Animal Bone Defect Research Articles

PLLA/GO Scaffolds Filled with Canine Placenta Hydrogel and Mesenchymal Stem Cells for Bone Repair in Goat Mandibles.

Bone defects in animals can arise from various causes, including diseases, neoplasms, and most commonly, trauma. Comminuted fractures that exceed the critical size may heal poorly due to deficient or interrupted vascularization, resulting in an insufficient number of progenitor cells necessary for bone regeneration. In this context, 3D printing techniques using poly-L-lactic acid/graphene oxide (PLLA/GO) aim to address this issue by creating customized scaffolds combined with canine placenta hydrogel and mesenchymal stem cells for use in goat mandibles, compared to a control group using titanium plate fixation. Ten canine placentas were decellularized and characterized using histological techniques. A hydrogel derived from the canine placenta extracellular matrix (cpECM) was produced to improve cell attachment to the scaffolds. In vitro cytotoxicity and cell adhesion to the cpECM hydrogel were assessed by scanning electron microscopy (SEM). The resulting biomaterials, cpECM hydrogel and PLLA/GO scaffolds, maintained their functional structure and supported cell adhesion, maintenance, and proliferation in vitro. Thermography showed that PLLA/GO scaffolds with cpECM hydrogel performed effectively, similar to the control group. Computed tomography scans revealed bone calluses, suggesting an ongoing repair process. These findings demonstrate the innovative technological potential of these materials for use in surgical interventions. Future studies on PLLA/GO scaffolds will provide further insights into their effects on goat models.

Machine learning-enabled constrained multi-objective design of architected materials

Architected materials that consist of multiple subelements arranged in particular orders can demonstrate a much broader range of properties than their constituent materials. However, the rational design of these materials generally relies on experts’ prior knowledge and requires painstaking effort. Here, we present a data-efficient method for the high-dimensional multi-property optimization of 3D-printed architected materials utilizing a machine learning (ML) cycle consisting of the finite element method (FEM) and 3D neural networks. Specifically, we apply our method to orthopedic implant design. Compared to uniform designs, our experience-free method designs microscale heterogeneous architectures with a biocompatible elastic modulus and higher strength. Furthermore, inspired by the knowledge learned from the neural networks, we develop machine-human synergy, adapting the ML-designed architecture to fix a macroscale, irregularly shaped animal bone defect. Such adaptation exhibits 20% higher experimental load-bearing capacity than the uniform design. Thus, our method provides a data-efficient paradigm for the fast and intelligent design of architected materials with tailored mechanical, physical, and chemical properties.

Evaluation of safety and efficacy of the bone marrow mesenchymal stem cell and gelatin-nano-hydroxyapatite combination in canine femoral defect repair.

Femoral shaft fracture is a common bone trauma in dogs. The limitation of mesenchymal stem cells in bone defect applications is that the cell suspension cannot be fixed to the bone defect site. In the study, our objective was to substantiate the combined application of canine bone marrow mesenchymal stem cells (cBMSCs) and gelatin-nano-hydroxyapatite (Gel-nHAP) and evaluate its therapeutic effect on bone defect diseases in dogs. Experiments were performed to evaluate the following: (1) the porosity of Gel-nHAP; (2) the adhesion of cBMSCs to Gel-nHAP; and (3) the effect of Gel-nHAP on cBMSC proliferation. The efficacy and safety of the combination of cBMSC and Gel-nHAP in the repair of femoral shaft defects were evaluated in animal experiments. The results showed that Gel-nHAP supported the attachment of cBMSCs and exhibited good biocompatibility. In the animal bone defect repair experiment, significant cortical bone growth was observed in the Gel-nHAP group at week 8 (p < 0.05) and in the cBMSCs-Gel-nHAP group at week 4 (p < 0.01). We demonstrated that Gel-nHAP could promote the repair of bone defects, and the effect of cBMSC-Gel-nHAP on the repair of bone defects was profound.

A Recombinant Parathyroid Hormone-Related Peptide Locally Applied in Osteoporotic Bone Defect.

