Rabbit Skull Research Articles

Geometric morphometric analysis of new zealand rabbit cranium

This study, aimed to determine the shape features of the New Zealand rabbit skull and to reveal the differences between individuals and genders in terms of shape features. For this purpose, the geometric morphometry method was used. A total of 10 female and 10 male New Zealand Rabbit craniums were used. The skulls were photographed in a dorsal, ventral and lateral view, and the mandible was photographed in a lateral view. Homologous landmarks were marked on the photographs. Consensus graphs were created by the TpsRelw (Version 1.70) program. Additionally, principal component analysis and relative warp analysis were performed. As a result of the study, principal components explained 34.813%, 57.225% and 42.427% of the total shape difference in the dorsal, ventral and lateral views of the skull, respectively. In the first principal component graph obtained as a result of principal component analysis, no significant clustering was observed between genders. According to the graphics obtained in the MorphoJ program, inter-individual variation was detected mainly in the viscerocranium, followed by the neurocranium. This study will contribute to morphological and archaeological studies on rabbit skulls.

Evaluation and 3D imaging of mineral structure changes of the rabbit (New Zealand) skull during developmental periods.

This study aimed to determine the morphometric measurements anatomically and CT images of skulls of healthy male and female rabbits during postnatal development, to analyse the data statistically and to demonstrate the structural changes in bone. A total of 40 rabbits (20 females and 20 males) were divided into four groups including prepubertal period (group I (0-1 month)), period between adolescence and adulthood (group II (3-5 month)) and later (young adult period as group III (1-3 years) and old adult period as group IV (3-5 years)), with five animals in each group. After the morphometric measurements, the surface area and volume values of the skull were calculated. The skulls were reconstructed using a 3D Slicer (5.0.2), which is used for 3D modelling. The cranial bones in each group were then crushed using a grinder so that the powdered samples were obtained for XRF (X-ray fluorescence technique). The p-value was statistically highly significant between group and gender (p < 0.001). In morphometric measurements, males were generally higher than females. Only PL, GBOC and GNB measurements were higher in females. The p-value between groups (in all measurements), between genders (in TL, GLN, FL, VL, OZB and GBN parameters) and between groups and genders (in TL, DL and VL parameters) was statistically highly significant (p < 0.001). The p-value between the groups, p-value between sexes and p-value between group and sex in Si, P, K, Ca, Ni, Zn, Sr, Sr and Ca/P elements were statistically significant (p < 0.001). Consequently, metric, volume and surface area measurements were taken through 3D modelling of skull bone in prepubertal period (group I), period between adolescence and adulthood (group II) and later (young adult period as group III and old adult period as group IV) of rabbits and the change in the mineral structure during postnatal development and effect of sex on this change were investigated. This might be the first study to assess both metric and mineral changes at four age intervals taken during the life span of rabbits.

Microgels-Encapsulated Magnesium/Emodin-based metal organic framework nanorods for diabetic bone regeneration

Diabetic bone defect repair is one of the major challenges in clinic, because the pathological microenvironments such as hyperglycemia, oxidative stress, and inflammation exist in the bone defect area of diabetes mellitus. Although the current tissue-engineered bone has achieved favorable bone regeneration and functional reconstruction, it is still unsatisfactory for diabetic bone defect repair only by correcting a single pathological factor. In this study, we develop a multifunctional nano-releasing system of GelMA/HAMA microgels-encapsulated Mg2+/Emodin (MgEm) nanorods based on MOF design principle (denoted as MEGH) for reversing the diabetic pathological microenvironment. For the slow-release system of MEGH microgels, Emodin exert the hypoglycemic, antioxidant, and anti-inflammatory function, while Mg2+ ions could promote angiogenesis for bone regeneration. Subsequently, we combine decalcified bone matrix with the bone regenerative units based on BMSCs-loaded MEGH microgels (BMSCs@MEGH-D) for the construction of tissue-engineered bone. Finally, the pre-constructed BMSCs@MEGH-D scaffolds successfully promote the vascularized bone regeneration in diabetic rabbit skull models due to the effective correction of diabetic pathological microenvironment. The underlying mechanism indicates a synergetic efficacy of regulate glucose, inflammation, oxygen-related bioprocesses, as well as osteogenesis-related pathways. Our findings provide a promising treatment for reversing the diabetic pathological microenvironment to accelerate bone defect repair.

