Construction And Properties Of 3D Degradable Polymer Network/Calcium Phosphate Cement Composite Material For Bone Repair

Calcium phosphate cement(CPC)as a bioactive material for bone repair has promising application prospect in orthopedics,dentistry and maxillofacial fields due to its characteristics of self-setting ability,easiness to shape,degradable,good biocompatibility and osteoconductivity.However,CPC degrades layer by layer,it shows too slow degradation rate because there are no interconnected macropores inside CPC,which are beneficial for the ingrowth of new bone tissues and blood vessels.Moreover,insufficient osteogenic activity of CPC severely influences its efficiency of bone regeneration.In this study,PLGAnw/CPC composite was constructed by incorporating CPC slurry into the poly(lactic-co-glycolic acid)network(PLGAnw).Three dimensional(3D)interconnected macropores were in-situ formed in the CPC matrix after the fast degradation of the PLGA network when the PLGAnw/CPC composite was implanted in vivo.The macropores can provide space for the ingrowth of new bone tissues.The addition of highly bioactive wollastonite(WS)and/or zinc silicate(ZS)into PLGAnw/CPC composite promotes the ingrowth of new bone tissues into the 3D interconnected macropores.Meanwhile,the osteogenesis of CPC can be synergistically promoted by combining the highly bioactive compounds with the interconnected macropores.In addition,the influence of the PLGA networks with different structures on bone repair in vivo was investigated,the PLGAnw/CPC composites capable of in-situ forming hierarchical pore structures were also constructed by adding PLGA microspheres with different diameters to the CPC matrix.The results showed that PLGA networks with regular morphology and 3D interconnected macropores was successfully prepared by the 3D printing technique.The PLGAnw/CPC composite was constructed by infiltrating CPC slurry into the PLGA network under pressures.The addition of PLGA network decreased the flexural strength of CPC,but significantly improved the toughness of CPC.PLGA network in the composite completely degraded after immersion in PBS for 28 days,and 3D interconnected macropores were in-situ formed in the composite.When the CPC matrix of the composites does not set,the composites have good plasticity after being heated at 50°C for 1 min.To promote the ingrowth of new bone tissues and blood vessels into the macropores,highly bioactive WS was added to the PLGAnw/CPC composite.The results showed that the addition of WS significantly promoted the proliferation and osteogenic differentiation of mouse bone marrow mesenchymal stem cells(mBMSCs),the optimum amount of WS was 20 wt.%.In addition,the incorporation of PLGA network can obviously promoted biodegradability and osteogenesis of CPC after being implanted in vivo.PLGAnw/20WS/CPC composite exhibited the highest amount of material degradation and new bone.Thus,the addition of WS can significantly accelerate bone regeneration of the PLGAnw/CPC composite.To further improve osteogenic activity of the PLGAnw/CPC composite,highly bioactive ZS and WS were added to PLGAnw/CPC composite in order to prepare osteoimmunomodulatory composite.The results showed that the addition of ZS can create immunologic microenvironment in favor of osteogenesis,the optimum amount of ZS was 10 wt.%.The addition of WS and ZS did not influence the hydration reaction of CPC,significantly increased compressive strength of the composite.The addition of ZS and WS further neutralized the acidic products produced by the degradation of the PLGA network,3D interconnected macropores in the composites were in-situ formed after immersion in Tris-HCl solution for 28 days.Although the addition of WS and ZS obviously inhibited the proliferation of mBMSCs,ALP activity and osteogenesis-related genes(ALP,Runx2,COL I and OCN)expression in vitro was significantly improved.The in vivo results showed that the addition of WS and ZS can markedly promote biodegradation and osteogenesis of the PLGAnw/CPC composite in comparison to the composite only containing WS.The influence of PLGA networks with different structures on in vivo bone repair was investigated,the results showed that the biodegradation and osteogenesis of the composite were obviously enhanced with increasing of PLGA network amount from 36.43 vol.% to 47.32 vol.% in the later period of implantation.The incorporation of PLGA networks prepared by single or double fibers stacking into CPC can form circular and peanut shaped macropores,respectively.The peanut shaped macropores distinctly promoted biodegradation and new bone formation in the later period of implantation in comparison to the circular macropores.The PLGAm/PLGAnw/CPC composites capable of in-situ forming hierarchical pore structures were successfully constructed by adding the PLGA microspheres with different diameters to the composites.The addition of PLGA microspheres with diameter of 53-106 ?m obviously increased compressive strength and toughness of the composite.After immersion in the HCl-Tris solution for 28 days,peanut shaped interconnected macropores with pore size of 468 × 785 ?m,isolated and partially interconnected spherical macropores with pore size of 53-106 ?m or 106-150 ?m in the composites in-situ formed.In addition,micropores and nanopores in the CPC matrix generated by the hydration reaction of CPC.However,the addition of PLGA microspheres inhibited the proliferation of mBMSCs in comparison to the composite without PLGA microspheres.