Search Results (25)

Background/Objectives: Cannabinoid use is rising among patients undergoing spinal fusion, yet its influence on bone healing is poorly defined. The endocannabinoid system (ECS)—through cannabinoid receptors 1 (CB1) and 2 (CB2)—modulates skeletal metabolism. We reviewed preclinical, mechanistic and clinical evidence to clarify how individual cannabinoids affect fracture repair and spinal arthrodesis. Methods: PubMed, Web of Science and Scopus were searched from inception to 31 May 2025 with the terms “cannabinoid”, “CB1”, “CB2”, “spinal fusion”, “fracture”, “osteoblast” and “osteoclast”. Animal studies, in vitro experiments and clinical reports that reported bone outcomes were eligible. Results: CB2 signaling was uniformly osteogenic. CB2-knockout mice developed high-turnover osteoporosis, whereas CB2 agonists (HU-308, JWH-133, HU-433, JWH-015) restored trabecular volume, enhanced osteoblast activity and strengthened fracture callus. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with CB2 bias, accelerated early posterolateral fusion in rats and reduced the RANKL/OPG ratio without compromising final union. In contrast, sustained or high-dose Δ⁹-tetrahydrocannabinol (THC) activation of CB1 slowed chondrocyte hypertrophy, decreased mesenchymal-stromal-cell mineralization and correlated clinically with 6–10% lower bone-mineral density and a 1.8–3.6-fold higher pseudarthrosis or revision risk. Short-course or low-dose THC appeared skeletal neutral. Responses varied with sex, age and genetic background; no prospective trials defined safe perioperative dosing thresholds. Conclusions: CB2 activation and CBD consistently favor bone repair, whereas chronic high-THC exposure poses a modifiable risk for nonunion in spine surgery. Prospective, receptor-specific trials stratified by THC/CBD ratio, patient sex and ECS genotype are needed to establish evidence-based cannabinoid use in spinal fusion. Full article

Chronic wounds and injuries remain a substantial healthcare challenge, with significant burdens on patient quality of life and healthcare resources. Mesenchymal stromal cells (MSCs) present an innovative approach to enhance tissue repair and regeneration in the context of wound healing. The intrinsic presence of MSCs in skin tissue, combined with their roles in wound repair, ease of isolation, broad secretory profile, and low immunogenicity, makes them especially promising for treating chronic wounds. This review explores the current landscape of MSC application, focusing on preclinical and clinical data across chronic wounds, diabetic ulcers, burns, non-union bone fractures, lower extremity venous ulcers, pressure ulcers, and genetic skin conditions like epidermolysis bullosa. Special emphasis is given to the mechanisms through which MSCs exert their regenerative effects, underscoring their potential in advancing wound healing therapies and supporting the broader field of regenerative medicine. Full article

The emerging paradigm of personalised bone repair embodies a transformative triad comprising bio-inspired design, digital fabrication, and the exploration of innovative materials. The increasing average age of the population, alongside the rising incidence of fractures associated with age-related conditions such as osteoporosis, necessitates the development of customised, efficient, and minimally invasive treatment modalities as alternatives to conventional methods (e.g., autografts, allografts, Ilizarov distraction, and bone fixators) typically employed to promote bone regeneration. A promising innovative technique involves the use of cellularised scaffolds incorporating mesenchymal stem cells (MSCs). The selection of materials—ranging from metals and ceramics to synthetic or natural bio-derived polymers—combined with a design inspired by natural sources (including bone, corals, algae, shells, silk, and plants) facilitates the replication of geometries, architectures, porosities, biodegradation capabilities, and mechanical properties conducive to physiological bone regeneration. To mimic internal structures and geometries for construct customisation, scaffolds can be designed using Computer-aided Design (CAD) and fabricated via 3D-printing techniques. This approach not only enables precise control over external shapes and internal architectures but also accommodates the use of diverse materials that improve biological performance and provide economic advantages. Finally, advanced numerical models are employed to simulate, analyse, and optimise the complex processes involved in personalised bone regeneration, with computational predictions validated against experimental data and in vivo studies to ascertain the model’s ability to predict the recovery of bone shape and function. Full article

