Histological and biomechanical analysis of bone and interface reactions around hydroxyapatite-coated intramedullary implants of different stiffness: a pilot study on the goat

We hypothesized that reduced stem stiffness of orthopaedic implants contributes to a high risk of loosening, since interface stresses and relative motions may exceed a tolerable range. To study this hypothesis, three types of load-bearing implant with different stiffnesses were inserted into the tibia of the goat. Histological analysis was performed of bone repair after insertion of the implant, bone ingrowth, interface disruption and loosening. A finite element model of the configuration provided the quantitative range of interface stresses and relative motions for the present experiment. The implants were made out of stainless steel, hollow titanium and a thin titanium core covered with a polyacetal coating. The stiffness ratios of these implants were approximately 10:4:1, respectively. All implants were coated with a layer of hydroxyapatite (HA) in order to minimize the possible biological effects of the different implant materials. Irrespective of the type of implant, there was a repair phase that lasted 6-12 weeks. The stiff implants functioned well. Large areas of bone bonding to the HA layer were found after the repair phase at 12 weeks postoperatively. After 24 weeks, some signs of loosening were observed. More loosening occurred with the hollow titanium and polyacetal implants, mainly during the repair phase. Three hollow titanium and three polyacetal coated implants survived this period, and were killed after 24 weeks. The integrity of the HA layer at the bone-implant interface of the titanium implants was good. In the polyacetal implants, the repair reaction of the cortical bone was incomplete. Bone ingrowth into HA was largely lacking. In conclusion, we found significant differences in the repair and interface reactions around implants of different stiffness. Stiff implants showed favourable initial interface conditions for bone ingrowth. Intermediate and flexible implants provoked unfavourable interface conditions for initial bone ingrowth. The finite element study showed that the flexible stems produce larger micromotions and higher interface stresses at the bone-prosthesis interface than the stiff stems, indicating an explanation for the histological findings.     

Recording properties and biocompatibility of chronically implanted polymer-based intrafascicular electrodes

We implanted polymer-based longitudinal intrafascicular electrodes (polyLIFEs) in feline dorsal rootlets acutely and for periods of two to six months to evaluate their electrical properties and biocompatibility. A total of 38 implanted electrodes were analyzed. Some 25 of the 38 electrodes were implanted with an insulative flexible polymer cuff, which was required for recording of afferent activity in situ. Electrode impedances remained stable for the duration of the experiments. The distributions of axons were measured at three levels of the implanted rootlets: the implant level, 1-2 mm proximal to the implant with respect to the cell body, and 1-2 mm distal to the implant with respect to the cell body. Similar measurements were made in five samples of fascicles neighboring an implant and six samples of control tissue from animals in which no implants were placed. The polyLIFEs demonstrated a high degree of biocompatibility, as no adverse effects on axon size were observed in either the implanted fascicle or neighboring neural tissue. However, the insulative cuffs were found to be a source of compression, resulting in necrosis of the neural tissue.     

Cellular responses to chemical and morphologic aspects of biomaterial surfaces. I. A novel in vitro model system

The clinical success of any implant is directly dependent upon the cellular behavior in the immediate vicinity of the interface established between the host tissue and the biomaterial(s) used to fabricate the device. All biomaterials have morphologic, chemical, and electrical surface characteristics that influence the cellular response to the implant. Quantitative measurement of specific aspects of this local host response to different but well-characterized biomaterial surfaces provides a crucial link in the understanding of the overall phenomenon of implant biocompatibility. A system has been devised for in vitro examination of responses of cells to controlled but independent changes in both the chemistry and morphology of polystyrene (PS) tissue culture surfaces. Micromachined silicon wafers were used as templates to solvent-cast PS replicas [using 0, 1, or 2 wt % styrene (S) monomer additions] with either none, 0.5- or 5.0-microns-deep surface grooves arranged in a radial array. When all possible morphologies were combined with all possible polymers, nine model biomaterial surfaces (MBSs) were produced. The chemical characteristics of the MBSs were determined using electron spectroscopy for chemical analysis, secondary ion mass spectroscopy, and contact angle techniques and were found to be distinct. The types and amount of proteins that adsorb onto these surfaces from serum containing media were examined and found to consist of multiple molecular layers of relatively uniform composition. Self-contained tissue culture vessels formed from the MBSs were capable of supporting the growth of confluent cultures of rat calvarial cells. The model biomaterial system described here can be used to examine how simultaneous stimuli resulting from the chemical and morphological characteristics of a test material may influence biologic responses. Such multifactorial biocompatibility research is needed to properly document material-host interactions.     

