Enhance Bone Healing Research Articles

Collagen scaffolds functionalised with copper-eluting bioactive glass reduce infection and enhance osteogenesis and angiogenesis both in vitro and in vivo

The bone infection osteomyelitis (typically by Staphylococcus aureus) usually requires a multistep procedure of surgical debridement, long-term systemic high-dose antibiotics, and – for larger defects – bone grafting. This, combined with the alarming rise in antibiotic resistance, necessitates development of alternative approaches. Herein, we describe a one-step treatment for osteomyelitis that combines local, controlled release of non-antibiotic antibacterials with a regenerative collagen-based scaffold. To maximise efficacy, we utilised bioactive glass, an established osteoconductive material with immense capacity for bone repair, as a delivery platform for copper ions (proven antibacterial, angiogenic, and osteogenic properties). Multifunctional collagen-copper-doped bioactive glass scaffolds (CuBG-CS) were fabricated with favourable microarchitectural and mechanical properties (up to 1.9-fold increase in compressive modulus over CS) within the ideal range for bone tissue engineering. Scaffolds demonstrated antibacterial activity against Staphylococcus aureus (up to 66% inhibition) whilst also enhancing osteogenesis (up to 3.6-fold increase in calcium deposition) and angiogenesis in vitro. Most significantly, when assessed in a chick embryo in vivo model, CuBG-CS not only demonstrated biocompatibility, but also a significant angiogenic and osteogenic response, consistent with in vitro studies. Collectively, these results indicate that the CuBG-CS developed here show potential as a one-step osteomyelitis treatment: reducing infection, whilst enhancing bone healing.

Osteogenic potential of human dental pulp-derived mesenchymal stem cells in bone regeneration of rabbit

Background/aim Human dental pulp-derived mesenchymal stem cells (hDP-MSCs) offer a promising source of progenitor cells for regenerative medicine and bone tissue engineering. Cranial defects are common complications that can arise secondary to trauma, surgery, or infection. This study aimed to evaluate the osteogenic differentiation potential of hMSCs isolated from dental pulp of third molar teeth in vitro cultures and the bone regenerative capacity of hDP-MSCs transplanted into induced temporomandibular joint (TMJ) defect in rabbits. Patients and methods hDP-MSCs were isolated from third molar teeth and cultured. Alizarin staining was performed to assess the osteogenic differentiation at the 14th and 28th days. The therapeutic potential of hDP-MSCs in craniofacial bone defects was investigated in the left side of the rabbits’ TMJ. The transplanted cells involved three groups: the osteogenic differentiated DP-MSCs (O), undifferentiated MSCs (M), and control group (cell-free matrix) (C). Cells were loaded on gel foam. Eighteen rabbits were used and sacrificed at subsequent three time points, 4, 6, and 9 weeks, after transplantation, with six rabbits/each time point and two rabbits/each cell group. Histopathological studies were applied to evaluate the healing potential of hDP-MSCs in the induced rabbit TMJ defect. Results hDP-MSCs showed a high proliferative potential and osteogenic differentiation in vitro. Histological results demonstrated a timely correlated mandibular defects’ repair in all the experimental groups, including the control group, with more enhanced bone healing effect for the osteogenic differentiated DP-MSCs. Conclusion hDP-MSCs possess high proliferation capacity and osteogenic differentiation potential in vitro. Histological observations revealed the osteogenic differentiated DP-MSCs have higher bone healing potential than the undifferentiated DP-MSCs at 9 weeks after transplantation, and gel foam promotes bone formation in the control group. The bone regenerative potential of osteogenic differentiated DP-MSCs revealed a significant capacity when implanted in rabbit TMJ defect. Hence, hDP-MSCs could be a promising source for craniofacial bone regeneration.

Combination of a Bioceramic Scaffold and Simvastatin Nanoparticles as a Synthetic Alternative to Autologous Bone Grafting.

