Time-dependent mechanical properties of HA/TCP particles in relation to morsellized bone grafts for use in impaction grafting

In reconstructive surgery human bone defects are sometimes filled with the use of the impaction bone grafting technique. Currently different types of biomaterial particles are being developed as bone-substitute materials. Before these biomaterials can be applied their mechanical and biological behavior should be characterized. In this study the time-dependent mechanical behavior of biomaterial particles with different tri-calcium-phosphate/hydroxy-apatite (TCP:HA) ratios, particle sizes, and porosities is determined and compared to the behavior of human bone grafts, the latter being the standard material currently used to augment bone defects. The mechanical properties were assessed with the use of dynamic confined compression creep tests with a loading and unloading phase. Different graft material groups were tested, consisting of 100% human bone grafts, 100% biomaterial particles, and 50:50 weight mixtures of human grafts and biomaterial particles. No damage to the particles was observed by the impaction in the test chamber or by the dynamic load. Relative to the human graft material, the biomaterial particles hardly deformed under loading, were much stiffer, and showed almost no viscoelastic behavior. The mixtures showed intermediate results. Particle size and porosity influenced the behavior of the biomaterial particles. TCP:HA ratio did not have a great effect. The conclusion is that the application of these particles should be done with great care, as their mechanical behavior is drastically different than that of the human graft material. Mixing it with human bone grafts gave the material some biphasic, viscoelastic behavior that may be important for its biological response.     

脊柱侧弯矫正融合中新型植骨材料的特点

背景：随着外科技术的进步,尤其脊柱侧凸矫形手术的推广,对植骨材料提出了更高的要求,要求植骨材料既有成骨活性,又要在结构和机械性能上显示与自然骨类似的特性,同时还要符合生物力学要求。 目的：综述脊柱侧弯矫正融合中新型植骨材料的应用进展。 方法：应用计算机检索2009至2012年 Elsevier全文数据库相关文章,检索词“nano-hydroxyapatite,hydroxyapatite,scoliosis”,并限定文章语言种类为English。同时计算机检索同方、知网中国期刊全文数据库相关文章,检索词为“脊柱侧凸,植骨材料,纳米人工骨,骨形态发生蛋白2,人工骨”,并限定文章语言种类为中文。最终纳入符合标准的文献27篇。 结果与结论：纳米人工骨具有良好的生物相容性及骨传导性,模仿天然骨的成分及结构特征,结构上与自然骨结晶部分基本一致,可为细胞提供与天然骨相类似的微环境。在脊柱外科中骨性融合是脊柱侧凸手术治疗成功的标志之一,植骨材料的来源一直困扰着脊柱外科医生。寻找一种能形成骨性融合又具有成骨活性的材料是目前国内外研究的热点,纳米人工骨在脊柱外科的应用展现了广阔的前景。     

The mechanically stable steam sterilization of bone grafts

Bone allografts are the standard material used in augmentative bone surgery. However, steam-sterilized bone has a low mechanical stability and limited ossification based on low strain-adapted bone remodelling. Here we describe a new technique which allows the bone to be autoclaved without losing its mechanical stability and osteoconductivity. The compression strength of the new material was compared with steam-sterilized and fresh bone based on mechanical testing using bone cylinders (n=30/group). Allogeneic new material and fresh bone were press-fit implanted into rabbit patellar grooves and examined under fluorescent light and conventional microscopy. Initial healing was assessed after 30 d (n=5/group). Osseous integration and remodelling was studied after 100 d (n=12/group). Steam-sterilized bone showed no mechanical stability, whereas the new material was stiff and had compression curves similar to fresh bone; both groups showed equal degrees of direct ossification after 30 d, advanced bony ingrowth and remodelling after 100 d, and similar ingrowth depths on histomorphometric analysis. The new method preserved the stiffness and osteoconductivity of bone after steam sterilization, and microstructure, mineralization, and composition were conserved. This technique could be useful for bone banking in Third World countries.     