УЛЬТРАСТРУКТУРНЫЕ ИЗМЕНЕНИЯ В ТВЕРДОЙ МОЗГОВОЙ ОБОЛОЧКЕ ПОСЛЕ КРАНИОПЛАСТИЧЕСКИХ ОПЕРАЦИЙ

Background. Performing cranioplasty is a method of treating trepanated syndrome. Modern cranioplastic material should be biocompatible and does not cause inflammatory changes in the adjacent membranes of the brain. Aim of the research. To study ultrastructural changes in the dura mater after cranial trepanation, after plasty of the skull defect with a titanium plate "Medbiotech" and material "Superfluvis" and compare with an intact meninges. Material and methods. Rabbits underwent experimental skull trepanation (group "control"), plastic closure of the trepanation defect with titanium (group "titanium"), material "Superfluvis" (group "experience"). The "intact" group consisted of rabbits without surgery. The thickness of the dura mater and ultrastructural changes in it were studied. Results. The average thickness of the dura mater when using the "Superfluvis" material in cranioplasty was 2.74 times (p=0.005) higher than the intact one, but its thickness was 1.66 times (p=0.008) and 1.39 times (p=0.005) less in comparison with the "titan" and "control" groups, respectively. Conclusions. Cranioplasty of the trepanation defect of the rabbit skull with a material separating the dura mater from the soft tissues of the head reduces the degree of hyperplasia of fibrous tissue in this shell. The use of the "Superfluvis" material to close the defect of the rabbit skull causes less pronounced fibrosis of the TMO subject, and also contributes to greater preservation of the structure of the layer of boundary dural cells than when using a titanium plate for the same purpose.

Regional variation of the cortical and trabecular bone material properties in the rabbit skull.

The material properties of some bones are known to vary with anatomical location, orientation and position within the bone (e.g., cortical and trabecular bone). Details of the heterogeneity and anisotropy of bone is an important consideration for biomechanical studies that apply techniques such as finite element analysis, as the outcomes will be influenced by the choice of material properties used. Datasets detailing the regional variation of material properties in the bones of the skull are sparse, leaving many finite element analyses of skulls no choice but to employ homogeneous, isotropic material properties, often using data from a different species to the one under investigation. Due to the growing significance of investigating the cranial biomechanics of the rabbit in basic science and clinical research, this study used nanoindentation to measure the elastic modulus of cortical and trabecular bone throughout the skull. The elastic moduli of cortical bone measured in the mediolateral and ventrodorsal direction were found to decrease posteriorly through the skull, while it was evenly distributed when measured in the anteroposterior direction. Furthermore, statistical tests showed that the variation of elastic moduli between separate regions (anterior, middle and posterior) of the skull were significantly different in cortical bone, but was not in trabecular bone. Elastic moduli measured in different orthotropic planes were also significantly different, with the moduli measured in the mediolateral direction consistently lower than that measured in either the anteroposterior or ventrodorsal direction. These findings demonstrate the significance of regional and directional variation in cortical bone elastic modulus, and therefore material properties in finite element models of the skull, particularly those of the rabbit, should consider the heterogeneous and orthotropic properties of skull bone when possible.

Application of Three-Dimension Printing Nano-Carbonated-Hydroxylapatite to the Repair of Defects in Rabbit Bone.

