Search Results (194)

Fracture healing depends on coordinated osteogenesis and restoration of the vascular microenvironment. Endothelial cells support skeletal repair through angiogenesis, tissue perfusion and angiocrine signaling that regulates osteoprogenitor recruitment and differentiation. This narrative review examines endothelial dysfunction (ED) as a potential systemic contributor to impaired fracture healing by integrating evidence from vascular biology, experimental models and clinical studies. ED is characterized by reduced nitric oxide (NO) bioavailability, oxidative stress, inflammation and impaired vascular repair. These changes may disrupt angiogenic–osteogenic coupling through altered hypoxia-inducible factor 1-alpha subunit (HIF-1α)/vascular endothelial growth factor (VEGF) signaling, endothelial Notch activity, platelet-derived growth factor (PDGF)-mediated vascular remodeling and endothelial progenitor cell (EPC) mobilization. Conditions associated with endothelial dysfunction, including diabetes, aging, chronic kidney disease (CKD), smoking, obesity and chronic inflammatory disease, are also linked to delayed union, nonunion and poorer orthopedic outcomes. Cardiovascular disease and perioperative cardiovascular instability may further impair perfusion and physiological reserve during repair. However, the available evidence is predominantly experimental or observational, and direct causal evidence in fracture patients remains limited. Prospective studies combining standardized endothelial assessments with fracture-healing outcomes are needed to clarify clinical relevance and identify potential therapeutic targets. Full article

Background/Objectives: Ankle fracture–dislocation is associated with prolonged recovery, posttraumatic osteoarthritis, and poor functional outcomes. However, the structural factors responsible for ankle fracture–dislocation remain incompletely understood. This study aimed to identify the injury characteristics associated with ankle fracture–dislocation and compare radiographic outcomes between patients with and without dislocation. Methods: A retrospective review was performed on 130 patients who underwent operative treatment for ankle fractures. Patients were divided into dislocation (n = 26) and non-dislocation (n = 104) groups. Demographic characteristics, injury mechanism, trauma energy, fracture morphology, posterior malleolar fracture classification, syndesmotic injury, and deltoid ligament injury were evaluated. Independent risk factors were identified using multivariate logistic regression analysis. Bone union time and postoperative osteoarthritis were also compared. Results: Haraguchi type II posterior malleolar fracture (p < 0.001) and syndesmotic injury (p = 0.017) were independently associated with ankle fracture–dislocation. Bone union took significantly longer in the dislocation group than in the non-dislocation group (7.04 ± 3.75 vs. 5.29 ± 3.48 months; p = 0.026). Postoperative osteoarthritis occurred more frequently in the dislocation group (42.3% vs. 24.0%), although the difference was not statistically significant (p = 0.063). Conclusions: Haraguchi type II posterior malleolar fracture morphology and syndesmotic injury were associated with ankle fracture–dislocation. These findings suggest that posteromedial structural disruption and syndesmotic instability play important roles in ankle fracture–dislocation. Furthermore, ankle fracture–dislocation was associated with delayed bone union, indicating a more severe injury pattern. Full article

Background and Clinical Significance: Scaphoid fractures and nonunion are uncommon in skeletally immature patients. Pediatric nonunion most often follows a missed or delayed diagnosis or failure of conservative treatment. Inferior-pole nonunion is particularly uncommon, and evidence guiding graft selection in children is limited. We report a case in which preoperative and intraoperative assessment of fragment viability supported the use of a non-vascularized graft. Case presentation: A 12-year-old boy sustained a right inferior-pole scaphoid fracture after falling onto an outstretched hand. The fracture was missed at the initial emergency-department visit. Thumb-spica immobilization was subsequently prescribed, but the patient repeatedly removed the cast, missed appointments, and was lost to follow-up. At referral six months after injury, radiographs and multiplanar CT demonstrated established inferior-pole nonunion. MRI showed preserved marrow fat signal in both fragments without osteonecrosis. Open reduction and internal fixation were performed through a dorsal approach using a 2.4 mm headless compression screw and approximately 1 cc of cancellous iliac-crest autograft. Intraoperatively, both fragments appeared viable, without cystic or sclerotic change. At two months, the patient was pain-free and radiographs showed progressing union. The Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score improved from 25 preoperatively to 10 at two months. CT at six months confirmed complete osseous union, with a QuickDASH score of 0. At 1.5 years, he remained pain-free, had full flexion with a 5° terminal extension lag, and had returned to table tennis without functional limitation. Conclusions: In this inferior-pole scaphoid nonunion, open reduction and internal fixation with iliac-crest cancellous autograft achieved CT-confirmed union and sustained functional recovery. MRI and intraoperative confirmation of viable bone supported selection of a non-vascularized graft. At 1.5 years, the patient was pain-free, had returned to sport without functional limitation, and had a QuickDASH score of 0. Full article

