Enhance Bone Healing Research Articles

Thrombopoietic agents enhance bone healing in mice, rats, and pigs.

Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, has renewed interest in investigating alternatives that provide safer, yet effective bone regeneration. Here we demonstrate the robust bone healing capabilities of the main megakaryocyte growth factor, thrombopoietin (TPO) and second generation TPO agents using multiple animal models including mice, rats, and pigs. This bone healing activity is shown in two fracture models (critical sized defect [CSD] and closed fracture) and with local or systemic administration. Our transcriptomic analyses, cellular studies, and protein arrays demonstrate that TPO enhances multiple cellular processes important to fracture healing, particularly angiogenesis, which is required for bone union. Finally, the therapeutic potential of thrombopoietic agents is high since they are used in the clinic for other indications (e.g., thrombocytopenia) with established safety profiles and act upon a narrowly defined population of cells.

Supplemental Magnesium Gluconate Enhances Scaffold-Mediated New Bone Formation and Natural Bone Healing by Angiogenic- and Wnt Signal-Associated Osteogenic Activation.

Local implantation or supplementation of magnesium gluconate (MgG) is being investigated as an effective approach to bone repair. Although studies have highlighted the possible mechanisms in Mg ion-stimulated new bone formation, the role of MgG in healing bone defects and the signaling mechanisms are not yet completely understood. In this study, we explored how supplemental MgG has bone-specific beneficial effects by delivering MgG locally and orally in animal models. We fabricated MgG-incorporated (CMC-M) and -free chitosan (CMC) scaffolds with good microstructures and biocompatible properties. Implantation with CMC-M enhanced bone healing in rat model of mandible defects, compared with CMC, by activating Wnt signals and Wnt-related osteogenic and angiogenic molecules. Oral supplementation with MgG also stimulated bone healing in mouse model of femoral defects along with the increases in Wnt3a and angiogenic and osteogenic factors. Supplemental MgG did not alter nature bone accrual and bone marrow (BM) microenvironment in adult mouse model, but enhanced the functioning of BM stromal cells (BMSCs). Furthermore, MgG directly stimulated the induction of Wnt signaling-, angiogenesis-, and osteogenesis-related molecules in cultures of BMSCs, as well as triggered the migration of endothelial cells. These results suggest that supplemental MgG improves bone repair in a way that is synergistically enhanced by Wnt signal-associated angiogenic and osteogenic molecules. Overall, this study indicates that supplemental MgG might ameliorate oxidative damage in the BM, improve the functionality of BM stem cells, and maintain BM-microenvironmental homeostasis.

Evaluation of stiffness-matched, 3D-printed, NiTi mandibular graft fixation in an ovine model

BackgroundManually bent, standard-of-care, Ti–6Al–4V, mandibular graft fixation devices are associated with a significant post-operative failure rate. These failures require the patient to endure stressful and expensive re-operation. The approach recommended in this report demonstrates the optimization of graft fixation device mechanical properties via “stiffness-matching” by varying the fixation device’s location, shape, and material composition through simulation of the device’s post-operative performance. This provides information during pre-operative planning that may avoid future device failure. Optimized performance may combine translation of all loading into compression of the bone graft with the adjacent bone segments and elimination or minimization of post-healing interruption of normal stress–strain (loading) trajectories.ResultsThis study reports a sheep mandibular graft model where four animals received virtually optimized, experimental nickel–titanium (NiTi) fixation plates fabricated using laser beam powder bed fusion (LPBF) additive manufacturing (AM). The last animal, our control, received a standard-of-care, manually bent, Ti–6Al–4V (aka Ti64) fixation plate. A 17.5-mm mandibular graft healed completely in all four animals receiving the experimental device. Experimental NiTi-implanted sheep experienced mandibular bone healing and restoration. The Ti64 plate, in the control animal, fractured and dislocated shortly after being implanted.ConclusionThe use of stiffness-matched implants, by means of plate material (NiTi) and geometry (porosity) enhanced bone healing and promoted better load transfer to the healed bone when compared to the bulk Ti64 found in the fixation plate that the Control animal received. The design technique and screw orientation and depth planning improved throughout the study leading to more rapid healing. The large animal model reported here provides data useful for a follow-on clinical trial.Graphical

Orthosilicic acid inhibits human osteoclast differentiation and bone resorption.