A 17-month-old domestic short-hair cat was referred due to a non-union in the left tibia. The initial repair, conducted 3 months prior at another animal hospital, involved an intramedullary (IM) pin and wire to address a comminuted fracture. Unfortunately, the wire knot caused a skin tract, resulting in osteomyelitis. Although the wire knot was removed at that hospital, the draining tract persisted, continuously discharging exudate. Upon evaluation, the first surgery was reassessed and revised, involving the removal of the IM pin and the application of external skeletal fixation alongside an antibiotic susceptibility test. After 118 days post-revision surgery, while some cortical continuity was observed, a significant bone defect persisted, posing a substantial risk of refracture should the implant be removed. A second revision surgery was performed, utilizing a bone plate combined with cancellous bone autograft, recombinant human bone morphogenetic protein-2, and xenograft featuring a canine-derived cancellous chip mixed with demineralized bone matrix. Remarkably, the bone completed its healing within 105 days following the subsequent surgery. Radiography demonstrated successful management of the large bone defect up to the 2-year postoperative check-up. During telephone follow-ups for 3.5 years after surgery, no complications were identified, and the subject maintained a favorable gait. Full article

Bone regeneration and repair are complex processes with the potential of added complications, like delayed repair, fracture non-union, and post-surgical infections. These conditions remain a challenge globally, pressurizing the economy and patients suffering from these conditions. Applications of nanotechnology (NBT) in the field of medicine have provided a medium for several approaches to support these global challenges. Tissue engineering is one such field that has been on the rise in the last three decades through the utilization of NBT for addressing the challenges related to bone regeneration. First, NBT enables the formation of scaffolds at the nanoscale needed for bone tissue engineering (BTE) using natural and synthetic polymers, as well as with minerals and metals. Then, it aids the development of the nano-formulation strategized to deliver antimicrobial drugs and/or growth factors through various ways to enhance bone repair through the scaffold. Third, NBT facilitates the use of specialized nanoparticles to image and track cellular events in vitro as well as in vivo. This review is an effort to bring together the current knowledge in the field of BTE and present the scope of ever-evolving NBT, a contribution towards precision medicine. Full article

The management of critical-sized bone defects caused by nonunion, trauma, infection, malignancy, pseudoarthrosis, and osteolysis poses complex reconstruction challenges for orthopedic surgeons. Current treatment modalities, including autograft, allograft, and distraction osteogenesis, are insufficient for the diverse range of pathology encountered in clinical practice, with significant complications associated with each. Therefore, there is significant interest in the development of delivery vehicles for growth factors to aid in bone repair in these settings. This article reviews innovative strategies for the management of critical-sized bone loss, including novel scaffolds designed for controlled release of rhBMP, bioengineered extracellular vesicles for delivery of intracellular signaling molecules, and advances in regional gene therapy for sustained signaling strategies. Improvement in the delivery of growth factors to areas of significant bone loss has the potential to revolutionize current treatment for this complex clinical challenge. Full article

The complex or compromised bone defects caused by osteomyelitis, malignant tumors, metastatic tumors, skeletal abnormalities, and systemic diseases are difficult to be self-repaired, leading to a non-union fracture. With the increasing demands of bone transplantation, more and more attention has been paid to artificial bone substitutes. As biopolymer-based aerogel materials, nanocellulose aerogels have been widely utilized in bone tissue engineering. More importantly, nanocellulose aerogels not only mimic the structure of the extracellular matrix but could also deliver drugs and bioactive molecules to promote tissue healing and growth. Here, we reviewed the most recent literature about nanocellulose-based aerogels, summarized the preparation, modification, composite fabrication, and applications of nanocellulose-based aerogels in bone tissue engineering, as well as giving special focus to the current limitations and future opportunities of nanocellulose aerogels for bone tissue engineering. Full article