Background. When free margins can be achieved and adjacent joints can be preserved, limb salvage surgery is the preferred treatment for intercalary paediatric bone tumours in the lower extremity. Biological reconstruction techniques include allograft, free vascularised fibular graft (FVFG), and allograft combined with FVGF (Capanna technique). This review summarises current evidence on outcomes and complications, and proposes directions for future research to refine patient selection. Methods. A systematic review was conducted using PubMed, Scopus, Embase, and Cochrane Library. Eligible studies reported outcomes of allograft, FVFG, or combined techniques for intercalary lower limb reconstruction in children or adolescents. Results. Twenty-five articles met the inclusion criteria (8 allograft, 7 FVFG, 14 Capanna); four studies reported two techniques. In total, 391 patients were included (allograft 147, FVFG 51, Capanna 193). Mean defect lengths were 14.9 cm (allograft), 14.5 cm (FVFG), and 14.7 cm (Capanna). Time to union was 8.5 months for allografts, 11.4 for Capanna, and 12.5 for FVFG. Non-union occurred in 14.7%, 13.2%, and 10.3%, and delayed union in 13.6%, 4.8%, and 7.9% for FVFG, allograft, and Capanna, respectively. Fractures were 40.5% for FVFG, 18.4% for allograft, and 23.5% for Capanna. Infections were least common with FVFG (2.7%). Conclusions. The reconstruction strategy should be tailored to anatomical location, defect size, and patient-specific factors. Although infections rates were lowest with FVFG, time to union was longer and the postoperative fracture rate was higher compared to the allograft or Capanna technique. Allografts demonstrated the shortest time to union and lowest fracture risk. The Capanna technique may be beneficial when factors including chemotherapy, poor host bone quality, or high mechanical load are present, but comes at a cost of morbidity and complexity. Full article

Fracture healing failure remains a major complication in trauma and orthopedic surgery. The transplantation of autologous cancellous bone grafts represents the gold standard for the treatment of atrophic non-unions. However, during revision surgery the grafts can be exposed to a significant period of intraoperative ischemia, which may have detrimental effects on their quality and functionality. Therefore, we analyzed the effects of different periods of ischemia (0, 30, 60 and 90 min) on cellular stress, gene expression and viability of the bone grafts, to determine a critical ischemia time window for transplantation. Graft samples were harvested from 24 patients undergoing revision surgery due to bone healing failure. Analyses included mRNA profiler arrays, reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Ischemia lasting 60 min or longer induced the expression of stress-induced genes, such as JUN and DUSP1. This was associated with early cellular stress within the grafts, as indicated by the presence of hypoxia-inducible factor (HIF)-1α-positive cells and an increased number of senescent p16-positive cells at early time points of ischemia. Additional analyses revealed a significantly higher number of apoptotic cleaved caspase-3-positive cells at 60 and 90 min of ischemia, demonstrating a compromised viability of the grafts. Moreover, RT-PCR analyses revealed a shift from a pro-osteogenic towards a pro-chondrogenic extracellular matrix (ECM) gene expression profile. Taken together, periods of ischemia of 60 min or longer after tissue harvesting should be avoided during cancellous bone graft transplantation to preserve graft viability. Full article

