| The therapy of critical-size bone defects from injury or trauma often causes a significant challenge in orthopedics and usually requires surgical treatment.Current surgical interventions mainly rely on autografts or allografts but suffer much concerned risks.Autografts need an additional surgical site with the risks of postoperative infections or donor-site morbidity,and allografts exhibit the potential risk of disease transmission and immunologic rejection.The development of biodegradable synthetic polymers,including poly(lactide)(PLA),poly(glycolide)(PGA),and their copolymer poly(lactide-co-glycolide)(PLGA),especially their composites with hydroxyapatite(HA),represents an encouraging solution for bone tissue engineering and bone substitutes.The materials can be employed to replace and repair the morbid and damaged bone tissues due to good biocompatibility,high mechanical properties,and easy processing.The HA/PLGA composite has attracted substantial attention in recent years because of their good biodegradability,osteoconductivity and non-inflammatory.In particular,the biodegradation rate of PLGA can be manipulated by altering the ratio of lactide to glycolide and molecular weight of the copolymer.This is an important characteristic due to that the biodegradation rate of composite should match the speed of bone reconstruction.However,the poor mechanical strength and preformed shapes of porous HA/PLGA composite limit its utilization for load-bearing orthopedic applications by minimally invasive surgery.In recent years,many researches have paid attention to fiber-reinforced composite biomaterials in order to improve the mechanical properties of composites.Poly(glycolide)(PGA)as a biodegradable aliphatic polyester is presently exploited in a series of medical applications because of its good biocompatibility,proper strength and low solubility in organic solvents.It has been proved that the mechanical properties of fibrin or collagen sponge can be improved evidently by adding PGA fibers,and their mechanical performance and retention is suitable for fixation of cancellous bone fracture.However,the PGA fibers in the reported studies were single-size and long fibers,and the composites made by these fibers were not injectable.Injectable in situ forming implants(ISI)based on phase separation by solvent exchange represent an attractive alternative to conventional preformed implants for parenteral applications.The composite can be injected to form a solidified implant or scaffold in vivo through a minimally invasive way,which can perfectly fill the irregular bone defect,significantly shorten the operation process,reduce patient risk and lead to a quick recovery.However,many injectable composites are hydrogel-based or nano-particulates for delivering drugs,and these materials typically have unsatisfactory mechanical properties for load-bearing sites.In this study,the micro/nano-hybrid PGA fibers were fabricated by melt-spinning and employed as a filler to strengthen the mechanical properties of HA/PLGA matrix for orthopedic application.The ternary composites were prepared by dispersing the crushed PGA fibers(0,30,50 and 70 wt%)into HA/PLGA solution with N-methyl pyrrolidone(NMP)as solvent.First,the injectability,solidification rate and cytotoxicity of the injectable composites were tested.Meanwhile,the morphology,mechanical strength and thermal properties of the solidified composites were further evaluated.Then,the in vitro degradation of ternary composites was evaluated with general observation,water absorption,mass loss,molecular weight,p H change,porosity,morphology and microstructure,thermal behavior,and mechanical properties.Finally,the composite scaffolds and composite scaffolds with DOPA-IGF1 were applied to repair long bone.The biocompatibility of PGA fiber reinforced material and the important role of DOPA-IGF1 in promoting osteogenesis in vivo were verified by the repair experiment of radius defect in rabbits.1.Preparation and characterization of injectable PGA fiber reinforced HA/PLGA composite scaffold.The fibers were obtained from melt-spinning and fiber diameter ranged from 70 nm to 191 μm.The injectability,mechanical strength,solidification rate and cytotoxicity of injectable composites were characterized.All composites achieved the acceptable injectability under an injection force of 100 N.The mechanical properties of composites were gradually enhanced by increasing PGA fiber contents.The compression strength of composite with 70 wt% content of PGA fibers was up to 31.1 MPa,which was four times stronger than that of composite without PGA fibers.In the solidification rate analysis,the compression strength of composites with 50 or 70 wt% PGA fibers in immersion time of only 45 min was similar to that of composite without fibers in immersion time of 4-5 h.The MTT test showed that exceeding 70% cells could survive in the fourfold dilution of extract,and its cytotoxicity focused on the first 4 h after immersing.2.In vitro degradation behavior of PGA fiber reinforced HA/PLGA composite scaffold.Water absorption showed a marked increase as the degradation progressed,and the composite with 70 wt% PGA fibers showed the highest final water uptake which was 3.89 times higher than the initial value.The mass loss of the composite with 70 wt% PGA fibers was 79.3 ± 6.47% at 16 weeks,which was the highest among all the composites.The molecular weight of the PLGA matrix decreased over time especially for the composites containing 70 wt% PGA fibers.The lowest p H of the buffer solution was also observed in the composite with 70 wt% PGA fibers.Environmental scanning electron microscopy(ESEM)and micro-computed tomography(micro-CT)results demonstrated that the porosity of the composites and the size of the pores gradually increased as the degradation progressed.The most significant change in compression strength was observed for the composite with 70 wt% PGA fibers which was reduced from an initial value of 20 MPa to approximately 1 MPa at 16 weeks.The results indicated that the in vitro degradation of the composites could be accelerated by increasing the content of PGA fibers.3.In vivo osteogenesis of PGA fiber reinforced HA/PLGA composite scaffolds.In this chapter,the osteogenic behaviors of PGA fiber reinforced scaffolds and scaffolds equipped with DOPA-IGF1 were studied in vivo by repairing rabbit radius defects.The results showed that the early mechanical strength and the degradation rate of the scaffolds determined the effect of bone repair in the pure material groups.The bone induction of the scaffolds equipped with DOPA-IGF1 was significantly higher than that of the pure material groups.The content of DOPA-IGF1 loaded on the material was affected by the porosity of the scaffolds.Overall,scaffold materials with the growth factor and 30 or 50% PGA fiber content had the best effect on bone repair in vivo.The results confirmed that the biodegradation rate of the composites matched with the speed of bone reconstruction,and further verified the biocompatibility,osteogenesis and growth factor carrying capacity of the composite scaffolds.The important role of DOPA-IGF1 in promoting osteogenesis repair in vivo was also exhibited. |
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