Transplantation therapy combining scaffolds and cells can be used for extensive bone regeneration (e.g., to manage severe alveolar bone defects). Gelatin methacryloyl (GelMA) may be a suitable scaffold for cell transplantation. We developed a novel GelMA that polymerizes under visible light, using riboflavin as a photoinitiator (GelMA-RF). Here we investigated the efficacy of bone-regenerative therapy combining GelMA-RF and immature osteoblasts in rats. Rat alveolar bone immature osteoblasts (RAOBs) from 70-week-old rats were encapsulated in GelMA-RF (aged RAOBs+GelMA-RF) and transplanted into palatal (control, RAOBs alone, and RAOBs+GelMA-RF groups; n=8, respectively) or femoral (control, GelMA-RF alone, RAOBs alone, and RAOBs+GelMA-RF groups; n=8, respectively) bone defects. Macroscopic assessment, micro-computed tomography, and histological analyses were performed, and mineralization (aged and young RAOBs with or without osteogenic differentiation (OD) groups; n=8, respectively) and the calcium/phosphorus ratio (aged and young RAOBs in OD+ or OD- groups; n=8, respectively) for RAOBs under 3D-culture conditions were evaluated. Bone differentiation-related gene expression (aged and young RAOBs in OD+ or OD- groups; n=8, respectively) was analyzed by quantitative polymerase chain reaction. Transplantation of RAOBs encapsulated in GelMA-RF into palatal or femoral defects resulted in significantly earlier bone-like tissue formation compared with controls. RAOBs showed sufficient mineralization in a 3D-culture environment. Bone differentiation-related gene expression was significantly increased in 3D cultures. Taken together, GelMA-RF, particularly when combined with RAOBs, provides a supportive scaffold for bone differentiation and may represent a novel bone-regeneration therapy for complex/extensive bone defects, even when combined with immature alveolar-bone osteoblasts from aged rats. Regenerative medicine combining scaffold materials and cell transplantation shows promise for widespread bone regeneration. This study focused on gelatin methacryloyl (GelMA) as a scaffold material. We developed GelMA (GelMA-RF) that gelated under visible light, avoiding the disadvantage of UV irradiation in conventional methods, and used it as a scaffold for cell transplantation. Furthermore, considering the increasing need for regenerative medicine in elderly patients, this study focused on using immature-osteoblasts derived from aged individuals as transplant cells to verify the bone regenerative capacity. In this study, immature-osteoblasts isolated from the alveolar bone of aged rats were encapsulated in GelMA-RF and transplanted into bone defects, confirming early bone regeneration sufficiently. Furthermore, in vitro analysis confirmed bone formation-related gene expression and calcification capacity, demonstrating that GelMA-RF is a suitable material for bone regeneration. These findings suggest that even alveolar bone immature-osteoblasts derived from aged individuals, when combined with GelMA-RF, hold promise as a novel therapeutic approach for regenerating complex and extensive bone defects.

This study aimed to evaluate the radiographic bone level in primary molars in a Brazilian population, define the prevalence of bone loss, and identify the local factors associated with early bone alterations. Radiographs of children who attended Piracicaba Dental School (Brazil) between 2014 and 2020 were evaluated. Two calibrated examiners measured the distance between the cementoenamel junction and the bone crest (CEJ-BC) in bitewing radiographs, and CEJ-BC>2mm represented bone loss. Local factors in the measured sites were screened. Multiple linear and logistic regressions were used in the analysis. 828 bitewing radiographs from 527 patients (8.27±1.71 years) were evaluated. The mean CEJ-BC distance was 1.12±0.40mm (0.0-3.4mm). 85 sites were positive for bone loss, with a prevalence of 2.62% at site and 13.28% (70 individuals) at patient levels. Male patients, increasing age, maxilla, first primary molars, and local factors were related to a higher CEJ-BC. Pulpectomies, fillings, and adjacent tooth eruption were positively associated with bone loss, and those statistically significant local factors were present in 42.4% of the sites with bone loss. The prevalence of radiographic bone alterations in primary molars was 13.28%. The CEJ-BC distance and bone loss were positively associated with local factors (58.8% of the cases); however, 41.2% of the sites positive for bone loss did not present the local factors evaluated in this study. Scientific rationale for this study: Bone loss can be present in children and adolescents, and radiographic evaluation could help to elucidate its prevalence and the factors associated with its occurrence. A prevalence of 13.28% bone loss was found at the patient level in primary molars in a Brazilian population, and local factors were positively associated with bone alterations. Despite some cases diagnosed with bone loss being related to local factors, 41.2% had no association with the local risk factors evaluated in the study. The findings regarding bone loss prevalence in primary dentition highlight the importance of careful radiographic examination in children and adolescents as an initial tool to diagnose periodontitis at early stages and to prevent severe damage. This study analyzed x-rays of Brazilian children to assess bone loss in primary molars. It aimed to determine how common bone loss is and to identify local factors linked to the associated bone loss. Researchers reviewed 828 x-rays from 527 children (average age 8.27 years) who visited Piracicaba Dental School between 2014 and 2020. Bone loss was identified when the distance between the cementoenamel junction and bone crest (CEJ-BC) was greater than 2mm. The results showed an average CEJ-BC distance of 1.12mm, with 85 areas showing bone loss. The bone loss prevalence was 2.62% per site and 13.28% per patient. Factors linked to higher bone loss included being male, older age, having teeth in the maxilla, first primary molars, and specific local factors. Procedures such as pulpectomies, fillings, and nearby tooth eruptions were associated with bone loss; however, 41.2% of cases identified with bone loss did not present the local factors evaluated in the study. The study concluded that 13.28% of children showed bone changes in their primary molars, with bone loss linked to local factors and other conditions.