Hydroxylapatite (HAp) is a biodegradable bone graft material with high biocompatibility. However, the clinical application of HAp has been limited due to the poor absorption rate in vivo. In this study, carbonated hydroxylapatite (CHAp) with a chemical composition similar to natural bone was synthesized. HAp and CHAp scaffolds were fabricated by 3D printing. Each material was designed by two types of scaffold model with a maximum width of 8 mm and a thickness of 2 mm, ie, structure I (round shape) and structure II (grid shape). Then, the HAp scaffolds were loaded with lutein. These scaffolds were implanted into the 8 mm bone defect on the top of the rabbit skull within 3 hours in the morning. The curative effects of the scaffolds were assessed two months after implantation. The 3D printed scaffolds did not cause severe inflammation or rejection after implantation. It showed that the porous structures allow bone cells to enter into the scaffolds. Furthermore, CHAp scaffolds were more biocompatible than HAp scaffolds, and showed a higher level of degradation and new bone formation after implantation. Structure II scaffolds with a smaller mineral content degraded faster than structure I, while structure I had better osteoconductive properties than structure II. Besides, the addition of lutein significantly enhanced the rate of new bone formation. The uniqueness of this study lies in the synthesis of 3D printed CHAp scaffolds and the implantation of CHAp in rabbit bone defects. The incorporation of suitable carbonate and lutein into HAp can enhance the osteoinductivity of the graft, and CHAp has a faster degradation rate in vivo, all of which provide a new reference for the research and application of apatite-based composites.

Melatonin-loaded mesoporous zinc- and gallium-doped hydroxyapatite nanoparticles to control infection and bone repair.

Effective treatment of infected bone defects resulting from multi-drug resistant bacteria (MDR) has emerged as a significant clinical challenge, highlighting the pressing demand for potent antibacterial bone graft substitutes. Mesoporous nanoparticles have been introduced as a promising class of biomaterials offering significant properties for treating bone infections. Herein, we synthesize antibacterial mesoporous hydroxyapatite substituted with zinc and gallium (Zn-Ga:mHA) nanoparticles using a facile sol-gel method. The resulting mesoporous nanoparticles are applied for the controlled release of melatonin (Mel). Zn-Ga:mHA nanoparticles with an average particle size of 36 ± 3 nm and pore size of 10.6 ± 0.4 nm reveal a Mel loading efficiency of 58 ± 1%. Results show that 50% of Mel is released within 20 h and its long-term release is recorded up to 50 h. The Zn-Ga:mHA nanoparticles exhibit highly effective antibacterial performance as reflected by a 19 ± 1% and 8 ± 2% viability reduction in Escherichia coli and Staphylococcus bacteria, respectively. Noticeably, Mel-loaded Zn-Ga:mHA nanoparticles are also cytocompatible and stimulate in vitro osteogenic differentiation of human mesenchymal stem cells (hMSCs) without any osteoinductive factor. In vivo studies in a rabbit skull also show significant regeneration of bone during 14 days. In summary, Mel-loaded Zn-Ga:mHA nanoparticles provide great potential as an antibacterial and osteogenic component in bone substitutes like hydrogels, scaffolds, and coatings.

DLP fabrication of HA scaffold with customized porous structures to regulate immune microenvironment and macrophage polarization for enhancing bone regeneration

The immune microenvironment plays a pivotal role in osteoanagenesis. Biomaterials can modulate osteogenic efficacy by inducing specific local immune reactions. As 3D-printing technology advances, digital light projection printing has emerged as a promising method for creating large scale, high-precision biomaterial scaffolds. By adjusting the solid content and the sintering conditions during printing, the pore size of biomaterials can be meticulously controlled. Yet, the systematic influence of pore size on the immune microenvironment remains uncharted. We fabricated 3D-printed hydroxyapatite bioceramic scaffolds with three distinct pore sizes: 400 μm, 600 μm, and 800 μm. Our study revealed that scaffolds with a pore size of 600 μm promote macrophage M2 polarization, which is achieved by upregulating interferon−beta and HIF-1α production. When these materials were implanted subcutaneously in rats and within rabbit skulls, we observed that the 600 μm scaffolds notably improved the long-term inflammatory response, fostered vascular proliferation, and augmented new bone growth. This research paves the way for innovative therapeutic strategies for treating large segmental bone defects in clinical settings.

