A Novel Shape Memory Degradable Composite Microsphere Scaffold For Large Segmental Bone Defects

Severe open trauma,bone infections leading to osteomyelitis,and large segmental bone defect sites resulting from bone tumor resection have prompted bone grafting to become the second most transplanted tissue each year.Traditional clinical treatment of large segmental bone defects requires the use of bone grafts,and the shortage of bone sources urgently requires the development of alternative bone repair materials.Synthetic polymeric materials can control the degree of polymerization(molecular weight),chemical composition and crystallinity to modify the mechanical strength and degradation rate of the material.By studying synthetic polymers and their related composites in the preparation of bone graft scaffolds have significant research implications.Nano-hydroxyapatite(n-HA)has good osteoconductivity.However,when combined with polymers,n-HA is not easily dispersed and easily agglomerated due to the large surface energy of n-HA.The formed composite scaffold is prone to stress concentration,which reduces the mechanical properties of the material.Dopamine has adhesion and a large number of functional groups.The surface modification of n-HA by co-soaking with n-HA resulted in the formation of poly(dopamine)(PDA)-based modified n-HA(abbreviated as PHA),which can be better blended with the polymer in order to obtain a homogeneous composite bone scaffold.In this study,polylactic acid copolymer trimethylene carbonate and polyglycolic acid terpolymer(PLLA-TMC-GA)were synthesized by ring-opening polymerization.The prepared ternary materials were characterized,and their physicochemical properties were tested.Ternary polymer microspheres and composite microspheres with different contents of PHA were prepared by the single emulsion method.The effects of surfactant PVA concentration and polymer concentration on the particle size of the microspheres were investigated.The surface morphology of the microspheres was observed and analyzed,and the actual PHA loading in the composite microspheres was detected.Subsequently,the microsphere scaffold was constructed by the thermal sintering method,and the effect of sintering temperature on the porosity and mechanical properties of the microsphere scaffold was investigated.In addition,the shape memory function of the microsphere scaffold was tested.Finally,a composite sodium alginate hydrogel drug-loaded microsphere scaffold was prepared by microsphere scaffold composite hydrogel.This new structure endows the microsphere scaffold with the function of drug loading,and cell biology experiments were carried out with other groups by co-culture with cells.The results are as follows:(1)Ternary polymer microspheres are prepared by single emulsion method,the particle size is influenced by the concentration of surfactant and polymer.PVA concentration in the range of 0.1%-1%,particle size decreases with increasing concentration.Polymer concentration in the range of 5%-20%,particle size increases with increasing concentration.The use of dopamine-modified nano-hydroxyapatite can effectively enhance its dispersibility in polymer solutions.With the increase of PHA content,the hydrophilic property of the composites was enhanced and the surface of the composite microspheres gradually became rough.(2)The microsphere scaffolds were prepared by thermal sintering method at 110°C,and suitable porosity(40%)and mechanical properties(130 MPa)could be obtained.There were no acidic degradation products after 12 weeks of in vitro degradation,and the porosity,water absorption and mass loss rate increased gradually with the degradation time.Furthermore,the prepared microsphere scaffolds have shape memory function at human body temperature of37 ℃.(3)The composite sodium alginate hydrogel microsphere scaffolds were prepared by cosoaking method.3wt% sodium alginate hydrogel can enter the internal pore size of the prepared microsphere scaffold.At the same time,the sodium alginate hydrogel could be loaded with Epimedium drug,giving the microspheres a new bone regeneration function.All components of the microsphere scaffolds have good cell adhesion and biocompatibility.The rougher the surface of microspheres,the higher the number of cells and the better the adhesion.It can accelerate the ability to promote cell proliferation as well as differentiation to osteoblasts.