Oxidized cellulose mesh. II. Using hydroxy-apatite bone grafting material in the treatment of infrabony defects

Biodegradable oxidized cellulose mesh has been used in conjunction with hydroxyapatite synthetic bone grafting material to enhance retention of the graft material and to improve post-operative healing of infrabony defects treated surgically. Initially a good healing response was achieved, but there was a tendency for the sites to relapse in the 8 wk following surgery. A tendency to relapse in reconstructive dentistry is well known, and the possible factors which limit the amount of regeneration of tissues are considered. Although there appear to be limitations on the regeneration possible in tissues, the factors that determine these limitations are poorly understood at present.     

Experimental procedure for the evaluation of the mechanical properties of the bone surrounding dental implants.

The mechanical stability of the fixture in bone is one of the most important factors for the long-term reliability of dental implants. This paper focuses on an experimental procedure to evaluate the mechanical properties of the bone surrounding dental implants. The procedure is based on a surgical animal model followed by mechanical tests. The experimental mechanical testing has been used for preliminary investigations on the role played by different parameters such as the healing time and the surgical technique (standard or with regenerative material). The procedure has been evaluated in some preliminary tests on a few specimens. Microradiographic analyses have been performed on the bone surrounding the implants in order to give an interpretation of the bone properties on the basis of the bone morphology and to distinguish the newly formed bone from the pre-existing bone. The preliminary results relevant to 10 threaded titanium implants are presented and discussed. Our findings show that the mechanical properties of the bone surrounding the implant improve with the increase in the healing time from 24 to 45 days. The ultimate loads recorded during mechanical tests arise from 395 N to 2665 N in case of coronal defects filled with bone regenerative and from 2200 N to 5700 N in case of standard technique.     

Impaction allografting--the effect of impaction force and alternative compaction methods on the mechanical characteristics of the graft

Revision total hip replacement with impaction allografting has an attractive potential for restoring bone stock, however, fractures and implant migration remain problematic. Postoperative graft deformation is believed to contribute to migration. Under compressive loading, the fluid in the graft takes up the load initially through fluid pressure that dissipates over time. Given the short duration of an impaction, we proposed two novel graft compaction techniques that allow more time for fluid flow: holding a compression force constant for 90 s (creep technique), and cycles of compressing the graft to a given force and then holding the displacement constant (cyclic relaxation technique). This study examined the effect of the impaction force on the density and mechanical characteristics of the graft, and explored the potential benefit of the proposed alternative compaction techniques. Increasing the impaction force from "low" to "high" increased graft density by 41%, and this translated to stiffness and shear strength increases of 93 and 164%, respectively. The creep technique improved the stiffness and shear strength by 14 and 16%, respectively, when compared with impaction, while the cyclic relaxation technique did not improve the mechanical properties. Although the creep technique could potentially provide a lower risk of intraoperative fracture over the use of larger impaction forces, any clinical benefit of the creep technique warrants further investigation. Our results point to the importance of maximizing impaction forces in impaction allografting surgery.     

骨髓富集骨移植材料在青少年特发性脊柱侧弯矫治中的应用

目的 比较骨髓富集骨移植材料和同种异体骨作为骨移植材料用于青少年特发性脊柱侧弯(AIS)矫治中的临床疗效。方法 自2014年7月至2016年9月,前瞻性选取31例青少年特发性脊柱侧弯LenkeⅠ-Ⅲ患者,按随机数表法将患者随机分为对照组(14例)与观察组(17例),其中对照组采用同种异体骨作为植骨融合材料,观察组采用骨髓富集骨移植材料作为植骨融合材料。术后随访24个月,对两组患者的手术时间、术中出血量、住院时间、主弯矫正率、矫正丢失、融合率、VAS评分、ODI评分、SRS-30评分、并发症发生情况进行比较。结果 两组手术时间、术中出血量、住院时间、矫正率、矫正丢失比较差异无统计学意义(P0.05)。所有患者末次随访时VAS评分、ODI评分、SRS-30评分均优于术前,但两组间术前与末次随访差异均无统计学意义(P0.05)。术后6个月观察组融合率高于对照组,末次随访时观察组脊柱融合Lenke分级情况略优于对照组。观察组出现术后伤口愈合不良1例,无其他并发症。结论 骨髓富集骨移植材料是一种安全、有效、易构建的植骨材料,用于脊柱融合可获得优于同种异体骨的融合效果。     