The local application of drug-loaded bioactive scaffold materials is one of the important directions to solve the clinical problem of osteoporotic (OP) bone defects. This study retains the advantages of drug loading and mechanical properties of natural 3D bioactive scaffolds. The scaffolds are functionally modified through chemical and self-assembly approaches with application of polydopamine (PDA) nanoparticles and parathyroid hormone-related peptide-1 (PTHrP-1) for efficient local drug loading. This study investigates the effects of the novel bioactive scaffolds on ossification, osteoclastogenesis, and macrophage polarization. This work elucidates the effects of the scaffolds in regulating osteoclastic activity and new bone formation in vitro. Further studies on the establishment and repair of OP bone defects in small animals are conducted, and the potential of natural bioactive porous scaffold materials to promote the repair of OP bone defects is initially verified. The preparation of safe and economical anti-OP bone repair material provides a theoretical basis for clinical translational applications.

X-ray macromorphological and biochemical assessment of consolidation of fractures of long tubular bones under conditions of osteoreplacement with calcium-phosphate ceramics doped with germanium for osteoporosis in rab-bits

Among several factors that can cause a violation of the course of reparative osteogenesis, previous diseases associated with a change in the structural and functional state of bone tissue and primarily osteoporosis are considered significant. Osteoporotic fractures are difficult to treat. Along with systemic therapy, locally applied bone substitute materials, particularly unalloyed and alloyed calcium phosphate ceramics with pronounced osteoconductive, osteoinductive, and osteointegration properties. The work aims to evaluate the effect of calcium-phosphate ceramics doped with germanium on post-traumatic bone regeneration in conditions of secondary osteoporosis in rabbits. Experimental osteoporosis in rabbits was induced by administration of 0.4 % dexamethasone solution (KRKA, Slovenia) for 21 days at a dose of 1.2 mg/kg of body weight. Experimental (n = 9) and control (n = 9) groups of animals were formed. Animals of the experimental group had defects replaced with granules of hydroxyapatite ceramics, synthesized based on hydroxyapatite and β-tricalcium phosphate, doped with germanium. In rabbits of the control group, bone defects healed under a blood clot. Blood samples to determine the level of total calcium (Ca) and inorganic phosphorus (P) were taken before surgery and on 7-,14th, 30th, and 60th day of the study. X-ray studies were performed on the RUM-20 X-ray machine on the 14th, 30th, and 60th day of reparative osteogenesis. Radiologically and macromorphologically, it was established that reparative osteogenesis in the experimental animals proceeds more dynamically compared to the control group and is characterized by a high density of bone tissue at the site of the defect already on the 14th day after the injury, a moderate periosteal and early appearance of the endosteal reaction. The content of total calcium in the animals of the experimental group on the 14th day after the injury was 1.3 times (P &lt; 0.001) higher than that of the control and animals before the operation, and on the 30th day, it was 1.2 times (P &lt; 0.001) in accordance. The concentration of inorganic phosphorus (P) on the 14th and 30th days of reparative osteogenesis in animals of the experimental group was 1.1 times (P &lt; 0.05) lower than in control animals, and on the 60th day in 1.4 times (P &lt; 0.01), respectively. Systemic osteoporosis in experimental animals causes a violation of reparative osteogenesis due to the prolongation of the inflammatory-resorptive stage and cartilaginous callus and complicated mineralization of bone regeneration. Calcium-phosphate ceramics is a promising material for replacing bone defects in animals with systemic secondary osteoporosis.

Current Methods in the Study of Nanomaterials for Bone Regeneration.

Nanomaterials show great promise as bone regeneration materials. They can be used as fillers to strengthen bone regeneration scaffolds, or employed in their natural form as carriers for drug delivery systems. A variety of experiments have been conducted to evaluate the osteogenic potential of bone regeneration materials. In vivo, such materials are commonly tested in animal bone defect models to assess their bone regeneration potential. From an ethical standpoint, however, animal experiments should be minimized. A standardized in vitro strategy for this purpose is desirable, but at present, the results of studies conducted under a wide variety of conditions have all been evaluated equally. This review will first briefly introduce several bone regeneration reports on nanomaterials and the nanosize-derived caveats of evaluations in such studies. Then, experimental techniques (in vivo and in vitro), types of cells, culture media, fetal bovine serum, and additives will be described, with specific examples of the risks of various culture conditions leading to erroneous conclusions in biomaterial analysis. We hope that this review will create a better understanding of the evaluation of biomaterials, including nanomaterials for bone regeneration, and lead to the development of versatile assessment methods that can be widely used in biomaterial development.

