Preparation And Osseointegration Investigation Of Multifunctional Gel Modified Carbon Fiber Reinforced Polyetheretherketone Implants

Bone tissue plays an important role in the life of a human.Bones serve crucial roles such protection,support,mobility,storage,and hematopoietic cell generation thanks to their distinctive composition and intricate structure.In natural bones,toughness is provided by organic components whereas stiffness is provided by inorganic components.Bone tissue has high strength and sufficient toughness due to the combination of organic and inorganic components.However,t bone has a limited capacity for tissue regeneration and recovery,especially for bone defects beyond critical size.Bone tissue engineering has emerged as a possible substitute for established treatment modalities like autograft and allograft in order to enhance the reconstruction of broken bones.In the process of healing a supercritical-size bone defect,bone tissue engineering implants need to coordinate different healing stages（immune regulation,vascularization,and bone regeneration）to restore bone tissue function at the defect.Currently,the primary materials used in bone tissue engineering implants are metal,polymer,ceramic,etc.The study of carbon fiber reinforced polyetheretherketone（CFRPEEK）,which offers excellent practical potential for the treatment of supercritical-sized bone lesions,has received particular attention from researchers in recent years.CFRPEEK has the advantages of non-toxic,corrosion resistance,wear resistance,high strength,high temperature resistance,high toughness,natural ray transmittability,elastic modulus matching with cortical bone,excellent sterilization performance,etc.However,the bioinertness and poor bone binding of CFRPEEK greatly limit its clinical application.From the perspective of biological function required for bone defect healing,combined with clinical demand for bone defect implants with larger than critical size,this paper adopts surface modification technologies such as sulfonation treatment and ultraviolet grafting.Three multifunctional bioactive gel-modified CFRPEEK orthopedic implants were developed by modifying dexamethasone-loaded methylacrylyl gelatine-polyacrylamide composite hydrogel,graphene oxide-hydroxyapatite cryogel and metal-organic framework hydrogel,respectively,to meet a variety of biological functions required in the bone healing environment.The application range of CFPEEK composite material in the biomedical field is expanded,which provides a new research and development idea and scientific reference for its clinical application.A dexamethasone（Dex）-loaded composite hydrogel modified CFRPEEK implant was designed and prepared for the treatment of supercritical-sized bone defects.Methacryloyl gelatin/polyacrylamide（GelMA/PAAM）loaded with dexamethasone（Dex）was modified onto the surface of the CFRPEEK implant by sulfonation treatment and ultraviolet grafting.The modified CFRPEEK had a 3D composite hydrogel network surface.The composite hydrogel network structure on the surface of CFRPEEK with a thickness of 50μm was observed by SEM images.Its water contact angle is 48.8±0.45°,showing excellent hydrophilicity.The Dex release efficiency of modified CFRPEEK was 53%within 21 days,and the slow and sustained Dex release ability was conducive to osteogenic differentiation.It formed more bone apatite in simulated body fluid and had excellent in vitro mineralization ability.In vitro cell results confirmed that GelMA/PAAM/Dex modified CFRPEEK demonstrated outstanding in vitro osteogenic performance and acceptable in vitro biocompatibility.The proliferation of bone marrow mesenchymal stem cells（BMSC）on SCP/GP/Dex was increased by42.11%and the activity of ALP was increased by 28.29%compared with that on SCP.In vivo experiments of rat cranial defects showed that GelMA/PAAM/Dex modified CFRPEEK had excellent in vivo osteogenic properties and could promote the healing of bone defects.A graphene oxide-hydroxyapatite（GO-HAP）cryogel modified CFRPEEK implant was designed and prepared with the goal of enhancing the angiogenesis and osteogenesis processes necessary for bone healing.First,GO-HAP nanocomposites were prepared using in situ bonding method.Then,the cryogel loaded with GO-HAP was grafted onto the surface of the CFRPEEK implant by sulfonation,and the cryogelation technique based on free radical photopolymerization.The cryogel layer was mainly composed of GO-HAP nanocomposite and methacryloyl gelatin/polyethylene glycol diacrylate（GelMA/PEGDA）.The results of in vitro angiogenesis experiments showed that the total branching length of the tube formed on GH₁₀₀increased by 111.18%compared with that of SCP,and the vascular network structure was the most dense,indicating that the 3D sponge-like macroporous structures on the surface of the multifunctional implant and GO promoted the growth and migration of human umbilical vein endothelial cells（HUVEC）.The in vitro angiogenesis ability of modified CFRPEEK implants was enhanced.The excellent surface hydrophilicity and controlled release of Ca²⁺of modified CFRPEEK promoted proliferation,adhesion,and osteogenic differentiation of BMSCs.The proliferation of BMSCs on GH₁₀₀ was increased by 24.41%compared with SCP,and the activity of ALP was increased by 157.08%.The rat cranial defect experiment further demonstrated that the GelMA/PEGDA/GO-HAP cryogel modified CFRPEEK implant could rapidly induce bone regeneration and new blood vessel formation in vivo and significantly improve the osteogenesis and bone remodeling ability of the CFRPEEK implant.A pH-responsive metal-organic framework（MOF）hydrogel modified CFRPEEK implant was designed and prepared to enhance the anti-inflammatory,vascularization,and osteogenic properties of CFRPEEK after implantation.Firstly,hydroxyapatite@magnesium-gallic acid（HAP@Mg-GA）metal-organic frame（MOF）nanoparticles with core-shell structure were prepared through coordination and coupling between HAP,gallic acid（GA）and magnesium ion(Mg²⁺).Methacryloyl chitosan（CSMA）hydrogel loaded with HAP@Mg-GA MOF nanoparticles was then grafted onto the surface of the CFRPEEK implant by sulfonation and ultraviolet grafting.Methacryloyl chitosan was not only a photopolymer but also pH-responsive.Therefore,the hydrogel could control the release of GA,Mg²⁺,and Ca²⁺in HAP@Mg-GA MOF nanoparticles with the change of pH of the physiological environment at the bone defect,so as to improve the anti-inflammatory,vascularization,and osteogenic differentiation abilities of the CFRPEEK implant.In vitro anti-inflammatory and angiogenesis experiments showed that,compared with SCP,the secretion of pro-inflammatory factor TNF-αdecreased by 67.09%,the secretion of anti-inflammatory factor IL-10 increased by284.19%and the total branching length of the tube increased by 81.82%on MGH.In vitro cell experiments showed that HAP@Mg-GA loaded on CSMA hydrogel first actively and accurately released anti-inflammatory drug GA and microelement Mg²⁺in response to inflammation in the inflammatory reaction stage,which created a good immune microenvironment for osteogenic differentiation in the following stage.Meanwhile,the released magnesium also promoted the formation of blood vessels in situ.The experiments of tibial defect in rabbits further showed the trabecular thickness of new bone around MGH was increased by 99.53%compared with SCP,indicating that the sustained long-term release of Ca²⁺facilitated new bone formation and restoration of bone homeostasis around the implant and promoted bone-implant integration.A series of multifunctional gel surface modified CFRPEEK implants were prepared through a variety of surface modification methods in this work.The surface properties,in vitro cell reactions,and in vivo osteointegration of multifunctional gel-modified carbon fiber reinforced polyether ether ketone implants were investigated,which provided scientific reference and new development ideas for further development and future clinical application of multifunctional bioactive carbon fiber reinforced polyetheretherketone orthopedic implants.