The fragile nature of porous bioceramic substitutes cannot match the toughness of bone, which limits the use of these materials in clinical load-bearing applications. Statins can enhance bone healing, but it could show rhabdomyolysis/inflammatory response after overdosing. In this study, the drug-containing bone grafts were developed from poly(lactic acid-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles encapsulating simvastatin (SIM) (SIM-PP NPs) loaded within an appropriately mechanical bioceramic scaffold (BC). The combination bone graft provides dual functions of osteoconduction and osteoinduction. The mechanical properties of the bioceramic are enhanced mainly based on the admixture of a combustible reverse-negative thermoresponsive hydrogel (poly(N-isopropylacrylamide base). We showed that SIM-PP NPs can increase the activity of alkaline phosphatase and osteogenic differentiation of bone marrow stem cells. To verify the bone-healing efficacy of this drug-containing bone grafts, a nonunion radial endochondral ossification bone defect rabbit model (N = 3/group) and a nonunion calvarial intramembranous defect Sprague Dawley (SD) rat model (N = 5/group) were used. The results indicated that SIM-PP NPs combined with BC can improve the healing of nonunion bone defects of the radial bone and calvarial bone. Therefore, the BC containing SIM-PP NPs may be appropriate for clinical use as a synthetic alternative to autologous bone grafting that can overcome the problem of determining the clinical dosage of simvastatin drugs to promote bone healing.

Effects of Extracorporeal Shock Wave Therapy on Distraction Osteogenesis in Rat Mandible.

Distraction osteogenesis has widespread clinical use in the treatment of congenital and acquired craniofacial deformities. Nonetheless, during the prolonged consolidation period, the newly regenerated bone carries the risk of complications. A known method for enhancing bone healing is extracorporeal shock wave therapy, which has been shown to induce neovascularization and promote tissue regeneration. The authors investigated whether extracorporeal shock wave therapy can accelerate bony consolidation and regeneration in distraction osteogenesis of the rat mandible and at which stage of distraction osteogenesis it should be applied. Twenty-four male Sprague-Dawley rats were subjected to distraction osteogenesis of the right mandible (latency period, 3 days; distraction period, 10 days; 0.5 mm/day). Experimental groups consisted of the following: group I (control), no extracorporeal shock wave therapy; group II, extracorporeal shock wave therapy (0.18 mJ/mm(2)) at the latency period; and group III, extracorporeal shock wave therapy (0.18 mJ/mm(2)) at the consolidation period. Explants were removed for evaluation after 4 weeks of consolidation. Histologic evaluation showed well-developed cortical cortex and a higher degree of bone formation and mature bone in group III; micro-computed tomography showed significantly increased bone mineral density, bone volume fraction, and trabecular thickness; immunohistochemistry demonstrated significantly increased expression of bone morphogenetic protein-2, vascular endothelial growth factor, and proliferating cell nuclear antigen. Extracorporeal shock wave therapy application at the consolidation period during distraction osteogenesis in the rat mandible enhances bone formation and osteogenic and angiogenic growth factors, improves bone mechanical properties, and accelerates bone mineralization.

Australian Dental Research Foundation Special Research Supplement 2018

Recent literature suggests that suppressed bone healing and angiogenesis contributes significantly to the pathogenesis of Medication induced osteonecrosis of jaws (MRONJ), a complex condition commonly associated with anti-resorptive agents. This in vitro study evaluated the effect of locally delivered angiogenic growth factor (VEGF165) with or without osteogenic growth factor (BMP-7) to enhance bone healing, thereby preventing the occurrence of MRONJ. A chemically defined hydrogel (HyStem-HP, Glycosan Biosciences) containing a combination of thiolmodified hyaluronan, heparin and denatured collagen was crosslinked with thiol-reactive, PEGDA. To establish the in vitro release kinetics, 100 and 200 ng of rat VEGF165 (Biovision) or BMP-7 (250 and 500 ng/mL) was loaded into a 500 lL hydrogel prior to crosslinking (Hystem-HP).

Noninvasive Localized Cold Therapy: A New Mode of Bone Repair Enhancement.