Can locally applied risedronate be an effective agent when combined with xenografts? An animal study

BackgroundTo examine the effects of local risedronate application with xenografts on healing of rabbit skull defects using histological, histomorphometric, immunohistochemical, and three-dimensional radiological methods.MethodsTwo critical-sized defects with a diameter of 10 mm were created in 16 rabbits and filled with xenogenic bone graft and xenogenic bone graft + 5 mg risedronate in the control I and risedronate (RIS) groups, respectively. Residual graft, new bone, soft tissue areas, and bone volume were evaluated in the 4- and 8-week study groups.ResultsIn both the 4- and 8-week samples, the RIS group samples had significantly higher mean new bone area values than the C group (p < 0.05). In both groups, the values for the new bone area were significantly higher in the 8-week-old samples than in the 4-week-old samples (p < 0.05). The h scores obtained for sialoprotein and osteopontin did not differ significantly between the groups at either time point (p > 0.05). The results of radiological evaluation showed that the bone density value was significantly higher in the C group than in the RIS group at either time point (p < 0.05).ConclusionsAlthough this study aimed to demonstrate the effect of risedronate on the osteoconductive properties of xenografts when applied locally, targeted results could not be achieved.

22. The Role of Orai1 in Osteogenic Differentiation Induced by Nanoparticulate Mineralized Collagen Glycosaminoglycan Materials

PURPOSE: Development of synthetic regenerative materials inspired by the extracellular matrix (ECM) has been a topic of significant interest due to the known properties of the ECM to direct cell fate determination via tunable material composition and biomechanical properties. Nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) is a low density, open-cell foam that has been evaluated in our laboratory to induce osteogenic differentiation of primary osteoprogenitors in vitro as well as regeneration of rabbit skull defects in vivo without pre-seeding with progenitor cells or addition of exogenous growth factors, which was not observed in non-mineralized collagen glycosaminoglycan (Col-GAG) materials. Given that the critical difference between MC-GAG and Col-GAG is the mineral content, the spatial concentration of inorganic ions on MC-GAG may be critical to its osteogenic properties. This is supported by prior research demonstrating that high calcium concentrations in the bone microenvironment stimulate osteoblastic differentiation. How these biochemical cues are transmitted to cells and activate downstream osteogenic signaling pathways should be further elucidated. Orai1 is a critical subunit of store-operated calcium release-activated calcium channels (CRAC) that has been implicated to be involved in bone homeostasis. In this work, we evaluated the contribution of Orai1 to MC-GAG-mediated osteogenesis. METHODS: To examine the role of extracellular calcium signaling through store-operated calcium channels, such as Orai1, on osteogenic differentiation of primary bone marrow-derived human mesenchymal stem cells (hMSCs), we treated 2D cell cultures with a small molecule inhibitor of store-operated calcium entry (SOCE), MRS1845, for 14 days. hMSCs were subsequently seeded on MC-GAG or Col-GAG for 7 days with or without MRS1845. Baseline Orai1 gene and protein expression was evaluated. Next, small interfering RNAs (siRNAs) targeting ORAI1 and a scrambled control were used to specifically knockdown ORAI1 expression in hMSCs cultured on Col-GAG and MC-GAG. Osteogenic gene and protein expression were measured using quantitative RT-PCR and western blot analyses, respectively. Mineralization was evaluated by Alizarin Red staining. RESULTS: To understand whether store-operated calcium entry was essential to osteogenic differentiation, we treated hMSCs in 2D cultures with a small molecule inhibitor of SOCE, MRS1845, and found a reduction in calcium depositions visualized with Alizarin Red staining when compared to untreated hMSCs. In 3D cultures, MRS1845 downregulated the gene expression of early osteogenic marker ALP and protein expression of the intracellular osteogenic mediator Runx2 specifically on MC-GAG compared to controls. As small molecule inhibitors lack channel specificity, we knocked down ORAI1 expression through siRNA transfection. When MC-GAG was compared with Col-GAG, baseline ORAI1 gene expression was 1.8-fold higher (p=0.02) and Orai1 protein expression was upregulated (p=0.003). ORAI1 knockdown reduced the protein expression of Runx2 and gene expression of late osteogenic marker BSP2 specifically on MC-GAG compared to scrambled control siRNA. Mineralization significantly diminished on MC-GAG with ORAI1 knockdown, whereas no effects were evident on Col-GAG as demonstrated by Alizarin Red staining. CONCLUSIONS: ORAI1-mediated calcium ion signaling was required for MC-GAG-induced osteogenic differentiation. Further elucidation of the osteogenic mechanisms and refinement of calcium levels on MC-GAG may facilitate its clinical application in the reconstruction of osseous defects.