Nonunion and delayed union are common complications of diabetes mellitus that pose a serious health threat to people. There are many approaches that have been used to improve bone fracture healing. Recently, exosomes have been regarded as promising medical biomaterials for improving fracture healing. However, whether exosomes derived from adipose stem cells can promote bone fracture healing in diabetes mellitus remains unclear. In this study, adipose stem cells (ASCs) and exosomes derived from adipose stem cells (ASCs-exos) are isolated and identified. Additionally, we evaluate the in vitro and in vivo effects of ASCs-exos on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone repair and the regeneration in a rat model of nonunion via Western blotting, immunofluorescence assay, ALP staining, alizarin red staining, radiographic examination and histological analysis. Compared with controls, ASCs-exos promoted BMSC osteogenic differentiation. Additionally, the results of Western blotting, radiographic examination and histological analysis show that ASCs-exos improve the ability for fracture repair in the rat model of nonunion bone fracture healing. Moreover, our results further proved that ASCs-exos play a role in activating the Wnt3a/β-catenin signaling pathway, which facilitates the osteogenic differentiation of BMSCs. All these results show that ASCs-exos enhance the osteogenic potential of BMSCs by activating the Wnt/β-catenin signaling pathway, and also facilitate the ability for bone repair and regeneration in vivo, which provides a novel direction for fracture nonunion in diabetes mellitus treatment. Full article

Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the osseous tissue. Particularly in long bones including the tibia, clavicle, humerus and femur, this process fails in 2–10% of all fractures, with devastating effects for the patient and the healthcare system. Underlying reasons for this failure are manifold, from lack of biomechanical stability to impaired biological host conditions and wound-immanent intricacies. In this review, we describe the cellular components involved in impaired bone healing and how they interfere with the delicately orchestrated processes of bone repair and formation. We subsequently outline and weigh the risk factors for the development of non-unions that have been established in the literature. Therapeutic prospects are illustrated and put into clinical perspective, before the applicability of biomarkers is finally discussed. Full article

The management and definitive treatment of segmental bone defects in the setting of acute trauma, fracture non-union, revision joint arthroplasty, and tumor surgery are challenging clinical problems with no consistently satisfactory solution. Orthopaedic surgeons are developing novel strategies to treat these problems, including three-dimensional (3D) printing combined with growth factors and/or cells. This article reviews the current strategies for management of segmental bone loss in orthopaedic surgery, including graft selection, bone graft substitutes, and operative techniques. Furthermore, we highlight 3D printing as a technology that may serve a major role in the management of segmental defects. The optimization of a 3D-printed scaffold design through printing technique, material selection, and scaffold geometry, as well as biologic additives to enhance bone regeneration and incorporation could change the treatment paradigm for these difficult bone repair problems. Full article

In orthopedics, a number of synthetic bone substitutes are being used for the repair and regeneration of damaged or diseased bone. The nature of the bone substitutes determines the clinical outcome and its application for a range of orthopedic clinical conditions. In this study, we aimed to demonstrate the possible applications of multichannel granular bone substitutes in different types of orthopedic clinical conditions, including bone tumor, fracture, and bone defect with arthroplasty. A clinical investigation on a single patient for every specific type of disease was performed, and patient outcome was evaluated by physical and radiographic observation. Brief physical characterization of the granular bone substitute and in vivo animal model investigation were presented for a comprehensive understanding of the physical characteristics of the granules and of the performance of the bone substitute in a physiological environment, respectively. In all cases, the bone substitute stabilized the bone defect without any complications, and the defect regenerated slowly during the postoperative period. Gradual filling of the defect with the newly regenerated bone was confirmed by radiographic findings, and no adverse effects, such as osteolysis, graft dispersion, and non-union, were observed. Homogeneous bone formation was observed throughout the defect area, showing a three-dimensional bone regeneration. High-strength multichannel granules could be employed as versatile bone substitutes for the treatment of a wide range of orthopedic conditions. Full article

