Enhancement Of Osteoinduction By Composite Nano-fibrous Scaffold Contained Simvastatin And Effect On Immune System

Maxillofacial bone defects or deficiencies caused by a variety of factorsignificantly impact on restoring facial morphology and function of patients andphysical and mental health of the patient. Repair of bone tissue is a major medicalhealth problem. Every year, repair of bone tissue surgery is up to more than1.3million around the world, most reasons for bone tissue defect is due to the diseaseand the occasional accident, which has become a threat to human health. Autologousor allogeneic bone graft has been mainly taken as the main treatment of bone tissuedefects technology for over the years. However, there are obvious shortcomingsabout these traditional methods, such as limited bone volume sources and immunerejection, and so on. Use of biomaterials for treating bone tissue defects become anew choice for bone tissue repair.Recently, with the development of tissue engineering, various biomedicalscaffolds for meeting the different requirements have been studied extensively. It isconsidered as an ideal scaffold for bone repair material should have somecharacteristics which include suitable mechanical and physical properties, goodbiocompatibility, biodegradability, good bone conduction, high permeability for themaximum amount of cells, surface chemistry and microstructure for bone cellgrowth and differentiation, etc. currently bone defect repair materia include collagencomplexes[1], silk[2], polylactic acid, polyglycolic acid and polylactic acid-glycolicacid copolymer[3]. Nanotechnology in the synthesis of scaffolds have to play a vitalrole, electrospinning[1], phase separation[4], self-assembly[5]and other methodshave been used for preparing above materials into nanofiber scaffolds, On accountof large surface area, porous three-dimensional structure similar to the extracellular matrix, which will be beneficial to adhesion, stretching and growth of cells, makingit as one of the best choice for tissue engineering scaffolds. In addition to the needfor good physical properties and functions with porous osteoconductive scaffoldmaterial for bone tissue engineering, a specific function of bone growth factors ordrugs also play a role in the osteoinduction. Many studies have shown that bothosteoconductive and osteoinductive specially promote bone regeneration. In recentyears, researchers have found that for cholesterol-lowering statins-simvastatincould promote osteoblast proliferation and differentiation[6]. In addition, systemic orlocal injection of simvastatin also enhanced bone regeneration in bone defect site[7,8].But systemic side effects of drugs as well as low drug utilization of local injection,so seeking a kind of good carrier for the drug become a hot topic.Drug delivery system is embodied in the form of nano-technology combinedwith good clinical medicine. Side effects of drugs and costs can be reduced byefficient drug delivery system as much as possible to achieve the same therapeuticeffect, while it also prevents drug diffusion and removal. Therefore, polylactic-glycolic acid (PLGA)/nano-hydroxyapatite (HA)/simvastatin (SIM)composite nano-fibrous scaffold was prepared using electrospinning. Scaffoldmorphology and hydrophilic were detected using scanning electron microscopy andcontact angle tester, while relationship between drug release dose and time ofnano-fibrous scaffolds was studied in vitro. In vitro experiments, MC3T3-E1cellswere seeded on scaffold surface to detect PLGA/HA/SIM nano-fibrous scaffold onosteoblast adhesion, proliferation, and differentiation by scanning electronmicroscopy, MTT, quantitative real-time PCR experiments. In addition, we implantnano-fibrous scaffold in rats skull defects to detect in vivo osteogenesis byMicro-CT and histological analysis. To further explore the effect of scaffolds onimmune system, various immunological reactions of nano-fibrous scaffold in vivowere analysed by ELISA kits, serology, histology and immunohistochemistry. Some preliminary results obtained by the above-mentioned experimental study showed:PLGA/HA/SIM scaffold showing time and dose dependent manner in PBS canrelease the drug slowly, and promote MC3T3-E1cell adhesion, growth anddifferentiation in vitro, while in vivo significantly increase new bone formation area,these results demonstrate PLGA/HA/SIM scaffold could become biomedicalmaterials. Further studies show that simvastatin could a certain extent inhibit localinflammatory reaction and provide a more favorable micro-environment for theformation of new bone.In summary, PLGA/HA/SIM nano-fibrous scaffolds can inhibit localinflammatory reaction and have a good ability to promote the formation of new bonetissue in vitro and in vivo, and therefore, it is a new form of the drug deliverysystems which may be a new choice as biomedical materials in the field of tissueengineering.