Osteochondral(OC)injuries are usually caused by congenital malformations,natural degeneration,and trauma-related injuries,and the incidence of OC injuries is increasing as the population ages.Despite the tremendous advances in the field of regenerative medicine,repairing osteochondral defects remains challenging because bone and cartilage have different histologies.In recent years,osteochondral tissueengineered grafts have been considered as a more promising therapeutic strategy for repairing OC.Considering the gradient nature and highly complex characteristics of osteochondral bone,monophasic osteochondral scaffolds have limited repair capacity,and therefore tissue-engineered scaffolds with osteochondral gradients are the preferred design for repairing OC defects.However,the lack of mimicry of natural osteochondral gradient structure in most current scaffolds is the main problem limiting their application in osteochondral repair,so the development of mimic osteochondral gradient scaffolds is of great importance for osteochondral tissue engineering.To address this challenge,the following studies were conducted in this study with the objective of designing and constructing a bionic gradient scaffold from the gradient properties of natural osteochondral units:In this paper,a biphasic osteochondral tissue engineering scaffold with discrete gradients was constructed by mimicking the viscoelastic cartilage in the osteochondral unit and the subchondral bone with hydroxyapatite(HAp)as the main component,a heterogeneous hydrogel reinforced with graphene oxide(GO)as the cartilage layer,and a thermally induced self-agglomerated nanofiber scaffold modified by polydopamine(PDA)and loaded with quercetin(Que),which promotes bone repair,as the subchondral bone layer,both of which were constructed by semi-embedding.A series of studies were conducted on the physicochemical properties and biocompatibility of the prepared biphasic composite scaffolds.The results showed that the addition of GO further improved the strength of the hydrogels,and the SEM results showed that the prepared hydrogel scaffolds had a good three-dimensional network structure with uniform pore size,connected voids,and three-dimensional nanofiber scaffolds with interconnected layered structural pores.In addition,the presence of PDA not only increases the affinity of the scaffold for cells,but also acts as a loading as well as a slow release of Que.The results of in vitro cellular experiments showed that the biphasic osteochondral scaffold has good biocompatibility and facilitates cell proliferation.Further,aerogel fiber scaffolds with continuous hydroxyapatite(HAp)gradients were prepared by temporal biomineralization after obtaining polylactic acid(PLLA)/gelatin(Gel)aerogels using electrostatic spinning,freeze-drying,and thermal cross-linking techniques,and alendronate sodium(ALN)was loaded on the gradient aerogels to further promote osteochondral defect repair.The HAp gradient,physicochemical properties and in vitro biocompatibility of the scaffold were also evaluated.SEM and TGA confirmed the existence of HAp gradient,compression experiments showed that the strength of the gradient aerogel was 1.1 MPa,which was more than three times higher than the non-mineralized strength,and in vitro cellular experiments showed that the gradient aerogel scaffold all had good biocompatibility.In addition,the ability of the aerogel scaffold to promote the repair of osteochondral defects was also investigated by using a rabbit osteochondral defect model through gross comparative observations.The results showed that the PG-H@ALN scaffold had the most significant osteochondral regenerative repair,followed by PG-H,but both were significantly better than the blank control group.The above study shows that two osteochondral tissue-engineered scaffolds possess gradient-changing physical and chemical properties,biological functions,and simulate the gradient properties of osteochondral units from discrete to continuous and simple to complex.The bionic composite scaffolds with compositional and structural gradients can effectively promote the repair of osteochondral defects,and this bionic osteochondral scaffold provides a new therapeutic idea for OC injury repair. |