A variety of biological, mechanical, and physical therapeutic modalities of varying complexity, efficacy, cost, and safety profile have been developed to enhance bone healing. There have been sporadic reports of spontaneous bone formation after repeated cold exposure. In this study we report for the first time, the anabolic effect of cold exposure on bone healing in vivo resulting in a doubling of bone volume. Although the precise mechanism is not fully understood, cold is well known to stimulate osteoclastogenesis and modulate inflammation. The impact of this finding is considerable for tissue regeneration because cold application is noninvasive, safe, and easily implemented.

Biomaterials Enabled Cell-Free Strategies for Endogenous Bone Regeneration.

Repairing bone defects poses a major orthopedic challenge because current treatments are constrained by the limited regenerative capacity of human bone tissue. Novel therapeutic strategies, such as stem cell therapy and tissue engineering, have the potential to enhance bone healing and regeneration, and hence may improve quality of life for millions of people. However, the ex vivo expansion of stem cells and their in vivo delivery pose technical difficulties that hamper clinical translation and commercial development. A promising alternative to cell delivery-based strategies is to stimulate or augment the inherent self-repair mechanisms of the patient to promote endogenous restoration of the lost/damaged bone. There is growing evidence indicating that increasing the endogenous regenerative potency of bone tissues for therapeutics will require the design and development of new generations of biomedical devices that provide key signaling molecules to instruct cell recruitment and manipulate cell fate for in situ tissue regeneration. Currently, a broad range of biomaterial-based deployment technologies are becoming available, which allow for controlled spatial presentation of biological cues required for endogenous bone regeneration. This article aims to explore the proposed concepts and biomaterial-enabled strategies involved in the design of cell-free endogenous techniques in bone regenerative medicine.

Frontal Bone Healing Is Sensitive to Wnt Signaling Inhibition via Lentiviral-Encoded Beta-Catenin Short Hairpin RNA.

The Wnt/β-catenin signaling pathway plays an integral role in skeletal biology, spanning from embryonic skeletal patterning through bone maintenance and bone repair. Most experimental methods to antagonize Wnt signaling in vivo are either systemic or transient, including genetic approaches, use of small-molecule inhibitors, or neutralizing antibodies. We sought to develop a novel, localized model of prolonged Wnt/β-catenin signaling blockade by the application and validation of a lentivirus encoding β-catenin short hairpin RNA (shRNA). Efficacy of lentiviral-encoded β-catenin shRNA was first confirmed in vitro using bone marrow mesenchymal stromal cells, and in vivo using an intramedullary long bone injection model in NOD SCID mice. Next, the effects of β-catenin knockdown were assessed in a calvarial bone defect model, in which the frontal bone demonstrates enhanced bone healing associated with heightened Wnt/β-catenin signaling. Lentivirus encoding either β-catenin shRNA or random sequence shRNA with enhanced green fluorescent protein (control) was injected overlying the calvaria of NOD SCID mice and bone defects were created in either the frontal or parietal bones. Among mice treated with lentivirus encoding β-catenin shRNA, frontal bone defect healing was significantly reduced by all radiographic and histologic metrics. In contrast, parietal bone healing was minimally impacted by β-catenin shRNA. In aggregate, our data document the application and validation of a lentivirus encoding β-catenin shRNA model that represents an easily replicable tool for examining the importance of locoregional Wnt/β-catenin signaling in bone biology and regeneration.

Histologic and histomorphometric evaluation of lyophilized amniotic membrane in bone healing: An experimental study in rabbit's femur

Amniotic membrane has been widely used in regenerative medicine especially ophthalmology. It has many advantages including anti-inflammatory, anti-fibrotic and antimicrobial properties. The purpose of the present work to study the effect of lyophilized human amniotic membrane on healing of bony defect in rabbits' femur. Eighteen male rabbits were used. Four mm wide and 5 mm deep defect was created in the femur diaphysis bilaterally in each rabbit. The defect of the right side was left empty (control), while the left side was filled with the amniotic membrane (study). Six rabbits were scarified at each of the experimental periods 2, 4 & 6 weeks postoperatively. The defect areas were dissected out and evaluated histologically & histomorphometrically. In the control group, at 2 weeks, woven bone spicules were seen extending from the periphery of the defect boundaries. At 4 weeks, the newly formed bone became more mature. At 6 weeks, the newly formed bone was more dense with newly formed osteons were seen. However, in the study group, the newly formed bone was much less in relation to the control group. Remnants of the amniotic membrane was seen folded at the center of the defect area surrounded by inflammatory cells. Histomorphometrically, the mean percentage of bone surface area in control group was higher than the study group in all experimental periods and the difference was statistically significant (p < 0.001). It was concluded that: freeze dried amniotic membrane is not suitable to enhance bone healing when used as a filling material in bone defects.

