Bone has the capacity to regenerate itself for relatively small defects; however, this regenerative capacity is diminished in critical-size bone defects. The development of synthetic materials has risen as a distinct strategy to address this challenge. Effective synthetic materials to have emerged in recent years are bioceramic implants, which are biocompatible and highly bioactive. Yet nothing suitable for the repair of large bone defects has made the transition from laboratory to clinic. The clinical success of bioceramics has been shown to depend not only on the scaffold's intrinsic material properties but also on its internal porous geometry. This study aimed to systematically explore the implications of varying channel size, shape, and curvature in tissue scaffolds on in vivo bone regeneration outcomes. 3D printed bioceramic scaffolds with varying channel sizes (0.3 mm to 1.5 mm), shapes (circular vs rectangular), and curvatures (concave vs convex) were implanted in rabbit femoral defects for 8 weeks, followed by histological evaluation. We demonstrated that circular channel sizes of around 0.9 mm diameter significantly enhanced bone formation, compared to channel with diameters of 0.3 mm and 1.5 mm. Interestingly, varying channel shapes (rectangular vs circular) had no significant effect on the volume of newly formed bone. Furthermore, the present study systematically demonstrated the beneficial effect of concave surfaces on bone tissue growth in vivo, reinforcing previous in silico and in vitro findings. This study demonstrates that optimizing architectural configurations within ceramic scaffolds is crucial in enhancing bone regeneration outcomes.Statement of significanceDespite the explosion of work on developing synthetic scaffolds to repair bone defects, the amount of new bone formed by scaffolds in vivo remains suboptimal. Recent studies have illuminated the pivotal role of scaffolds’ internal architecture in osteogenesis. However, these investigations have mostly remained confined to in silico and in vitro experiments. Among the in vivo studies conducted, there has been a lack of systematic analysis of individual architectural features. Herein, we utilized bioceramic 3D printing to conduct a systematic exploration of the effects of channel size, shape, and curvature on bone formation in vivo. Our results demonstrate the significant influence of channel size and curvature on in vivo outcomes. These findings provide invaluable insights into the design of more effective bone scaffolds.

There is an unmet clinical need for a spinal fusion implant material that recapitulates the biological and mechanical performance of natural bone. We have developed a bioceramic, Sr-HT-Gahnite, which has been identified as a potential fusion device material. This material has the capacity to transform the fu -ture of the global interbody devices market, with follow on social, economic, and environmental benefits, rooted in its remarkable combination of mechanical properties and bioactivity. In this study, and in line with FDA requirements, the in vivo preclinical systemic biological safety of a Sr-HT-Gahnite interbody fu-sion device is assessed over 26 weeks in sheep under good laboratory practice (GLP). Following the in-life phase, animals are assessed for systemic biological effects via blood haematology and clinical biochem-istry, strontium dosage analysis in the blood and wool, and histopathology examination of the distant organs including adrenals, brain, heart, kidneys, liver, lungs and bronchi, skeletal muscle, spinal nerves close to the implanted sites, ovaries, and draining lymph nodes. Our results show that no major changes in blood haematology or biochemistry parameters are observed, no systemic distribution of strontium to the blood and wool, and no macroscopic or histopathological abnormalities in the distant organs when Sr-HT-Gahnite was implanted, compared to baseline and control values. Together, these results indicate the systemic safety of the Sr-HT-Gahnite interbody fusion device. The results of this study extend to the systemic safety of other Sr-HT-Gahnite implanted medical devices in contact with bone or tissue, of sim-ilar size and manufactured using the described processes.Statement of significanceThis paper is considered original and innovative as it is the first that thoroughly reports the systemic biological safety of previously undescribed bioceramic material, Sr-HT-Gahnite. The study has been per-formed under good laboratory practice, in line with FDA requirements for assessment of a new interbody fusion device, making the results broadly applicable to the translation of sheep models to the human cer-vical spine; and also the translation of Sr-HT-Gahnite as a biomaterial for use in additional applications. We expect this study to be of broad interest to the readership of Acta Biomaterilia. Its findings are directly applicable to researchers and clinicians working in bone repair and the development of synthetic biomaterials.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Here we report the first atom probe study to reveal the atomic-scale composition of the interface between bioceramic scaffolds (strontium-hardystonite-gahnite) and bone tissue after 12-month implantation in a large bone defect in sheep tibia. The composition of the newly formed bone tissue differs to that of mature cortical bone tissue, and elements from the degrading bioceramic implant, particularly aluminium (Al), are present in both the newly formed bone and in the original mature cortical bone tissue at the perimeter of the bioceramic implant. Atom probe tomography confirmed that the trace elements are released from the bioceramic and are actively transported into the newly formed bone. NanoSIMS mapping, as a complementary technique, confirmed the distribution of the released ions from the bioceramic into the newly formed bone tissue within the scaffold. This study demonstrated the combined benefits of atom probe and nanoSIMS in assessing nanoscopic chemical composition changes at precise locations within the tissue/biomaterial interface, opening avenues for further development of biomedical implants.