Alveolar bone resorption during the socket healing process compromises subsequent restoration outcomes. Recent clinical evidence suggests that dental implant placement can effectively prevent such bone loss, yet the mechanisms remain elusive. In this study, combined multi-dataset screening pinpointed sorting nexin 5 (Snx5) as a potential regulator of mechanotransduction, whose expression was downregulated in early peri-implant bone remodeling zones following implant placement. Functional studies showed that loss of Snx5 abolished the additional osteogenic enhancement normally induced by mechanical stimulation. In vivo, Snx5 deficiency disrupted the mechanosensitive activation of LepR+ MSCs and compromised implant-induced osteogenesis. Mechanistically, Snx5 facilitates the recycling of phosphorylated EGFR (p-EGFR) back to the plasma membrane to sustain EGFR signaling. Loss of Snx5 redirects EGFR trafficking toward late endosomes and lysosomal degradation, thereby weakening its signaling. These findings uncover a previously unrecognized role for Snx5 in mediating the osteogenic fate of peri-implant BMSCs in response to mechanical cues, expanding the functional repertoire of the Snx family. Collectively, these findings highlight Snx5 as a novel regulator of mechanosensitive bone remodeling and suggest that its downregulation may contribute to peri-implant bone adaptation. This study provides new insights into how the mechanical microenvironment regulates bone repair and highlights Snx5 as a promising molecular target for modulating skeletal mechano-responsiveness in clinical bone regeneration.

This study investigated the synergistic effect of early bone marrow-derived mesenchymal stem cells (BM-MSC) transplantation and endurance training on exercise-induced ventricular ectopy, myocardial infarction-induced injury and cardiac function in rats. 90 male Wistar rats (7-8 weeks) randomly distributed following groups, 1: Healthy control (HC, n = 15), 2: Sham (Sham, n = 15), 3 Myocardial infarction (MI, n = 15), 4: Myocardial infarction with BM-MSC transplantation (MI-SC, n = 15), 5: Myocardial infarction with Endurance training (MI-ET, n = 15) and 6: Myocardial infarction with Endurance training and BM-MSC transplantation (MI-ET + SC, n = 15). Myocardial infarction was induced by permanent obstruction of the cardiac left anterior descending artery. One day after MI induction, 1 × 106 BM-MSC were injected via a caudal vein in MI-SC and MI-ET + SC groups, and training rat subjects were to run on a rodent treadmill for 10 weeks. BM-MSC alone decreased serum LDH, CK-MB, left ventricular Bax, and infarction size, and promoted serum IL-10, cardiac function and exercise capacities. These effects would be stronger if cell therapy was combined with exercise training. Cell therapy insignificantly decreased TNF-α and promoted left ventricular Bcl-2, but cell therapy with exercise training significantly reduced TNF-α and promoted Bcl-2. Despite the greater reduction of cardiac arrhythmia after exercise in the MI-ET + SC group, there was no significant difference between the treatment groups. The results of this study showed that exercise training and BM-MSC transplantation synergistically promoted myocardial infarction-induced injury healing and reduced ventricular ectopy after exercise in myocardial infarction rats via inflammation and apoptosis reduction.