The effect of the platelet-rich plasma on osteogenic potential of the periosteum in an animal bone defect model.

Objectives This study aims to investigate whether plasma-rich plasma (PRP) enhances the osteogenic potential of periosteal grafts used to repair bone defects and maintains both histologically and biomechanically more durable bone tissue.Materials and methods A standard bone defect was formed to the left femurs of 54 Sprague-Dawley rats and three groups were formed. In the first group (n=18), no periosteal repair was done for bone defect. In the second group (n=18), periosteal graft tissue was sutured to cover the defect entirely. In the third group (n=18), before periosteal repair, a 1 mL of PRP fibrin was applied into the bone defect. All femoral specimens were compared histologically at four and six weeks and biomechanically by three-point bending test at six weeks after treatment.Results In the PRP applied group, healing of the bone defect at four weeks was significantly better than the other groups in terms of histological new bone formation (p<0.05). At six weeks, new bone formation in both of the periosteum preserved groups was superior to the first group (p<0.05, for both). There was no statistically significant difference between the second and third groups at the end of the sixth week in the biomechanical analysis, although both groups were significantly stronger than the first group (p<0.05).Conclusion Stimulation of the periosteum with PRP application causes early osteogenic differentiation of precursor cells. Although, at biomechanical basis, PRP application does not create any significant difference, in the recovery of the bone defects at very early period, application of PRP may play a role to accelerate fracture healing and to decrease nonunions.

Low Dose BMP2-Doped Calcium Phosphate Graft Promotes Bone Defect Healing in a Large Animal Model.

Background: Bone grafts are in high demand due to the increase in the cases of bone defects mainly caused by trauma, old age, and disease-related bone damages. Tissue-engineered calcium phosphate (CaP) biomaterials match the major inorganic contents of bone, thereby could be the potential bone graft substitute. However, CaP-bone grafts lack the osteoinductivity that is vital for effective bone regeneration. In this study, we aimed to test the bone defect healing potential of biomimetically fabricated low dose BMP2-doped CaP (BMP2.BioCaP) grafts in a large animal model.Methods: Low dose BMP2 was doped internally (BMP2-int.BioCaP) or on the surface of CaP (BMP2-sur.BioCaP) grafts during the fabrication process. Our previous study showed the robust bone regenerative potential of BMP2-int.BioCaP and BMP2-sur.BioCaP grafts in the rat ectopic model. In this study, we investigated the bone defect healing potential of BMP2.BioCaP grafts in sheep humerus/femoral defects, as well as compared with that of autologous bone graft and clinically used deproteinized bovine bone (DBB) xenograft.Results: Different ways of BMP2 doping did not affect the surface morphology and degradation properties of the graft materials. Micro-CT and histology results showed robustly higher bone defect-healing potential of the BMP2.BioCaP grafts compared to clinically used DBB grafts. The bone defect healing potential of BMP2.BioCaP grafts was as effective as that of the autologous bone graft. Although, BMP2-int.BioCaP doped half the amount of BMP2 compared to BMP2-sur.BioCaP, its' bone defect healing potential was even robust. The BMP2.BioCaP grafts showed less immunogenicity compared to BioCaP or DBB grafts. The volume density of blood vessel-like and bone marrow-like structures in both BMP2.BioCaP graft groups were in a similar extent to the autologous group. Meticulous observation of higher magnification histological images showed active bone regeneration and remodeling during bone defect healing in BMP2.BioCaP graft groups.Conclusion: The robust bone regenerative potential of BMP2.BioCaP grafts in the ectopic model and in-situ bone defects in small and large animals warrant the pre-clinical studies on large animal critical-sized segmental bone defects.

