High strength bioresorbable bone plates: preparation, mechanical properties and in vitro analysis

Biodegradable bone plates were prepared as semi-interpenetrating networks (SIPN) of crosslinked polypropylene fumarate (PPF) within a host matrix of either poly(lactide-co-glycolide)-85:15 (PLGA) or poly(1-lactide-co-d,l-lactide)-70:30 (PLA) using N-vinylpyrrolidone (NVP), ethylene glycol dimethacrylate (EGDMA), 2-hydroxyethyl methacrylate (HEMA), and methyl methacrylate (MMA) as crosslinking agents. Hydroxyapatite (HAP), an inorganic filler material, was used to further augment mechanical strength. The control crosslinking agent (NVP) was replaced partially and totally with other crosslinking agents. The amount of crosslinking agent lost, the characterization change in the mechanical properties and the dimensional stability of the bone plates after in vitro treatment was calculated. The optimum crosslinking agent was selected on the basis of low in vitro release of NVP from SIPN matrix. Bone plates were then prepared using this crosslinking agent at 5 MPa pressure and at temperatures between 100-140 degrees C to determine if there was any augmentation of mechanical properties in the presence of the crosslinked network. In vitro analysis showed that 90% of the crosslinking agent was lost on plates using NVP as a crosslinking agent. This loss was reduced to 50% when NVP was partially replaced with EGDMA or MMA. EGDMA was determined to be superior because (1) its low release as a crosslinking agent, (2) flexural plate strength of 50-67 MPa, (3) flexural modulus of 7-13 GPa, and (4) manufacturability stiffness of 300-600 N/m. HAP-loading resulted in an additional increase in values of mechanical parameters. Substituting PLGA with PLA in the PPF-SIPN did not show any additional improvement of mechanical properties.     

Mechanical properties of some fibre reinforced polymer composites after implantation as fracture fixation plates

Continuous fibre reinforced composite bone plates made from graphite/polysulphoneand glass/epoxy laminates were implanted for 16 weeks on osteotomized canine femurs and for 12 months on intact femurs. After sacrifice, the plates were removed and tested in four point bending for stiffness and strength. There were no significant differences in properties between control and implanted plates in the 16 week study. Both the glass/epoxy and the graphite/polysulphone systems showed deterioration after implantation for 12 months.     

The combined effects of crosslinking and high crystallinity on the microstructural and mechanical properties of ultra high molecular weight polyethylene

Ultra high molecular weight polyethylene (PE) has been used for more than forty years as the bearing surface in total joint replacements. In recent years, there have been numerous advances in processing conditions that have improved the wear resistance of this material. In particular, crosslinking has been shown to dramatically improve the wear behavior of this orthopedic polymer in simulator studies. This benefit to wear resistance, however, is accompanied by a decrease in mechanical properties such as ultimate tensile strength, ductility, toughness and fatigue resistance. This degradation to mechanical properties may have serious implications for devices with high stress concentrations or large cyclic contact stresses. Tailoring microstructure for improved structural performance is essential for implant design. In this work we examined the role of crystallinity and crosslinking on the microstructure and mechanical properties of PE. Crystallinity was increased with a high pressure process and crosslinking was obtained with gamma irradiation. Crystallinity was beneficial to fatigue crack propagation resistance and when coupled with crosslinking a polymer with both wear and fatigue resistance was obtained.     

Effect of annealing on the mechanical properties of PLA/PCL and PLA/PCL/LTI polymer blends

The effects of annealing on the mechanical properties of polymer blends of poly(lactic acid) (PLA) and poly(ε-caprolactone) (PCL) were investigated. The bending strength and modulus of PLA/PCL tend to increase due to crystallization of the PLA phase by annealing. The mode I fracture energy, J(in), of PLA/PCL decreases dramatically due to the suppression of the ductile deformation of the spherical PCL phase by annealing. The immiscibility of PLA and PCL can be improved by adding lysine triisocyanate (LTI) as a result of additional polymerization. The phase transformation due to LTI addition reduces the size of the spherical PCL phase, resulting in higher fracture energy. An annealing process applied to PLA/PCL/LTI further strengthens the microstructure, resulting in effective improvement of the fracture energy.     