ABSTRACT Post‐traumatic ankle osteoarthritis (PTOA) lacks effective conservative therapeutic strategies and requires the simultaneous mitigation of chronic inflammation, lubrication dysfunction, and progressive cartilage degeneration. In this study, spermidine‐derived carbon quantum dots (Spd‐CDs, SCD) were synthesized, and self‐healing lubricating microspheres were fabricated from aldehyde hyaluronic acid (AHA) and 2,2′‐diselanediyldiethanamine dihydrochloride (Sel). These microspheres (AHA+Sel, ASM) possess aldehyde‐functionalized surfaces that enable preferential localization to damaged cartilage, and exhibit intrinsic self‐healing capability through the synergistic effects of dynamic Schiff base bonds and diselenide bonds. Highly permeable SCD was subsequently encapsulated into ASM to construct a sustained‐release system (ASM@SCD). In vitro, SCD exerted pronounced anti‐inflammatory and antioxidative effects, inhibited chondrocyte ferroptosis, and restored dysregulated cartilage extracellular matrix metabolism. Mechanistically, bulk RNA‐sequencing combined with targeted lipidomics revealed that SCD enhanced ferroptosis resistance by promoting ACSL3‐dependent incorporation of monounsaturated fatty acids into plasma membranes, displacing polyunsaturated fatty acid‐containing phospholipids, and thereby reducing susceptibility to lipid peroxidation. In vivo, ASM@SCD treatment suppressed early cartilage degeneration and aberrant subchondral bone remodeling, improved joint function, preserved normal gait patterns, and significantly attenuated PTOA progression. Collectively, ASM@SCD represents a promising non‐surgical therapeutic strategy for PTOA.

Background: Objective of present study was to evaluate the efficacy of synthetic (zinc fluorophosphate) and biological (platelet rich plasma) bone substitutesalong with locking compression plate fixation for repair of long bone fractures in dogs. Methods: In this study, 36 clinical cases of fractures of different long bones were divided in three groups having 12 animals each.In group I animals, fracture was stabilized with Locking Compression Plate (LCP), while in groupsIIand III, platelet rich plasma (PRP) and zinc fluorophosphates, respectively were additionally used at the fracture site along with LCP. Result: Different clinical, radiographic and haemato-biochemical parameters were evaluated up to 3 months post-operatively, the progress of the fracture healing was assessed using a radiographic scoring system for bone formation and union. Highest values of bone formation, union and weight bearing score were observed in group III at all intervals as compared to other groups. Functional outcome, lameness grading and radiographic observations revealed that LCP with zinc fluorophosphate had superior outcomes, early bone formation, bone union, better weight bearing and improved gait, as compared to LCP alone or LCP with PRP. Results suggested that zinc fluorophosphate, along with LCP, is better than PRP and only LCP for osteosynthesis of long bones in dogs. In present study, Group III yielded best result followed by Group II and Group I.

ObjectiveThe purpose of this study was to investigate the effect of alveolar bone grafting (ABG) on the eruption timing and the need for deliberation of the permanent maxillary canine in cleft lip and/or palate patients.Materials and methodsThe study group included 45 cleft sites from a total of 39 unilateral cleft lip and alveolus (CLA, n = 5) and unilateral (n = 22) cleft lip and palate (CLP) and bilateral (n = 12) CLP patients who had undergone treatment in the Oulu Cleft Center (OCC). A split-mouth approach and linear mixed-effects regression analysis was used to compare findings between single individual grafted and non-grafted alveolar sites.ResultsThe maxillary canine angulation had a significant role in the timing of the canine eruption (estimate 0.06, 95% CI 0.04 to 0.08). While ABG seemed to delay the canine eruption, this result was not statistically significant. The eruption of the maxillary canine tooth on the bone grafted side was delayed compared to the eruption of the maxillary canine on the non-grafted side (estimate -0.55, 95% CI -0.99 to -0.11). Another factor affecting the canine eruption was surgical exposure of the canine, and it typically emerged about a year after it had been surgically exposed and deliberated (estimate 1.05, 95% CI 0.40 to 1.70).ConclusionThe permanent maxillary canine eruption was slightly delayed after the ABG. Also, the maxillary canine was found to typically emerge about a year after it has been deliberated. The early bone graft had no benefit in terms of the timing of canine eruption. The angulation of the maxillary canine should be taken into consideration when planning ABG to facilitate its eruption. Careful planning and timing of the ABG and multidisciplinary approach have an important role in cleft patients’ treatment.