Genistein Improves Bone Healing via Triggering Estrogen Receptor Alpha-Mediated Expressions of Osteogenesis-Associated Genes and Consequent Maturation of Osteoblasts.

Osteoporosis-associated fractures may cause higher morbidity and mortality. Our previous study showed the effects of genistein, a phytoestrogen, on the induction of estrogen receptor alpha (ERα) gene expression and stimulation of osteoblast mineralization. In this study, rat calvarial osteoblasts and an animal bone defect model were used to investigate the effects of genistein on bone healing. Treatment with genistein caused a time-dependent increase in alkaline phosphatase (ALP) activity in rat osteoblasts. Levels of cytosolic and nuclear ERα significantly augmented following exposure to genistein. Subsequently, genistein elevated levels of ALP mRNA and protein in rat osteoblasts. Moreover, genistein induced other osteogenesis-associated osteocalcin and Runx2 mRNA and protein expressions. Knocking-down ERα using RNA interference concurrently inhibited genistein-induced Runx2, osteocalcin, and ALP mRNA expression. Attractively, administration of ICR mice suffering bone defects with genistein caused significant increases in the callus width, chondrocyte proliferation, and ALP synthesis. Results of microcomputed tomography revealed that administration of genistein increased trabecular bone numbers and improved the bone thickness and volume. This study showed that genistein can improve bone healing via triggering ERα-mediated osteogenesis-associated gene expressions and subsequent osteoblast maturation.

Injectable mineralized microsphere-loaded composite hydrogels for bone repair in a sheep bone defect model

The efficacy of cell-based therapies as an alternative to autologous bone grafts requires biomaterials to localize cells at the defect and drive osteogenic differentiation. Hydrogels are ideal cell delivery vehicles that can provide instructional cues via their composition or mechanical properties but commonly lack osteoconductive components that nucleate mineral. To address this challenge, we entrapped mesenchymal stromal cells (MSCs) in a composite hydrogel based on two naturally-derived polymers (alginate and hyaluronate) containing biomineralized polymeric microspheres. Mechanical properties of the hydrogels were dependent upon composition. The presentation of the adhesive tripeptide Arginine-Glycine-Aspartic Acid (RGD) from both polymers induced greater osteogenic differentiation of ovine MSCs in vitro compared to gels formed of RGD-alginate or RGD-alginate/hyaluronate alone. We then evaluated the capacity of this construct to stimulate bone healing when transplanting autologous, culture-expanded MSCs into a surgical induced, critical-sized ovine iliac crest bone defect. At 12 weeks post-implantation, defects treated with MSCs transplanted in composite gels exhibited significant increases in blood vessel density, osteoid formation, and bone formation compared to acellular gels or untreated defects. These findings demonstrate the capacity of osteoconductive hydrogels to promote bone formation with autologous MSCs in a large animal bone defect model and provide a promising vehicle for cell-based therapies of bone healing.

Potential of growth factor incorporated mesoporous bioactive glass for in vivo bone regeneration

Mesoporous bioactive glass (MBG) has drawn much attention due to its superior surface texture, porosity and bioactive characteristics. Aim of the present study is to synthesize MBG using different surfactants, viz., hexadecyltrimethylamonium(CTAB) (M1), poly-ethylene glycol (PEG) (M2) and pluronic P123 (M3); bioactivity study; and to understand their bone regeneration efficacy in combination with insulin-like growth factors (IGF-1) in animal bone defect model. SBF study revealed the formation of calcium carbonate (CaCO3) and hydroxyapatite (HAp) phase over 14 days. Formation of apatite layer was further confirmed by FTIR, FESEM and EDX analysis. M1 and M2 showed improved crystallinity, while M3 showed slightly decrease in crystalline peak of CaCO3 and enhanced HAp phase. More Ca-P layer formed in M1 and M2 supported the in vivo experiments subsequently. Degree of new bone formation for all MBGs were high, i.e., M1 (80.7 ± 2.9%), M2 (74.4 ± 2.4%) and M3 (70.1 ± 1.9%) compared to BG (66.9 ± 1.8%). In vivo results indicated that the materials were non-toxic, biodegradable, biocompatible, and is suitable as bone replacement materials. Thus, we concluded that growth factor loaded MBG is a promising candidate for bone tissue engineering application.

