Research On Preparation And Performance Of Composite Hydrogel For Bone Tissue Repair

Aging,accidental injury and developmental disorders give causes for tumor and loss of mobility to become the chief reasons of bone defects.Traditionally adverse reactions to medication result in compromised functional side effects in patients and organ transplant can lead to complications problems of donor site scarcity,immune and pathogen transfer.To meet the progressive requirements for bone regeneration purpose,injectable hydrogels have been extensively explored as substrates into the defect sites within easy and homogenous drug or cell distribution for bone tissue engineering applications,potentially avoiding an open surgery procedure and facilitating the use of minimally invasive approaches for material delivery.In this thesis,we report a facile method to prepare injectable and degradable polysaccharide-based hydrogels doubly integrated with hydroxyapatite(HAp)nanoparticles and calcium carbonate microspheres(CMs)under physiological condition.Firstly,oxidized alginate(OAlg)was obtained by redox of alginate using sodium periodate,and then the mechanism of cross-linking is attributed to the Schiffbase reaction between amino and aldehyde groups of carboxymethyl chitosan(CMCS)and oxidized alginate,respectively.Synchronously,tetracycline hydrochloride loaded calcium carbonate microspheres(TH/CMs)were fabricated by the precipitation reaction in the presence of carboxymethyl cellulose at room temperature with an average diameter of 6.62 ?m.To enhance bioactive and mechanical properties,nanoHAp and TH/CMs were encapsulated into the polysaccharide-based hydrogel to form injectable gel scaffolds for imitation of bone niche.The prepared HAp/gel and TH/CMs were characterized and analyzed in the experiment so as to determine the best preparation parameters.The gelation time,morphology,mechanical properties,swelling ratio and in vitro degradation of the gel scaffolds could be controlled by varying HAp and CMs contents.Moreover,drugs release calculation,antibacterial and self-healing properties of the composite gel scaffolds were evaluated based on the optimum parameters.In conclusion,injectable OAlg-CMCS gel scaffolds combined with HAp and TH/CMs were developed via the Schiff-base reaction.The water-dispersed HAp nanoparticles were homogeneously distributed into gel system(HAp/gel)and acted as reinforcing fillers.HAp can not only improve the mechanical properties significantly but also stabilize the network of hydrogels.Cytotoxicity test revealed the good biocompatibility of HAp/gel.Meanwhile,the TH was encapsulated within CMs and embedded in the hydrogels,resulting in a delayed burst release.These drug loaded composite gel scaffolds,especially the one consisting of 6%(w/v)HAp and 30 mg/mL CMs,exhibited the best comprehensive properties for bone regeneration applications.Our results demonstrated that this gel scaffold displayed excellent injectability,suitable degradation and high mechanical property.As a drug release system,this gel scaffold showed effective antibiotic activity against E.coli and S.aureus.In addition,the gel scaffolds were found to be self-healing due to dynamic equilibrium of the Schiff-base linkages.These results reveal that the composite gel scaffold is potential candidate for bone tissue engineering and drug delivery.