Combating the accumulated senescent cells and the healing of osteoporotic bone fractures in the older remains a significant challenge. Nicotinamide mononucleotide (NMN), a precursor of NAD+, is an excellent candidate for mitigating aging-related disorders. However, it is unknown if NMN can alleviate senescent cell induction and enhance osteoporotic bone fracture healing. Here we show that NMN treatment partially reverses the effects of tumor necrosis factor-alpha (TNF-α) on human primary osteoblasts (HOBs): senescent cell induction, diminished osteogenic differentiation ability, and intracellular NAD+ and NADH levels. Mechanistically, NMN restores the mitochondrial dysfunction in HOBs induced by TNF-α evidenced by increased mitochondrial membrane potential and reduced reactive oxidative species and mitochondrial mass. NMN also increases mitophagy activity by down-regulating P62 expression and up-regulating light chain 3B-II protein expression. In addition, the cell senescence protective effects of NMN on HOBs are mitigated by a mitophagy inhibitor (Bafilomycin A1). In vivo, NMN supplementation attenuates senescent cell induction in growth plates, partially prevents osteoporosis in an ovariectomized mouse model, and accelerates bone healing in osteoporotic mice. We conclude that NMN can be a novel and promising therapeutic candidate to enhance bone fracture healing capacity in the older.

Supplementary Figure Legend from Vitamin D Deficiency Promotes Human Breast Cancer Growth in a Murine Model of Bone Metastasis

The selection of biomaterials as biomedical implants is a significant challenge. Ultra-high molecular weight polyethylene (UHMWPE) and composites of such kind have been extensively used in medical implants, notably in the bearings of the hip, knee, and other joint prostheses, owing to its biocompatibility and high wear resistance. For the Anterior Cruciate Ligament (ACL) graft, synthetic UHMWPE is an ideal candidate due to its biocompatibility and extremely high tensile strength. However, significant problems are observed in UHMWPE based implants, such as wear debris and oxidative degradation. To resolve the issue of wear and to enhance the life of UHMWPE as an implant, in recent years, this field has witnessed numerous innovative methodologies such as biofunctionalization or high temperature melting of UHMWPE to enhance its toughness and strength. The surface functionalization/modification/treatment of UHMWPE is very challenging as it requires optimizing many variables, such as surface tension and wettability, active functional groups on the surface, irradiation, and protein immobilization to successfully improve the mechanical properties of UHMWPE and reduce or eliminate the wear or osteolysis of the UHMWPE implant. Despite these difficulties, several surface roughening, functionalization, and irradiation processing technologies have been developed and applied in the recent past. The basic research and direct industrial applications of such material improvement technology are very significant, as evidenced by the significant number of published papers and patents. However, the available literature on research methodology and techniques related to material property enhancement and protection from wear of UHMWPE is disseminated, and there is a lack of a comprehensive source for the research community to access information on the subject matter. Here we provide an overview of recent developments and core challenges in the surface modification/functionalization/irradiation of UHMWPE and apply these findings to the case study of UHMWPE for ACL repair.