Reconstructing Bone with Natural Bone Graft: A Review of In Vivo Studies in Bone Defect Animal Model.

Bone defects caused by fracture, disease or congenital defect remains a medically important problem to be solved. Bone tissue engineering (BTE) is a promising approach by providing scaffolds to guide and support the treatment of bone defects. However, the autologous bone graft has many defects such as limited sources and long surgical procedures. Therefore, xenograft bone graft is considered as one of the best substitutions and has been effectively used in clinical practice. Due to better preserved natural bone structure, suitable mechanical properties, low immunogenicity, good osteoinductivity and osteoconductivity in natural bone graft, decellularized and demineralized bone matrix (DBM) scaffolds were selected and discussed in the present review. In vivo animal models provide a complex physiological environment for understanding and evaluating material properties and provide important reference data for clinical trials. The purpose of this review is to outline the in vivo bone regeneration and remodeling capabilities of decellularized and DBM scaffolds in bone defect models to better evaluate the potential of these two types of scaffolds in BTE. Taking into account the limitations of the state-of-the-art technology, the results of the animal bone defect model also provide important information for future design of natural bone composite scaffolds.

Preparation and in vivo biocompatibility studies of different mesoporous bioactive glasses

A new generation of nanostructured glasses called mesoporous bioactive glasses (MBGs) exhibit superior surface texture, porosity and bioactive characteristics. The present study is carried out to develop and detailed characterize of ternary SiO2-CaO-P2O5 MBG structure, fabricated by three different variations using different surfactants, e.g., hexadecyltrimethylammonium bromide (CTAB), poly-ethylene glycol,(PEG) and Pluronic P123. After thorough physico-chemical characterization, MBG granules were investigated for in vivo bone regeneration in animal bone defect model (rabbit) where standard S53P4 bioactive glass was used as control. All the synthesized MBG powders showed nano-range median particle size of 80–120 nm (MBG-CTAB), 50–70 nm (MBG-PEG and MBG-P123) while their specific surface area as 473.2, 52.2 and 169.3 m2/g respectively. All MBGs showed mesoporous nature corroborating transmission electron microscopy (TEM) observation as well. Bone regeneration property was measured after 45 and 90 days post-implantation at distal epiphysis of rabbit femur by radiography, histology, fluorochrome labeling, micro computed tomography (micro-CT) and vital organ histology. Results from in vivo studies indicated that the MBG materials produce minimal toxicity to the body. Furthermore, the biocompatibility and biodegradability of the implant makes them more suitable for application in bone tissue engineering. Among various implants, MBG fabricated using suitable surfactant (CTAB) shown the best result compared to other implants. Nonetheless, all the materials are suitable for application in bone tissue engineering and have potential for bone regeneration and healing.

Blood Prefabrication Subcutaneous Small Animal Model for the Evaluation of Bone Substitute Materials.

Because of the size of bone substitute material particles, large animal bone defect models are usually required for the assessment of these materials. However, these models have several disadvantages including high cost, complicated operation procedures, ethical issues, and difficulties in sample analysis. In addition, for mimicking the bone environment, conventional subcutaneous models require the addition of osteogenic factors and stem cells, resulting in an expensive model with a complex experimental procedure. To avoid these issues, in this study, we proposed a convenient and effective blood prefabrication subcutaneous small animal model that could be applied to assess bone substitute materials. Our results demonstrated that blood prefabrication could be an economical, convenient, and useful "adhesive" for handling bone substitute particles. This process provided porcine hydroxyapatite (PHA) with a microenvironment enriched with mesenchymal stem cells and growth factors. Using this strategy, a bonelike structure could form in a rat subcutaneous pocket. Furthermore, the optimized subcutaneous model was used to evaluate the PHA's osteoinductivity, producing results similar to those of the calvarial bone defect in terms of osteogenesis, osteoclastogenesis, and blood vessel formation. These results collectively imply that the blood prefabrication subcutaneous small animal model is convenient and effective for the assessment of osteoinductivity of bone substitute materials.