Silicon (Si), which is present in the diet in the bioavailable form of orthosilicic acid (OSA) and is detected as a dissolution product of certain bone-substitute materials, is suggested to promote bone health, and enhance bone healing, respectively. Silicon has been shown to stimulate osteoblastic cell differentiation and function, although the effect of Si on human osteoclasts is unclear. The present study investigated the direct effects of Si on human osteoclast differentiation, gene expression, and bone resorption. Human CD14+ monocytes were isolated from buffy coats and cultured with M-CSF and RANKL in medium without or with Si (50 μg/ml; constituting 75% OSA). The effects of Si on osteoclast differentiation were evaluated by TRAP-staining and the expression levels of CtsK, CalcR, TRAP, and DC-STAMP measured by RT-qPCR. The effect of Si on the expression level of AQP9, which encodes a potential Si transporter, was also analyzed. Bone resorption was determined based on the number of resorption pits formed when the RANKL-stimulated monocytes were cultured on bone slices, and by the levels of type I collagen fragments released into the cell culture medium. Silicon significantly inhibited the number of TRAP+ multinucleated cells and the expression of osteoclast related genes but increased the late expression of AQP9. Furthermore, Si significantly inhibited the number of resorption pits and the amount of collagen fragments in the medium when cells were cultured on bone slices. Our results demonstrate that OSA inhibits RANKL-stimulated human osteoclast differentiation, gene expression of osteoclast phenotypic markers, and bone resorption.

RhBMP-2-loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite promotes bone regeneration in a novel rat femoral nonunion model.

Nonunion following fracture treatment remains a significant clinical challenge, adversely affecting the patient's quality of life and imposing a substantial economic burden. The emergence of bone morphogenetic protein 2 (BMP-2) for bone regeneration represents a promising avenue, albeit limited by side effects such as inflammatory reactions primarily due to suboptimal drug delivery systems. This study focuses on NOVOSIS putty (NP), a novel biomaterial designed for the sustained release of BMP-2, aiming to mitigate these limitations and enhance bone healing. This research aimed to evaluate the effectiveness of NP, a hydroxyapatite granules/β-tricalcium phosphate hydrogel composite (HA/β-TCP/hydrogel), as a BMP-2 carrier for promoting bone regeneration in a new rat nonunion model of long bone. Using Sprague Dawley rats, a 2-mm silicone disk was interposed at the femoral fracture site, and intramedullary fixation with K-wire was performed to create a nonunion with a 2-mm bone defect. After 3weeks, internal fixation with a plate, removal of the silicon disk, and refreshing the nonunion site were performed by implanting three different materials into the nonunion sites: allogenic iliac bone (IB), collagen sponge (CS) containing 10μg of BMP-2, or NP containing 10μg of BMP-2. Bone healing was evaluated weekly using micro-computed tomography (CT); ex vivo micro-Ct and histological evaluation were conducted at 6weeks. At 6weeks, NP demonstrated a significantly higher bone union rate (76.5%) compared with the CS group (35.3%, p = 0.037), and the IB group (6.3%, p < 0.0001). Bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were also significantly higher in the NP group compared with the CS group (BMD, p < 0.0001; BV/TV, p = 0.031). Histological analysis showed the fracture gap in the NP group was filled with more trabecular bone and less fibrous tissue compared with the CS group. The study confirms NP is a highly effective BMP-2 carrier, significantly improving bone union rates and new bone formation in nonunion fractures. The sustained release of BMP-2 from the hydrogel component reduced inflammatory responses and enhanced bone regeneration. NP can be a promising alternative to collagen-based BMP-2 delivery systems.

