Injectable and drug-loaded gelatin methacrylate and carboxymethylated-sulfated xanthan gum hydrogels as biomimetic mineralization constructs

Injectable and drug-loaded hydrogels based on gelatin and xanthan gum derivatives were biomineralized to form organic-inorganic hybrid composites with osteoconductivity and controllable release of antibiotic drug for inducing bone generation. Gelatin was amidated to get gelatin methacrylate (GM) for supporting cell adhesion and photo-crosslinkability. Xanthan gum was chemically modified to obtain carboxymethalated and sulfated derivatives (CMXG and SXG) with high negative charges for mimicking chondroitin sulfate in bone. GM was co-dissolved with CMXG/SXG and ciprofloxacin hydrochloride (CPFXH), and photo-crosslinked with lithium phenyl-2,4,6-tri methylbenzoylphosphinate (LAP) to fabricate drug-loaded CMXG/SXG-GM-CPFXH-LAP hydrogels, which possessed swelling ratio of 1.30 ± 0.03 and controlled release of CPFXH in PBS for 24 h. The 7d-mineralized CMXG/SXG3-GM12-CPFXH-LAP hydrogel showed dense mineral layers with Ca/P atomic ratio of 1.79, degree of crystalline of 77.3 %, mineral content of 50.8 %, and 2.6 times higher shear modulus than original one. The CMXG/SXG3-GM12-CPFXH-LAP solution was acted as “inks” to “write” word (BONE) and Chinese character (“Gu”) manually, and was transferred into moulds to obtain hydrogel constructs with good fidelity of patterns, suggesting injectability and printability. The injectable, mineralizable, biocompatible and drug-loaded CMXG/SXG-GM-CPFXH-LAP hydrogels possess promising applications in bone tissue engineering due to facilitating osteoconductivity, recruiting cells, and reducing inflammation.