalised, synthetic scaffolds. In vitro results show that the BFs act to recruit and promote differentiation of MSCs. A preliminary in vivo study in the repair of chondral defects in sheep, demonstrated that our bioactive chondral implants promoted superior cartilage regeneration at 4 weeks compared to non-functionalised scaffolds. They are currently conducting a second in vivo efficacy study with our osteochondral implants and expect to see similar results with superior cartilage formation at 4- and 16-week time points.

Benefits

• Accelerated cartilage regeneration and improved cartilage quality and compared to other cell-free scaffolds, due to exploitation of native MSCs.
• The cell‑free approach avoids the need for multiple surgery sites or patient biopsy associated with autografting and autologous chondrocyte implantation.
• Low, physiological concentrations of the BFs are required, minimising both cost and the risk of potential side effects.

Applications

• The coating technology can be applied to a wide range of scaffold types for the treatment of chondral and osteochondral defects, to promote improved tissue regeneration.
• Repair of cartilage defects in early‑stage osteoarthritis.
• Repair of traumatic cartilage lesions.
• Use alongside microfracture, micropicking or subchondral drilling to retain MSCs and promote hyaline cartilage formation.
• Alternative to autograft and allograft.
• Coated scaffolds could be used alongside Autologous Chondrocyte Implantation (ACI) procedures.
• Potential to adapt this coating technology to promote the healing of a variety skeletal tissue types (e.g. bone, meniscus, tendon and ligament) by selecting appropriate BFs.

Opportunity

• The University is seeking an industrial partner to co-develop an enhanced cartilage regeneration scaffold, incorporating the patent-protected coating technology.
• Alternatively, they are open to out-licensing the technology for development by a commercial partner.

The team’s academic expertise in cartilage regeneration and extracellular matrix biology and access to their intellectual property would make them a valuable partner for the development of next-generation cartilage implants.