生物降解材料在临床骨科中的应用

生物降解材料从 6 0年代开始应用于临床 ,由于其可在体内降解 ,无需二次手术取出 ,故被作为一种内固定材料广泛应用。近年来 ,随着材料科学和加工工艺的改进 ,可降解材料制成的接骨板在力学特性上有了显著的提高 ,在临床骨科中正被逐渐应用于关节内骨折和非承载骨骨折的固定 ,但仍不能单独用于四肢长管状骨骨折的固定。目前 ,可吸收材料制品在临床应用中面临的最大的问题是非感染性异物反应的发生。本综述主要介绍了生物降解材料近几年来在生物特性和临床应用上最新的进展 ,并展望了其今后在临床骨科中的应用前景。     

Art of replacing craniofacial bone defects

In the history of medicine, many surgeons have been tried to reconstruct lost tissue and correct deformity, attempts to use implant materials have probably paralleled those involving autogenous tissue. Recently there has been an acceleration in the understanding of the requirements and potentials of implant materials caused by collaboration between material scientists, biomaterials engineers, clinicians, and clinical investigators. Alloplastic materials have become an essential part of reconstructing the function and contour of the craniofacial skeleton. Bone is a specialized form of connective tissue, which provides support, and protects vital and delicate organs. Bone is embryologically derived from mesenchymal tissue through membranous and endochondral ossification. In the clinical field, the need for bone graft has been increased due to trauma, tumor, craniosynostosis, and pure esthetic bone surgery. Various types of bone grafts have been used to repair craniofacial bone defects over many years, but the autogenous graft has many disadvantages, such as, limited donor sites, donor morbidity, pain, growth deformity and resorption. Many surgeons working in a number of centers around the world have created substitutes and simpler methods for bone replacement. As the alloplatic bone substitute has been advanced, many synthetic substitutes are replaced by bone in vivo over time. The ideal material should be cost effective, non-toxic, non-antigenic, non-carcinogenic, and inert in the body fluids, be easily shaped at the operating table, and maintain its desired form and consistency in situ. This article reviews several of the more commonly used materials for craniofacial reconstruction and summarizes their mechanical properties and clinical aspects.     

The application of human bone marrow stromal cells and poly(dl-lactic acid) as a biological bone graft extender in impaction bone grafting

Concerns over disease transmission, high costs and limited supply have led to interest in synthetic grafts in the field of impaction bone grafting (IBG). Poly(DL-lactic acid) (PLA) grafts are attractive alternatives due to their biocompatibility, established safety and versatile manufacturing process. This study examined the potential of PLA scaffolds augmented with human bone marrow stromal cells (HBMSCs) in IBG. In vitro and in vivo studies were performed on impacted morsellised PLA seeded with HBMSC and compared to PLA alone. In vitro samples were incubated under osteogenic conditions and in vivo samples were implanted subcutaneously into severely compromised immunodeficient mice, for 4 weeks. Biochemical, histological, mechanical and 3D micro-computed tomography analyses were performed. HBMSC viability, biochemical activity and histological evidence of osteogenic cellular differentiation, post-impaction were observed in vitro and in vivo in PLA/HBMSC samples compared to impacted PLA alone. In vitro PLA/HBMSC samples demonstrated evidence of mechanical enhancement over PLA alone. In vivo studies showed a significant increase in new bone and blood vessel formation in the PLA/HBMSC constructs compared to PLA alone. With alternatives to allograft being sought, these studies have demonstrated PLA/HBMSC living composites, to be a potential prospect as a biological bone graft extender for future use in the field of IBG.     