Enhanced bone healing in porous Ti implanted rabbit combining bioactive modification and mechanical stimulation.

To improve the bone healing efficiency of porous titanium implants, desired biological properties of implants are mandatory, involving bioactivity, osteoconductivity, osteoinductivity and a stable environment. In this study, bare porous titanium (abbr. pTi) with the porosity of 70% was fabricated by vacuum diffusion bonding of titanium meshes. Hydroxyapatite-coated pTi (abbr. Hap-pTi) was obtained by successively subjecting pTi to alkali heat treatment, pre-calcification and simulated body fluid. Both pTi and Hap-pTi were respectively implanted into the tibia defect model (ϕ10 mm × 6 mm) in New Zealand white rabbits, then subjected to non-invasively axial compressive loads at high-magnitude low-frequency (HMLF), which were denoted as F-pTi and F-Hap-pTi, respectively. Bone repairing efficiencies were analyzed by postoperative X-ray examination, optical observation and HE staining after 14 and 30 days of implantation. ALP and OCN contents in serum were also examined at 30 days. Results showed that the sham group and sham group with mechanical stimulation (abbr. F-sham) preferably caused bone fractures. Qualitatively, Hap-pTi reduced the risk of bone fractures and enhanced bone healing slightly more effectively compared to bared pTi. However, both Hap-pTi combined with mechanical stimulation and F-pTi in the case of bioactive modification could result in a higher bone healing efficiency (F-Hap-pTi). The molecular signaling investigation of ALP and OCN contents in serum further revealed a probable synergistic effect of Hap coating coupling with HMLF compression on improving bone repairing efficiency. It provides a candidate of clinically applicable therapy for osseous defects.

Low-intensity pulsed ultrasound promotes alveolar bone regeneration in a periodontal injury model

Periodontitis is a common oral disease characterized by progressive destruction of periodontal tissue and loss of teeth. However, regeneration of periodontal tissue is a time-consuming process. Low-intensity pulsed ultrasound (LIPUS) is a widely used non-invasive intervention for enhancing bone healing in fractures and non-unions. With the hypothesis that LIPUS may accelerate periodontal regeneration, the effects of LIPUS on periodontal tissue regeneration were investigated both in vitro and in vivo. LIPUS (90 mw/cm2, 20 min/d, 1.5 MHz) was applied to stimulate dog periodontal ligament cells (dPDLCS). The mRNA expression of BSP (P < 0.05), OPN (P < 0.05) and COL3 (P < 0.05) was increased significantly in the LIPUS group. The positive stained mineralized nodules by alizarin red in the LIPUS group were greater than in the control group (P < 0.05). Eight male beagle dogs were divided into 4 groups: guided tissue regeneration (GTR) group (G1), LIPUS + GTR group (G2), LIPUS group (G3), and control group (G4, no treatment). A 4 × 5 mm2 defect was created in the buccal alveolar bone. The modeling areas in the G2 and G3 groups were then exposed to LIPUS. Eight weeks after surgery, histological assessment indicated increased periodontal tissue in the LIPUS + GTR group. Micro computed tomography (micro-CT) showed that the regenerated bone volume (BV) in the G2 was significantly higher than that in the G1, G3 and G4 groups (P < 0.05). The bone surface (BS) trabecular number (Tb.N) and trabecular thickness (Tb.Th) in G2 were markedly higher than in G4 (P < 0.05). It is concluded that LIPUS + GTR can accelerate new alveolar bone formation, with a prospective for promoting periodontal tissue repair.