Bone Mineral Density Prediction from CT Image: A Novel Approach using ANN.

Though treatable, osteoporosis continues as a substantially underdiagnosed and undertreated condition. Bone mineral density (BMD) monitoring will definitely aid in the prediction and prevention of medical emergencies arising from osteoporosis. Although quantitative computed tomography (QCT) is one of the most widely accepted tools for measuring BMD, it lacks the contribution of bone architecture in predicting BMD, which is significant as aging progresses. This paper presents an innovative approach for the prediction of BMD incorporating bone architecture that involves no extra cost, time, and exposure to severe radiation. In this approach, the BMD is predicted using clinical CT scan images taken for other indications based on image processing and artificial neural network (ANN). The network used in this study is a standard backpropagation neural network having five input neurons with one hidden layer having 40 neurons with a tan-sigmoidal activation function. The Digital Imaging and Communications in Medicine (DICOM) image properties extracted from QCT of human skull and femur bone of rabbit that are closely associated with the BMD are used as input parameters of the ANN. The density value of the bone which is computed from the Hounsfield units of QCT scan image through phantom calibration is used as the target value for training the network. The ANN model predicts the density values using the image properties from the clinical CT of the same rabbit femur bone and is compared with the density value computed from QCT scan. The correlation coefficient between predicted BMD and QCT density valued to 0.883. The proposed network can assist clinicians in identifying early stage of osteoporosis and devise suitable strategies to improve BMD with no additional cost.

Functionalized acellular periosteum guides stem cell homing to promote bone defect repair

The periosteum plays a key role in bone tissue regeneration, especially in the promotion and protection of new bones. However, among the bone repair materials, many biomimetic artificial periosteum lack the natural periosteal structure, stem cells, and immunoregulation required for bone regeneration. In this study, we used natural periosteum to produce acellular periosteum. To retain the appropriate cell survival structure and immunomodulatory proteins, we grafted the functional polypeptide SKP on the surface collagen of the periosteum via an amide bond, providing the acellular periosteum with the ability to recruit mesenchymal stem cells. Thus, we developed a biomimetic periosteum (DP-SKP) with the ability to promote stem cell homing and immunoregulation in vivo. Compared to the blank and simple decellularized periosteum groups, DP-SKP was more conducive to stem cell adhesion, growth, and osteogenic differentiation in vitro. Additionally, compared with the other two groups, DP-SKP significantly promoted mesenchymal stem cell homing to the periosteal transplantation site, improved the bone immune microenvironment, and accelerated new lamellar bone formation in the critical size defect of rabbit skulls in vivo. Therefore, this acellular periosteum with a mesenchymal stem cell homing effect is expected to be used as an extracellular artificial periosteum in clinical practice.

Doped Electrospinned Material-Guides High Efficiency Regional Bone Regeneration.