In vivo evaluation of calcium polyphosphate for bone regeneration

Current problems associated with bone allografts include risk of disease transmission, limited availability, and cost. Synthetic scaffolds have been proposed as substitute graft materials to address these issues. Calcium polyphosphate is a novel synthetic scaffold material that has shown good mechanical properties and biocompatibility. Here, we evaluated calcium polyphosphate in terms of its ability to support cell proliferation and differentiation in?vivo. Calcium polyphosphate, morsellized cancellous bone, and hydroxyapatite/tricalcium phosphate particles were seeded with marrow stromal cells and implanted subcutaneously in the back of NOD/Scid mice. At 7, 14, and 28 days the samples were harvested and the proliferation characteristics and gene expression were analyzed. All tested graft materials had similar proliferation characteristics and gene expression. The subcutaneous environment had a stronger impact on the proliferation and differentiation of the cells than the scaffold material itself. However, it was shown that calcium polyphosphate is superior to hydroxyapatite/tricalcium phosphate and bone in its ability to support cell survival in?vivo. The study confirmed that calcium polyphosphate has potential for replacing morsellized cancellous bone as a graft material for bone regeneration.     

Bioactive glass as bone-graft substitute for posterior spinal fusion in rabbit

Bioactive glass S53P4 and autogenous bone were studied as bone graft materials for spinal fusion in a rabbit model. Sixteen rabbits underwent surgery by a dorsal approach. A bioactive glass, a combination of bioactive glass and autogenous bone (70/30 vol%), and autogenous bone were implanted at two thoracolumbar vertebraes for 4 and 12 weeks. The volume, consolidation to vertebrae, and fusion of the graft material were evaluated with plain-film radiology, computed tomography (CT) and bone-mineral density measurements, and compared with histomorphometrical measurements. Radiological consolidation by CT of bone graft to underlying vertebrae at 12 weeks was observable in all groups. This was histologically confirmed as bone was growing from the vertebrae into the graft material. Radiologic fusion of vertebraes was, at 12 weeks, observable in all groups in 50--75% of the cases. The radiologic fusion seen at the CT scans could, however, not be confirmed by histology in any of the three groups. Significant differences for graft material and observation period with the use of bone-mineral density measurements (Hounsfield units) were also observable, with the highest measured values for the bioactive glass group and the lowest for the autogenous bone group. The results indicate that bioactive glass have potential as bone-graft material in spinal fusion. The reliability of radiologic evaluation methods in spinal surgery using bone substitutes is also questioned and discussed.     

The role of rhFGF-2 soaked polymer membrane for enhancement of guided bone regeneration

Abstract

The purposes of this study are to confirm the role of Fibroblast Growth Factor-2 (FGF-2) in bone regeneration by adding various concentrations of FGF-2 to the collagen membrane and applying it to the Biphasic Calcium Phosphate (BCP) bone graft site for guided bone regeneration, to explore the potential of collagen membrane as FGF-2 carrier, and to determine the optimum FGF concentration for enhancement of bone regeneration. Four bone defects of 8 mm in diameter were created in 18 New Zealand rabbit calvaria. After BCP bone graft, graft material was covered with collagen membranes adding various concentration of FGF-2. The concentration of FGF-2 was set at 1.0, 0.5, 0.1 mg/ml, and same amount of saline was used in the control group. To confirm the bone regeneration over time, six New Zealand rabbits were sacrificed each at 2, 4, and 12 weeks, and the amounts of new bone and residual bone graft material were analyzed by histologic and histomorphometric analysis. Qualitative analyses are also conducted through immunohistochemistry, Tetrate-resistant acid phosphatase (TRAP) stain and Russell-Movat pentachrome stain. As the healing period increased, the formation of new bone increased and the amount of residual graft material decreased in all experimental groups. Immunohistochemistry, TRAP staining and pentachrome staining further showed that the addition of FGF-2 promoted bone regeneration in all experimental groups. It was also confirmed that polymer collagen membrane can be used as a useful carrier of FGF-2 when enhanced early stage of new bone formation is required.     