Distal radial and ulnar fractures in miniature- and toy-breed dogs are associated with high rates of delayed union, non-union, and refracture. This retrospective observational study evaluated the outcomes of simple distal radial and ulnar fractures treated by open reduction and internal fixation using a locking plate in a non-rigid configuration. Ten fractures in eight dogs weighing less than 5 kg were included. Cases were selected according to predefined biomechanical construct criteria, including a plate bridge ratio > 0.7, plate span ratio > 10, plate working length > 40% of the plate length, and screw density < 0.6. The median radiographic follow-up was 224 days (range, 46–408 days). Radiographic bone healing was achieved in all cases, with a mean time to union of 53 days (range, 28–113 days), and healing occurred faster in skeletally immature dogs. Indirect bone healing with callus formation was observed in 7 of 10 fractures. Minor postoperative complications occurred in three cases and resolved with local treatment. No implant failures or refractures associated with previous screw holes were observed. A reduction in ulnar thickness was identified in evaluable cases, although this finding remained stable during follow-up and did not appear clinically relevant. These findings suggest that locking plate fixation in a non-rigid configuration provides reliable bone healing with a low complication rate in simple distal radial and ulnar fractures of miniature- and toy-breed dogs. Full article

Background/Objectives: To evaluate the clinical and demographic characteristics of patients with impaired union of long bone fractures admitted to a specialized orthopedic center and to identify factors associated with infection on admission. Methods: A retrospective, single-center cohort study was conducted at the National Scientific Center of Traumatology and Orthopedics named after Academician N.D. Batpenov. The study included patients hospitalized between 2023 and 2025 with diagnoses of fracture nonunion or delayed union. Demographic characteristics, lesion location, interval from injury to hospitalization, previous treatment, presence of revision osteosynthesis, infection on admission, and length of hospitalization were analyzed. Univariate analysis and multivariate logistic regression were used to identify factors associated with infection. Patients with osteomyelitis were excluded from the regression model to avoid definitional collinearity. Results: During the study period, 360 hospitalizations were recorded in 336 unique patients. The annual incidence increased from 79 in 2023 to 166 in 2025. The median patient age was 50 years, with women accounting for 52.5% of the sample. The most common bone sites were the femur (36.1%), humerus (23.6%), and tibia (15.0%). The median interval from injury to hospitalization at a specialized center was 2 years. Prior revision osteosynthesis was noted in 34.2% of patients. Infection on admission was detected in 20.3% of patients and was associated with a longer hospital stay. In an exploratory multivariable model (EPV ≈ 2.8), previous revision osteosynthesis was associated with infection on admission (OR 8.26; 95% CI 2.76–24.74; p < 0.001). Conclusions: Patients with nonunion and delayed union of long-bone fractures referred to a specialized center represent a clinically complex population characterized by prolonged time from injury, previous surgical interventions, and a substantial burden of infection. In an exploratory multivariable analysis, previous revision osteosynthesis was associated with infection on admission and may represent a marker of clinical complexity and prior treatment burden rather than a causal determinant of infection. Further prospective studies are required to clarify factors associated with infection and treatment outcomes in this patient population. Full article

Background/Objectives: Delayed bone healing remains a relevant complication after polytrauma, where fracture repair occurs in the setting of systemic inflammation and repeated physiologic stress. This study evaluated whether serial changes in interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen are associated with delayed union in polytrauma patients with long-bone fractures. Methods: We performed an exploratory retrospective cohort study including 115 adult polytrauma patients with long-bone fractures treated at a single tertiary trauma center between 2 January 2022 and 14 December 2024. Serum IL-6, CRP, and fibrinogen were recorded at 24 h, 72 h, 1 week, 2 weeks, and 4 weeks after injury. IL-6 was measured in the institutional clinical laboratory using routine immunoassay methods, whereas CRP and fibrinogen were measured using standard hospital analytical methods, including an immunoturbidimetric assay for CRP and the Clauss clotting method for fibrinogen. Radiographic healing was assessed at 6, 12, and 24 weeks using an mRUST-based healing score. The primary endpoint was clinician-assigned delayed union at 24 weeks; nonunion at 9 months was assessed secondarily. Complete-case multivariable logistic regression was performed in 86 patients, and exploratory longitudinal biomarker analyses used generalized estimating equations. Results: Delayed union at 24 weeks occurred in 39/115 patients (33.9%), while nonunion at 9 months occurred in 7/115 patients (6.1%). Patients with delayed union had longer time to definitive fixation (35.3 ± 10.2 h vs. 29.0 ± 14.0 h; p = 0.003) and more frequent shock on admission (43.6% vs. 23.7%; p = 0.047). IL-6 was higher in the delayed-union group at 1 week (57.3 ± 30.3 vs. 46.5 ± 29.2 pg/mL; p = 0.043) and 4 weeks (21.2 ± 11.6 vs. 17.1 ± 10.3 pg/mL; p = 0.022), whereas CRP was markedly higher at 4 weeks (29.4 ± 14.2 vs. 16.3 ± 10.6 mg/L; p < 0.001). After false-discovery-rate correction, only CRP at 4 weeks remained significant among serial biomarker comparisons. In multivariable analysis of 86 complete cases, CRP at 4 weeks remained independently associated with delayed union (adjusted OR 2.16 per 10 mg/L, 95% CI 1.36–3.43; p = 0.001). The model showed apparent discrimination with an AUC of 0.80 and acceptable calibration (Hosmer–Lemeshow p = 0.41). In sensitivity analysis excluding deep surgical-site infection cases, the association between CRP and delayed union persisted (adjusted OR 2.02 per 10 mg/L, 95% CI 1.26–3.26; p = 0.004). Conclusions: In this exploratory retrospective cohort of polytrauma patients with long-bone fractures, persistent post-traumatic CRP elevation at 4 weeks was associated with clinician-assigned delayed union, whereas IL-6 findings were weaker and exploratory. Because CRP is a nonspecific inflammatory marker, the observed association may reflect delayed healing, infection, reoperation, and/or persistent postoperative inflammatory burden. These data support association rather than validated prediction and require prospective validation with standardized outcome adjudication. Full article