Nanocarrier-Assisted Delivery of Berberine Promotes Diabetic Alveolar Bone Regeneration by Scavenging ROS and Improving Mitochondrial Dysfunction.

Oxidative stress and mitochondrial dysfunction are potential contributors to the compromised tissue regeneration capacity of alveolar bone in diabetic patients. Berberine, an active plant alkaloid, exhibits multiple pharmacological effects including antioxidation, blood glucose- and blood lipid-lowering properties. However, it remains uncertain whether berberine can improve impaired osteogenesis in type 2 diabetes mellitus (T2DM), and its poor solubility and oral bioavailability also constrain its applications in bone regeneration. Thus, our study aimed to probe the effects of berberine on bone marrow stem cells (BMSCs) in a diabetic microenvironment, with a greater emphasis on developing a suitable nano-delivery system for berberine and assessing its capability to repair diabetic alveolar bone defects. Firstly, BMSCs were exposed to berberine within a high glucose and palmitate (HG+PA) environment. Reactive oxygen species levels, mitochondrial membrane potential, ATP generation, cell apoptosis, and osteogenic potential were subsequently assessed. Next, we explored the regulatory mechanism of autophagy flux in the positive effects of berberine. Furthermore, a nanocarrier based on emulsion electrospinning for sustained local delivery of berberine (Ber@SF/PCL) was established. We assessed its capacity to enhance bone healing in the alveolar bone defect of T2DM rats through micro-computed tomography and histology analysis. Berberine treatment could inhibit reactive oxygen species overproduction, mitochondrial dysfunction, apoptosis, and improve osteogenesis differentiation by restoring autophagy flux under HG+PA conditions. Notably, Ber@SF/PCL electrospun nanofibrous membrane with excellent physicochemical properties and good biological safety had the potential to promote alveolar bone remodeling in T2DM rats. Our study shed new lights into the protective role of berberine on BMSCs under T2DM microenvironment. Furthermore, berberine-loaded composite electrospun membrane may serve as a promising approach for regenerating alveolar bone in diabetic patients.

Addressing Model Uncertainties in Finite Element Simulation of Electrically Stimulated Implants for Critical-Size Mandibular Defects.

Electrical stimulation is known to enhance bone healing. Novel electrostimulating devices are currently being developed for the treatment of critical-size bone defects in the mandible. Previous numerical models of these devices did not account for possible uncertainties in the input data. We present the numerical model of an electrically stimulated minipig mandible, including optimization and uncertainty quantification (UQ) methods that allow us to determine the most influential parameters. Uncertainties in the optimized finite element model are quantified using the polynomial chaos method that is implemented in the open-source Python toolbox Uncertainpy. The volumes of understimulated, beneficially stimulated, and overstimulated tissue are considered quantities of interest because they may significantly impact the expected healing success. Further, the current is a substantial quantity, limiting the lifetime of a battery-driven stimulation unit. With sensitivity analyses, the most critical parameters in the numerical model can be identified. Thus, we can learn which parameters are particularly relevant, for example, when conceptualizing the stimulation unit or planning the manufacturing process. The results of this study show that the parameters of the electrode-tissue interface (ETI), as well as the conductivity within the defect volume, have the most significant impact on the model results. The UQ results suggest that careful characterization of the ETI and the dielectric tissue properties is crucial to reduce these uncertainties. The numerical model regarding uncertainties yields important implications for reliable implant design and clinical translation.

The Advantages and Shortcomings of Stem Cell Therapy for Enhanced Bone Healing.