The main target of bone tissue engineering is to design biomaterials that support bone regeneration and vascularization. Nanostructured membranes of (MMA)1-co-(HEMA)1/(MA)3-co-(HEA)2 loaded with 5% wt of SiO2-nanoparticles (Si-M) were doped with zinc (Zn-Si-M) or doxycycline (Dox-Si-M). Critical bone defects were effectuated on six New Zealand-bred rabbit skulls and then they were covered with the membranes. After six weeks, a histological analysis (toluidine blue technique) was employed to determine bone cell population as osteoblasts, osteoclasts, osteocytes, M1 and M2 macrophages and vasculature. Membranes covering the bone defect determined a higher count of bone cells and blood vessels than in the sham group at the top regions of the defect. Pro-inflammatory M1 appeared in a higher number in the top regions than in the bottom regions, when Si-M and Dox-Si-M were used. Samples treated with Dox-Si-M showed a higher amount of anti-inflammatory and pro-regenerative M2 macrophages. The M1/M2 ratio obtained its lowest value in the absence of membranes. On the top regions, osteoblasts were more abundant when using Si-M and Zn-Si-M. Osteoclasts were equally distributed at the central and lateral regions. The sham group and samples treated with Zn-Si-M attained a higher number of osteocytes at the top regions. A preferential osteoconductive, osteoinductive and angiogenic clinical environment was created in the vicinity of the membrane placed on critical bone defects.

Co-culture bioprinting of tissue-engineered bone-periosteum biphasic complex for repairing critical-sized skull defects in rabbits.

Tissue engineering based on bioprinting technology has broad prospects in the treatment of critical-sized bone defect. Nevertheless, it is challenging to construct composite tissues or organs with structural integrity. Periosteum and stem cells are important in bone regeneration, and it has been shown that co-culture engineering system could successfully repair bone defects. Here, a strategy of co-culture bioprinting was proposed, and a tissue-engineered bone-periosteum biphasic complex was designed. Poly-L-lactic acid/hydroxyapatite (PLLA/HA) was used to construct the supporting scaffold of bone phase. Gelatin methacryl (GelMA) loaded with rabbit bone mesenchymal stem cells (BMSCs) and periosteum-derived stem cells (PDSCs) were used to simulate the extracellular matrix and cellular components of bone and periosteum, respectively, and a co-culture layer was formed between the bone and the periosteum phase. By adjusting material ratios of PLLA/HA and crosslinking time of GelMA, a complex with good mechanical strength and cell activity was constructed and then implanted into the defect area of rabbit skull. The quantitative results of imaging and histology showed that the repair effect of bone-periosteum biphasic complex group was significantly better than that of other control groups, which demonstrated that the bone-periosteum biphasic complex was advantageous to both bone repair and regeneration. In general, using the co-culture bioprinting to construct engineered tissue is a very promising strategy, which is expected to be applied in the construction of more complex tissues and solid organs for tissue repair and organ transplantation.

Effects of a locally administered risedronate/autogenous bone graft combination on bone healing in a critical-size rabbit defect model

BackgroundRisedronate is a bisphosphonate with poor oral absorption. An extremely hydrophilic molecule that has a high affinity for bone, risedronate also inhibits the farnesyl diphosphate synthase enzyme, inhibiting osteoclastic activity and reducing bone turnover and resorption. Autogenous bone grafts contain osteogenic cells and osteoinductive factors that are essential for bone regeneration and are therefore considered the gold standard. Thus, this study aimed to investigate the impact of local risedronate administered with autogenous bone grafts on the healing of defects in rabbit skulls using histological, histomorphometric, immunohistochemical, and three-dimensional radiological methods.MethodsTwo 10-mm-diameter critical-size defects were created in 16 rabbits and filled with autogenous bone graft and autogenous bone graft + 5 mg risedronate in the control (C) and risedronate (RIS) groups, respectively. Residual graft, new bone, soft tissue areas, and bone volume were evaluated in the 4- and 8-week study groups.ResultsThere were no statistically significant differences in bone graft, new bone, or soft tissue area between the groups at 4 weeks (p > 0.05). At 8 weeks, the new bone area was significantly higher in the RIS group than in the C group (p < 0.05). The h scores obtained from sialoprotein and osteopontin did not differ significantly between the groups (p > 0.05). The radiologically measured total bone volume was significantly higher in the RIS group than in the C group at both time points (p < 0.05).ConclusionsIn this study, risedronate enhanced the osteoconductive properties of autogenous bone grafts and rapidly created better-quality bone. This could improve future patient outcomes.

