Designing biological models of hysteresis live systems of osseous tissue and periosteum

Biological models of osseous tissue and periosteum have been developed. Biocompatible materials of titaniumnickel as an integral part of implant-tissue composites have been already functioning for five years, substituting for damaged bone fragments. The defects of skeletal kinematic sections of the mandible of experimental animals were replaced by biomechanical models of implant-tissue composites of the osseous tissue and periosteum. The composites were formed by joining the models of extracellular matrixes of osseous tissue and periosteum and the natural tissues. The validity of methodological propositions and optimal technological solutions have been proved by the absence of life-time signs of biochemical, biomechanical, hysteresis or thermodynamic incompatibility on tissue and skeletal levels.     

Biomechanical evaluation of two halo pin designs, with, and without, intact periosteum.

The presence of periosteum has been hypothesized to adversely affect halo pin penetration and performance (Voor, 1992. Ph.D. Dissertation, Tulane University, New Orleans, LA). However, biomechanical testing of halo pins has historically been conducted on bone specimens with periosteum removed. This may have lead to an unrealistic measure of biomechanical pin performance. Our study compares the biomechanical performance of two halo pin designs on bovine bone specimens with, and without, intact periosteum. The two pin designs included in this study were the conventional pin (Bremer Medical) with conical tip, and a newly released trochar-style pin (DePuy AcroMed). Results showed the mean peak load before failure of the trochar-style pin (mean +/- 95% confidence interval: 656+/-29 N) to be significantly higher than the conventional pin (517+/-53 N) on bone with intact periosteum (p = 0.001). With the periosteum removed, the mean peak load of the trochar-style pin (655+/-99 N) remained statistically the same (p = 0.987), while the mean peak load of the conventional pin (634+/-65 N) increased significantly (p = 0.026). Variation of the data of the conventional pin significantly decreased from 32 to 19% on removal of periosteum (sigma = 165-103 N, respectively, p = 0.0967), while variation of the trochar-style remained statistically the same at 30-29% (sigma = 193-188 N, respectively, p = 0.954). These results show that the trochar-style pin may be biomechanically superior to the conventional pin for vertical forces experienced during immobilization. The performance of this new pin style may also not be significantly affected by overlying soft tissue. Use of this new pin style may, therefore, improve overall stability and fixation of the halo apparatus.     

Evaluation of bone remodeling around single dental implants of different lengths: a mechanobiological numerical simulation and validation using clinical data

Algorithmic models have been proposed to explain adaptive behavior of bone to loading; however, these models have not been applied to explain the biomechanics of short dental implants. Purpose of present study was to simulate bone remodeling around single implants of different lengths using mechanoregulatory tissue differentiation model derived from the Stanford theory, using finite elements analysis (FEA) and to validate the theoretical prediction with the clinical findings of crestal bone loss. Loading cycles were applied on 7-, 10-, or 13-mm-long dental implants to simulate daily mastication and bone remodeling was assessed by changes in the strain energy density of bone after a 3, 6, and 12 months of function. Moreover, clinical findings of marginal bone loss in 45 patients rehabilitated with same implant designs used in the simulation (n = 15) were computed to validate the theoretical results. FEA analysis showed that although the bone density values reduced over time in the cortical bone for all groups, bone remodeling was independent of implant length. Clinical data showed a similar pattern of bone resorption compared with the data generated from mathematical analyses, independent of implant length. The results of this study showed that the mechanoregulatory tissue model could be employed in monitoring the morphological changes in bone that is subjected to biomechanical loads. In addition, the implant length did not influence the bone remodeling around single dental implants during the first year of loading.     

Influence of clinically relevant factors on the immediate biomechanical surrounding for a series of dental implant designs

The objective of the present study was to assess the influence of various clinically relevant scenarios on the strain distribution in the biomechanical surrounding of five different dental implant macrogeometries. The biomechanical environment surrounding an implant, i.e., the cortical and trabecular bone, was modeled along with the implant. These models included two different values of the study parameters including loading conditions, trabecular bone elastic modulus, cortical/trabecular bone thickness ratio, and bone loss for five implant designs. Finite element analysis was conducted on the models and strain in the bones surrounding the implant was calculated. Bone volumes having strains in four different windows of 0-200?με, 200-1000?με, 1000-3000?με, and > 3000 με were measured and the effect of each biomechanical variable and their two-way interactions were statistically analyzed using the analysis of variance method. This study showed that all the parameters included in this study had an effect on the volume of bones in all strain windows, except the implant design, which affected only the 0-200?με and >3000?με windows. The two-way interaction results showed that interactions existed between implant design and bone loss, and loading condition, bone loss in the 200-1000?με window, and between implant design and loading condition in the 0-200 με window. Within the limitations of the present methodology, it can be concluded that although some unfavorable clinical scenarios demonstrated a higher volume of bone in deleterious strain levels, a tendency toward the biomechanical equilibrium was evidenced regardless of the implant design.     