This review explores the regenerative potential of key progenitor cell types and therapeutic strategies to improve healing of complex fractures and bone defects. We define, summarize, and discuss the differentiation potential of totipotent, pluripotent, and multipotent stem cells, emphasizing the advantages and shortcomings of cell therapy for bone repair and regeneration. The fundamental role of mesenchymal stem cells is highlighted due to their multipotency to differentiate into the key lineage cells including osteoblasts, osteocytes, and chondrocytes, which are crucial for bone formation and remodeling. Hematopoietic stem cells (HSCs) also play a significant role; immune cells such as macrophages and T-cells modulate inflammation and tissue repair. Osteoclasts are multinucleated cells that are important to bone remodeling. Vascular progenitor (VP) cells are critical to oxygen and nutrient supply. The dynamic interplay among these lineages and their microenvironment is essential for effective bone restoration. Therapies involving cells that are more than "minimally manipulated" are controversial and include embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). ESCs, derived from early-stage embryos, possess pluripotent capabilities and have shown promise in preclinical studies for bone healing. iPSCs, reprogrammed from somatic cells, offer personalized medicine applications and can differentiate into various tissue-specific cell lines. Minimally manipulative cell therapy approaches such as the use of bone marrow aspirate concentrate (BMAC), exosomes, and various biomaterials for local delivery are explored for their effectiveness in bone regeneration. BMAC, which contains mostly immune cells but few mesenchymal and VPs, probably improves bone healing by facilitating paracrine-mediated intercellular communication. Exosome isolation harnesses the biological signals and cellular by-products that are a primary source for cell crosstalk and activation. Safe, efficacious, and cost-effective strategies to enhance bone healing using novel cellular therapies are part of a changing paradigm to modulate the inflammatory, repair, and regenerative pathways to achieve earlier more robust tissue healing and improved physical function. Impact Statement Stem cell therapy holds immense potential for bone healing due to its ability to regenerate damaged tissue. Nonmanipulated bone marrow aspirate contains mesenchymal stem cells that promote bone repair and reduce healing time. Induced pluripotent stem cells offer the advantage of creating patient-specific cells that can differentiate into osteoblasts, aiding in bone regeneration. Other delivery methods, such as scaffold-based techniques, enhance stem cell integration and function. Collectively, these approaches can improve treatment outcomes, reduce recovery periods, and advance our understanding of bone healing mechanisms, making them pivotal in orthopedic research and regenerative medicine.

Osteoinductivity enhancement by tailoring the surface chemical bond status: A strategy to mobilize host bone growth factors for in situ bone regeneration

The incorporation of growth factors and biomaterials is a promising strategy for improving osseointegration. However, current strategies to develop biomaterials with exogenous growth factors present disadvantages like inefficiency, difficult deployment, and potential off-target activation, making their translation into clinical practice challenging. This study reveals a bioactive N-doped tantalum carbide (TaC) solid solution film that can be used to construct a TaCN film via bionic interface engineering to recruit host bone growth factors to the wounded site and improve bone regeneration. X-ray photoelectron spectroscopy (XPS) and protein absorption analysis reveal that the performance of TaCN is related to the surface chemical bonds of films. The introduction of N to TaC causes a cascade effect wherein negative charges enrich on the TaCN surface, and the recruitment of positively charged bone growth factors around the TaCN film is facilitated. Under these circumstances, the endogenous bone growth factors enhance bone healing. The TaCN film shows an outstanding performance for in vivo osteogenic differentiation along with a superior in vitro cytocompatibility. Incorporation of N atoms into TaC provides a new clinically translatable strategy to mobilize host bone growth factors for in situ bone regeneration without the need for incorporation of exogenous growth factors.

Effect of magnesium supplementation on diaphyseal tibia fractures: a pilot study

Background: This study aimed to assess and compare the efficacy of magnesium supplementation in patients with long diaphyseal tibia fractures who have undergone surgical management with intramedullary interlocking nailing. Methods: In a prospective, randomized trial, thirty patients were included, with half receiving magnesium (420 mg/day) along with calcium (500 mg/day) supplementation for 3 months alongside surgical treatment. Radiological outcomes were evaluated through postoperative X-rays using the radiographic union scale for tibia fractures (RUST) scoring system at 6 and 12 weeks. Results: A significant difference was observed between the two groups. Patients receiving magnesium supplementation exhibited a notable improvement in RUST score, indicating an accelerated bone healing process. Conclusions: This study demonstrates the efficacy of magnesium supplementation in achieving superior radiologic outcomes compared to patients who did not receive such supplementation. The findings suggest that adjuvant magnesium supplementation could be a viable therapeutic option to enhance bone healing outcomes in individuals with tibia diaphyseal fractures.