Background: Vitamin K2 (menaquinone) has been studied as a molecule with important effects on bone metabolism and has been proposed as a potential adjuvant in fracture healing, particularly under osteoporotic conditions. However, its functional impact on osteoporotic fracture healing remains largely undefined. The aim of this study was to evaluate the effects of vitamin K2 supplementation, in the form of menaquinone-4 (MK-4) and menaquinone-7 (MK-7), on fracture healing in an ovariectomized rat model of osteoporosis. Methods: Forty Wistar rats were included in this study and allocated to four equal groups: Sham control, ovariectomized control, MK-4, and MK-7. Osteoporosis was induced by bilateral ovariectomy, and 12 weeks after ovariectomy, a femoral fracture was produced and fixed by intramedullary nailing. Starting on postoperative day 2, the MK-4 group received 5 mg/kg/day of MK-4, while the MK-7 group received MK-7 at a dose of 0.05 mg/kg/day. Fracture healing was assessed primarily by biomechanical testing using a three-point bending test and was further analyzed by histological and biochemical parameters, including CTXI, PINP, ucOC, BALP, and ALT. Results: Vitamin K2 supplementation did not improve functional fracture healing. In both treatment groups, fractures showed nonunion-like mechanical behavior, precluding meaningful quantitative biomechanical comparison. Although histological and biochemical findings, particularly in the MK-4 group, showed some degree of biological activity, these changes did not translate into mechanically competent bone union. Both treatment groups showed a tendency toward impaired healing, with progression toward nonunion-like behavior under the present experimental conditions. No significant hepatic toxicity was observed. Conclusions: In this ovariectomized rat femoral fracture model, vitamin K2 supplementation with either MK-4 or MK-7 did not enhance functional fracture healing despite evidence of biological activity of the treatment. These findings suggest a discrepancy between molecular or histological effects and biomechanical outcomes, indicating that, under the conditions tested, vitamin K2 is insufficient to overcome impaired healing in osteoporotic bone and may adversely influence fracture repair under these experimental conditions, although the mechanism remains uncertain. Full article

Atrophic fracture nonunion is a clinically challenging form of failed bone repair, particularly under inflammatory conditions, but the cell-intrinsic programs that impair the function of skeletal stem/progenitor cells (SSPCs) remain incompletely defined. Here, we integrated public and in-house single-cell RNA sequencing datasets from mouse periosteum, normal fracture healing, and inflammation-associated fracture nonunion models to characterize stromal cell fate changes. Trajectory inference, transcription factor network analysis, and intercellular communication modeling were combined with in vitro and in vivo validation experiments. SSPCs in the nonunion microenvironment were arrested in an undifferentiated state and acquired a pro-inflammatory and pro-ferroptotic phenotype, with enrichment of ferroptosis-related genes including Acsl4. Computational analyses nominated IL-1β as a candidate upstream inflammatory signal, with neutrophils representing a potential source, and linked this signal to NF-κB activation and increased Epas1 activity in SSPCs. In primary SSPCs, IL-1β induced lipid peroxidation, intracellular ferrous iron accumulation, ferroptosis-related protein expression, and impaired osteochondrogenic differentiation. Ferroptosis inhibitor treatment further attenuated IL-1β-induced ferroptosis-related protein changes, supporting pathway specificity. Pharmacological inhibition of EPAS1 with PT2385 attenuated IL-1β-induced ferroptotic stress and restored SSPC differentiation in vitro, while also improving IL-1β-impaired fracture repair in vivo. Mendelian randomization analysis provided additional genetic evidence supporting potential links among IL-1β, EPAS1, and human nonunion risk. Together, these findings suggest that an IL-1β/EPAS1-associated ferroptotic program contributes to SSPC dysfunction during inflammation-associated fracture nonunion and may represent a potential targetable mechanism for improving impaired bone repair. Full article