Friction and wear behavior of ultra-high molecular weight polyethylene as a function of polymer crystallinity

In this study the friction, wear and surface mechanical behavior of medical-grade ultra-high molecular weight polyethylene (UHMWPE) (GUR 1050 resin) were evaluated as a function of polymer crystallinity. Crystallinity was controlled by heating UHMWPE to a temperature above its melting point and varying the hold time and cooling rates. The degree of crystallinity of the samples was evaluated using differential scanning calorimetry (DSC). A higher degree of crystallinity in the UHMWPE resulted in lower friction force and an increase in scratch resistance at the micro- and nanoscales. On the nanoscale, the lamellar structure appeared to affect the observed wear resistance. Reciprocating-wear tests performed using a microtribometer showed that an increase in crystallinity also resulted in lower wear depth and width. Nanoindentation experiments also showed an increase in hardness values with an increase in sample crystallinity.     

聚醚醚酮/牙源性双相生物陶瓷复合材料的制备及力学性能

背景：牙齿的物理性质和化学组成与人体骨组织极为相似,且无机成分所占比例较大,因此可以考虑将牙齿作为一个潜在的自体或同种异体骨缺损修复材料。 目的：制备聚醚醚酮/牙源性双相生物陶瓷复合材料,并测试其机械性能。 方法：收集临床上废弃的人离体牙,经初步煅烧去除有机成分,将其浸泡于磷酸氢二铵溶液24 h后再次煅烧,制备成以羟基磷灰石和β-磷酸三钙为主要成分的双相陶瓷,粉碎后过200目筛,采用有机泡沫浸渍法制备出聚醚醚酮/牙源性双相生物陶瓷,行物相分析、扫描电镜、元素分析、孔隙率、抗压强度、黏结强度检测。 结果与结论：聚醚醚酮/牙源性双相生物陶瓷为多孔网状结构,且孔间相互连通,孔径100-800 µm,孔隙率为73.65%,抗压强度为(165.260±11.703) N,黏结强度为(14.63±6.21) MPa,陶瓷中P元素含量占19.8%、Ca元素含量占40.5%,主要物相为β-磷酸三钙、羟基磷灰石。结果说明制备的聚醚醚酮/牙源性双相生物陶瓷具有良好的力学性能。  中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

In vitro change in mechanical strength of beta-tricalcium phosphate/copolymerized poly-L-lactide composites and their application for guided bone regeneration

