Bioactive implants to tackle joint degeneration
Knees are complex joints that are vulnerable to a variety of injuries. Osteochondral defects, which involve damage to the articular cartilage and underlying bone, are a particular cause of concern. Many osteochondral defects in older active people are caused by slow cartilage deterioration, and like osteoarthritis, can spread unless treated. “First stages are usually treated by protein supplementation, anti-inflammatory drugs, and injections of hyaluronic acid into the joint,” explains iP-OSTEO project coordinator Eva Filova from the Institute of Experimental Medicine of the Czech Academy of Sciences. Current surgical treatments include various graft and implantation techniques. If these do not work, total joint replacement – an expensive and highly intrusive procedure – remains a final option.
Bioactive substances to support cartilage regeneration
In order to avoid this scenario, scientists have been looking at ways to enhance cell regeneration and stop the progression of osteoarthritis, through using cell-free biomaterials. By releasing bioactive substances, these can prevent or significantly postpone total joint replacement. The iP-OSTEO project, which was supported by the Marie Skłodowska-Curie Actions programme, sought to advance research in this field. “Main objectives included developing biodegradable scaffolds that contain bioactive substances to support cartilage and bone tissue formation,” explains Filova. “These substances work by inducing pluripotent stem cells (iPSCs) and/or mesenchymal stems cells (MSCs).” iPSCs can be prepared by reprogramming animal or human differentiated cells. These cells have the potential of taking on many forms in the body, including all of the more than 200 different cell types. Similarly, MSCs can separate into various cell types, including cells in bone and cartilage. The team also sought to improve in vitro and pre-clinical testing of these scaffolds, and to find ways of scaling up development for clinical use.
Composite substitute for treating bone defects
The project advanced SmartBonePep, a new composite bone substitute for the regeneration of bone defects. SmartBonePep scaffolds are biodegradable and contain bioactive molecules that stimulate MSCs to produce bone matrix. “SmartBonePep, has potential applications in clinical settings, pending further development and regulatory approvals,” notes Filova. A new 3D-printed chamber for a bioreactor for dynamic cell culture on scaffolds was also developed. The aim is that this will be further developed and made commercially available. “We were able to develop cell-free composite nanofibrous scaffolds that stimulate osteochondral regeneration in rabbits,” she adds. “Different 3D scaffolds based on hydrogels or foams were tested with bioactive supplements.”
Controlled release of bioactive compounds
The hope is that this pioneering research on the controlled release of bioactive compounds from scaffolds will open up new avenues of care, and reduce the need for joint replacement. Next steps include pre-clinical and clinical studies on the SmartBonePep scaffold, to test its efficacy in animals and patients. Another important element of the project was that it involved extensive networking, training and secondments for early-stage researchers. In total, over 200 secondments took place, helping to integrate academic and industrial stakeholders across Europe. Seven companies, along with seven academic institutions were involved. This new generation of scientists will now continue this important work, transforming how we approach and treat damage to cartilage and bone, and improving the lives of patients.
Keywords
iP-OSTEO, cartilage, bone, bioactive, implants, osteoarthritis, knees