Biocompatibility of fixation materials in the brain

Recent clinical reports documenting passive intracranial translocation of microplates and microscrews have prompted concerns regarding brain biocompatibility and neurotoxicity of fixation hardware used in craniofacial surgery. Although the effects of commercially pure titanium. Vitallium (cobalt-chromium-molybdenum), stainless steel, and various alloys have been well assessed in bone and soft tissues, there are no comprehensive studies of these materials in the brain. To investigate this, the biocompatibility of titanium, vitallium, and 316L stainless steel was evaluated in the rabbit brain and compared with silicone elastomer shunt tubing, a material that is used commonly as a neurosurgical implant material with well-established brain biocompatibility. Forty-eight juvenile New Zealand White rabbits were randomly assigned to one of three groups and underwent placement of either commercially pure titanium microscrews, vitallium microscrews, or 316L monofilament stainless steel wire into the parietal region. Silicone elastomer strips of similar size were implanted in the contralateral hemisphere of each rabbit. Animals were assessed daily for signs of neurotoxicity. Rabbits in each group were sacrificed at 2, 4, 8, and 26 weeks following implantation. Brains were sectioned at the implantation site and were examined by means of standard hematoxylin and eosin stains and with immunohistochemical markers sensitive to inflammatory changes in the brain. None of the animals showed any behavioral changes or neurologic deficits suggestive of either systemic or localized toxicity from the implant materials. Silicone clastomer was found to cause the least amount of inflammation relative to other materials tested at all sacrifice points, suggesting that as a standard neurosurgical implant material, it is an appropriate control for studies of brain biocompatibility. At 2 weeks, titanium was found to cause the largest inflammatory response in surrounding brain parenchyma based on analysis of markers for microglial proliferation, gliosis, and leukocyte infiltration. At the 26-week endpoint of our study, the biocompatibility of titanium was nearly equal to the biocompatibility of vitallium based on all studied markers of inflammation. A progressive increase in the inflammatory response surrounding stainless steel implants was noted at 8 and 26 weeks. Relative to all materials studied, at 26 weeks the greatest leukocyte response was found with stainless steel implants. Our results indicate that at the 26-week end-point of our study, titanium and vitallium incited a similar inflammatory response in the rabbit brain that was greater than the response found with silicone elastomer, a standard neurosurgical implant material, but less than that found with stainless steel wire, which is commonly recommended as an alternative fixation material.     

Morphology of the bone that supports endosteal dental implants. Transmission electron microscopic and high voltage electron microscopic observations

The morphologic features of the bone-dental implant interface were investigated using an in vivo dog model. The undecalcified bone and associated support tissues were serially sectioned and examined with both conventional and high voltage transmission electron microscopy. A varied morphologic appearance of the tissues supporting clinically and radiographically appearing integrated implants was observed. Osteoblasts were observed at the implant interface, and osteocytes were routinely seen encased within lacunae extremely close to the implant surface. Often these osteocytes extended cellular projections to the implant surface. The variable tissue types observed were suggestive of healthy lamellar and appositional type mineralization patterns adjacent to the implants.     

Microscopical features in retrieved human Branemark implants: a report of 19 cases

The authors present a histologic analysis of 19 Branemark titanium implants retrieved for different causes: four implants were removed for abutment fracture, one for dental nerve dysesthesia, two for bone overheating, two for peri-implantitis, nine for mobility, one for unknown causes. In the implants removed for fracture a high bone-implant contact percentage was present (71.83 +/- 4.96%) with compact, mature bone at the interface. The picture of the failure due to bone overheating was characteristic with the presence of bone sequestra and of a gap between implant and bone filled by lymphocytes and plasma cells: many bacteria surrounded the necrotic bone and no newly regenerated bone was present. In peri-implantitis an inflammatory infiltrate was observed in the peri-implant tissues: a dense fibrous connective tissue was present around implants failed for mobility. The microscopical picture is certainly extremely important in identifying the causal determinants of an implant failure.     