Bone marrow mesenchymal stem cells: Aging and tissue engineering applications to enhance bone healing

Bone has well documented natural healing capacity that normally is sufficient to repair fractures and other common injuries. However, the properties of bone change throughout life, and aging is accompanied by increased incidence of bone diseases and compromised fracture healing capacity, which necessitate effective therapies capable of enhancing bone regeneration. The therapeutic potential of adult mesenchymal stem cells (MSCs) for bone repair has been long proposed and examined. Actions of MSCs may include direct differentiation to become bone cells, attraction and recruitment of other cells, or creation of a regenerative environment via production of trophic growth factors. With systemic aging, MSCs also undergo functional decline, which has been well investigated in a number of recent studies. In this review, we first describe the changes in MSCs during aging and discuss how these alterations can affect bone regeneration. We next review current research findings on bone tissue engineering, which is considered a promising and viable therapeutic solution for structural and functional restoration of bone. In particular, the importance of MSCs and bioscaffolds is highlighted. Finally, potential approaches for the prevention of MSC aging and the rejuvenation of aged MSC are discussed.

The effect of plasma treatment on the osseointegration of rough titanium implant: A histo-morphometric study in rabbits

Background/purposeThe surface properties, such as hydrophilicity and functional OH groups, play an important role in bone fixation in vivo. In our previous study, the plasma treatments of large grit and acid etching (SLA) method produce functional OH groups on the rough surface. There is no report in discussing the integration between basic Ti—OH groups and bone-to-implant contact (BIC). The aim of this study was to evaluate the effect of the functional OH groups on the rough surface both in vitro and in vivo.Materials and methodsFunctional hydroxyl groups were produced on a SLA-treated surface. The surface topography, roughness, wettability, and chemical composition were examined using various techniques. Twenty-four implants were inserted into the proximal tibia of four New Zealand white rabbits. The biological responses were measured in terms of histomorphometric analysis 4 and 8 weeks post-implantation.ResultsThe surface morphology and roughness were similar among all groups. However, the concentration of OH groups and hydrophilicity were found increased in the plasma treatment. The cell morphology in RF-plasma treated groups had more polygonal type and higher expression of actin and vinculin. The bone-to-implant contact (BIC) ratios of RF-200W were significantly higher than other groups (P < 0.05). The relationship between basic OH groups and BIC showed linear correspondence.ConclusionThe Ti—OH groups introduced on the rough surface by plasma treatments can trigger cell adhesion which further initiate new bone apposition. We propose that RF-plasma treatment can help to enhance bone healing at 4 and 8 weeks.

Combined effect of parathyroid hormone and strontium ranelate on bone healing in ovariectomized rats.

Parathyroid hormone (PTH) enhances bone healing. Strontium ranelate (SR) is an antiresorptive agent that increases bone formation. Reports about combined effects of PTH and SR on local bone regeneration in osteoporotic subjects are limited. We aimed at investigating the efficacy of PTH and SR for promoting new bone formation in critical-sized defects of ovariectomized rats. Parathyroid hormone- and/or SR-containing poloxamer implant tablets with/without chitosan microparticles were delivered locally to calvarial defects of 90 Wistar rats. Biopsies were analyzed histologically and histomorphometrically at 4 and 8weeks of healing. Histomorphometry revealed that PTH alone promoted new bone formation at 4weeks but the efficiency declined in 8weeks. There was no positive effect of SR alone on bone formation at 4 or 8weeks. Calvarial defects treated with PTH+SR combinations showed statistically significant greater new bone formation than either treatment alone at both time intervals. Tissue responses were modest and supported the good biocompatibility of the biomaterials used. Parathyroid hormone and SR combinations can be effective for calvarial bone regeneration of ovariectomized rats. PTH plus SR may have potential use as bone graft material in orthopedic and dental surgery to enhance bone healing and osseointegration.