Mechanistic,Mathematical Model to Predict the Dynamics of Tissue Genesis in Bone Defects via Mechanical Feedback and Mediation of Biochemical Factors

The link between mechanics and biology in the generation and the adaptation of bone has been well studied in context of skeletal development and fracture healing. Yet, the prediction of tissue genesis within - and the spatiotemporal healing of - postnatal defects, necessitates a quantitative evaluation of mechano-biological interactions using experimental and clinical parameters. To address this current gap in knowledge, this study aims to develop a mechanistic mathematical model of tissue genesis using bone morphogenetic protein (BMP) to represent of a class of factors that may coordinate bone healing. Specifically, we developed a mechanistic, mathematical model to predict the dynamics of tissue genesis by periosteal progenitor cells within a long bone defect surrounded by periosteum and stabilized via an intramedullary nail. The emergent material properties and mechanical environment associated with nascent tissue genesis influence the strain stimulus sensed by progenitor cells within the periosteum. Using a mechanical finite element model, periosteal surface strains are predicted as a function of emergent, nascent tissue properties. Strains are then input to a mechanistic mathematical model, where mechanical regulation of BMP-2 production mediates rates of cellular proliferation, differentiation and tissue production, to predict healing outcomes. A parametric approach enables the spatial and temporal prediction of endochondral tissue regeneration, assessed as areas of cartilage and mineralized bone, as functions of radial distance from the periosteum and time. Comparing model results to histological outcomes from two previous studies of periosteum-mediated bone regeneration in a common ovine model, it was shown that mechanistic models incorporating mechanical feedback successfully predict patterns (spatial) and trends (temporal) of bone tissue regeneration. The novel model framework presented here integrates a mechanistic feedback system based on the mechanosensitivity of periosteal progenitor cells, which allows for modeling and prediction of tissue regeneration on multiple length and time scales. Through combination of computational, physical and engineering science approaches, the model platform provides a means to test new hypotheses in silico and to elucidate conditions conducive to endogenous tissue genesis. Next generation models will serve to unravel intrinsic differences in bone genesis by endochondral and intramembranous mechanisms.     

Influence of custom-made implant designs on the biomechanical performance for the case of immediate post-extraction placement in the maxillary esthetic zone: a finite element analysis

Due to the increasing adoption of immediate implantation strategies and the rapid development of the computer aided design/computer aided manufacturing technology, a therapeutic concept based on patient-specific implant dentistry has recently been reintroduced by many researchers. However, little information is available on the designs of custom-made dental implant systems, especially their biomechanical behavior. The influence of the custom-made implant designs on the biomechanical performance for both an immediate and a delayed loading protocol in the maxillary esthetic zone was evaluated by means of the finite element (FE) method. FE models of three dental implants were considered: a state of the art cylindrical implant and two custom-made implants designed by reverse engineering technology, namely a root-analogue implant and a root-analogue threaded implant. The von Mises stress distributions and micro-motions around the bone-implant interfaces were calculated using ANSYS software. In a comparison of the three implant designs for both loading protocols, a favorable biomechanical performance was observed for the use of root-analogue threaded implant which approximated the geometry of natural anterior tooth and maintained the original long-axis. The results indicated that bone-implant interfacial micro-motion was reduced and a favorable stress distribution after osseointegration was achieved.     

X-ray manifestations of fibrous dysplasia of the facial bones]

The paper is concerned with roentgenological characterization of mono- and poly-osseous fibrous dysplasia in cranial facial bones of 60 persons of both sexes and at a different age, of them 14 persons were under 14. Mono-osseous lesions after radical operations were shown to be capable of continued growth of rearranged osseous tissue in those cases when the periosteum was not completely removed.     