Mitochondria in tumor cells are functionally different from those in normal cells and could be targeted to develop new anticancer agents. We showed recently that the aryl-ureido fatty acid CTU is the prototype of a new class of mitochondrion-targeted agents that kill cancer cells by increasing the production of reactive oxygen species (ROS), activating endoplasmic reticulum (ER)-stress and promoting apoptosis. However, prolonged treatment with high doses of CTU were required for in vivo anti-tumor activity. Thus, new strategies are now required to produce agents that have enhanced anticancer activity over CTU. In the present study we prepared a novel aryl-urea termed 3-thiaCTU, that contained an in-chain sulfur heteroatom, for evaluation in tumor cell lines and in mice carrying tumor xenografts. The principal finding to emerge was that 3-thiaCTU was several-fold more active than CTU in the activation of aryl-urea mechanisms that promoted cancer cell killing. Thus, in in vitro studies 3-thiaCTU disrupted the mitochondrial membrane potential, increased ROS production, activated ER-stress and promoted tumor cell apoptosis more effectively than CTU. 3-ThiaCTU was also significantly more active than CTUin vivo in mice that carried MDA-MB-231 cell xenografts. Compared to CTU, 3-thiaCTU prevented tumor growth more effectively and at much lower doses. These findings indicate that, in comparison to CTU, 3-thiaCTU is an aryl-urea with markedly enhanced activity that could now be suitable for development as a novel anticancer agent.

The cancer cell mitochondrion is functionally different from that in normal cells and could be targeted to develop novel experimental therapeutics. The aryl-ureido fatty acid CTU (16({[4-chloro-3-(trifluoromethyl)phenyl]-carbamoyl}amino)hexadecanoic acid) is the prototype of a new class of mitochondrion-targeted agents that kill cancer cells. Here we show that CTU rapidly depolarized the inner mitochondrial membrane, selectively inhibited complex III of the electron transport chain and increased reactive oxygen species (ROS) production. From RNA-seq analysis, endoplasmic reticulum (ER)-stress was a major activated pathway in CTU-treated cells and in MDA-MB-231 tumor xenografts from CTU-treated nu/nu mice. Mitochondrion-derived ROS activated the PERK-linked ER-stress pathway and induced the BH3-only protein NOXA leading to outer mitochondrial membrane (OMM) disruption. The lipid peroxyl scavenger α-tocopherol attenuated CTU-dependent ER-stress and apoptosis which confirmed the critical role of ROS. Oleic acid protected against CTU-mediated apoptosis by activating Mcl-1 expression, which increased NOXA sequestration and prevented OMM disruption. Taken together, CTU both uncouples mitochondrial electron transport and activates ROS production which promotes ER-stress-dependent OMM disruption and tumor cell death. Dual-mitochondrial targeting agents like CTU offer a novel approach for development of new anti-cancer therapeutics.

An ongoing challenge in the field of orthopedics is to produce a clinically relevant synthetic ceramic scaffold for the treatment of 'critical-sized' bone defects, which cannot heal without intervention. We had developed a bioactive ceramic (baghdadite, Ca3ZrSi2O9) and demonstrated its outstanding bioactivity using traditional manufacturing techniques. Here, we report on the development of a versatile stereolithography printing technology that enabled fabrication of anatomically-shaped and -sized Baghdadite scaffolds. We assessed the in vivo bioactivity of these scaffolds in co-delivering of bone morphogenetic protein-2 (BMP2) and zoledronic acid (ZA) through bioresorbable coatings to induce bone formation and increase retention in a rat model of heterotopic ossification. Micro-computed tomography, histology, mechanical tests pre- and post-implantation, and mechanical modelling were used to assess bone ingrowth and its effects on the mechanics of the scaffolds. Bone ingrowth and the consequent mechanical properties of the scaffolds improved with increasing BMP2 dose. Co-delivery of ZA with BMP2 further improved this outcome. The significant bone formation within the scaffolds functionalized with 10 mu g BMP2 and 2 mu g ZA made them 2.3 x stiffer and 2.7 x stronger post-implantation and turned these inherently brittle scaffolds into a tough and deformable material. The effects of bone ingrowth on the mechanical properties of scaffolds were captured in a mechanical model that can be used in future clinical studies for non-destructive evaluation of scaffold's stiffness and strength as new bone forms. These results support the practical utilization of our versatile stereolithographic printing methods and BMP2/ZA functionalization to create fit-for-purpose personalized implants for clinical trials. Statement of significance In this study, we addressed a long-standing challenge of developing a ceramic printing technology that enables fabrication of customizable anatomically-shaped and -sized bioceramic scaffolds with precise internal architectures using an inexpensive desktop printer. We also addressed another challenge related to delivery of pharmaceuticals. BMP2, currently available as a bone-inducing bioactive protein, is clinically administered in a collagen scaffold that has limited moldability and poor mechanical properties. The comparably stiffer and stronger 3D printed personalized Baghdadite scaffolds developed here can be readily functionalized with bioresorbable coatings containing BMP2 +/- ZA. These innovations considerably improve on the prior art and are scalable for use in human surgery. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Migration and invasion promote tumor cell metastasis, which is the leading cause of cancer death. At present there are no effective treatments. Epidemiological studies have suggested that ω-3 polyunsaturated fatty acids (PUFA) may decrease cancer aggressiveness. In recent studies epoxide metabolites of ω-3 PUFA exhibited anti-cancer activity, although increased in vivo stability is required to develop useful drugs. Here we synthesized novel stabilized ureido-fatty acid ω-3 epoxide isosteres and found that one analogue - p-tolyl-ureidopalmitic acid (PTU) - inhibited migration and invasion by MDA-MB-231 breast cancer cells in vitro and in vivo in xenografted nu/nu mice. From proteomics analysis of PTU-treated cells major regulated pathways were linked to the actin cytoskeleton and actin-based motility. The principal finding was that PTU impaired the formation of actin protrusions by decreasing the secretion of Wnt5a, which dysregulated the Wnt/planar cell polarity (PCP) pathway and actin cytoskeletal dynamics. Exogenous Wnt5a restored invasion and Wnt/PCP signalling in PTU-treated cells. PTU is the prototype of a novel class of agents that selectively dysregulate the Wnt/PCP pathway by inhibiting Wnt5a secretion and actin dynamics to impair MDA-MB-231 cell migration and invasion.