The Role of Locking Plate Stiffness in Bone Fracture Healing Stabilized by Far Cortical Locking Technique

The locking plate fixations have been developed to enhance bone healing by wide bridging of the fracture and allowing some level of interfragmentary movement (IFM) at the fracture site. However, the IFM induced by conventional locking plate constructs is not uniform at the fracture site and so result in asymmetric callus formation, and ultimately delayed healing. The far cortical locking technique has been recently innovated to address this issue by inducing a uniform IFM. However, the far cortical locking technique is still in its infancy and more research efforts are required before its practical clinical application. Using the theory of porous media and computational methods, this study investigated the effectiveness of far cortical locking technique in presence of different mechanical stiffness of locking plate. The research outcomes indicate that the application of far cortical looking technique enhances IFM at near cortex, and so reduce the difference of IFM between near and far cortex. Further, it shows that, under far cortical locking technique, the bending stiffness of a locking plate plays an important role in bone healing. The use of a stiffer locking plate together with far cortical locking screws encourages more uniform tissue development across the fracture gap. The current research underlines the importance of the optimal selection of plate stiffness for application of far cortical locking technique.

Multilayered coating of titanium implants promotes coupled osteogenesis and angiogenesis in vitro and in vivo

We used surface-modified titanium (Ti) substrates with a multilayered structure composed of chitosan-catechol (Chi-C), gelatin (Gel) and hydroxyapatite (HA) nanofibers, which were previously shown to improve osteogenesis, as a platform to investigate the interaction of osteogenesis and angiogenesis during bone healing. Combined techniques of Transwell co-culture, wound healing assay, enzyme linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemical staining were used to evaluate adhesion, morphology and migration of adipose-derived mesenchymal stem cells (Ad-MSCs) and human umbilical vein endothelial cells (HUVECs) grown on different Ti substrates. We investigated the effect of substrates on the osteogenic differentiation of Ad-MSCs and reciprocal paracrine effects of Ad-MSCs on HUVECs or vice versa. The multilayered Ti substrates directly regulated the cellular functions of Ad-MSCs and angiogenic HUVECs and mediated communication between them by enhancing paracrine effects via cell–matrix interactions in vitro. The in vivo results showed that the change of microenvironment induced by surface-modified Ti implants promoted the adhesion, recruitment and proliferation of MSCs and facilitated coupled osteogenesis and angiogenesis in bone healing. The study proved that multilayer-film-coated Ti substrates positively mediated cellular biological function in vitro and improved bone healing in vivo. Statement of SignificanceRecent studies have revealed that osteogenesis and angiogenesis are coupled, and that communication between osteoblasts and endothelial cells is essential for bone healing and remodeling processes; however, these conclusions only result from in vitro studies or in vivo studies using transgenic murine models. Relatively little is known about the communication between osteoblasts and endothelial cells in peri-implants during bone healing processes. Our results revealed the cellular/molecular mechanism of how multilayered Ti substrates mediate reciprocal paracrine effects between adipose-derived mesenchymal stem cells and human umbilical vein endothelial cells; moreover, the interactions between the cell-matrix and peri-implant was proven in vivo with enhanced bone healing. This study contributes to our understanding of the fundamental mechanisms of angiogenesis and osteogenesis that affect peri-implantation, and thus, provides new insights into the design of future high-quality orthopedic implants.

Improvement of Bone Healing by Neutralization of microRNA-335-5p, but not by Neutralization of microRNA-92A in Bone Marrow Mononuclear Cells Transplanted into a Large Femur Defect of the Rat

Transplanted bone marrow mononuclear cells (BMC) support the healing of large bone defects. Neutralization of microRNA (MiR) that negatively affects key processes of the reparative response in BMC might help to further improve the beneficial effect of transplanted BMC in bone healing. Hence, the aim of this study was to evaluate if the neutralization of MiR-92A (vascularization) and MiR-335-5p (osteogenic differentiation) in BMC using specific antiMiRs leads to a further improvement of the BMC-supported therapy of large bone defects. BMC transiently transfected with antiMiR- 92A, antiMiR-335, antiMiR-92A, and antiMiR-355 or control antiMiR were seeded on β-TCP (beta-tricalcium phosphate) and placed in a femoral large bone defect (5 mm) in Sprague-Dawley rats. Ultimate load as well as osseous integration of the β-TCP-scaffolds were significantly improved in the antiMiR-335 group compared to the control group after 8 weeks, whereas neutralization of antiMiR-92A lead to an improvement of early vascularization after 1 week, but not to enhanced bone healing after 8 weeks. We demonstrated that the targeted inhibition of MiRs in transplanted BMC is a new approach that enhances BMC-supported bone healing.

