Preparation And Characterization Of Drug Sequential Delivery System Containing BFGF And Chlorhexidine Acetate

Tissue defect is often accompanied by inflammation.In order to repair tissue defect,the therapeutic approaches need to limit infection firstly.It is a hot and difficult problem that how to fabricate a drug delivery system to achieve the sequential delivery of growth factors and antibiotics,which can inhibit inflammation quickly and induce tissue regeneration continuously.Self-healing hydrogel can recover its original shape and mechanical capacity because of its internal covalent and non-covalent bonds after it is damaged,which is beneficial for tissue regeneration.However,the related research is seldomly reported so far.The heavy brust release is a common problem for both microspheres and hydrogels.Therefore,the drug sequential release and improving brust release of drug delivery system are important for tissue regeneration.In this study,the drug sequential delivery systems(NGel/ODex/ADH)self-healing hydrogel and PLGA-GC microspheres containing bFGF and CHA were prepared and the potential to be used for tissue regeneration was evaluated.The main contents are as follows:(1)The NGel/ODex/ADH self-healing hydrogels were fabricated mixed with aminated gelatin,oxidized dextran and adipic dihydrazide.SEM results indicated that the hydrogels had porous structure and the aperture was 70±10μm.With the increase of gelatin,the swelling fold,degradation rate and storage modulus increased and self-healing ability weakened.With the adding of ADH,the storage modulus decreased and self-healing capacity enhanced.MTT results showed the hydrogels exhibited non-cytotoxicity.After subcutaneous injection of the rats,there was no obvious immunological rejection,which showed the hydrogel had good biocompatibility.(2)The bFGF/CHA sequential delivery hydrogels were prepared containing bFGF-loading PLGA microspheres,CHA and NGel/ODex/ADH hydrogels.The results suggested that the microspheres were distributed into the hydrogel evenly.The swelling fold,degradation ratio and release rate of bFGF and CHA could be adjusted by the proportion of gelatin and ADH.The bFGF release rate was obviously faster than that of CHA.The hydrogels had good antibacterial ability and biocompatibility,which could promote the proliferation and adhesion of 3T3 cells.(3)GC modified PLGA microspheres containing CHA at the GC shell and bFGF at the core of PLGA microspheres were fabricated for bFGF/CHA sequential delivery system.SEM showed that the average size of microspheres was 5.71-5.88μm.GC was successfully modified to the surface of the PLGA microspheres.The microspheres had an ability to deliver drugs in sequence.The CHA was rapidly released,whereas the proteins presented a sustained release.Antibacterial assay and cell proliferation tests suggested that the released CHA and bFGF retained their antimicrobial activity and bioactivity during preparation.The microspheres exhibited non-cytotoxicity against 3T3 cells and had a good biocompatibility.In conclusion,the above self-healing hydrogel and microspheres had the ability to release bFGF and CHA in sequence and prevent infection,and had good biocompatibility.Therefore,they have a potential to be used as drug sequential delivery system for tissue regeneration.