Regeneration of joint articular cartilage with porous biomaterials
The aim of this project was to investigate the use of additive manufacturing technology to create 3D instructive scaffolds for tissue regeneration. For this purpose, they used proprietary polymers from Polyganics, which have been shown successful applications in soft tissue regeneration. As their mechanical bulk properties are also amenable for skeletal applications, they investigated here possible applications in the field of articular cartilage. The scaffolds proposed in this project may provide a single-surgery solution for articular cartilage regeneration with an implant that is mechanically stable and provide inductive cues to steer resident stem cells to differentiate into chondrocytes. Such chondroinductive scaffolds could be therefore implanted without the need of expanded cells before application, which is a cost-effective solution not yet available in the clinic.
Worldwide >100 million patients are in need of an effective regenerative treatment for joint disorders, giving rise to an estimated 21 billion € market potential in 2020. For instance, if we consider osteoarthritis as an example direct costs in 2002 exceeded 1.6 billion € contributing about 1.7% of expenses of the health insurance system. Cell therapies and other regenerative medicine solutions have been developed for skeletal injuries and are currently in clinical trial evaluation or already regularly in use. In the specific case of articular cartilage, these typically comprise autologous cartilage cells (chondrocytes) taken from a non-load bearing area. Despite cell therapies significantly increased the time life of our joints, still the majority of treated patients today suffer from re-degeneration 6-12 months after surgery.
They first designed and optimised the fabrication process of 3D printed scaffolds with the proprietary polymers from Polyganics. They then characterised these scaffolds biologically, with different cells. Initially with articular chondrocytes, and then with adult stem cells derived from the bone marrow, as these are ultimately the cells in contact with the scaffolds in a clinical application.
In summary, they have found out that a specific biomaterial composition of Polyganics, namely PU5, holds great promise as a candidate for scaffolds for articular cartilage regeneration. To date there are no biomaterials that have displayed inductive properties for the chondrogenic differentiation of resident adult stem cells. Their in vitro results indicate that PU5 possesses such properties. In addition, they showed in an ex vivo experimental set-up that PU5 can be used with whole bone marrow. Such combination supports their original goal to obtain a scaffold that could be used acellularly, in combination with already established surgical techniques such as microfracture. Follow-up studies in vivo should be planned to confirm these results. In case these preclinical studies would support their findings, the PU5 scaffolds could be considered as a competitive cost-effective new product in the cartilage repair market, with a significantly simpler regulatory route. In fact, such scaffolds would qualify as a medical device, thus significantly simplifying the route to clinical translation compared to currently used advanced therapy medicinal products (ATMPs) in the clinic.
