| Background:Many kinds of critical bone tissue injuries caused by accidents,tumors,inherited or metabolic diseases have always been important problems for orthopedic doctors and patients.In view of this type of bone tissue injury,the method of autologous bone or allogeneic bone transplantation was usually used to reconstruct the bone defect.Although autologous or allogeneic bone grafts have good histocompatibility and bone conductivity,whether the grafts derived from autologous or allogeneic has many shortcomings which are difficult to solve,such as donor limitation,immune rejection,poor mechanical strength,donor complications and so on.Therefore,it is urgent to apply the principles and technologies of life science and material engineering to prepare a series of engineering scaffold materials with bone repair and replacement functions,so as to maintain and promote the repair and functional recovery of injured bone tissue.This is exactly the research content and direction of bone tissue engineering.The scaffold materials,seed cells and osteogenic growth factors are the three major elements of bone tissue engineering.Among them,the scaffold material is the core of bone tissue engineering,which plays a role of filling the defect and providing mechanical support in the early stage of bone tissue damage.The introduction of osteogenic growth factor can further improve the osteogenic activity of these scaffold materials and enhance their repair effect in bone tissue engineering.A large number of studies have shown that growth factors can effectively promote the repair of body damage.Because growth factor belongs to the substance that normal cell secretes,with the advantage such as low toxicity,low immunity,high effect consequently.However,due to the shortcoming of short half-life and easy to be diffused and lost with blood,the growth factor cannot act on the lesion in a long-term and stable way,which hinders the development of its clinical application.At present,the adsorption of growth factors on bone tissue engineering materials enhanced by polydopamine is a stable,effective and safe method with broad research and application value.Objective:The objective of this study was to prepare a PLGA/HA composite porous scaffold carrying BMP-7 for bone tissue engineering.It was expected that the scaffold could induce osteoblast differentiation in vitro and promoted the generation of new bone tissue in vivo,so as to achieved the goal of promoting bone repair.Methods:(1)PLGA/HA composite bone tissue engineering scaffold with fixed ratio was prepared by phase transformation/particle leaching.BMP-7 was modified on the surface and inside of the scaffold material by means of polydopamine modification to enhance adsorption.And then PLGA/HA composite porous scaffold containing BMP-7 was finally prepared for bone tissue engineering repair.After that,the surface morphology,internal pore structure,hydrophilicity and BMP-7 protein adsorption and release were further characterized by various methods.(2)Bone marrow mesenchymal stem cells(BMSCs)from rats were implanted on simple PLGA/HA scaffolds,dopamine-modified PLGA/HA scaffolds and BMP-7loaded PLGA/HA scaffolds,respectively.The adhesion,proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells on the three scaffolds were detected to verify the in vitro osteogenic activity of PLGA/HA composite porous scaffold modified with polydopamine and BMP-7.(3)Simple PLGA/HA scaffolds,PLGA/HA scaffolds modified with polydopamine and PLGA/HA composite porous scaffold modified with polydopamine and BMP-7were respectively implanted in the cranial defects of rats.After 8 weeks,rats were sacrificed,and the in vivo bone repair ability of the scaffold was tested and evaluated to further verify the osteogenic ability of PLGA/HA composite porous scaffold modified with polydopamine and BMP-7.Results:(1)By means of phase transformation/particle leaching,a kind of PLGA/HA composite scaffold material with three-dimensional porosity was successfully prepared,which has a well-connected internal micro-nano mixed pore structure;BMP-7 was successfully adhered to PLGA/HA composite porous scaffold by means of polydopamine modification to enhance adhesion.This method effectively promoted the adhesion and sustained release of BMP-7 on PLGA/HA composite porous scaffold.The PLGA/HA composite porous scaffold modified by polydopamine has better hydrophilicity and water absorption,and the degradation rate matching with bone tissue regeneration.(2)PLGA/HA composite porous scaffold modified with polydopamine and BMP-7had good biocompatibility and could effectively promote the adhesion and proliferation of BMSCs on the surface of the material;The PLGA/HA composite porous scaffold modified with polydopamine and BMP-7 has good osteogenic activity and the ability to induce BMSCs to differentiate into osteoblasts,which is manifested in that it can significantly improve the ALP activity of BMSCs and promote calcium deposition.PLGA/HA composite porous scaffold modified with polydopamine and BMP-7 can significantly up-regulate the expression of osteogenic genes in BMSCs,so as to induce BMSCs to differentiate into osteoblasts and promote the synthesis and secretion of osteogenic extracellular matrix and minerals.(3)PLGA/HA composite porous scaffold modified with polydopamine and BMP-7could effectively promote the synthesis,secretion and maturation of collagen in the cranial defect of rats in vivo;PLGA/HA composite porous scaffold modified with polydopamine and BMP-7 can effectively promote the mineralization of the skull defect in rats in vivo;PLGA/HA composite porous scaffold modified with polydopamine and BMP-7 has good bone conduction and bone integration characteristics in vivo,thus improving the mechanical strength of tissue repair.Conclusion:PLGA/HA composite porous scaffold modified with polydopamine and BMP-7shows excellent three-dimensional porous structures and hydrophilicity,which can effectively promote the adhesion,proliferation of rat bone marrow mesenchymal stem cells on the material,and induce the osteogenesis related gene expression.In vivo,it can promote the synthesis,secretion and mineralization of collagen matrix.With good bone conduction and bone integration,PLGA/HA composite porous scaffold modified with polydopamine and BMP-7 is a promising material for bone tissue engineering. |
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