Locking Plate Fixation with Calcium Phosphate Bone Cement Augmentation for Elderly Proximal Humerus Fractures-A Single-Center Experience and Literature Review.

Proximal humerus fractures (PHFs) are among the most common upper-extremity fractures, with a rising incidence linked to the growing elderly population. Treatment options include non-surgical and surgical methods, but the best approach for geriatric PHFs remains debated. Patient selection for treatment must consider clinical and functional outcomes and the potential complications of surgery. Osteoporosis, a key factor in elderly PHFs, meaning those in patients over 65 years old, often results from low-energy trauma and necessitates treatments that enhance bone healing. Bone cement, such as calcium phosphate, is widely used to improve fracture stability and healing. However, the benefits of surgical fixation with bone cement augmentation (BCA) for elderly PHF patients remain controversial. Hence, in this article, we searched databases including MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science to analyze the evidence on locking plate fixation (LPF) with BCA for proximal humeral fractures. We aim to provide readers with updates concerning the above issues.

Enhancing Bone Healing Through Localized Cold Therapy in a Murine Femoral Fracture Model.

Fracture healing, a critical and complex biological process, often presents challenges in clinical practice with the current standards failing to fully address the medical needs for rapid and effective recovery. In this work, a localized cold therapy is investigated as an alternative approach to expedite bone healing. We hypothesized that optimized cold application can enhance bone healing within a fracture model by inducing hypoxia, leading to accelerated angiogenesis along with improved osteogenesis. A short, localized cold exposure is directly applied to the fracture site over a 4-week period in a mouse fracture model, aiming to assess its impact on bone formation through mechanisms of angiogenesis and osteogenesis. Our results revealed a significantly greater volume of new bone tissue and enhanced vascularity at the fracture site in the cold-treated group compared with controls. Calcified tissue histology analysis showed that the accelerated callus maturation and development of the vascular network following cold exposure were associated with an activity increase of alkaline phosphatase and transient receptor potential vanilloid 1. These biological changes were accompanied by a hypoxic environment induced during cold therapy. The study provides compelling evidence supporting the efficacy of intermittent cold therapy in accelerating fracture healing. These promising results highlight the need for further research in larger-scale studies and diverse fracture models, underlining the potential of cold therapy as a novel, noninvasive treatment strategy in orthopedic care.

Bio-materials Used to Enhance Bone Healing in Implant Dentistry – A Review from the Past to Current

Abstract An alternating way of replacing the missing teeth involves the use of implants. In implant dentistry, an adequate amount of bone is crucial for the long-term prognosis. Bone volume loss can be caused by congenital, post-traumatic or post-surgical abnormalities, as well as disease processes. In scenarios with a bone defect at a site, where the primary stability of an implant cannot be established or where implant placement is not achievable in the best possible position for subsequent prosthetic therapy, guided bone regeneration before implantation represents the method of choice. During implant placement, a partial discrepancy between the implant’s surface and the socket’s osseous walls frequently leaves the peri-implant region with insufficient bone. It has been shown that barrier membranes can be successfully placed to allow the peri-implant space to be filled with new bone rather than lowering the height of the alveolar ridge to produce a sufficient breadth for implantation.

Comparative Analysis of Osteointegration in Hydroxyapatite and Hydroxyapatite-Titanium Implants: An In Vivo Rabbit Model Study.