Regenerating bone with bioactive glass scaffolds: A review of in vivo studies in bone defect models.

Bioactive glasses are at the centre of increasing research efforts in bone tissue engineering as the number of research groups around the world carrying out research on this type of biomaterials continues to increase. However, there are no previous reviews in literature which specifically cover investigations of the performance of bioactive glass scaffolds in bone defect animal models. This is the topic of the present review, in which we have analysed comprehensively all available literature in the field. The review thus fills a gap in the biomaterials literature providing a broad platform of information for researchers interested in bioactive glasses in general and specifically in the outcomes of in vivo models. Bioactive glass scaffolds of different compositions tested in relevant bone defect models are covered.

Research progress in osteogenesis and osteogenic mechanism of heparan sulfate

To discuss the role of heparan sulfate (HS) in bone formation and bone remodeling and summarize the research progress in the osteogenic mechanism of HS. The domestic and abroad related literature about HS acting on osteoblast cell line in vitro, HS and HS composite scaffold materials acting on the ani-mal bone defect models, and the effect of HS proteoglycans on bone development were summarized and analyzed. Many growth factors involved in fracture healing especially heparin-binding growth factors, such as fibroblast growth factors, bone morphogenetic protein, and transforming growth factor β, are connected noncovalently with long HS chains. HS proteoglycans protect these proteins from protease degradation and are directly involved in the regulation of growth factors signaling and bone cell function. HS can promote the differentiation of stem cells into osteoblasts and enhance the differentiation of osteoblasts. In bone matrix, HS plays a significant role in promoting the formation, maintaining the stability, and accelerating the mineralization. The osteogenesis of HS is pronounced. HS is likely to become the clinical treatment measures of fracture nonunion or delayed union, and is expected to provide more choices for bone tissue engineering with identification of its long-term safety.

A comparative study of tissue-engineered constructs from Acropora and Porites coral in a large animal bone defect model.

ObjectivesTo compare the therapeutic potential of tissue-engineered constructs (TECs) combining mesenchymal stem cells (MSCs) and coral granules from either Acropora or Porites to repair large bone defects.Materials and MethodsBone marrow-derived, autologous MSCs were seeded on Acropora or Porites coral granules in a perfusion bioreactor. Acropora-TECs (n = 7), Porites-TECs (n = 6) and bone autografts (n = 2) were then implanted into 25 mm long metatarsal diaphyseal defects in sheep. Bimonthly radiographic follow-up was completed until killing four months post-operatively. Explants were subsequently processed for microCT and histology to assess bone formation and coral bioresorption. Statistical analyses comprised Mann-Whitney, t-test and Kruskal–Wallis tests. Data were expressed as mean and standard deviation.ResultsA two-fold increaseof newly formed bone volume was observed for Acropora-TECs when compared with Porites-TECs (14 sd 1089 mm3 versus 782 sd 507 mm3; p = 0.09). Bone union was consistent with autograft (1960 sd 518 mm3). The kinetics of bioresorption and bioresorption rates at four months were different for Acropora-TECs and Porites-TECs (81% sd 5% versus 94% sd 6%; p = 0.04). In comparing the defects that healed with those that did not, we observed that, when major bioresorption of coral at two months occurs and a scaffold material bioresorption rate superior to 90% at four months is achieved, bone nonunion consistently occurred using coral-based TECs.DiscussionBone regeneration in critical-size defects could be obtained with full bioresorption of the scaffold using coral-based TECs in a large animal model. The superior performance of Acropora-TECs brings us closer to a clinical application, probably because of more suitable bioresorption kinetics. However, nonunion still occurred in nearly half of the bone defects.Cite this article: A. Decambron, M. Manassero, M. Bensidhoum, B. Lecuelle, D. Logeart-Avramoglou, H. Petite, V. Viateau. A comparative study of tissue-engineered constructs from Acropora and Porites coral in a large animal bone defect model. Bone Joint Res 2017;6:208–215. DOI: 10.1302/2046-3758.64.BJR-2016-0236.R1.