Towards an ideal polyurethane graft for hemodialysis

Numerous studies have been reported in the field of vascular graft in recent years. The main interest in these studies has focused on producing either a small diameter arterial graft or prosthesis for veins. Polyurethane polymers are emerging because of their superior mechanical, chemically stable and biocompatible nature. Above all, the prominent blood compatibility and elasticity has attracted many investigators to investigate the material for vascular grafts with small diameter. Although several difficulties still remain to be solved, important factors such as anti-thrombogenicity of materials, compliance in long term, porosity, surface microstructure, and permeability are discussed on the basis of many experimental results. In addition, our basic as well as clinical examination of polyurethane graft as a blood access for hemodialysis are presented along with future prospects and difficulties to overcome.     

An anatomical study of the vascularisation of the first dorsal interosseous space in the hand,and a description of a bony pedicle graft arising from the second metacarpal bone (23.11.90)

We have used this vascularised bony graft mainly for recurrent pseudarthrosis of the scaphoid bone. An account of our series will be the subject of a future publication.The use of the vascularised pedicle graft at the expense of the head of the second metacarpal has seemed to us to give encouraging results. The technique, although meticulous, is simple to carry out. The good vascularisation of the graft is assured through the large amount of fatty and connective tissue around the base of the pedicle. The use of vascularised bone in hand surgery has been shown to be useful. This graft, easy to raise, has through the length of its pedicle, a limited displacement. Other donor sites do not have the advantages described here.     

Augmentation of osteoinduction with a biodegradable poly(propylene glycol-co-fumaric acid) bone graft extender. A histologic and histomorphometric study in rats

We investigated the feasibility of enhancing the regeneration of skeletal tissues by augmenting bone grafts with a composite biodegradable bone graft extender material based on the polymer poly(propylene fumarate), PPF. The material was mixed with autograft and allograft and placed directly into a cylindrical metaphyseal defect made in the rat tibia. These formulations were compared to defects without any graft material, autografts, allografts and PPF alone. Nine animals were included in each group. Animals were sacrificed at 1 and 4 weeks postoperatively. Implantation sites were then evaluated using histologic and histomorphometric methods. Results of this study showed that defects did not heal in sham operated animals. In the experimental groups, there was early new woven bone formation in the autograft group with near complete healing of the defect at four weeks. When PPF was used alone, gradual ingrowth of new bone was seen. Mixing of the PPF bone graft extender with either allograft or autograft material resulted in enhancement of new bone formation with both allo- and autograft. However, significantly more new bone formation than in the autograft group was only seen when the PPF bone graft extender was mixed with fresh autograft. Histomorphometry corroborated these findings. Results of this study suggest that a PPF-based material may be used to increase the volume of smaller amounts of bone grafts supporting the concept of "bone graft extenders" by application of engineered biodegradable porous scaffolds.     

人重组骨形态发生蛋白-2在脊柱融合中的作用

脊柱融合是治疗脊柱结核、感染、畸形、椎间盘退行性病变脊柱疾患的有效手段,促进脊柱融合成骨率的方法之一就是使用自体骨移植,但其存在来源有限、取骨处疼痛等弊端,目前人重组骨形态发生蛋白-2(The role of recombinant human bone morphogenetic 2,rh BMP-2)负载于载体是一种理想的自体骨移植材料的替代物,广泛应用于脊柱融合术中,但近来发现了与其相关的一些副反应。本文就其在脊柱融合中的应用的安全性、有效性及相关的副反应进行综述。     

Achieving the ideal properties for vascular bypass grafts using a tissue engineered approach: a review

The multiple demands placed on small calibre cardiovascular bypass grafts have meant that a synthetic prosthesis with good long-term patency has not been developed. A tissue-engineered graft could fulfil the ideal characteristics present in an artery. However, the great disadvantage of such a conduit is the time necessary for maturation leading to unacceptable delays once the decision to intervene surgically has been made. This maturation process is essential to produce a graft which can withstand haemodynamic stress. Once implanted, the tissue-engineered graft can contract in response to immediate haemodynamic conditions and remodel in the long term. We review the latest tissue engineering approaches used to give the favourable properties of mechanical strength, arterial compliance, low thrombogenicity, long-term resistance towards biodegradation as well as technological advances which shorten the time required for production of an implantable graft.     