The bone regenerative properties of calcium phosphate cements (CPCs) may be improved by the addition of growth factors, such as recombinant human transforming growth factor-beta1 (rhTGF-beta1). Previously, we showed that rhTGF-beta1 in CPC stimulated the differentiation of preosteoblastic cells from adult rat long bones. The intermixing of rhTGF-beta1 in CPC, which was subsequently applied to rat calvarial defects, enhanced bone growth around the cement and increased the degradation of the cement. However, it is unknown whether the addition of rhTGF-beta1 changes the material properties of CPC and what the characteristics of the release of rhTGF-beta1 from CPC are. Therefore, we determined in this study the release of rhTGF-beta1, in vitro, from the cement pellets as implanted in the rat calvariae. The possible intervening effects of rhTGF-beta1 intermixing on the clinical compliance of CPC were studied through an assessment of its compressive strength and setting time, as well as its crystallinity, calcium-to-phosphorus ratio, porosity, and microscopic structure. We prepared CPC by mixing calcium phosphate powder (58% alpha-tricalcium phosphate, 25% anhydrous dicalcium phosphate, 8.5% calcium carbonate, and 8.5% hydroxyapatite) with a liquid (3 g/mL). The liquid for standard CPC consisted of water with 4% disodium hydrogen phosphate, whereas the liquid for modified CPC was mixed with an equal amount of 4 mM hydrochloride with 0.2% bovine serum albumin. The hydrochloride liquid contained rhTGF-beta1 in different concentrations for the release experiments. Most of the rhTGF-beta1 incorporated in the cement pellets was released within the first 48 h. For all concentrations of intermixed rhTGF-beta1 (100 ng to 2.5 mg/g of CPC), approximately 0.5% was released in the first 4 h, increasing to 1.0% after 48 h. Further release was only about 0.1% from 2 days to 8 weeks. CPC modification slightly increased the initial setting time at 20 degrees C from 2.6 to 5 min but had no effect on the final setting time of CPC at 20 degrees C or the initial and final setting times at 37 degrees C. The compressive strength was increased from 18 MPa in the standard CPC to 28 MPa in the modified CPC only 4 h after mixing. The compressive strength diminished in the modified CPC between 24 h and 8 weeks from 55 to 25 MPa. No other significant change was found with the CPC modification for rhTGF-beta1. X-ray diffraction revealed that standard and modified CPCs changed similarly from the original components, alpha-tricalcium phosphate and anhydrous dicalcium phosphate, into an apatite cement. The calcium-to-phosphorus ratio, as determined with an electron microprobe, did not differ for standard CPC and modified CPC. Standard and modified CPCs became dense and homogeneous structures after 24 h, but the modified CPC contained more crystal plaques than the standard CPC, as observed with scanning electron microscopy (SEM). SEM and back- scattered electron images revealed that after 8 weeks the cements showed equally and uniformly dense structures with microscopic pores (<1 microm). Both CPCs showed fewer crystal plaques at 8 weeks than at 24 h. This study shows that CPC is not severely changed by its modification for rhTGF-beta1. The prolonged setting time of modified cement may affect the clinical handling but is still within acceptable limits. The compressive strength for both standard and modified cements was within the range of thin trabecular bone; therefore, both CPCs can withstand equal mechanical loading. The faster diminishing compressive strength of modified cement from 24 h to 8 weeks likely results in early breakdown and so might be favorable for bone regeneration. Together with the beneficial effects on bone regeneration from the addition of rhTGF-beta1 to CPC, as shown in our previous studies, we conclude that the envisaged applications for CPC in bone defects are upgraded by the intermixing of rhTGF-beta1. Therefore, the combination of CPC and rhTGF-beta1 forms a promising synthetic bone graft.     

The roles of matrix polymer crystallinity and hydroxyapatite nanoparticles in modulating material properties of photo-crosslinked composites and bone marrow stromal cell responses

Two poly(?-caprolactone fumarate)s (PCLFs) with distinct physical properties have been employed to prepare nanocomposites with hydroxyapatite (HA) nanoparticles via photo-crosslinking. The two PCLFs are PCLF530 and PCLF2000, named after their precursor PCL diol with molecular weight of 530 and 2000 g mol^?1, respectively. Crosslinked PCLF530 is amorphous while crosslinked PCLF2000 is semi-crystalline with a melting temperature (T_m) of ～40 °C and a crystallinity of 40%. Consequently, the rheological and mechanical properties of crosslinked PCLF2000 are significantly greater than those of crosslinked PCLF530. Structural characterizations and physical properties of both series of crosslinked PCLF/HA nanocomposites with HA compositions of 0%, 5%, 10%, 20%, and 30% have been investigated. By adding HA nanoparticles, crosslinked PCLF530/HA nanocomposites demonstrate enhanced rheological and mechanical properties while the enhancement in compressive modulus is less prominent in crosslinked PCLF2000/HA nanocomposites. In vitro cell attachment and proliferation have been performed using rat bone marrow stromal cells (BMSCs) and correlated with the material properties. Cell attachment and proliferation on crosslinked PCLF530/HA nanocomposite disks have been enhanced strongly with increasing the HA composition. However, surface morphology and surface chemistry such as composition, hydrophilicity, and the capability of adsorbing protein cannot be used to interpret the cell responses on different samples. Instead, the role of surface stiffness in regulating cell responses can be supported by the correlation between the change in compressive modulus and BMSC proliferation on these two series of crosslinked PCLFs and PCLF/HA nanocomposites.     