Bone's outstanding biomechanical performance is derived from cooperative interactions between its composition and microarchitecture. Towards developing bioceramic scaffolds with similar biomechanical performance for repairing large bone defects under load, we have developed 13 new bioceramic compositions by doping various concentrations of iron and magnesium into Baghdadite (a Zr-Ca-Silicate: Ca3ZrSi2O9). The resulting bioceramics were printed into scaffolds with precisely controlled internal and external shapes using a versatile photopolymerization-based stereolithography technique. The biomechanical performance of new compositions and scaffolds were determined using mechanical tests with in situ imaging, in vitro cell study, an in vivo animal study, histological analysis, and microcomputed tomography. Mg-doped Baghdadite with composition Ca3Mg0.1Zr0.9Si2O8.9 demonstrated superior bioactivity and mechanical properties, compared to Baghdadite. 3D printed Mg-doped Baghdadite scaffolds with 35% porosity and designed architecture matched the stiffness and strength of cortical bone. These scaffolds were 2-5 times stronger than other bioceramic and bioglass scaffolds with the same porosity made with photopolymerization techniques. In vivo bone ingrowth was 2.2 times higher in Mg-doped Baghdadite than Baghdadite, effectively transforming these mechanically brittle scaffolds into deformable and tough ceramic-bone composites. Mg-doped Baghdadite scaffolds demonstrate a combination of favorable mechanical properties and bone regeneration capacity that show their potential for clinical success. (C) 2021 Elsevier Ltd. All rights reserved.

Internal architecture of tissue scaffolds plays a significant role in their ability to heal critical-size bone defects. Many studies have investigated these effects but lack isolating architectural features in 3D space, hindering optimization of pore shape to improve bone ingrowth and consequently clinical outcome. To address this challenge, we developed a systematic design strategy and a high-fidelity and-precision ceramic printing technique using a stereolithography desktop printer. We used these techniques to print 5 scaffold architectures with different surface convexities/concavities, pore interconnectivities, and permeabilities, while maintaining the same porosity, average pore size, and surface area. We determined the mechanical effects of the architecture using mechanical tests with in-situ imaging, finite element, and computational fluid dynamic simulations. The effects of architecture on bioactivity and bone ingrowth were determined in a rabbit calvarial critical-size defect model at 12-week implantation, using mu-computed tomography, and histology. The results showed that bone ingrowth is significantly affected by pore interconnectivity in 3D space and maximum fluid permeability in 3D regardless of flow direction, but not permeability in one or few directions. Surface convexity/concavity did not affect bone formation in our 3D scaffolds. Bone ingrowth in scaffolds with highly interconnected pores resulted in a significantly tougher and stronger bioceramic/bone composites, compared to the inherently brittle scaffolds pre-implantation. Our findings provide a rational design of 3D scaffolds architectures for effective translation to the clinic and could be used to predict the tissue regeneration capacity of scaffolds with other architectures or made of other materials. (c) 2021 Elsevier Ltd. All rights reserved.