Adenosquamous carcinoma of the tongue: report of a case with histochemical, immunohistochemical, and ultrastructural study and review of the literature

The histologic examination of dental implants retrieved from humans is important to establish the causal determinants of implant failure, and to compare and validate the results obtained from animal studies. This study presents a retrospective review of the histologic features of 230 implants retrieved in an 8-year period (1989-1996). All the implants were treated to obtain thin (20 to 30 microm) ground sections. The majority of implants were retrieved because of mobility (n=56), peri-implantitis (n=54), or fractures (n=90). Peri-implantitis occurred more frequently before (n=44) than after (n=10) abutment connection. A dense fibrous connective tissue with no inflammatory cells was present at the interface in the implants retrieved for mobility; bone was found only in the most apical part. In many of these implants epithelial cells were present. The main histologic features of peri-implantitis consisted of the presence of a bone sequestrum near the implant, many bacteria present on the implant surface, and an inflammatory infiltrate (macrophages, lymphocytes, and plasma-cells) nearby. Histology showed that in the implants removed for fracture, there was a very high percentage (80 to 100%) of peri-implant bone.     

Activation of periprosthetic connective tissue in aseptic loosening of total hip replacements

In aseptic loosening of initially well inserted total hip prostheses, implant wear debris and cyclic mechanical loading lead to a foreign body type of chronic inflammatory reaction, then to osteolysis, and finally to loosening of the implant. In the present work the reactive and adaptive changes of the periprosthetic tissues and pseudojoint were characterized by analysis of the local cell proliferation. Immunohistochemical demonstration of proliferating cells was performed by application of affinity purified rabbit antihuman Ki-67 antibodies to periprosthetic tissues obtained from revision operations for loose total hip prostheses. The fibrous areas and, in particular, the cell rich, vascular areas of the interface tissue (between implant and bone) and the pseudocapsule around aseptically loosened implants contained higher numbers of proliferating cells than the tissues around well fixed implants. In addition, the pseudosynovial lining occasionally contained some Ki-67 positive proliferating cells. Somewhat surprisingly, proliferating vascular endothelial cells were relatively rare. These findings suggest that reactive (interface tissues) and adaptive (pseudojoint and capsule formed around the artificial joint) tissue changes in loosening total hip prostheses comprise proliferation of local fibroblastlike cells. It is concluded that periprosthetic tissues of the loosened total hip prosthesis represent activated mesenchymal tissue.     

不同弹性模量的基台-种植体组合对周围成骨性能的影响

利用有限元分析软件计算了不同静力作用下的多种基台-种植体周围骨组织的应力分布.模拟结果显示, 基台-种植体组合中Ti6Al4V钛合金-聚醚醚酮(TC4-PEEK)相对于其他实验组其应力集中程度现象可以有效降低, 周围骨组织的应力分布较为均匀, 最大应力值为40~60 MPa.在轴向加载条件下, 不同基台-种植体系统中PEEK种植体的应力水平较小, 而周围骨组织应力水平较大; 在斜向45°加载条件下, 相对于其他两种基台-种植体系统, TC4-PEEK的应力水平更低, 其周围骨组织中的皮质骨承受的最大应力值为55 MPa, 松质骨承受的最大应力值为5 MPa, 综合来看的应力水平最小, 有助于骨沉积和成骨量增加, 从而有效提高种植体的界面稳定性.      

