A Research Of Graft Modified Gelatin And Its Composite Hydrogel Scaffolds

Gelatin is a hydrolysis product of collagen, has good biological activity, and can be degraded by various of protease in vivo, so it is widely used as tissue engineering scaffolds, drug delivery system and other fields. Among all its applications, gelatin as a hydrogel for critical bone defect repair, especially for non weight bearing bone, has attracted attention of many researchers. Because of its good hydrophilicity, the hydrogel scaffolds must be crosslinked to reduce the dissolve or swelling, so as to maintain the stability of support structure. Usually the use of chemical crosslinking agents, which are small molecules, bringing toxicity to scaffolds and causing adverse effects on cells or the loaded bioactive substances. On the contrary, physical crosslinking can avoid these problems. It is considered to be an effective method for gelatin crosslinking as taking advantage of the physical interactions occurs between the grafted polymers on gelatin side chains.In this paper, we introduced two synthetic polymer chain segments to the side chain of gelatin respectively, and the effects of these two grafted copolymers on gelatin crossling were studied. Firstly, gelatin was modified with a-bromoisobutyryl bromide (BIBB) to prepare the bromine substituted gelatin (Gel-Br), as the macro-initiator of atom transfer radical polymerization (ATRP). By regulating the feeding ratio of BIBB and gelatin, different bromine substitution degree of macromolecular initiator was accessible. In the next work, we synthesised two different grafted gelatin copolymers and examined their structure and properties respectively:(1) Due to thermosensitive feature of NIPAAm, whose low critical solution temperature (LCST) is around32℃, we synthesized the PNIPAAm grafted gelatin (gelatin-g-PNIPAAm) copolymer, demonstrated obvious thermal phase transition behavior under37℃, so it could be used as a kind of injectable hydrogel. Analyzed by differential scanning calorimetry and ultraviolet-visable spectrophotometer, it is confirmed that the LCST of gelatin-g-PNIPAAm can be adjusted by altering the grafting length and content of PNIPAAm. The results of in vitro osteoblasts co-culture reveal that the Gel-g-PNIPAAm hydrogels possess good biocompatibility and cell affinity, support cell proliferation; in vivo reconstruction of skull defect of rat suggesting a potential substrate for the regeneration of non load-bearing bone defects.(2) PLA oligomers were modified to get PLA macromonomers with methylacrylate group (PLA-MA), which could be grafted to gelatin via ATRP. The grafting ratio and the molecular weight of PLA oligomer could be controlled by adjusting relative reaction parameters. The final hybrid (Sc-Gel-g-PLA) could be simply obtained by mixing solutions of Gel-g-PLLA and Gel-g-PDLA, since crosslinking was established physically by stereocomplex formation between enantiomeric oligomeric lactic acid chains. XRD and DSC analysis were performed to prove the formation of stereocomplexation (Sc-Gel-PLA). Preliminary confirmed that this method can be used for the gelatin crosslinking.