Autogenous bone particle/titanium fiber composites for bone regeneration in a rabbit radius critical-size defect model

ABSTRACTPurpose: To explore the effects of autogenous bone particle/titanium fiber composites on repairing segmental bone defects in rabbits. Materials and methods: A model of bilateral radial bone defect was established in 36 New Zealand white rabbits which were randomly divided into 3 groups according to filling materials used for bilaterally defect treatment: in group C, 9 animal bone defect areas were prepared into simple bilateral radius bone defect (empty sham) as the control group; 27 rabbits were used in groups ABP and ABP-Ti. In group ABP, left defects were simply implanted with autogenous bone particles; meanwhile, group ABP-Ti animals had right defects implanted with autogenous bone particle/titanium fiber composites. Animals were sacrificed at 4, 8, and 12 weeks, respectively, after operation. Results: Micro-CT showed that group C could not complete bone regeneration. Bone volume to tissue volume values in group ABP-Ti were better than group ABP. From histology and histomorphometry Groups ABP and ABP-Ti achieved bone repair, the bone formation of group ABP-Ti was better. The mechanical strength of group ABP-Ti was superior to that of other groups. Conclusions: These results confirmed the effectiveness of autologous bone particle/titanium fiber composites for promoting bone regeneration and mechanical strength.

The Balance between Bone Formation and Material Resorption in Unidirectional Porous β-Tricalcium Phosphate Implanted in a Rabbit Tibia

We examined the balance between bone formation and material resorption in β-tricalcium phosphate, with unidirectional pores (porosity of 57%) and micropore structure. Using an animal bone defect model, rapid bone formation reached to the center of the material, while the material remained at the same period. Histomorphometric analysis showed that the sum total area of formed bone and material gradually increased with time throughout the experiment. These results indicate that the balance between bone formation and material resorption in this material is satisfactory.

Potential application of nano-hydroxyapatite in treatment of osteoporotic bone healing - a preliminary study

Event Abstract Back to Event Potential application of nano-hydroxyapatite in treatment of osteoporotic bone healing - a preliminary study Xiao Yang1, Pengfei Xie1, Xuening Chen1, Xiangdong Zhu1, Yujiang Fan1 and Xingdong Zhang1 1 Sichuan University, National Engineering Research Center for Biomaterials, China Osteoporotic fracture is a significant cause of morbidity and mortality in elderly population. Delayed bone union or nonunion often occurred in clinical osteoporotic fracture. Natural osteoporotic bone hydroxyapatite crystal is within nano-dimension[1]. Thus, we hypothesized that material which contains hydroxyapatite nano particles (HANP) would have good biocompatibility with osteoporotic bone derived osteoblast (bone forming cell). HANP is made by traditional two-step synthesis method and later confirmed by TEM and XRD. Primary osteoblast culture is isolated from osteoporotic and healthy rat long bones. The osteoblasts are treated with different concentration of HANP, ranging from 0 to 500 ug/ml. MTT, confocal imaging, ELISA and RT-PCR were done to characterize cellular response to HANP. We found that 100 ug/ml HANP treated osteoporotic osteoblast had larger cell spread area (+48%, p=0.034) and higher bone related protein secretion (alkaline phosphatase and osteocalcin etc.). At this concentration of HANP, bone forming marker genes: bsp, ocn, alp and osx mRNA expression is significantly increased (p<0.05 vs. 0 ug/ml). These positive alterations may attribute to a higher cellular calcium ion concentration, measured by flow cytometry. Significant increase in cellular sodium-potassium ATPase level with exposure to 100 ug/ml HANP played an important role in cellular calcium intake. Animal bone defect model showed that with 100 ug/ml injection of HANP, ovariectomized rat had faster bone healing rate as compare with non-treated control. We conclude that below 500 ug/ml, HANP is non-toxic and could effectively promote osteoporotic osteoblast differentiation, as well as bone integration process. Materials delivering HANP would be a promising solution for osteoporotic bone nonunion. National Science and Technology Supporting Project, Grant No. 2012BAI17B01