Interpenetrating Polymer Network Hydrogels via a One-Pot and in Situ Gelation System Based on Peptide Self-Assembly and Orthogonal Cross-Linking for Tissue Regeneration

Construction of the interpenetrating polymer network (IPN) in hydrogels has received increased attention because it not only improves their mechanical properties but also mimics the extracellular matrix, which can be used as cell culturing scaffolds for tissue engineering. Usually, IPN gels are prepared using separated procedures, in which primal networks, followed by other networks, are formed by adding chemical reagents or subjecting to external stimuli. Herein, we designed a one-pot and in situ gelation system, which involved strategic selection of precursors for constructing IPN gels by simply mixing them. This design involved two types of gelation processes: RADA16 peptide self-assembling and covalent bond formation between chitosan (CH) and N-hydroxysuccinimide ester-terminated poly(ethylene glycol) (NHS–PEG–NHS). The gelation kinetics suggested that RADA16 peptide networks were formed independently, followed by the formation of CH/PEG networks in the mixture containing the three components. Culturing chondrocytes in CH/PEG/RADA16 demonstrated that construction of the IPN structure promoted the embedded chondrocyte properties for the formation of the articular cartilage. Moreover, lower inflammation and higher protein production were observed in mice implanted with CH/PEG/RADA16-containing chondrocytes than in those with clinically used atelocollagen gel, appealing the feasibility of the proposed IPN hydrogel design for use as cell culturing scaffolds in tissue regeneration.