Background/Objectives: Rami fractures in anteroposterior compression (APC)-type pelvic ring injuries show favorable outcomes with conservative management in isolated settings; however, the necessity of direct rami fixation when posterior instability is present remains unclear. This study aimed to determine whether adding direct rami fixation to symphyseal plating improves clinical and radiologic outcomes in APC-type pelvic ring injuries. Methods: This retrospective cohort study included a final cohort of 98 patients with APC type II or III pelvic ring injuries and concomitant pubic rami fractures treated at a Level 1 trauma center (2014–2022). All patients underwent plate-based symphyseal fixation, classified into four groups by fixation strategy. Primary outcomes were rami nonunion and implant-related complications, analyzed with parsimonious multivariate logistic regression (events-per-variable ratio ≥ 10). Results: Among 98 patients (mean age 45.4 ± 16.2 years; 76.5% male), complete posterior ring injury was independently associated with rami nonunion (aOR 8.176; 95% CI 2.448–27.309; p = 0.001), implant-related complications (aOR 3.364; 95% CI 1.250–9.049; p = 0.016), and overall complications (aOR 4.292; 95% CI 1.640–11.233; p = 0.003). Female sex was an additional independent predictor of overall complications (aOR 4.226; 95% CI 1.443–12.378; p = 0.009). Direct rami fixation was not a significant predictor of any outcome but consistently increased operative time in pairwise subgroup comparisons (Group 1 vs. 2: 64.9 vs. 106.9 min, p < 0.001; Group 3 vs. 4: 95.1 vs. 153.5 min, p < 0.001). Pairwise subgroup comparisons were severely underpowered (power range 5–16%); therefore, the absence of statistically significant differences between fixation strategies should not be interpreted as evidence of equivalence. Because more complex fractures were more likely to receive additional fixation, confounding by indication further limits these comparisons. Conclusions: Complete posterior ring injury was the dominant predictor of adverse outcomes in APC-type pelvic ring injuries. In this underpowered exploratory analysis, adding direct rami fixation to symphyseal plating did not demonstrate a statistically significant reduction in complications but was associated with longer operative time. Direct rami fixation may be reserved for selected cases with marked displacement, poor indirect reduction, or compromised bone quality; larger prospective studies are needed before firm recommendations can be made. Full article

One of the complications of both surgical and non-surgical treatment of fractures is the development of non-union. The 5–10% incidence of non-union quoted in the international literature is thought to be an underestimate of the real magnitude of this clinical problem. The etiology of atrophic non-union is multifactorial, involving biological, mechanical, infectious, and host-related factors. Much of the evidence regarding its pathogenesis is heterogenous and largely hypothesis generating. This heterogenicity has contributed to the wide range of treatment strategies used to address an atrophic non-union, with variable success rates. This structured narrative review summarizes current insights into the pathogenesis of atrophic non-union, including the inflammatory and immune response, the role of mesenchymal stem cells, bone morphogenetic protein, and the mechanisms of remodeling and angiogenesis. It also outlines an algorithmic approach to management, including the exclusion of occult infection, assessment of mechanical stability, optimization of modifiable host factors, and, finally, a graded approach to enhance the biological and mechanical environment of the non-union. Full article