大鼠胫骨骨折固定术后同侧股骨骨密度和生物力学性能的变化

目的探讨胫骨骨折后大鼠股骨骨密度及股骨生物力学性能变化及其与胫骨骨折愈合状况的关系。方法将40只3月龄雌性SD大鼠随机分为2组:手术组和对照组,每组20只。手术组实行右侧胫骨中段骨折内固定术。手术前和实行手术后第2、4、6、8、10、12周测量右侧股骨骨密度,第6周和第12周分别处死10只手术组和10只对照组大鼠,进行右侧胫骨和股骨生物力学性能的测量。结果术后6周,胫骨骨折的放射学愈合率为50%,机械愈合率为70%;术后12周胫骨骨折的放射学和机械愈合率均为100%。手术组股骨骨密度与对照组相比,术后2、4、6、8周降低(P<0.05),术后10、12周时与对照组差异无统计学意义。术后6周右侧胫骨和股骨的生物力学性能明显低于术后12周(P<0.05)。相关分析显示胫骨愈合情况与力学性能高度相关(P<0.01),胫骨力学性能与股骨骨密度和股骨力学性能高度相关(P<0.001)。结论胫骨骨折早期同侧股骨骨密度及生物力学性能下降,发生了废用性骨质疏松;但晚期随胫骨骨折愈合,股骨的骨密度和生物力学性能恢复正常。     

自体骨髓移植、体外冲击波以及石膏固定治疗胫骨疲劳骨折的比较

背景：疲劳骨折是部队训练常见伤,目前多以保守治疗为主,愈合时间长,功能恢复差,尚无明确的治疗方案。 目的：比较体外冲击波、自体骨髓移植以及石膏固定治疗3种方法对疲劳骨折愈合的促进作用。 方法：将临床确诊为疲劳骨折Ⅱ型的30例男性士兵,随机分为3组：①体外冲击波组：在CT定位下以疲劳骨折断裂带中心点为冲击点,单次治疗。②自体骨髓移植组：取髂前上棘下部或髂后上棘骨板较厚的部位骨髓3~5 mL注入疲劳骨折断端,单次治疗。③石膏固定组：采用休息,固定,口服活血化淤药物的方法治疗。3组分别于治疗后第2,4,6,8周依照X线影像学及功能恢复标准判定骨折愈合情况。 结果与结论：根据X射线结果,体外冲击波组与自体骨髓移植组在治疗后第8周时骨折愈合效果差异无显著性意义,但二者均优于石膏固定组(P < 0.05)。功能恢复观察结果显示,体外冲击波组优于自体骨髓移植组,自体骨髓移植组优于石膏固定组。提示体外冲击波治疗是一种促进疲劳骨折愈合的有效方法。 关键词：冲击波;疲劳骨折;愈合;骨髓移植;固定;治疗 doi:10.3969/j.issn.1673-8225.2012.09.042     

Characterization of the mechanical and ultrastructural properties of heat-treated cortical bone for use as a bone substitute.

Heat-treated bovine cortical bone has been proposed as an alternative to bone grafts and synthetic bone substitutes because it may combine the advantages of allografts (high stiffness and strength) and synthetic materials (abundant supply, reduced risk of rejection and disease transfer). Its mechanical properties and ultrastructure, however, are not well characterized. To address this, we compared the compressive (n = 20, bovine bone) and tensile (n = 26, bovine bone) mechanical properties and the ultrastructure (n = 12, human bone) of intact versus 350 degrees C heat-treated cortical bone. The 350 degrees C heat-treated bone had a mean +/- SD elastic modulus similar to the intact bone for both compression (16.3 +/- 2.2 GPa, pooled; p = 0.68) and tension (16.3 +/- 3.7 GPa, pooled; p = 0.95). It also maintained 63% of the intact strength in compression but only 9% in tension (p < 0.001). Infrared scans and X-ray diffraction patterns showed no differences between the 350 degrees C heat-treated and intact bone but large differences between ashed (700 degrees C) and intact bone. Similarly, heat-treated bone previously has been shown to be biocompatible and osteoconductive. We conclude, therefore, that 350 degrees C heat-treated cortical bone may be an excellent load-bearing bone substitute provided that it is loaded in compression only in vivo and is shown by future work to have acceptable fatigue properties.     