The study evaluates the osteointegration of hydroxyapatite (HAp) and hydroxyapatite-titanium (HApTi) biocomposites implanted in the femurs of rabbits. The biocomposites were fabricated using powder metallurgy and subjected to a two-step sintering process. Scanning electron microscopy (SEM) was employed to analyze the morphology, while mesenchymal stem cells were cultured to assess cytotoxicity and proliferation. In vivo experiments involved the implantation of HAp in the left femur and HApTi in the right femur of twenty New Zealand white rabbits. Computed tomography (CT) scans, histological, immunohistochemical, and histomorphometric analyses were performed to assess bone density and osteoblast activity. Results demonstrated that HApTi implants showed superior osteointegration, with higher peri-implant bone density and increased osteoblast count compared to HAp implants. This study concluded that HApTi biocomposites have potential for enhanced bone healing and stability in orthopedic applications.

An Outline on the Advancements in Surgical Management of Osteoporosis-Associated Fractures.

Osteoporosis significantly impairs bone density and increases fracture risk, representing a substantial global health challenge. The effectiveness of traditional treatments such as calcium supplementation and exercise in completely preventing fractures is limited. This review explores recent advancements in surgical techniques and treatment modalities to manage osteoporotic fractures better and improve patient outcomes. Osteoporotic fractures demand specialized surgical techniques due to compromised bone quality. Vertebroplasty and kyphoplasty are minimally invasive procedures that provide rapid pain relief and structural support using bone cement. While vertebroplasty is effective, it carries risks of cement leakage and new fractures. Kyphoplasty, with added balloon inflation, reduces leakage risk and improves vertebral height restoration but is costlier. Cement-augmented screws enhance fixation but can increase adjacent fracture risk and pose long-term complications. Surgical advancements encompass robotic-assisted surgery, offering precision and accelerated recovery, alongside biologic agents like bone morphogenetic proteins (BMPs), which enhance bone healing while reducing secondary interventions and eliminating donor site morbidity. Bone graft substitutes such as calcium phosphate cements enhance biomechanical compatibility, decrease morbidity, and reduce fracture loss and pain. Balloon kyphoplasty aids in height restoration and pain relief and diminishes the risk of subsequent vertebral fractures. Bioglass scaffolds promote bone regeneration by improving bone mineral density and lowering the incidence of new fractures. Optimal perioperative care, including patient selection, nutritional management, and early mobilization strategies, is crucial for mitigating risks in vulnerable populations. While current surgical interventions provide significant pain relief and functional benefits, ongoing research and multidisciplinary collaboration are crucial to prospectively refine these techniques and reduce the burden of osteoporosis. New technologies, such as tissue engineering and gene editing, hold potential for future treatment paradigms.

Brain-Bone Crosstalk in a Murine Polytrauma Model Promotes Bone Remodeling but Impairs Neuromotor Recovery and Anxiety-Related Behavior.

Traumatic brain injury (TBI) and long bone fractures are a common injury pattern in polytrauma patients and modulate each other's healing process. As only a limited number of studies have investigated both traumatic sites, we tested the hypothesis that brain-bone polytrauma mutually impacts neuro- and osteopathological outcomes. Adult female C57BL/6N mice were subjected to controlled cortical impact (CCI), and/or osteosynthetic stabilized femoral fracture (FF), or sham surgery. Neuromotor and behavioral impairments were assessed by neurological severity score, open field test, rotarod test, and elevated plus maze test. Brain and bone tissues were processed 42 days after trauma. CCI+FF polytrauma mice had increased bone formation as compared to FF mice and increased mRNA expression of bone sialoprotein (BSP). Bone fractures did not aggravate neuropathology or neuroinflammation assessed by cerebral lesion size, hippocampal integrity, astrocyte and microglia activation, and gene expression. Behavioral assessments demonstrated an overall impaired recovery of neuromotor function and persistent abnormalities in anxiety-related behavior in polytrauma mice. This study shows enhanced bone healing, impaired neuromotor recovery and anxiety-like behavior in a brain-bone polytrauma model. However, bone fractures did not aggravate TBI-evoked neuropathology, suggesting the existence of outcome-relevant mechanisms independent of the extent of brain structural damage and neuroinflammation.

