The invention is a novel synthesis procedure to create hydrogels with mechanical properties desirable for musculoskeletal tissue engineering.
The invention is a novel synthesis procedure to create hydrogels with mechanical properties desirable for musculoskeletal tissue engineering, with moduli (stiffnesses) comparable to cartilage and failure properties (strength and toughness) far beyond hydrogels currently used in tissue engineering. KU researchers developed a novel synthesis procedure by combining two commonly used hydrogels, agarose and poly(ethylene glycol)-diacrylate (PEG-DA) into an interpenetrating network (IPN) with vastly improved mechanical properties compared to the individual constituents. An IPN is a polymer net work that is comprised of two (or more) chemically distinct but physically interlocked networks. In this case, the agarose gel is formed by thermal gelation, then soaked in a PEG-DA solution along with a photoinitiator. When irradiated with UV light, the PEG-DA polymerizes into a network that penetrates throughout the agarose network yet is not covalently linked to the agarose network. Living cells can be entrapped in the thermally gelling agarose (demonstrated with chondrocytes). The PEG-DA is non toxic to the cells, and the photopolymerization occurs in minutes and does not significantly harm the cells.
These hydrogels have overcome a major limitation of current hydrogel scaffolds as high toughness is crucial for them to withstand fracture in demanding environments such as human knee and hip.
This novel IPN hydrogel has an instantaneous compressive modulus close to that of native cartilage, and researchers have demonstrated that chondrocytes maintain their viability throughout the IPN fabrication process. Most importantly, the toughness of the IPN (the energy required to fracture under compression) was 5 and 100 times larger than PEG-DA or agarose alone, respectively. The significance of this discovery is that by creating IPNs of high toughness, one can overcome a major limitation of current hydrogel scaffolds, as high toughness is crucial to constructs for them to withstand fracture in demanding environments such as a human knee or hip. The method is adaptable to other combinations of biocompatible networks, such as chondrotin sulfate- PEG-DA. Furthermore, the photopolymerization synthesis method has been proven to be compatible with encapsulating living cells and maintaining their viability.