Preparation and characterization of biodegradable chitosan/hydroxyapatite nanocomposite rods via in situ hybridization: a potential material as internal fixation of bone fracture

A transparent and slight yellow chitosan (CS)/hydroxyapatite (HA) nanocomposite with high performed, potential application as internal fixation of bone fracture was prepared by a novel and simple in situ hybridization. The method solves the problem of the nano-sized particle aggregation in polymer matrix. XRD, TEM and SEM were used to determine component and morphology of the composite. Results indicated that nano-HA particles were dispersed well in CS matrix, which can also be proved by the transparent appearance of composite rod, and that the structure of composite is assembled by CS molecule in the order of layer-by-layer. The mechanical properties of the composite were evaluated by using bending strength and modulus, and compared with some other bone replacement materials such as PMMA and bone cement. The initial mechanical properties of bending strength and modulus of composite are 86 MPa and 3.4 GPa, respectively, which is double or triple times stronger than that of PMMA and bone cement. It was found that the bending strength and modulus of CS/HA with ratio of 100/5 (wt/wt) is slightly higher than that of pure CS rod. The addition of HA can also reduce the ratio of water absorption of composite, which postponed the retention of mechanical properties of CS/HA composite under moisture condition. The phenomenon can be predicted with the fit exponential function according the data measured.     

Mechanical properties and biocompatibility of melt processed,self-reinforced ultrahigh molecular weight polyethylene

The low efficiency of fabrication of ultrahigh molecular weight polyethylene (UHMWPE)-based artificial knee joint implants is a bottleneck problem because of its extremely high melt viscosity. We prepared melt processable UHMWPE (MP-UHMWPE) by addition of 9.8 wt% ultralow molecular weight polyethylene (ULMWPE) as a flow accelerator. More importantly, an intense shear flow was applied during injection molding of MP-UHMWPE, which on one hand, promoted the self-diffusion of UHMWPE chains, thus effectively reducing the structural defects; on the other hand, increased the overall crystallinity and induced the formation of self-reinforcing superstructure, i.e., interlocked shish-kebabs and oriented lamellae. Aside from the good biocompatibility, and the superior fatigue and wear resistance to the compression-molded UHMWPE, the injection-molded MP-UHMWPE exhibits a noteworthy enhancement in tensile properties and impact strength, where the yield strength increases to 46.3 ± 4.4 MPa with an increment of 128.0%, the ultimate tensile strength and Young's modulus rise remarkably up to 65.5 ± 5.0 MPa and 1248.7 ± 45.3 MPa, respectively, and the impact strength reaches 90.6 kJ/m². These results suggested such melt processed and self-reinforced UHMWPE parts hold a great application promise for use of knee joint implants, particularly for younger and more active patients. Our work sets up a new method to fabricate high-performance UHMWPE implants by tailoring the superstructure during thermoplastic processing.     

Phase morphology, physical properties, and biodegradation behavior of novel PLA/PHBHHx blends

In this study, two biodegradable polyesters [i.e., polylactic acid (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)] with complementarity in terms of mechanical performance have been combined, and a series of blends with a broad range of compositions has been prepared by thermal compounding. The evolution of phase morphologies with the variation of compositions has been characterized by using Fourier transform infrared spectroscopic imaging together with scanning electron microscope analyses. Thermal, mechanical, and biodegradation properties of the PLA/PHBHHx blends were systematically investigated. Mechanical properties were further analyzed by using theoretical models and correlated with the results of the morphology/structure and compatibility of the blends. Results indicate that PLA/PHBHHx blends are immiscible but can be compatible to some extent at certain compositions (e.g., PLA/PHBHHx (w/w) = 80/20 and 20/80). The physical properties of the blend could be fine tuned by adjusting the blend composition.     