Effects of Sapindus mukorossi Seed Oil on Bone Healing Efficiency: An Animal Study.

Natural products have attracted great interest in the development of tissue engineering. Recent studies have demonstrated that unsaturated fatty acids found in natural plant seed oil may exhibit positive osteogenic effects; however, few in vivo studies have focused on the use of plant seed oil for bone regeneration. The aim of this study is to investigate the effects of seed oil found in Sapindus mukorossi (S. mukorossi) on the osteogenic differentiation of mesenchymal stem cells and bone growth in artificial bone defects in vivo. In this study, Wharton-jelly-derived mesenchymal stem cells (WJMSCs) were co-cultured with S. mukorossi seed oil. Cellular osteogenic capacity was assessed using Alizarin Red S staining. Real-time PCR was carried out to evaluate ALP and OCN gene expression. The potential of S. mukorossi seed oil to enhance bone growth was assessed using an animal model. Four 6 mm circular defects were prepared at the parietal bone of New Zealand white rabbits. The defects were filled with hydrogel and hydrogel-S. mukorossi seed oil, respectively. Quantitative analysis of micro-computed tomography (Micro-CT) and histological images was conducted to compare differences in osteogenesis between oil-treated and untreated samples. Although our results showed no significant differences in viability between WJMSCs treated with and without S. mukorossi seed oil, under osteogenic conditions, S. mukorossi seed oil facilitated an increase in mineralized nodule secretion and upregulated the expression of ALP and OCN genes in the cells (p < 0.05). In the animal study, both micro-CT and histological evaluations revealed that new bone formation in artificial bone defects treated with S. mukorossi seed oil were nearly doubled compared to control defects (p < 0.05) after 4 weeks of healing. Based on these findings, it is reasonable to suggest that S. mukorossi seed oil holds promise as a potential candidate for enhancing bone healing efficiency in bone tissue engineering.

Redefining Surgical Materials: Applications of Silk Fibroin in Osteofixation and Fracture Repair.

Silk and silk derivatives have emerged as a possible alternative in surgical device development, offering mechanical strength, biocompatibility, and environmental sustainability. Through a systematic review following PRISMA guidelines, this study evaluated silk fibroin's application across pre-clinical and clinical settings, focusing on its role as screws and plates for osteofixation. A comprehensive search yielded 245 studies, with 33 subjected to full-text review and 15 ultimately included for qualitative analysis. The findings underscore silk fibroin's superior properties, including its tunable degradation rates and ability to be functionalized with therapeutic agents. In vivo and in vitro studies demonstrated its efficacy in enhancing bone healing, offering improved outcomes in osteofixation, particularly for craniofacial defects. Silk fibroin's remarkable attributes in biodegradation and drug release capabilities underscore its potential to enhance patient care. Ultimately, silk fibroin's integration into surgical practices promises a revolution in patient outcomes and environmental sustainability. Its versatility, coupled with the continuous progress in fabrication techniques, signals a promising horizon for its widespread acceptance in the medical field, potentially establishing a new benchmark in surgical treatment. Further research is expected to solidify the transition of silk products from basic science to patient care, paving the way for widespread use in various surgical applications.