Bone fractures and critical-sized bone defects present significant health threats for the elderly who have limited capacity for regeneration due to the presence of functionally compromised senescent cells. A wide range of synthetic materials has been developed to promote the regeneration of critical-sized bone defects, but it is largely unknown if a synthetic biomaterial (scaffold) can modulate cellular senescence and improve bone regeneration in aged scenarios. The current study investigates the interaction of Baghdadite (Ca3ZrSi2O9) ceramic scaffolds with senescent human primary osteoblast-like cells (HOBs) and its bone regeneration capacity in aged rats. A senescent HOB model was established by repeatedly passaging HOBs till passage 7 (P7). Compared to the clinically used hydroxyapatite/tricalcium phosphate (HA/TCP), Baghdadite prevented senescence induction in P7 HOBs and markedly negated the paracrine effect of P7 HOB secretomes that mediated the up-regulations of cellular senescence-associated gene expression levels in P2 HOBs. We further demonstrated that conditioned media extracted from Baghdadite corrected the dysfunctional mitochondria in P7 HOBs. In vivo, the bone regeneration capacity was enhanced when 3D printed Baghdadite scaffolds were implanted in a calvaria critical-sized bone defect model in both young and aged rats compared to HA/TCP scaffolds, but a better effect was observed in aged rats than in young rats. This study suggests that Baghdadite ceramic represents a novel and promising biomaterial approach to promote bone regeneration capacity in the elderly by providing an anti-senescent microenvironment.

COVID-19 is the official name describing the coronavirus disease causing by the virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Its higher infection rate has led to worldwide spread making it a more dangerous threat than other coronavirus related diseases. As this virus spreads and responses from governments become more constraining of normal activities, we are seeing levels of anxiety among people increase over a relatively short period of time. When we are stressed the immune system’s ability to defend us from infections is reduced. Stress can suppress the innate immune system that provides the initial defence against viral infection making us more susceptible to Covid-19. In contrast, stress can cause overactivity of the adaptive immune system making a cytokine storm response leading to severe disease and death more likely. Management of stress levels has become an important strategy to reduce the risks of COVID-19.

The induced pluripotent stem cell (iPSC) is a promising cell source for tissue regeneration. However, the therapeutic value of iPSC technology is limited due to the complexity of induction protocols and potential risks of teratoma formation. A trans-differentiation approach employing natural factors may allow better control over reprogramming and improved safety. We report here a novel approach to drive trans-differentiation of human fibroblasts into functional osteoblasts using insulin-like growth factor binding protein 7 (IGFBP7). We initially determined that media conditioned by human osteoblasts can induce reprogramming of human fibroblasts to functional osteoblasts. Proteomic analysis identified IGFBP7 as being significantly elevated in media conditioned with osteoblasts compared with those with fibroblasts. Recombinant IGFBP7 induced a phenotypic switch from fibroblasts to osteoblasts. The switch was associated with senescence and dependent on autocrine IL-6 signaling. Our study supports a novel strategy for regenerating bone by using IGFBP7 to trans-differentiate fibroblasts to osteoblasts.

The development of suitable synthetic scaffolds for use as human tendon grafts to repair tendon ruptures remains a significant engineering challenge. Previous synthetic tendon grafts have demonstrated suboptimal tissue ingrowth and synovitis due to wear particles from fiber-to-fiber abrasion. In this study, we present a novel fiber-reinforced hydrogel (FRH) that mimics the hierarchical structure of the native human tendon for synthetic tendon graft material. Ultrahigh molecular weight polyethylene (UHMWPE) fibers were impregnated with either biosynthetic polyvinyl alcohol/gelatin hydrogel (FRH-PG) or with polyvinyl alcohol/gelatin + strontium-hardystonite (Sr-Ca2ZnSi2O7, Sr-HT) composite hydrogel (FRH-PGS). The scaffolds were fabricated and assessed to evaluate their suitability for tendon graft applications. The microstructure of both FRH-PG and FRH-PGS showed successful impregnation of the hydrogel component, and the tendon scaffolds exhibited equilibrium water content of similar to 70 wt %, similar to the values reported for native human tendon, compared to similar to 50 wt % water content retained in unmodified UHMWPE fibers. The tensile strength of FRH-PG and FRH-PGS (77.0-81.8 MPa) matched the range of human Achilles' tendon tensile strengths reported in the literature. In vitro culture of rat tendon stem cells showed cell and tissue infiltration into both FRH-PG and FRH-PGS after 2 weeks, and the presence of Sr-HT ceramic particles influenced the expression of tenogenic markers. On the other hand, FRH-PG supported the proliferation of murine C2C12 myoblasts, whereas FRH-PGS seemingly did not support it under static culture conditions. In vivo implantation of FRH-PG and FRH-PGS scaffolds into full-thickness rat patellar tendon defects showed good collagenous tissue ingrowth into these scaffolds after 6 weeks. This study demonstrates the potential viability for our FRH-PG and FRH-PGS scaffolds to be used for off-the-shelf biosynthetic tendon graft material.