Numerical investigation of bone remodelling around immediately loaded dental implants using sika deer (Cervus nippon) antlers as implant bed

This study combines finite element method and animal studies, aiming to investigate tissue remodelling processes around dental implants inserted into sika deer antler and to develop an alternative animal consuming model for studying bone remodelling around implants. Implants were inserted in the antlers and loaded immediately via a self-developed loading device. After 3, 4, 5 and 6 weeks, implants and surrounding tissue were taken out. Specimens were scanned by μCT scanner and finite element models were generated. Immediate loading and osseointegration conditions were simulated at the implant-tissue interface. A vertical force of 10 N was applied on the implant. During the healing time, density and Young’s modulus of antler tissue around the implant increased significantly. For each time point, the values of displacement, stresses and strains in the osseointegration model were lower than those of the immediate loading model. As the healing time increased, the displacement of implants was reduced. The 3-week immediate loading model (9878 ± 1965 μstrain) illustrated the highest strains in the antler tissue. Antler tissue showed similar biomechanical properties as human bone in investigating the bone remodelling around implants, therefore the use of sika deer antler model is a promising alternative in implant biomechanical studies.     

A finite element model of the L4-L5 spinal motion segment: biomechanical compatibility of an interspinous device

The biomechanical compatibility of an interspinous device, used for the "dynamic stabilization" of a diseased spinal motion segment, was investigated. The behaviour of an implant made of titanium based alloy (Ti6Al4V) and that of an implant made of a super-elastic alloy (Ni-Ti) have been compared. The assessment of the biomechanical compatibility was achieved by means of the finite element method, in which suitable constitutive laws have been adopted for the annulus fibrosus and for the metal alloys. The model was aimed at simulating the healthy, the nucleotomized and the treated L4-L5 lumbar segment, subjected to compressive force and flexion-extension as well as lateral flexion moments. The computational model has shown that both the implants were able to achieve their main design purpose, which is to diminish the forces acting on the apophyseal joints. Nevertheless, the Ni-Ti implant has shown a more physiological flexural stiffness with respect to the Ti6Al4V implant, which exhibited an excessive stiffness and permanent strains (plastic strains), even under physiological loads. The computational models presented in this paper seems to be a promising tool able to predict the effectiveness of a biomedical device and to select the materials to be used for the implant manufacturing, within an engineering approach to the clinical problem of the spinal diseases.     

Quantification of soft tissue balance in total knee arthroplasty using finite element analysis

Unbalanced contact force on the tibial component has been considered a factor leading to loosening of the implant and increased wear of the bearing surface in total knee arthroplasty. Because it has been reported that good alignment cannot guarantee successful clinical outcomes, the soft tissue balance should be checked together with the alignment. Finite element models of patients' lower extremities were developed to analyse the medial and lateral contact force distribution on the tibial insert. The distributions for four out of five patients were not balanced equally, even though the alignment angles were within a clinically acceptable range. Moreover, the distribution was improved by changing soft tissue release and ligament tightening for the specific case. Integration of the biomechanical modelling, image matching and finite element analysis techniques with the patient-specific properties and various dynamic loading would suggest a clinically relevant pre-operative planning for soft tissue balancing.     

Circadian Rhythm in Mammary Cytoplasmic Estrogen Receptor Content of Balb/C Female Mice with and Without Pituitary Isografts

Cytoplasmic estrogen receptors were determined by the dextran-coated charcoal method in inguinal breast tissue of three groups of Balb/C female mice 6-8 weeks following subcutaneous implantation into the intact animals of three pituitary glands and three pieces of skeletal muscle (group I), three pituitary glands and three segments of hypothalamic tissue (group II), or three pieces of skeletal muscle (group III) obtained from animals of the same inbred strain as control. A circadian rhythm in estrogen receptor content was statistically quantified by cosinor analysis in the muscle implanted control and the pituitary and hypothalamic implant groups. In the pituitary and muscle implant group the circadian rhythm is of borderline significance with a P-value between 0.05 and 0.10. The timing (acrophase) and extent of change (amplitude) are similar in all three treatment groups. The average receptor content (MESOR) in the two pituitary-implanted groups, which in previous studies were shown to have an increased breast cancer incidence is about twice that of the control group. The reduction in the pituitary induced breast cancer rate by hypothalamic tissue addition to a cancer incidence between the animals with pituitary and muscle isograft and the mice carrying no pituitary at all has also been shown previously in this strain of mice and is not reflected in receptor content.     