Osteoprotegerin-eluting nanoparticulate mineralized collagen scaffolds improve skull regeneration

Custom synthesis of extracellular matrix (ECM)-inspired materials for condition-specific reconstruction has emerged as a potentially translatable regenerative strategy. In skull defect reconstruction, nanoparticulate mineralized collagen glycosaminoglycan scaffolds (MC-GAG) have demonstrated osteogenic and anti-osteoclastogenic properties, culminating in the ability to partially heal in vivo skull defects without the addition of exogenous growth factors or progenitor cell loading. In an effort to reduce catabolism during early skull regeneration, we fabricated a composite material (MCGO) of MC-GAG and recombinant osteoprotegerin (OPG), an endogenous anti-osteoclastogenic decoy receptor. In the presence of differentiating osteoprogenitors, MCGO demonstrated an additive effect with endogenous OPG limited to the first 14 days of culture with total eluted and scaffold-bound OPG exceeding that of MC-GAG. Functionally, MCGO exhibited similar osteogenic properties as MC-GAG, however, MCGO significantly reduced maturation and resorptive activities of primary human osteoclasts. In a rabbit skull defect model, MCGO scaffold-reconstructed defects displayed higher mineralization as well as increased hardness and microfracture resistance compared to non-OPG functionalized MC-GAG scaffolds. The current work suggests that MCGO is a development in the goal of reaching a materials-based strategy for skull regeneration.

Osseointegration behavior of carbon fiber reinforced polyetheretherketone composites modified with amino groups: An in vivo study.

Polyetheretherketone (PEEK) has become increasingly popular in dentistry and orthopedics due to its excellent chemical stability, reliable biosafety, and low elastic modulus. However, PEEK's biomechanical strength and bioactivity are limited and need to be increased as an implant material. The previous study in vitro has shown that the amino-functionalized carbon fiber reinforced PEEK (A-30%-CPEEK) possessed enhanced mechanical property and bioactivity. This study aims to evaluate the effect of amino groups modification on the osseointegration behavior of carbon fiber reinforced PEEK (30%-CPEEK) in rabbits. Herein, 30%-CPEEK and A-30%-CPEEK implant discs were implanted in rabbit skulls for 5 weeks, with pure titanium implants serving as a control. The bone-forming ability and osseointegration in vivo were systematically investigated by micro-computed tomography analysis, scanning electron microscope observation, and histological evaluation. Our results showed that all detection parameters were significantly different between the A-30%-CPEEK and 30%-CPEEK groups, favoring those in the A-30%-CPEEK, whose appraisal parameters were equal to or better than pure titanium. Therefore, this study supported the importance of amino groups in facilitating the new bone formation and bone-implant integration, suggesting that A-30%-CPEEK with enhanced osseointegration will be a promising material for dental or orthopedic implants.

PCL-nHAC/Mg-Ca alloy composite and preliminary study of its osteogenesis property.

