Composite Scaffolds Based On Dendritic Mesoporous Silicon-based Nanomaterials For Soft And Hard Tissur Regeneration

There are still unsolved problems although tissue engineering scaffolds have achieved many results in the regeneration of soft and hard tissues.Among them,angiogenesis is the most difficult challenge.Because the tissue needs nutrition and oxygen,which are effectively diffused through blood vessels.When cells are far away from capillaries,tissue will suffer from hypoxia and nutrient shortage,which limits cell proliferation and affects the effective regeneration of tissues.In recent years,nanocomposites and their drug delivery properties play a significant role in the repair of defective tissues with organic/inorganic hybrid scaffolds,which provides a new idea for the effective vascularization of tissue engineering scaffolds.In addition,the structure and function of different tissue are particular,so the selection of nanomaterials and scaffold structure are very important for the realization of tissue vascularization.Silica based mesoporous bioactive glasses(MBGs),as inorganic nanomaterials,which are effective delivery carriers.The difference of MBGs is bioactivity and biocompatibility,which has been verified.MBGs have effects on wound healing,bone defect and bone-cartilage regeneration,such as antibacterial,anti-inflammatory,and vascularization.MBGs could promote the growth,proliferation and differentiation of cells,especially osteoblasts and fibroblasts.In addition,we believe that MBGs could provide an effective solution to the insufficient angiogenesis of traumatic tissue in view of the excellent vascularization of MBGs.Therefore,dendritic bioactive glass(dMBG)was optimized and prepared for the design and construction of vascularized biomimetic scaffolds.The animal models of hypertrophic wound,full-thickness articular cartilage and skull defect were used to study and evaluate the materials and biology,it mainly includes the following contents:1.In order to improve the loading efficiency of MBGs,dMBG with tunneled mesopore was successfully prepared by two-phase method and calcination.It was found that dMBG with the particle size stabilized at 190 nm and mesoporous aperture at 7.79 nm.It is an excellent carrier for active molecules and drugs with a large specific surface area(888.146 m~2/g).dMBG could be mineralized into hydroxyapatite within two weeks and showed good biological activity.The nanoparticles can be mineralized into hydroxyapatite(HAP)within two weeks.dMBG showed good vascularization and stable biosafety through co-culturing with human umbilical vein endothelial cells(HUVEC),which suitable for vascularized tissue regeneration.2.In this study,a 5-fluorouracil(5-Fu)-loaded dMBG was synthesized by hydrogen bonding and adsorption(drug loading rate:23%),and pod-like nanofibers((F@B)/P)@PU were prepared by coaxial electrospinning to improve the phenomenon of insufficient vascularization and abnormal scar hyperplasia caused by severe wound.The core of((F@B)/P)@PU was a mixture of5-Fu@dMBG and polyoxyethene(PEO),and the shell layer was(PEEUU).The formed((F@B)/P)@PU exhibited a uniform and smooth morphology,appropriate surface wettability,high protein adsorption rate,as well as mechanical properties matching with autologous skin tissue and5-Fu@dMBGs were dispersed in the PEO matrix.Importantly,the loaded 5-Fu within((F@B)/P)@PU exhibited sustained-release profile and anti-proliferation to inhibit the growth of He La cells,which is a model cell with the property of rapid proliferation.The results of animal experiments and histological tests show that there are a large number of angiogenesis with a good morphology,collagen deposition,and effectively inhibit the inflammation in the wound treated with((F@B)/P)@PU.It has potential application in skin tissue repair.3.dMBG-REDV was prepared by chemical grafting in order to achieve the vascularization of subchondral bone layer and smooth transition with upper cartilage,and gradient bionic scaffold(GBS)was prepared by double-layer pouring and freeze-drying method with dMBG-REDV and gelatin composites.GBS presented gradient distribution in composition and pore structure.The scaffold aperture increased with the addition of dMBG-REDV,and there was an obvious transition zone between the subchondral bone region(Gel/0.3%DMBG-REDV)and the cartilage region(Gel).In addition,the bionic subchondral bone zone of the GBS had excellent mechanical properties and could effectively release the REDV.The prepared GBS could promote the proliferation and migration of HUVEC,and bionic subchondral bone zone has the ability of vascularization.H?E,MASSON,safranin O-fast green and collagen?staining were used to evaluate the repair effect of AC defect of New Zealand rabbits.The results showed that the GBS has a significant effect on the regeneration of full-layer cartilage.The defect site was completely filled,and both cartilage and subchondral bone were regenerated within 12 weeks,.The new tissue had a smooth surface,high collagen density,and similar structure to autologous tissue,showing consistency and integrity with the original tissue.4.dMBG/Sr grafted with vascular endothelial growth factor(VEGF)was introduced to the modified hyaluronic acid(HA)hydrogel,which enhanced the vascularization and osteogenesis ability of the scaffold aimed at the problem of insufficient vascular in bone defect repair.Meanwhile,PLGA/Gel flexible nanofiber was added to toughen the hydrogel to adapt to intracranial pressure.The short nanofibers are connected to the hydrogel segment by an amide bond,and a non-covalent interaction(hydrogen bond)occurs between dMBG/Sr-VEGF nanoparticles and the nanofiber interface.The grafting rate of the HAMA hydrogel was 24%.The enhanced and toughened hydrogel precursor HAMA/NF/NPs quickly geled in 90 seconds,which was injectable.Photocured HAMA/NF/NPs hydrogels are not easily broken after swelling,and exhibit good elasticity and compression properties.At the same time,they have an appropriate degradation rate and effective sustained release of VEGF.In addition,HAMA/NF/NPs hydrogel could promote the proliferation of mouse embryonic osteoblasts(3T3-E1),and more importantly,it has the ability to induce HUVEC to form blood vessels.The rat skull repaired by HAMA/NF/NPs hydrogel was evaluated by CT,which showed excellent repair effect with a new bone volume with 96.45%and high bone density at 8 weeks.Meanwhile,histology showed excellent repair results.