Cemented femoral component surface finish mechanics

A cemented femoral component's surface finish may influence implant function through variations in cement adhesion and abrasion properties. Morphologic characterization of historic and current femoral hip prosthesis surface finishes show greater than x 20 range in implant roughness. Early implants typically had relatively smooth surfaces, whereas many of the more recent implants have rougher surface finishes. Smoother implant surfaces have lower cement-metal interface fixation strength, whereas rougher surfaces have greater fixation strength. With interface motion, the smoother surfaces are less abrasive of bone cement, whereas rougher implant surfaces are more abrasive. Because of enhanced bone cement attachment, rougher implant surfaces may have a lower probability of interface motion, while at the same time, a higher debris generation consequence if motion occurs. In contrast, smoother implant surfaces may have a higher probability of interface motion with a lower debris generating consequence of that motion. The prolonged use of cemented total hip replacement may be approached by either extending the duration of implant function after cement-metal interface loosening with smooth surfaced implants or, in contrast, by extending the duration of cement-metal interface adhesion with rougher surfaced implants.     

A dynamic modal testing technique for noninvasive assessment of bone-dental implant interfaces

A dynamic modal testing technique has been developed to noninvasively assess the interface surrounding an endosseous dental implant with a lateral tap from an impedance head hammer. The technique assesses the rotational stiffness of the interface based on the shape of the power spectrum of the force-time curve produced on impact. In vitro experiments were performed to determine the sensitivity of the technique for detecting clinically relevant structural differences between interfaces. The modal test data were able to distinguish interfaces based on the type of bone at the interface and the degree of fixation between the implant and the interface.     

When people with pre-existing disabilities age in place: implications for social work practice

Dental implants are subject to large and highly complex loads of varying magnitude, duration and vector. Bridge performance is closely related to load transmission both at the bone to implant interface and between components within the implant-abutment-bridge cylinder complex. The design of the interface between components within this complex may have a profound influence on the long term function of the implant supported prosthesis. An in vitro evaluation of implants 3.5 mm in diameter, utilizing an internal conical interface has demonstrated increased resistance to bending moments at the fixture-abutment interface (P = 0.00010) and at the abutment-bridge cylinder interface (P < 0.01), when compared to a standard 3.75 mm implant with a hex mediated, butt joint interface. The relatively small values for coefficient of variance measured in both systems would confirm that whilst the size of data is small, it is nonetheless a reliable indication of the relative strength of these implant designs.     

Present status and future of blood management in Japan]

The ability of shear strains to inhibit bony ingrowth was investigated by use of a transcortical porous-coated cylindrical plug implant in a functionally isolated turkey ulna model in which the mechanical loading environment could be accurately controlled and rigorously defined. The distribution of ingrowth at the bone-implant interface was quantified following 8 weeks of in vivo loading consisting of 100 seconds per day of a 20 Hz sinusoidal stimulus sufficient to cause a local peak strain of approximately 100 microstrain in the cortex at the bone-implant interface in four turkeys. A nonuniform but repeatable pattern of bony ingrowth, from 33 +/- 6 to 72 +/- 6% (mean +/- SE), was observed. The mechanical environment in the vicinity of the bone-implant interface was calculated using a three-dimensional elastic orthotropic finite element model. The general stress-strain state of the bone as predicted by the finite element model was validated in two additional turkeys using four three-element rosette strain gauges, while high resolution moiré interferometry was used to determine the mechanical state of the region immediately adjacent to the implant itself. Shear strains and stresses were evaluated at the interface and correlated to the pattern of bony ingrowth circumscribing the implant interface. Linear regressions between ingrowth and both shear strain and shear stress were negative, with the values of R = -0.75 and R = -0.78 (p < 0.001), respectively, indicating significant inhibition of ingrowth where shear components were maximal. These results suggest that the minimization of shear stress and strain components is a major determinant in achieving successful ingrowth of bone into a prosthesis.     

Preliminary studies of the use of nail as a material for reconstructive or cosmetic surgery

The purpose of this study was to assess the biocompatibility and stability of implanted nail as a preliminary step in the assessment of its potential as a material for small scale reconstructive or cosmetic surgery. Rat nails were placed subcutaneously in the back of 12 Lewis rats, which were then sacrificed in groups of 4 at 4, 8, and 12 months for macroscopic and microscopic examination of the implants. A layer of strongly adherent connective tissue, containing inflammatory cells, had formed around the nails at 4 months, but by 8 to 12 months this reaction had subsided, leaving the nails imbedded in connective tissue adhering to the dermal wall, with no evidence of implant rejection, granuloma formation, or degradation. The results suggest that nail merits further study as a surgical implant material, because of its staying power and lack of immunogenicity.     