In-vitro assessment of biocompatibility and antimicrobial properties of 85S bio-glass and SrTiO3 composites

Strontium-containing ceramics enhance bone healing and graft osseointegration, but bacterial infections may impede the process, risking surgical failure. In this study, we explore the development of composites comprising strontium titanate (SrTiO3) and 85S (85SiO2–10CaO–5P2O5 mol%) bio-glass at varying concentrations using in-vitro tests such as simulated body fluid (SBF), MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide), hemolysis, and antibacterial assays. X-ray diffractogram (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) analyses confirm the development of the hydroxyapatite layer after immersing in SBF. Notably, 10 wt% of SrTiO3 in 85S bio-glass (STO_10) exhibits exceptional bone formation properties. Furthermore, MTT assays reveal non-cytotoxicity and high cell proliferation behaviour towards MG_63 cells even after 168 h, particularly for 25 mg/ml of high concentration, and are hemocompatible up to STO_10. Additionally, STO_10 demonstrates a 62 % reduction in the growth of E. coli and a 55 % reduction in S. aureus, highlighting its antimicrobial efficacy. These compelling in-vitro findings unveil the significant potential of STO_10 in the field of bone tissue regeneration.

The effect of cannabinoids on single-level lumbar arthrodesis outcomes in a rat model

BACKGROUND CONTEXTThe opioid epidemic is a public health crisis affecting spine care and pain management. Medical marijuana is a potential nonopioid analgesic yet to be studied in the surgical setting since its effects on bone healing are not fully understood. Studies have demonstrated analgesic and potentially osteoinductive properties of cannabinoids with endocannabinoid receptor expression in bone tissue. PURPOSEWe hypothesize that tetrahydrocannabinol (THC) and cannabidiol (CBD) will not decrease bone healing in spinal fusion. STUDY DESIGNSeventy-eight adult Sprague-Dawley rats were used for this study. Utilizing allogenic bone grafts (6 donor rats), posterolateral inter-transverse lumbar fusion at the L4–L5 level was performed. The animals were equally divided into four treatment groups, each receiving 0.1 ml intraperitoneal injections weekly as follows: placebo (saline), 5 mg/kg THC, 5 mg/kg CBD, and a combination of 5 mg/kg THC and 5mg/kg CBD (Combo). METHODSCallus tissue was harvested 2- and 8-weeks postsurgery for qPCR assessment to quantify changes in the expression of osteogenic genes. Manual palpation was done to assess the strength of the L4–L5 arthrodesis on all rats. μCT image-based callus analysis and histology were performed. One-way ANOVA followed by post hoc comparisons was performed. RESULTSμCT demonstrated no significant differences. Treatment groups had slightly increased bone volume and density compared to control. qPCR at 2 weeks indicated downregulated RANKL/OPG ratios skewing towards osteogenesis in the CBD group, with the THC and CBD+THC groups demonstrating a downward trend (p>.05). ALPL, BMP4, and SOST were significantly higher in the CBD group, with CTNNB1 and RUNX2 also showing an upregulating trend. The CBD group showed elevation in Col1A1 and MMP13. Data at eight weeks showed ALPL, RUNX2, BMP4, and SOST were downregulated for all treatment groups. In the CBD+THC group, RANK, RANKL, and OPG were downregulated. OPG downregulation reached significance for the THC and CBD+THC group compared to saline. Interestingly, the RANKL/OPG ratio showed upregulation in the CBD and CBD+THC groups. RANKL showed upregulation in the CBD group. At 2 and 8 weeks, the CBD treatment group showed superior histological progression, increasing between time points. CONCLUSIONThis study demonstrates that CBD and THC have no adverse effect on bone healing and the rate of spinal fusion in rats. Osteogenic factors were upregulated in the CBD-treated groups at 2 weeks, which indicates a potential for bone regeneration. In this group, compared to control, the RANKL/OPG ratio at the early healing phase demonstrates the inhibition of osteoclast differentiation, enhancing bone formation. Interestingly, it shows promoted osteoclast differentiation at the later healing phase, enhancing bone remodeling. This aligns with the physiological expectation of a lower ratio in the early phases and a higher ratio in the later remodeling phases. CLINICAL SIGNIFICANCECBD and THC showed no inhibitory effects on bone healing in a spinal fusion model. Moreover, histologic and gene expression analysis demonstrated that CBD may, in fact, enhance bone healing. Further research is needed to confirm the safe usage of THC and CBD in the postoperative setting following spinal fusions.