Injectable Hydrogel-loaded Nano-hydroxyapatite That Improves Bone Regeneration And Alveolar Ridge Promotion

Objective: Post‐extraction,the alveolar dimensional alterations inevitably occur that are attributable to resorption of the alveolar as a tooth‐supported construction.The main consequences are sustained absorption of the alveolar ridge and reduction of soft tissue,which not only affects subsequent implantation,but also leads to loss of function and appearance of the maxillofacial region.In order to reconstruct the defect of alveolar bone and soft tissue,people have tried to use the technology of alveolar ridge preservation(ARP)and a variety of bone transplantation materials to study the regeneration of alveolar bone.Despite this,regrettably,the clinical application of traditional bone transplantation materials is considerably limited owing to the factors such as donor shortage,postoperative infection,potential infection risk,and inherent immunogenicity.Meanwhile,the bioscaffolds application in tissue engineering shows advantageous bone regeneration in the bone defect area,making it worthwhile to employ high-performance bioscaffold materials for alveolar ridge preservation.Injectable hydrogel materials that have excellent cell compatibility,strong load capacity,and sound mechanical properties,are now commonly used in tissue engineering research.The excellent biological properties of hydrogels also can simulate the natural extracellular matrix(ECM),and can be used as a delivery vehicle for direct application to drugs/cells.In spite of this,conventional polymer hydrogels have poor cell orientation and adhesion,and lack the proteins required for osteoblast action,hence they cannot bind directly to host bone.Nano-hydroxyapatite(n HA)is the most widely used bioceramic material in human bone graft replacement.It has a similar chemical composition and crystal structure to skeleton,and is the main inorganic component of skeleton,accounting for 60% of natural skeletal ECM.Furthermore,nano-hydroxyapatite not only supports the attachment and migration of osteoblasts on host bone,but it also has bone conduction and osteoinductivity,and has been used as an emerging material for studying oral bone tissue regeneration.Notwithstanding the shortcomings of hydroxyapatite,such as the lack of hardness,fragility and flexibility required for osteogenic stents,it is difficult to directly transplant and fix in the bone defect area.In order to overcome the limitations of hydrogel and hydroxyapatite,the combination of hydrogel and hydroxyapatite has been used to study the osteogenic expression of mesenchymal stem cells,cartilage and bone tissue regeneration.Aside from this,hydrogels and nano-hydroxyapatite materials are now being gradually introduced in dental studies,such as proliferation and differentiation of dental pulp stem cells,periodontal tissue regeneration,and regeneration of the jaw bone.Therefore,it is worth studying the combination of optimized hydrogels and n HA to form a new composite scaffold that can be transplanted into the tooth extraction area for bone regeneration and alveolar ridge preservation.Methods: The hydrogel / hydroxyapatite composite scaffold(GH)was formed after synthesis of nano hydroxyapatite.The microstructure and gel transition properties were examined by SEM and rheology;The injectability and selfhealing properties of GH scaffolds were tested by syringe 26 and physical defect model;The biocompatibility,cell migration and osteogenic potential of pure hydrogel and GH were detected by in vitro co culture experiment.A rat model of alveolar bone defect was established by minimally invasive surgery.The rats were randomly divided into control group,hydrogel group and GH stent group,with 6 rats in each group.The hydrogel and GH scaffold were then implanted into the extraction.After 2,4 weeks,the healing of soft tissue was observed and recorded.The bone formation and absorption of alveolar ridge were analyzed by micro CT and CS 3D software.Then the regeneration of alveolar bone was detected by hematoxylin eosin(H&E)staining.Results: In the hydrogel system,nano hydroxyapatite was added to form a stable scaffold structure.The electron microscope results showed that the GH scaffold was homogeneous and porous polymer network scaffold.The rheological results showed that the addition of nanoparticles did not change the gel transition property of the hydrogel.GH scaffold can promote cell proliferation and differentiation;After 4 weeks,the Micro-CT results showed that the bone mass in the GH extraction group was 1.5 times higher than that in the control group and the pure hydrogel group(P<0.05).By analyzing the soft tissue recovery and alveolar ridge loss in each group,the results showed that the soft tissue in the GH scaffold group could recover completely in 2 weeks,the gums were of good color and firm texture,and the alveolar ridge loss rate was only 0.5 times higher than that of the control group and the hydrogel group(P<0.05).Conclusion:1.GH composite scaffolds have excellent properties of injectability,self-repair and self-degradation,as well as good biocompatibility and great osteogenic potential.2.GH scaffold material has good potential of alveolar ridge preservation,which can obviously promote the early healing of soft tissue and reduce the absorption of alveolar ridge.