Comparison of canine mandibular bone regeneration by distraction osteogenesis versus acute resection and rigid external fixation

The present study was performed (1) to explore the mechanism of skeletal healing following distraction osteogenesis of the mandible and to evaluate whether the same process is involved following acute mandibular resection and rigid external fixation, and (2) to examine the role of the periosteum in skeletal healing in both models. The study was performed using 16 mongrel dogs divided into two equal groups. In the first group, distraction of 20 mm was performed at a rate of 1 mm/day. In the second group, bone resection of 20 mm was performed, followed by rigid external fixation. The buccal periosteum was stripped in four dogs from each group, and the periosteum was left intact in the remaining four dogs. Dogs were euthanized after a survival period of either 2 or 3 months, and the new bone regenerate was evaluated. Analysis consisted of three-dimensional computed tomography scanning, histometric analysis, and immunostaining. Analysis of bone mineral content in the residual gap was conducted. Bone mineral content was increased in 3- versus 2-month survival for all groups (p < 0.05). The distracted groups had greater bone mineral content than their acutely resected counterparts, with the difference achieving statistical significance by 3-month survival (p < 0.05). Although periosteal preservation resulted in increased bone mineral content over time for all groups (p = 0.044), periosteal preservation had no significant effect on bone mineral content in the distracted groups. After periosteal stripping, however, bone mineral content was significantly increased in dogs that underwent distraction rather than acute resection and rigid external fixation (p = 0.022). Regarding histometric analysis, analysis of fibrous tissue content in the bone regenerate demonstrated that by 3 months the distracted groups had significantly less fibrous tissue in the new bone regenerate than did the acutely resected groups (p < 0.001). Regarding immunostaining, diffuse localization of transforming growth factor-beta1 was observed in all groups at 2 months, returning to nearly baseline levels by 3 months. These data demonstrate that significant bone formation in a segmental gap can be achieved after acute mandibular resection and rigid external fixation if the periosteum is preserved. However, after periosteal injury or stripping, significant bone formation can only be achieved by distraction osteogenesis. In both processes, bone formation is preceded by up-regulation of transforming growth factor-beta1.     

Application of mechanoregulatory models to simulate peri-implant tissue formation in an in vivo bone chamber

Several mechanoregulatory tissue differentiation models have been proposed over the last decade. Corroboration of these models by comparison with experimental data is necessary to determine their predictive power. So far, models have been applied with various success rates to different experimental set-ups investigating mainly secondary fracture healing. In this study, the mechanoregulatory models are applied to simulate the implant osseointegration process in a repeated sampling in vivo bone chamber, placed in a rabbit tibia. This bone chamber provides a mechanically isolated environment to study tissue differentiation around titanium implants loaded in a controlled manner. For the purpose of this study, bone formation around loaded cylindrical and screw-shaped implants was investigated. Histologically, no differences were found between the two implant geometries for the global amount of bone formation in the entire chamber. However, a significantly larger amount of bone-to-implant contact was observed for the screw-shaped implant compared to the cylindrical implant. In the simulations, a larger amount of bone was also predicted to be in contact with the screw-shaped implant. However, other experimental observations could not be predicted. The simulation results showed a distribution of cartilage, fibrous tissue and (im)mature bone, depending on the mechanoregulatory model that was applied. In reality, no cartilage was observed. Adaptations to the differentiation models did not lead to a better correlation between experimentally observed and numerically predicted tissue distribution patterns. The hypothesis that the existing mechanoregulatory models were able to predict the patterns of tissue formation in the in vivo bone chamber could not be fully sustained.     

Nano-hydroxyapatite-thermally denatured small intestine sub-mucosa composites for entheses applications

The objective of the present in vitro study was to estimate the adhesion strength of nanometer crystalline hydroxyapatite (HA)-small intestine sub-mucosa (SIS) composites on model implant surfaces. Techniques of thermal denaturation (60 degrees C, 20 min) of SIS were used to enhance the adhesion strength of entheses materials to underlying implants. Specifically, results indicated that the adhesion strength of thermally denatured SIS was 2-3 times higher than that for normal unheated SIS. In addition, aqua-sonicated, hydrothermally treated nano-HA dispersions enhanced the adhesion strength of SIS on implant surfaces. Importantly, results of the present study demonstrated that human skeletal muscle cell (hSkMC) numbers were not affected by thermally denaturing SIS in nano-HA composite coatings; however, they increased on aqua-sonicated nano-HA/SIS composites compared with SIS alone. Interestingly, thermally denatured SIS that contained aqua-sonicated, hydrothermally treated nano-HA decreased human osteoblasts (hOBs) numbers compared with respective unheated composites; all other composites when thermally denatured did not influence hOB numbers. Results also showed that the number of hOBs increased on nano-HA/SIS composites compared with SIS composites alone. Human mesenchymal stem cell (hMSC) numbers were not affected by the presence of nano-HA in SIS composites. For these reasons, the collective results of this in vitro study demonstrated a technique to increase the coating strength of entheses coatings on implant surfaces (using thermally denatured SIS and aqua-sonicated, hydrothermally prepared nano-HA) while, at the same time, supporting cell functions important for entheses regeneration.     

