Development Of Nanocomposite Colloidal Gels For Tissue Repair

Injectable hydrogels have received great attention in the biomedical field due to their injectability for applications in minimally invasive surgery.Among them,colloidal gels,as a novel injectable hydrogel,show desired shear thinning and self-healing properties due to introduction of reversible interactions between particles.However,because conventional colloidal gels are mainly designed based on assembly via reversible non-covalent interactions,their macroscopic mechanical properties are typically poor and cannot meet the requirements of load-bearing applications,which significantly restrains their widespread applications of colloidal gels.Therefore,the design of colloidal gels with improved mechanical strength,excellent biological properties without compromising their injectability and moldability is of great research value.In this thesis,gelatin particles are used as the basic structural unit,and colloidal gel materials with both functionality and excellent mechanical strength are prepared through the core-shell structure and double cross-linked network design of the particles.This novel class of nanocomposite functional biomaterials have shown great potential for the biomedical applications such as bone defect repair and wound healing.We first designed and prepared composite nanoparticles with core-shell structure by encapsulating hydroxyapatite nanoparticles using gelatin polymer shell layer;this allowed to obtain high mechanical strength,self-healing behavior upon the formation of colloidal gels.The characterization results of transmission electron microscopy(TEM)and scanning electron microscopy(SEM)images fully demonstrated the successful synthesis of such core-shell nanoparticles,which exhibited good structural integrity when the inorganic component hydroxyapatite was maintained constant.Further rheological tests further that these composite gels possessed higher mechanical strength and self-healing property.At the same time,we also evaluated the degradation performance and drug release behavior of the composite colloidal gels.The results showed that the nanocomposite colloidal gels allowed slow degradation and sustained release of small drug molecules such as vancomycin,which can be used as antibacterial application meanwhile facilitating tissue regeneration.It was further verified that the composite colloid gels showed excellent biocompatibility based on in vitro cell culture experiment.Finally,it is proved that the injectable composite colloidal gel material has a good ability to promote bone repair through a mouse model of parietal bone bone defect.In the second part of this thesis,we further characterized the properties of gelatin-based colloidal gels as hemostatic adhesives.Herein,we designed a class of injectable hemostatic adhesive hydrogels based on light-curable gelatin nanoparticles combined with another continuous phase of photocrosslinkable polymer,which endowed the hydrogels with adjustable mechanical properties and tissue adhesiveness to allow firmly bind to the host tissues.Further experiments showed that the hemostatic adhesive showed good biocompatibility,fast crosslinking process,and hemostatic effects,which provided a highly effective solution for defect closure and hemostasis of acute wounds.The ultraviolet(UV)polymerization process to enable tissue adhesion made the gels easier to be manipulated.We further demonstrated this injectable hemostatic adhesive had a broad application in the field of minimally invasive surgery.In summary,this thesis systematically analyzed and characterized two novel classes of nanocomposite colloidal gels for bone repair and wound healing,confirming the great potential of these hydrogel materials for applications in tissue repair.These injectable hydrogel materials have shown potential for future clinical applications.