The selection of biomaterials for biomedical application is a significant challenge. In the last few decades, various bioabsorbable and stable biopolymers have been applied for use as biomedical devices in orthopedic applications. Ultra-high molecular weight polyethylene (UHMWPE) has been extensively used in medical implants, notably in the bearings of hip, knee, and other joint prostheses, owing to its biocompatibility and high wear resistance. For the ACL graft, synthetic UHMWPE is an ideal candidate due to its biocompatibility and its extremely high tensile strength. Despite the appeal of new advanced materials such as carbon fiber, poly-ether-ether ketone, and other load-bearing materials, UHMWPE remains a primary load-bearing candidate material for ACL reconstructions because of its extremely high strength, the simplicity of the fabrication process, its biocompatibility, and low friction. However, some significant problems are observed in UHMWPE based implants, such as wear debris, and oxidative degradation due to the generation of free radicals when exposed to irradiation with gamma rays for grafting or sterilization. Various innovative methodologies have been developed to resolve those problems and enhance the properties of UHMWPE. In this review, we will explore in detail the methods for surface functionalization of UHMWPE and will apply these findings to the case study of UHMWPE for Anterior Cruciate Ligament repair.

Achieving adequate healing in large or load-bearing bone defects is highly challenging even with surgical intervention. The clinical standard of repairing bone defects using autografts or allografts has many drawbacks. A bioactive ceramic scaffold, strontium-hardystonite-gahnite or "Sr-HT-Gahnite" (a multi-component, calcium silicate-based ceramic) is developed, which when 3D-printed combines high strength with outstanding bone regeneration ability. In this study, the performance of purely synthetic, 3D-printed Sr-HT-Gahnite scaffolds is assessed in repairing large and load-bearing bone defects. The scaffolds are implanted into critical-sized segmental defects in sheep tibia for 3 and 12 months, with bone autografts used for comparison. The scaffolds induce substantial bone formation and defect bridging after 12 months, as indicated by X-ray, micro-computed tomography, and histological and biomechanical analyses. Detailed analysis of the bone-scaffold interface using focused ion beam scanning electron microscopy and multiphoton microscopy shows scaffold degradation and maturation of the newly formed bone. In silico modeling of strain energy distribution in the scaffolds reveal the importance of surgical fixation and mechanical loading on long-term bone regeneration. The clinical application of 3D-printed Sr-HT-Gahnite scaffolds as a synthetic bone substitute can potentially improve the repair of challenging bone defects and overcome the limitations of bone graft transplantation.

OBJECTIVE:The aim of this study was to assess the potential of improving orthodontic miniscrews' (MSs) primary stability in vivo by evaluating the dispersion capacity of an injectable bone graft substitute (iBGS) through a newly designed hollow MS [The Sydney Mini Screw (SMS)] and its integration with the cortical and trabecular bone by using the femur and tibia in a New Zealand rabbit animal model.METHODS:In total, 24 MSs were randomly placed in each proximal tibia and femur of 6 New Zealand rabbits with an open surgery process. Aarhus MSs were used as controls and the effect of injection of iBGS was studied by implanting SMSs with and without iBGS injection. The dispersion of iBGS and the integration of the SMS were studied by using micro Computed Tomography (μCT) and histochemical analysis at two time points, 0 day and 8 weeks post-implantation.RESULTS:iBGS was successfully injected through the SMS and hardened in situ. After 8 weeks, μCT results revealed that the iBGS particles were resorbed and bone tissue was formed around the SMS and within its lateral exit holes.CONCLUSIONS:This pilot animal study showed the high potential of the combined use of iBGS and SMS as a newly developed technique to promote the primary stability of MSs.