Deformation, yielding, fracture and fatigue behavior of conventional and highly cross-linked ultra high molecular weight polyethylene

Medical grade ultra high molecular weight polyethylene (UHMWPE) has been used as the bearing surface of total joint replacements for over four decades. These polymeric devices are susceptible to accumulated cyclic damage in vivo. Wear debris formation that ultimately leads to a need for revision surgery is linked to the plasticity, fatigue and fracture mechanisms of UHMWPE. This paper examines the deformation, yielding, fracture and fatigue behavior of conventional and highly cross-linked medical grade UHMWPE. Such properties play an important role in determining the long-term success of orthopedic devices. The mechanical properties discussed include the deformation behavior of UHMWPE, the yielding associated with quasi-static tension and compression, fracture toughness, cyclic loading, and fatigue resistance.     

Physicochemical, mechanical, and biological properties of bone cements prepared with functionalized methacrylates

Bone cements prepared with methyl methacrylate (MMA) as a base monomer and either methacrylic acid (MAA) or diethyl amino ethyl methacrylate (DEAEMA) as comonomers were characterized in terms of curing behavior, mechanical properties, and their in vitro biocompatibility.The curing time and setting temperature were found to be composition dependent while the residual monomer was not greatly affected by the presence of either acidic or alkaline comonomers in the bone cements. For samples with MAA comonomer, a faster curing time and higher setting temperature were observed when compared to the cement with DEAEMA comonomer.In terms of mechanical properties, the highest compressive strength was exhibited by formulations containing MAA, while the highest impact strength was shown by the formulations prepared with DEAEMA. There were no differences observed between the two formulations for tensile, shear, and bending strength values. Similarly, fatigue crack propagation studies did not reveal differences with the addition of either DEAEMA or MAA.No differences were observed in the initial number of attached primary rat femur osteoblasts on the different bone cements and positive controls. However, after 48 h there was a reduced proliferation in the cells grown on bone cements containing MAA.     

Effect of chondroitin sulphate on material properties and bone remodelling around hydroxyapatite/collagen composites

Chondroitin sulphate (CS) has an anti-inflammatory effect and increases the regeneration ability of injured bone. The goal of this study was to characterize the material properties and osteoconductive potency of calcium phosphate bone cements modified with CS. The early interface reaction of cancellous bone to a nanokristalline hydroxyapatite cement containing type I collagen (HA/Coll) without and with CS (HA/Coll/CS) in a rat tibia model was evaluated. Cylindrical implants were inserted press-fit into defect of the tibial head. Six specimens per group were analyzed at 2, 4, 7, 14, and 28 days. HA/Coll/CS composite cylinders showed a 15% increase in compressive strength and by investigations with powder X-ray diffraction more nontransformed cement precursor was found. The microstructures of both types of implants were similar. A significantly higher average number of TRAP positive osteoclasts and ED1 positive mononuclear cells were observed in the interface around HA/Coll/CS implants on day 4 and 7 (p < 0.05). At 28 days the direct bone contact and the percentage of newly formed bone were significantly higher around HA/Coll/CS implants (p < 0.05). The addition of CS appears to enhance bone remodelling and new bone formation around HA/Coll composites in the early stages of bone healing. Possible mechanisms are discussed.     

Bioactivity and mechanical properties of cellulose/carbonate hydroxyapatite composites prepared in situ through mechanochemical reaction

Organic-inorganic composites, prepared from bone-bonding bioactive ceramics and organic polymers, are useful for novel bone substitutes having mechanical properties analogous to natural bone. We synthesized composites from cellulose and carbonate hydroxyapatite (CHAp) in situ through mechanochemical reaction. They contained B-type CHAp analogous to bone apatite. They showed a bending strengths of 10-13 MPa and Young's modulus of 1.5-2.2 GPa. We predicted their microstructure by comparing the measured density with the theoretical one. Cellulose was assumed to be distributed in the pore of CHAp at low cellulose content, and in grain boundaries of CHAp at high cellulose content. The composites formed calcium phosphate on their surfaces in simulated body fluid, meaning that they have a potential to be bioactive.