Fabrication Of Functionalized PMMA Bone Cement With Water Absorption And Swelling Capacity

Polymethyl methacrylate(PMMA)bone cement has been widely used as the gold standard for filling treatment in surgery and arthroplasty,etc.However,the solid-liquid two-phase polymerization reaction of bone cement produces volume contraction,which causes sterile loosening and affects its long-term stability in the human body.Meanwhile,PMMA bone cement is mainly used clinically as a drug carner for antibacterial and treatment of osteoporosis,while the encapsulation of hydrophobic PMMA causes disadvantages such as low release ratio of internal water-soluble drugs,mismatch between drug release cycle and human demand,and single drug release function.In addition.PMMA bone cement also has the disadvantages of high elastic modulus causing factional wear and even secondary fractures to normal human bone tissue,as well as high temperature during the setting of bone cement causing burns to normal human tissue.To address the above problems,this study proposed to modulate the hydrophilic groups and three-dimensional mesh structure within the polymer,and constructed a water absorption pathway composed of polymer within the PMMA bone cement to completely solve the problem of volume shrinkage of PMMA bone cement.On this basis,the solid and liquid phases of the swellable bone cement were modified separately to increase the number of hydrophilic groups while introducing multiple water absorption pathways,which accelerated the water absorption and expansion behavior of the bone cement before solidification,thus maximizing its own water absorption and expansion capacity.While using the absorption pathway to improve the water absorption and swelling properties of the bone cement,antibiotics and anti-osteoporosis drugs were added to the bone cement.By adjusting the loading methods of two drugs and the formation of the absorption pathway within the bone cement,the multifunctional PMMA-based bone cement with long-lasting and graded release of two drugs was obtained.The curing parameters,water absorption and swelling properties,mechanical properties,drug release properties,antibacterial properties and biocompatibility of the functionalized bone cements Investigated.The diffusion mechanism of water in different components of the functionalized bone cements,the kinetics of water absorption and swelling,and the kinetics of drug release were investigated.The main contents and key findings of this research were as follows:The P(MMA-AA)copolymers with different hydroxyl content and different cross-linking degree were obtained by regulating the monomer ratios of acrylic acid and methyl methacrylate and the content of the cross-linking agent N,N-methylenebisacrylamide in the solution polymerization method.When the AA content was 50%and the MBA content was 5%,the P(MMA-AA)copolymer formed water absorption pathways within the bone cement,the water absorption and swelling ratios of P(MMA-AA)bone cement were up to 61.8 ± 2.5%and 60.2 ±2.1%.Rapidly water-absorbing swelling P(MMA-AA)bone cement with multiple water absorption pathways was obtained by introducing GO and HEMA into the solid and liquid phases of P(MMA-AA)bone cement by chemical grafting and physical mixing,respectively.The diffusion of water molecules in the fast water-absorbing and swelling bone cement was found to be a non-Fickian mechanism,and the water-absorbing and swelling behaviors were consistent with the primary and secondary kinetics,respectively,and the water-absorbing and swelling efficiencies before solidification were increased by 2.08 and 2.16 times,respectively,compared with those of P(MMA-AA)bone cement,and the water-absorbing and swelling multiplicities were up to 92.5±1.7%and 97.4 ± 2.1%,respectively.In addition,the mechanical properties of the expandable PMMA-based bone cement were enhanced by the introduction of GO in the reaction system,overcoming the bottleneck of deteriorated mechanical properties caused by the promoted water absorption and expansion capacity of bone cement,and meeting the requirements of ISO5833-2002.The expansion stresses generated during the expansion of P(MMA-AA)bone cements with low,medium and high ratios were also quantified.The expansion stresses of the different components of the expandable bone cements ranged from 26.64 MPa to 114.27 MPa,which generated compressive stresses on the bone trabeculae,thus providing superior support to the surrounding tissues.The controllable swelling force provided P(MMA-AA)-based bone cement potential application value in vertebroplasty,bone screw,dental filler,medical aesthetics.Dual drug-loaded microspheres with different particle size ranges and drug distribution in the form of core(ALN)and shell(GS)were prepared by pigmenting alendronate sodium(ALN)and gentamicin sulfate(GS)in gelatin microspheres by emulsion polymerization and impregnation methods,and a dual drug-loaded gelatin/PMMA composite bone cement with drug release pathway was obtained through the dissolution and degradation of the dual drug-loaded gelatin microspheres in the bone cement.The bone cement had superior water absorption and swelling properties while the cumulative drug release rates of GS and ALN were 73.6 ± 1.75%and 68.5 ± 1.92%,respectively.Two drugs achieved a staggered and controlled release,with the rapid release of GS dominating the initial 24-hour system to effectively inhibit bacterial growth,and the gradual release of ALN in the system after 3 weeks and slow release up to 12 weeks to provide long-term anti-osteoporotic function.In addition,the bone cement promoted the proliferation and adhesion of osteoblasts on the cement surface,and exhibited excellent histocompatibility,thus providing excellent biocompatibility.The P(MMA-AA)-ALN nano-drug-loaded microspheres of different particle sizes were obtained by solution polymerization,the rapidly swelling and long-lasting drug release was obtained by using the electrostatic attraction of gentamicin sulfate and P(MMA-AA)-ALN nano-drug-loaded microspheres to rearrange in the bone cement,and the reverse drug release by the water absorption pathway constructed by the nano-drug-loaded microspheres.P(MMA-AA)bone cement with long-lasting drug release function was obtained.The release mechanism of both gentamicin sulfate and alendronate in the system was Fick diffusion,and the cumulative release rates of both could reach 74.67±1.02%and 75.23±1.96%.The release cycles were 4 weeks and 15 weeks,respectively,which effectively prevented infection and the growth of drug-resistant strains,and also had the release cycle of anti-osteoporosis drugs matching the human bone healing cycle.The bone cement had superior antibacterial ability and biocompatibility,which could meet the different clinical needs of bone repair in the future,thus offering a wide range of prospects for clinical use.