The effect of the chemical nature of implant materials on regeneration processes in an implant site

The literature data on implant materials for recovering from osseous injuries and defects were reviewed. Hydroxyapatite and bioactive glass are the leading artificial implant materials. Chitosan, polylactide, adgelon, and salicylic acid have found application in this area as biocompatible surgical materials that also promote wound healing and regeneration. When using hydroxyapatite as an implant material, its active groups, such as phosphate, hydroxyl, and others provide contacts; cell migration and adhesion on the matrix surface, formation of an intermediate layer of osteoid type, and fusion of bone and implant then occur. In the case of bioactive glass, the silanol groups are involved in bond formation. The study of mechanisms of bond formation between biological tissue and implant material and search for new biocompatible materials are important tasks of medical research in the field of implantation and post-traumatic regeneration.     

Identification of the critical level of implantation of an osseointegrated prosthesis for above-knee amputees

The aim of our study was to identify potential critical levels of implantation of an osseointegrated prosthesis for above-knee amputees. The implant used was the OPRA system. It was inserted in the femur at four different amputation heights, characterized by their residual limb ratios (0.299, 0.44, 0.58 and 0.73). The stress and strain distribution was evaluated in the bone-implant system during walking, considering a body mass of 100 kg. Considerably high stimulus (11,489 με) in the tissue near the tip was found at the highest implantation level. All models presented small non-physiologic stress values in the tissue around the implant. The results revealed that the implantation level has a decisive effect on bone-implant performance. Mainly, the analysis indicates adverse biomechanical conditions for implantations in very short residual limbs.     

Macroscopic features of scurvy in human skeletal remains: A literature synthesis and diagnostic guide

The past two decades have seen a proliferation in bioarchaeological literature on the identification of scurvy, a disease caused by chronic vitamin C deficiency, in ancient human remains. This condition is one of the few nutritional deficiencies that can result in diagnostic osseous lesions. Scurvy is associated with low dietary diversity and its identification in human skeletal remains can provide important contextual information on subsistence strategy, resource allocation, and human-environmental interactions in past populations. A large and robust methodological body of work on the paleopathology of scurvy exists. However, the diagnostic criteria for this disease employed by bioarchaeologists have not always been uniform. Here we draw from previous research on the skeletal manifestations of scurvy in adult and juvenile human skeletal remains and propose a weighted diagnostic system for its identification that takes into account the pathophysiology of the disease, soft tissue anatomy, and clinical research. Using a sample of individuals from the prehistoric Atacama Desert in Northern Chile, we also provide a practical example of how diagnostic value might be assigned to skeletal lesions of the disease that have not been previously described in the literature.     

石墨化炭/炭复合材料＋羟基磷灰石涂层（C/C＋HA）复合骨植入材料研究

目的：通过建立兔股骨缺损的动物实验模型,对采用等温化学气相沉积法和等离子喷涂技术所制备的石墨化炭/炭复合材料＋羟基磷灰石涂层（C/C＋HA）复合骨植入材料进行骨植入实验的的生物相容性进行评价,探索该复合材料作为植入机体骨组织的可行性依据。方法：采用骨科钻在实验动物股骨髁上钻孔的方法建立骨缺损的动物实验模型,将待研究比较的实验材料分别植入实验动物的股骨髁内,持续观察8周,在术后第2、4、8周时应用X线照片、组织学染色和扫描电镜技术,分别观察所研究材料在机体内对骨缺损愈合及其对机体的影响,进行组间比较和相关性分析。结果：石墨化炭/炭复合材料＋羟基磷灰石涂层（C/C＋HA）复合骨植入材料的骨植入实验生物相容性良好,材料与骨组织结合牢固,界面中成骨细胞生长明显,且炭颗粒脱落现象少,未见炎症细胞浸润。植入动物体内的材料在植入期未引起机体局部的炎症浸润反应且表面脱落的碳颗粒在机体组织中也未引起局部严重的炎症反应。在实验动物植入材料后的连续8周观察期中,组织学观察显示：表面涂有HA的炭/炭复合材料对骨组织形态改建上表现良好,其与骨组织接界处所形成的纤维结缔组织膜层厚度明显比未涂HA的材料要小,与骨组织结合更为紧密和牢固;碳颗粒出现脱落游离的现象明显减少。结论：在炭/炭复合材料表面涂以HA生物涂层对骨的形态改建和促进骨小梁生长等方面具有良好的作用,是一种具有发展潜力的骨修复材料。