Strontium in the bone-implant interface

Total hip replacement surgery is being performed on an increasingly large part of the population and at increasingly younger age. Because we live and stay physically active longer, and since hip replacement surgery has become quite successful, the treatment is being offered to progressively more patients. Unfortunately, about 17% of hip replacement surgeries currently involve revisions. Consequently, the longevity of both the primary and revision implant is an issue and warrants further investigation. Implants undergoing early instability or even subsidence correlate with an increased risk of aseptic loosening, subsequently requiring revision. Thus, the goal is early fixation by osseointegration of the implant. For revision implants, this is an even greater challenge since an allograft is often needed during surgery to obtain immediate stability of the implant. Bone grafts are rapidly resorbed. Thus, instability of the prosthesis may develop before new bone formation is well established and can mechanically secure the prosthesis. Strontium is a dual action drug; being both bone anabolic and anti-catabolic. In the form of strontiumranelate, it is used in the treatment of osteoporosis. Strontium may potentially improve the early osseointegration and fixation of implants. This dissertation consists of three studies investigating the effect of strontium at the bone-implant interface. The questions were firstly, what is the optimal delivery method for strontium to the interface, and secondly, can strontium exercise its dual action at the interface? The studies were performed in a cementless, experimental gap model in canine. The effects of strontium were evaluated by histomorphometrical analysis of the osseointegration and mechanical push-out test of implant fixation. Different stereological methods were used for the histomorphometrical analysis of each study. The methods used were reviewed critically and found valid. Study I compared a 5% strontium-substituted hydroxyapatite (HA) coating with an HA coating after 4 weeks and 12 weeks observation time. We examined whether fixation of the implant was improved by the strontium substitution. It was found that fixation of the implant was not improved by the strontium substituted HA coating at any of the two time points. Study II compared a 5% strontium-doped HA bone graft extender with an HA bone graft extender. The bone graft extender was mixed with allograft and impacted around a titanium implant. The objective of this study was to determine whether strontium doping of the bone graft extender could protect the allograft from fast resorption and increase gap healing, leading to the improved fixation of the implant. We found that the strontium doping increased gap healing and protected the allograft, however, results of the mechanical test were inconclusive. The reason might have been that the increased gap healing had not yet reached the implant during the 4 weeks observation time, so ongrowth onto the implant was not improved. Study III investigated the effects of bioactive glass coating with a 0%, 10% or 50% strontium-substitution versus HA coating of grit-blasted titanium alloy implants. The goal was to determine whether fixation of the implant would be improved by the bioactive glass coating, and then further improved by the strontium-substitution of the coating in a dose-dependent manner. Unfortunately, the bioactive glass coating failed, presumably due to aluminum contamination originating from the grit-blasting powder. The HA coated implants were superior in all parameters of osseointegration and the mechanical fixation of the implants. These studies show the importance of performing further experimental investigation. Even when investigating a known agent for use in a new application. Strontium delivered as doping of an HA bone graft extender showed potential as a dual acting agent in the interface. However, delivery methods of strontium to the bone-implant interface clearly need further investigation.     

Nanophase bone substitute in vivo response to subcutaneous implantation

A collagen-apatite composite designed as a load-bearing bone substitute implant is used to characterize the relationship between implant morphology and in vivo behavior. This nanophase bone substitute (NBS) is studied morphologically using a nondestructive imaging technique and biologically using the rodent subcutaneous model. Porosity and pore interconnectivity are correlated with histological outcomes showing cellular invasion occurs with average pore sizes below 100 μm. Crosslinking with D-ribose is shown to affect cellular infiltration in a dose-response manner. These data suggest that collagen-apatite bone substitutes can support cellular infiltration with pore size significantly smaller than 100 μm, an encouraging result regarding development of the NBS into a platform of biomaterials with enhanced mechanical properties. The data also indicate that increasing crosslinking density decreases cellular infiltration of NBS. Thus, modulating mechanical properties of the material by altering crosslink density is likely to produce decreased biological response within the material.