Owing to their excellent properties, magnesium alloys are widely used in bone tissue engineering. However, considerable work has been conducted to control the degradation rate and improve the cytocompatibility of magnesium alloys. In this study, low-cost production introduced a new bone repair composite (PCL-nHAC/Mg-Ca), which was composed of nano-hydroxylapatite-collagen (nHAC), polycaprolactone (PCL) and Mg-Ca alloy substrate treated by micro- arc oxidation (MAO). The experimental results showed that compared with the Mg-Ca alloy treated by MAO alone, the PCL-nHAC/Mg-Ca composite has a porous structure and a slower degradation rate. Cell experiments showed that the PCL-nHAC/Mg-Ca composite had good biocompatibility and significantly enhanced the proliferation of the MC3T3-E1 cells. The rabbit skull defect model further proved that the PCL-nHAC/Mg-Ca composite could regulate the degradation rate of the Mg-Ca alloy and promote the formation of bone tissue. Histological analyses showed that the PCL-nHAC/Mg-Ca composite had good stability in vivo and could better accelerate bone formation.

A novel pilot animal model for bone augmentation using osseous shell technique for preclinical in vivo studies.

Bone grafting is commonly used to reconstruct skeletal defects in the craniofacial region. Several bone augmentation models have been developed to evaluate bone formation using novel bone substitute materials. The aim of this study was to evaluate a surgical animal model for establishing a three-dimensional (3D) grafting environment in the animal's mandibular ramus for bone augmentation using the osseous shell technique, as in humans. Osteological survey of New Zealand white (NZW) rabbit skull (Oryctolagus cuniculus): Initial osteological and imaging surveys were performed on a postmortem skull for a feasibility assessment of the surgical procedure. Postmortem pilot surgery and cone beam computed tomography imaging: a 3D osseous defect was created in the mandibular ramus through a submandibular incision. The osseous shell plates were stabilized with osteosynthesis fixation screws, and defects were filled with particular bone grafting material. In vivo surgical procedure: surgeries were conducted in four 8-week-old NZW rabbits utilizing two osseous shell materials: xenogeneic human cortical plates and autogenous rabbit cortical plates. The created 3D defects were filled using xenograft and allograft bone grafting materials. The healed defects were evaluated for bone formation after 12 weeks using histological and cone beam computed tomography imaging analysis. Clinical analysis 12 weeks after surgery revealed the stability of the 3D grafted bone augmentation defects using the osseous shell technique. Imaging and histological analyses confirmed the effectiveness of this model in assessing bone formation. The proposed animal model is a promising model with the potential to study various bone grafting materials for augmentation in the mandibular ramus using the osseous shell technique without compromising the health of the animal. The filled defects could be analyzed for osteogenesis, quantification of bone formation, and healing potential using histomorphometric analysis, in addition to 3D morphologic evaluation using radiation imaging.

DLP fabricating of precision GelMA/HAp porous composite scaffold for bone tissue engineering application

The hydrogel composited hydroxyapatite (HAp) scaffold shown biomimetic extracellular matrix and osteogenic activity, which is a promising bone regeneration biomaterial. 3D printing has been widely used in fabrication of customized and complex bone regeneration scaffold. However, it is still a challenge to prepare high-precision HAp reinforced composites by digital light processing (DLP) printing that can effectively promote bone regeneration. In this study, shear-thinning gelatin methacrylamide (GelMA)/hydroxyapatite (HAp) composite inks were prepared to fabricate high-precision scaffolds by DLP printing for bone repair. Firstly, GelMA hydrogels with adjustable mechanical, rheological and printing properties were synthesized to screen hydrogel concentration and degree of substitution. Then carefully selected biocompatible dispersants to reduce the agglomeration of hydroxyapatite. The actual printing resolution of the GelMA/HAp porous composite scaffolds with excellent mechanical strength through DLP 3D printing was up to about 100 μm. In vitro, the 3D printed composite scaffold significantly promoted the adhesion and proliferation of osteoblasts, as well as promoted osteogenic differentiation. In vivo, the GelMA/HAp porous composite scaffolds showed excellent ability in accelerating the formation of new bone in rabbit skull defects. The GelMA/HAp porous composite scaffolds fabricated by the composite inks with good printability, mechanical properties and osteogenic activity have fascinating potential in bone repair application.