Background: Long-bone non-unions complicated by osteomyelitis remain a major reconstructive and healthcare challenge, particularly in resource-limited settings with a high prevalence of multidrug-resistant (MDR) pathogens. Conventional staged management is associated with a prolonged treatment burden, repeated procedures, and delayed functional recovery. This study evaluated the clinical, radiological, functional, and short-term safety outcomes of a single-stage approach using custom-threaded antibiotic-coated locking nails (TACLNs) in a high-resistance cohort. Methods: This prospective single-center cohort study enrolled 30 adults with osteomyelitis-associated femoral or tibial nonunion at a tertiary hospital in Peshawar, Pakistan. All patients underwent radical debridement and single-stage stabilization with a chest tube mold TACLN loaded with vancomycin and gentamicin, with culture-directed adjunctive antibiotics for resistant organisms. Outcomes were assessed at baseline, Weeks 3 and 6, and Month 6 using inflammatory markers, RUST score, VAS pain, EQ-5D-5L, ASAMI criteria, and return to work or usual activity. No formal sample size calculation was performed, and this study was exploratory in nature. Results: The cohort (mean age 44.9 ± 9.9 years) had a challenging microbiological profile, with 40.0% MDR and 13.3% extensively drug-resistant (XDR) infections. By Month 6, short-term infection control was achieved in 96.7% of patients, with significant reductions in ESR and CRP (both p < 0.001). Radiographic union was achieved in 90.0% of cases at a mean of 18.6 weeks, and the mean RUST score improved from 4.87 to 10.43 at the final follow-up. The VAS pain decreased from 5.23 at week 3 to 0.73 at month 6, EQ-5D-5L improved from 0.39 to 0.84, and 90.0% returned to work or usual activity by month 6. No cement debonding, implant failure, or nephrotoxicity was noted. Conclusions: In this single-arm exploratory cohort, TACLNs were associated with favorable short-term infection control, radiographic union, and functional recovery in osteomyelitis-associated long-bone nonunion, including in an MDR/XDR setting. The independent contribution of the threaded core design cannot be established. Larger multicenter comparative studies with longer follow-ups are needed to confirm the durability and implementation feasibility. Full article

Bone is a dynamic and multifunctional tissue that provides mechanical support, regulates mineral homeostasis, supports hematopoiesis, and relies on complex interactions among multiple cell types. The increasing incidence of bone-related diseases, such as osteoporosis, osteoarthritis, fracture non-union, and bone cancer, highlights the need for in vitro models that better reflect human bone physiology. Bone-on-a-chip technology, developed through advances in microfluidics, biomaterials, and tissue engineering, offers a promising approach to recreate key features of the bone microenvironment in vitro. By incorporating bone-mimicking materials, relevant bone cells, vascular components, fluid perfusion, and mechanical stimulation, these platforms allow more realistic investigation of bone remodeling, regeneration, disease mechanisms, and drug responses. In parallel, bone organoids and their integration with microfluidic chips have further expanded the capabilities of in vitro bone models by enabling the formation of self-organized, human-relevant bone tissues with increased cellular complexity. This review summarizes recent progress in bone-on-a-chip systems, including models for osteogenesis and bone regeneration, vascularized bone, bone marrow and hematopoietic niches, cancer bone metastasis, and mechanobiological studies. Key design principles, materials, cellular components, and applications in disease modeling, drug screening, toxicity assessment, and personalized medicine are discussed. Current challenges and future directions are also discussed to support the continued development of more physiologically relevant in vitro bone models. Full article

Fracture nonunion or delayed union remains a significant clinical problem that burdens both the patient and the healthcare system. Defined as failure for bone to unite 9 months post injury or 3 months with no progression toward union, the pathology of nonunion may require multiple surgical interventions with associated morbidity. Increasing evidence has highlighted that nonunion is a multifaceted problem, not only a result of mechanical failure, but also a product of persistent dysregulation of the osteoimmune microenvironment manifested as impaired osteogenesis and bone healing. While current approaches focus on enhanced fixation and various bone grafting strategies, these treatments often fail to coordinate healing with osteoimmune regulation. This review summarizes the emerging biologic and bioengineering approaches that target osteoimmunology to enhance fracture repair. Scaffold systems, including metals, bioceramics, hydrogels, and micro/nanoparticle formulations, are being increasingly engineered to provide structural support while directing macrophage polarization and stimulating osteogenic signaling. We also review cell-based therapies and gene-modified constructs that are being developed to introduce osteoimmunology cues that halt chronic inflammation and promote an osteogenic microenvironment. Full article