| Large bone defects, such as acute injuries, fall fractures in osteoporotic patients, or tumors and congenital malformations of the musculoskeletal system, are very common in the clinical cases of orthopedics. It is necessary to resect the affected parts of the bone, which is a major therapeutic challenge for the reconstructive surgery after resection. Recently, great progress has been made in bone tissue engineering,which is promising for treatment of bone defects and bone regeneration. Scaffold is one of the critical elements, and it is generally acknowledged that appropriate physical structure and good biocompatibility are two important characteristics that are considered ideal for bone tissue engineering. The scaffold, as a temporary template or substrate, formulates the final shape of the new bone, and the architecture of the scaffold, a key property of the scaffolds, determines its interaction with the targeted cells. Target cells behave distinctively when they grow on different scaffolds.(hydrophilicity and surface roughness, etc.). In the previous study, we had fabricated3-dimensional porous poly(lactic-co-glycolic acid)(PLGA)/β-tricalciumphosphate (β-TCP)(PLGA/β-TCP) scaffold via low-temperature deposition manufacturing (LDM). In vitro and in vivo experiments had proved that the scaffold had favourable mechanical strength, high pority ratio, adjustable biodegradation rate, and facility of process and molding, which satisfied the essential requirements of the scaffold for the bone tissue engineering. However, the hydrophobic surface of PLGA/β-TCP is not adequate for cell adhesion, proliferation and osteoblastic differentiation, which limited the repairing ability of the scaffold. Satisfactory hydrophilicity and favourable biocompatibility of the scaffold could guarantee the cells to adhere, proliferate and differentiate, and it also could promote infiltration of oxygen and nutritive material of the body fluid inside the scaffold, which is vital to the successful repair of bone defects. Therefore, it is important to modify the surface of the scaffold to achieve satisfied surface characteristics for cell adhesion, proliferation and differentiation.Research proved that water-absorption ratio of the porous scaffold could be improved remarkably by covering the surface of the scaffold with collagen. Some studies reported that the adhesion, proliferation and the differentiation to osteoblast directionally of the bone marrow stromal cells (BMSCs) could be improved when the cells cultured on the Type Ⅰ collagen. For these reasons, we have fabricated the core-sheath structure composite scaffold composed of PLGA/β-TCP skeleton wrapped with Type Ⅰ collagen on the surface.This research can be subdivided into the following3parts:1. Preparation of the core-sheath structure composite scaffold. The core-sheath structure composite scaffold was a3-dimensional structural bone bracket stuff fabricated by a kind of controllable tachy-forming annulus drivepipe sprayer via LDM. Its materials and structure of the scaffold are fairly biomimetic, and the production of the scaffold is based on the bionic principle through simulating human bone actual architecture.2. Examining the physical properties and the biocompatibility of the core-sheath structure composite scaffold in comparison with PLGA/β-TCP skeleton in vitro. Physical properties were evaluated by means of analyzing the pority ratio, aperture, compressive strength and Young’s modulus. The morphology of the scaffolds and the BMSCs on the surfaces of the scaffolds were investigated by Scanning electron microscope (SEM). The hydrophilicity was assessed by means of water absorption, and the proliferation of the cells were assessed by3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT). The function of the differentiated BMSCs was monitored by measuring alkaline phosphates activity (ALP) of the cells. The results indicated that physical properties of the novel scaffold were as good as those of the control group, hydrophilicity was observably better (p<0.01) than that of control group, and abilities of proliferation and osteogenic differentiation of BMSCs on novel scaffold were significantly greater (p<0.05) than those of control group.3. Study on treatment of bone defect of rabbit radius of the core-sheath structure composite scaffold in comparison with PLGA/β-TCP skeleton. BMSCs were seeded into each group of the composite scaffold in order to repair1.5cm segmental defect of the rabbit radius. The scaffolds’degradation rate and the new bone formation were evaluated by radiograph, Micro CT and histology. The results suggested that the core-sheath structure composite scaffold was degradated completely in bone defect position and bone remodeling was completed at the same time, and repaired the bone defect successfully in48weeks after postoperation, in addition, the new bone formation rate and the scaffolds’degradation rate was matching. The osteogenic capacity and the ability of repairing the bone defect of the novel scaffold were significantly greater than those of control group.Our research has demonstrated that the core-sheath structure composite scaffold possesses preferable physical properties and biocompatibility, and can repair the bone defect successfully supplemented with bone marrow stromal cells, which suggests that the novel scaffold may act as an ideal implant into bone defect, and has high value in bone tissue engineering. |
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