In vivo safety and efficacy testing of a thermally triggered injectable hydrogel scaffold for bone regeneration and augmentation in a rat model.

Bone loss resulting from degenerative diseases and trauma is a significant clinical burden which is likely to grow exponentially with the aging population. In a number of conditions where pre-formed materials are clinically inappropriate an injectable bone forming hydrogel could be beneficial. The development of an injectable hydrogel to stimulate bone repair and regeneration would have broad clinical impact and economic benefit in a variety of orthopedic clinical applications.We have previously reported the development of a Laponite® crosslinked pNIPAM-co-DMAc (L-pNIPAM-co-DMAc) hydrogel delivery system, loaded with hydroxyapatite nanoparticles (HAPna), which was capable of inducing osteogenic differentiation of mesenchymal stem cells (MSCs) without the need for additional growth factors in vitro. However to enable progression towards clinical acceptability, biocompatibility and efficacy of the L-pNIPAM-co-DMAc hydrogel to induce bone repair in vivo must be determined.Biocompatibility was evaluated by subcutaneous implantation for 6 weeks in rats, and efficacy to augment bone repair was evaluated within a rat femur defect model for 4 weeks. No inflammatory reactions, organ toxicity or systemic toxicity were observed. In young male rats where hydrogel was injected, defect healing was less effective than sham operated controls when rat MSCs were incorporated. Enhanced bone healing was observed however, in aged exbreeder female rats where acellular hydrogel was injected, with increased deposition of collagen type I and Runx2. Integration of the hydrogel with surrounding bone was observed without the need for delivered MSCs; native cell infiltration was also seen and bone formation was observed within all hydrogel systems investigated.This hydrogel can be delivered directly into the target site, is biocompatible, promotes increased bone formation and facilitates migration of cells to promote integration with surrounding bone, for safe and efficacious bone repair.

Effects of static magnetic fields on bone microstructure and mechanical properties in mice

ABSTRACTAll the living organisms originate, evolve and live under geomagnetic field (GMF, 20–70 µT). With rapid development in science and technology, exposure to various static magnetic fields (SMFs) from natural and man-made sources remains a public environmental topic in consideration of its probable health risk for humans. Many animal studies related to health effect have demonstrated that SMF could improve bone formation and enhance bone healing. Moreover, most of the studies focused on local SMF generated by rod-type magnet. It was difficult to come to a conclusion that how SMF affected bone metabolism in mice. The present study employed hypomagnetic field (HyMF, 500 nT), and moderate SMF (MMF, 0.2 T) to systematically investigate the effects of SMF with continuous exposure on microstructure and mechanical properties of bone. Our results clearly indicated that 4-week MMF exposure did not affect bone biomechanical properties or bone microarchitecture, while HyMF significantly inhibited the growth of mice and elasticity of bone. Furthermore, mineral elements might mediate the biological effect of SMF.

Sr2+-Substituted CaCO3 Nanorods: Impact on the Structure and Bioactivity

Strontium is a natural trace element found in biominerals such as aragonitic coral skeletons and bone apatite. Sr2+substitution in biomaterials has been found to regulate the cellular metabolism, thus enhancing bone healing. Even though Ca2+ substitution for Sr2+ has been described in many phosphate minerals, the impact of such substitution on bioactivity and structure in pure carbonate phases has not been explored. Therefore, here we used a biomimetic approach to synthesize carbonate particles with a controlled size in which Ca2+ was progressively substituted for Sr2+. Through structural investigation by X-ray diffraction, Raman spectroscopy, and electron microscopy techniques including high-resolution transmission electron microscopy and electron diffraction, we studied the precipitation mechanism of Sr-substituted CaCO3 nanorods showing that increasing Sr2+/(Ca2+ + Sr2+) molar fractions lead to stabilization of strontianite, a mineral from the aragonite group, increasing the carbonate crystalline latti...