Osteogenesis at the dental implant interface: high-voltage electron microscopic and conventional transmission electron microscopic observations

The osteogenesis of mandibular bone to endosteal dental implants was examined using an in vivo dog model. One half of the implants examined were unloaded implants, with the remaining one half prosthodontically loaded for 6 months. Undecalcified mandibular implant samples were examined with both high-voltage electron microscopy (HVEM) stereology and routine transmission electron microscopy. The osseous interface to integrated implants was shown to vary in its morphology. Mineralized bone was observed directly apposing the implant, often separated from the implant by an electron-dense deposit of approximately 50 nm. Within this densely mineralized matrix, osteocytes were routinely observed. Adjacent areas were shown to contain slightly wider zones of either a less dense mineralized matrix or, alternatively, unmineralized tissue. Other zones consisted of wider unmineralized matrices containing collagen fibers and osteoblasts. These latter zones were consistent with the appearance of an appositional type of bone growth. Because bone is a dynamic, actively remodeling tissue, a varied morphology of the support tissues to dental implant is not unexpected. Areas of mature bone interfacing with successfully integrated implants were demonstrated, as well as areas adjacent to the mature bone that were undergoing remodeling or mineralization. This study has also shown that HVEM stereology is a valuable research tool to investigate the oral tissue interface with dental implants.     

Aseptic loosening of the femoral implant after cemented total hip arthroplasty in dogs: 11 cases in 10 dogs (1991-1995)

Aseptic loosening of the femoral implant (ALFI) was diagnosed in 10 dogs that had undergone cemented total hip arthroplasty (THA). One dog had bilateral ALFI. Loosening developed at the stem-cement interface a mean of 30 months after THA. The most common clinical sign was intermittent subtle or non-weight-bearing lameness. On radiographs obtained after THA, the distal stem tip was in contact with the cortical endosteum in all dogs. Radiographic changes at the time of diagnosis of ALFI included asymmetric periosteal reaction along the femoral diaphysis (n = 11), radiolucent zone at the stem-cement interface (6), altered implant position (4), and femur fracture (1). Surgical revision resulted in a good or excellent outcome in 9 dogs. In 1 dog, the implant became infected. In another, aseptic loosening recurred. Aseptic loosening of the femoral implant was significantly more common when initial positioning of the implant resulted in contact between the distal tip of the implant and cortical endosteum than when there was no contact.     

Production of platelet-derived growth factor in aseptic loosening of total hip replacement

Aseptic loosening is the predominant cause of total hip implant failure. It has been assumed that a layer or membrane, containing macrophages, fibroblasts and vascular endothelial cells, of synovial-like tissue develops at the implant-to-bone interface almost invariably and, with time, somehow leads to loosening of the components from the surrounding bone. These cells produce a variety of cytokines and proteolytic enzymes which stimulate bone resorption. Platelet derived growth factor (PDGF) may be one of the cytokines which stimulate bone resorption and contribute to aseptic loosening in total hip replacement (THR). Synovial-like membrane from the implant or cement-to-bone interface (n = 10) and pseudocapsule (n = 10) were obtained from ten patients operated on for aseptic loosening of THR. As a control, nine samples of connective tissues were obtained from patients who had mandibular or maxillary fractures fixed with bone implant. The avidin-biotin-peroxidase complex (ABC) method with polyclonal rabbit anti-human IgG against the A-chain and B-chain of PDGF was used for staining. ABC-alkaline phosphatase-anti-alkaline-phosphatase double staining with monoclonal mouse anti-human fibroblast IgG1 and CD68 antibodies was used to ascertain the cellular origin of PDGF. Results of the PDGF staining were quantitated by a semi-automatic VIDAS image analysis system. The PDGF-A and PDGF-B chain containing cells were found in all periprosthetic tissues, in particular in macrophages with phagocytosed particulate debris, but to some extent also in fibroblasts and in endothelial cells. The numbers of PDGF-A and PDGF-B chain positive cells per mm 2 in synovial-like interface membrane (1881 +/- 486 and 1877 +/- 214) and pseudocapsule (1786 +/- 236 and 1676 +/- 152) were higher (P < 0.01) around loose THR than in control tissue (821 +/- 112 and 467 +/- 150), respectively. The results of the present study suggest that PDGF is preferably expressed by macrophages, which to an increased extent produce it in the synovial-like interface membrane and pseudocapsular synovial-like membrane. Because of its role in bone resorption, it may well play a role in periprosthetic bone loss and aseptic loosening and deserves more detailed study as a mediator and potential target in the modulation or prevention of loosening of THR.     