Background: Long bone fractures display significant non-union rates, but the exact biological mechanisms implicated in this devastating complication remain unclear. The combination of osteogenetic and angiogenetic factors at the fracture site is an essential prerequisite for successful bone regeneration. The aim of this study is to investigate the results of the clinical implantation of growth factors for intraoperative enhancement of osteogenesis for the treatment of long bone fractures and non-unions. Methods: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and Web of Science databases from the date of inception of each database through to 10 January 2022. Specific inclusion and exclusion criteria were applied in order to identify relevant studies reporting on the treatment of upper and lower limb long bone non-unions treated with osteoinductive or cellular factors. Results: Overall, 18 studies met the inclusion criteria and examined the effectiveness of the application of Bone Morphogenetic Proteins-2 and -7 (BMPs), platelet rich plasma (PRP) and mesenchymal stem cells (MSCs). Despite the existence of limitations in the studies analysed (containing mixed groups of open and close fractures, different types of fractures, variability of treatment protocols, different selection criteria and follow-up periods amongst others), their overall effectiveness was found significantly increased in patients who received them compared with the controls (I² = 60%, 95% CI = 1.59 [0.99–2.54], Z =1.93, p = 0.05). Conclusion: Administration of BMP-2 and -7, PRP and MSCs were considered effective and safe methods in fracture treatment, increasing bone consolidation, reducing time to repair and being linked to satisfactory postoperative functional scores. Full article

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing. Full article

The human skeleton is a dynamic and remarkably organized organ system that provides mechanical support and performs a variety of additional functions. Bone tissue undergoes constant remodeling; an essential process to adapt architecture/resistance to growth and mechanical needs, but also to repair fractures and micro-damages. Despite bone’s ability to heal spontaneously, certain situations require an additional stimulation of bone regeneration, such as non-union fractures or after tumor resection. Among the growth factors used to increase bone regeneration, bone morphogenetic protein-2 (BMP2) is certainly the best described and studied. If clinically used in high quantities, BMP2 is associated with various adverse events, including fibrosis, overshooting bone formation, induction of inflammation and swelling. In previous studies, we have shown that it was possible to reduce BMP2 doses significantly, by increasing the response and sensitivity to it with small molecules called “BMP2 enhancers”. In the present study, we investigated the effect of N-Vinyl-2-pyrrolidone (NVP) on osteoblast and osteoclast differentiation in vitro and guided bone regeneration in vivo. We showed that NVP increases BMP2-induced osteoblast differentiation and decreases RANKL-induced osteoclast differentiation in a dose-dependent manner. Moreover, in a rabbit calvarial defect model, the histomorphometric analysis revealed that bony bridging and bony regenerated area achieved with NVP-loaded poly (lactic-co-glycolic acid (PLGA) membranes were significantly higher compared to unloaded membranes. Taken together, our results suggest that NVP sensitizes BMP2-dependent pathways, enhances BMP2 effect, and inhibits osteoclast differentiation. Thus, NVP could prove useful as “osteopromotive substance” in situations where a high rate of bone regeneration is required, and in the management of bone diseases associated with excessive bone resorption, like osteoporosis. Full article

Fracture-healing is a complex multi-stage process that usually progresses flawlessly, resulting in restoration of bone architecture and function. Regrettably, however, a considerable number of fractures fail to heal, resulting in delayed unions or non-unions. This may significantly impact several aspects of a patient’s life. Not surprisingly, in the past few years, a substantial amount of research and number of clinical studies have been designed, aiming at shedding light into the cellular and molecular mechanisms that regulate fracture-healing. Herein, we present the current knowledge on the pathobiology of the fracture-healing process. In addition, the role of skeletal cells and the impact of marrow adipose tissue on bone repair is discussed. Unveiling the pathogenetic mechanisms that govern the fracture-healing process may lead to the development of novel, smarter, and more effective therapeutic strategies for the treatment of fractures, especially of those with large bone defects. Full article