Construction Of Biomimetic Integrated Scaffold For Osteochondral Defect Repair Via Selective Laser Sintering Technique

Osteochondral defect is often caused due to joint disease,aging and trauma in our daily life and it will lead to arthritis and a variety of joint degenerative diseases if the patients can not be treated effectively.However,conventional treatment strategies including autologous cartilage transplantation and artificial cartilage patches always encounter several issues of limited sources and prone fibrosis of newly formed cartilage.The kernel reason is that the current approaches only focus on the repair and regeneration of single cartilage phase and seriously ignore the comprehensive reconstruction of cartilage and subchondral bone.Due to the complex hierarchical structure and composition of the articular cartilage,it is necessary to take the integrated and comprehensive repair of articular cartilage into consideration.In this study,we firstly proposed a new strategy of comprehensive repair of osteocartilage-based on the inspiration from the native structure of articular cartilage.Polycaprolactone(PCL)as a FDA-approved biodegradable biomaterial was used to prepare PCL microspheres with different particle sizes by solvent evaporation method.The PCL microspheres were used as basic substrates to fabricate an integrated tissue engineering scaffold which was named Inconsecutive-pore scaffold,for osteochondral comprehensive repair through SLS technique.The upper layer of scaffold consisted of PCL microspheres with diameter of 50-100 μm and exhibited smooth and dense characteristics,simulating the natural superficial cartilage layer.The lower layer of scaffold consisted of PCL microspheres with diameter of 100-150 μm,simulating the porous subchondral bone.Moreover,the bone phase(lower layer)of the scaffold was designed with uniformly distributed channels in the diameter of 500 μm to improve the nutrient transport capacity.The internal structure,mechanical strength and porosity of the SLS-derived scaffold were characterized by means of scanning electron microscope(SEM),mechanical property testing,and porosity measurement,respectively.The results revealed that the use of industrial-grade SLS technology could complete bionic stacks with micron-level fine internal structures.Also,the prepared scaffold exhibited the ability to match the mechanical support of cartilage(10.26 MPa compression strength,2.20 MPa compression modulus)and high porosity(57.5%),which could meet the criteria for cartilage-bone orthotopic defect repair.Results of cell experiments in vitro showed that all three SLS-derived scaffolds with different internal structure were able to well support the proliferation and adhesion of rat bone marrow mesenchymal stem cells(r BMSCs),and there was no significant difference on cell adhesion and proliferation due to the excellent biocompatibility of pure PCL.The full-thickness osteochondral defect repair experiment in rabbits was used to evaluate the SLS-derived biomimetic integrated scaffolds on osteochondral repair in vivo.Results of Micro-CT,histological staining and immunological staining solidly demonstrated that the Inconsecutive-pore scaffolds with discontinuous channels could not only promote the regeneration of superficial zone and subchondral bone,but also modulated the reginal vascular regulating effect.This feature could prevent new blood vessels in the subchondral bone from invading the superficial zone to cause calcification and promote the cartilage-bone integration repair.In summary,this study focused on the crucial issues of the integrated repair for osteochondral defects.According to the material composition,molding technology,structural and mechanical balance of the scaffold,we explored the feasible construction principles and technologies of integrated bionic laminated scaffolds for the first time.Our findings showed that the well-designed biomimetic scaffolds were able to support cell adhesion and proliferation,separately induced cartilage regeneration and bone remodeling.The current work not only achieves a novel and effective repaired material for osteochondral reconstruction,but also provides a feasible methodology to enhance the cartilage repair from sole cartilage phase to comprehensive osteochondral phase.