新型微弧氧化钛基种植材料的细胞毒性研究

采用四甲基偶氮唑盐微量酶反应比色法（MTT法）对微弧氧化处理的钛基种植材料的细胞毒性进行研究，并用相差显微镜对细胞形态进行了观察与分析。本研究采用原代培养鉴定后的成骨细胞，与不同材料三维培养，进行种植体材料的细胞毒性研究。结果表明：微弧氧化处理的材料表面细胞形态良好，生长旺盛，细胞计数及MTT测定结果与其它组比较，具有显著性差异，细胞毒性级别优于0级，具有良好的细胞相容性。     

Quantitative histologic evaluation of LTI carbon, carbon-coated aluminum oxide and uncoated aluminum oxide dental implants

The response of mandibular bone to identical geometry LTI carbon, carbon-coated aluminum oxide, and uncoated aluminum oxide blade-type dental implants in baboons for 2 years was evaluated using histologic, microradiographic, and scanning electron microscopic methods. In addition, a quantitative histologic analysis was performed identifying the type, amount, and distribution of tissue surrounding the dental implant systems. This is the final phase of a study investigating the effect of implant elastic modulus and implant surface chemical composition on the performance of dental implants. Previous studies have utilized clinical and radiographic evaluations, postretrieval mechanical testing, and finite element stress analysis to evaluate the dental implant performance. The results of the histologic study revealed a direct implant-bone interface with no intervening soft tissue in 16 of the 21 implants (76%). A fibrous tissue interface was observed in 5 of 21 implants (24%). Quantitative histologic results for the implants with a direct implant-bone interface showed statistically larger crestal cortical plates (p less than 0.05) and greater area fraction crestal cancellous bone (p less than 0.05) in the LTI carbon implant compared to the carbon-coated and uncoated aluminum oxide implants. The carbon-coated and uncoated aluminum oxide implants demonstrated statistically greater area fraction cancellous bone at the inferior region of the implant (p less than 0.05) and thinned and reduced crestal cortical plates when compared to the LTI carbon implants. The results indicate that significant stress shielding of the crestal bone had occurred with the rigid carbon-coated and uncoated aluminum oxide implants when compared to the LTI carbon implants which had a material elastic modulus similar to cortical bone. Based upon the histologic results, it appears that the LTI carbon implants with the direct implant-bone interface exhibited a greater potential for long-term successful performance compared to the aluminum oxide substrate implants.     

Bone response to implant surface morphology

This study was designed to measure implant osseointegration using different surface treatments. Bilateral distal intramedullary implantation of titanium cylinders 25 mm x 5 mm was performed in 60 rabbits. The 3 surfaces tested were fiber mesh, mean pore size 400 microns; grit-blasted, mean surface roughness 6 microns; and acid-etched, mean surface roughness 18 microns. Scanning electron microscopy was used to measure the percentage of the surface of each implant in contact with bone at 2, 6, and 12 weeks postimplantation. Mechanical pull-out testing of the bone-implant interface was performed at 12 weeks. Overall, acid-etched surfaces demonstrated greater mean osseointegration than fiber mesh surfaces. All 3 surfaces demonstrated similar interface strengths. Acid etching has potential as a means of enhancing bony apposition in cementless fixation.