Patients with spinal cord injury frequently develop neurogenic heterotopic ossification, whose pathogenesis remains incompletely understood. Existing research models struggle to accurately simulate the complex pathological process. To establish a reliable neurogenic heterotopic ossification research model, elucidate its pathogenesis, and explore early intervention strategies, this study successfully developed a spinal cord injury-induced neurogenic heterotopic ossification mouse model. Significant ectopic bone formation, restricted hip and knee joint mobility, and motor dysfunction were observed, accompanied by elevated expression of the osteogenic markers alkaline phosphatase, runt-related transcription factor 2, sex-determining region Y-box 9, and osteocalcin . Proteomics and quantitative polymerase chain reaction analysis revealed upregulation of chemokine (C-X-C motif) ligand (CXCL)12, C-X-C chemokine receptor type 4 (CXCR4), and LYN proto-oncogene, whereas CXCL1 was downregulated in the neurogenic heterotopic ossification group. In vivo experiments confirmed abnormal accumulation of M1 macrophages in muscles surrounding early ectopic bone tissue, with markedly elevated CXCL12 expression. In vitro studies further revealed that M1 macrophages are the primary source of CXCL12 secretion, and their cell culture supernatants promote the proliferation, migration, and osteoblastic differentiation potential of bone marrow mesenchymal stem cells. Mechanistically, CXCL12 activates the phosphatidylinositol 3-kinase/protein kinase B pathway by binding to the CXCR4 receptor, thereby driving the osteogenic differentiation of bone marrow mesenchymal stem cells. These findings indicate a causal relationship between the pathological process of neurogenic heterotopic ossification following spinal cord injury and the activation of the CXCL12-CXCR4-phosphatidylinositol 3-kinase-protein kinase B signaling axis, which modulates bone marrow mesenchymal stem cell function through M1 macrophage polarization. This study reveals a key mechanism driving the osteogenic differentiation of bone marrow mesenchymal stem cells, providing new directions for early warning and targeted treatment of neurogenic heterotopic ossification following spinal cord injury.

Contemporary prostate cancer prognostic models do not include imaging and generally are based on pretreatment parameters. We sought to develop an externally validated model that used novel quantification of soft-tissue and bone disease, integrated with standard clinical and serum biomarkers, at baseline and up to 6 months of treatment. Two randomized phase 3 trials, Cougar COU-AA-302 (NCT00887198; for derivation) and Alliance A031201 (NCT01949337; for validation), were used to evaluate the added value of early on-treatment bone imaging and more than 1,000 radiomics features on CT, used in conjunction with clinical and serum biomarkers in first-line metastatic castration-resistant prostate cancer. Predictive accuracy measures were computed to determine whether these early on-treatment biomarkers could reliably sort patients into risk groups that inform overall survival (OS) and whether the patient-specific biomarker risk score could precisely predict their OS time. Imaging improved patient risk stratification but did not improve individual survival predictions. The strongest risk prediction model was developed for patients with bone-only metastases. This model was also the least complex, relying on just 16 risk factors, whereas all other models were high-dimensional, incorporating approximately 1,100 intercept and 1,100 slope features from the early on-treatment biomarker trajectories. Pretreatment and early on-treatment serum and automated quantitative imaging markers can well discriminate risk of death. Imaging improves this risk categorization relative to serum biomarkers alone. Such models can give early outcome predictions and can be used in future trials that involve imaging, even using traditional techniques such as bone scintigraphy.

Early bone formation around implants depends on both the chemical composition and the micro-, nanoscale architecture of the implant surface. Nanoscale modifications can accelerate osseointegration, and laser processing offers a versatile method of creating such features. In this study, titanium substrates were modified using a single-step nanosecond laser treatment at two energy regimes (1.95mJ/pulse for P_0.5; 4.00mJ/pulse for P_0.4). The resulting surfaces were characterized by SEM, EDS, XRD, Raman spectroscopy, ToF-SIMS, contact angle, and topography measurements, with biological assessment performed using a mouse preosteoblast cell line. Analyses revealed various titanium oxo clusters (TiO3-, TiO2-, TiO-) and moderate oxidation levels (25-31 at% O). Both laser regimes produced rough, hydrophobic surfaces. Cytotoxicity tests confirmed that the materials were non-toxic, and proliferation assays showed increasing preosteoblast numbers over time, indicating that both surfaces supported cell division. Good adhesion of preosteoblasts was observed on P_0.4 and P_0.5. This work demonstrates that nanosecond laser processing alone can generate micro-, nanostructured titanium implant surfaces with favourable biocompatibility, achieving performance comparable to more complex femtosecond methods while offering a cost-effective and scalable surface engineering strategy.

Scaffolds for bone tissue engineering have traditionally been designed to mimic the inorganic-to-organic ratio of mature bone, aiming to recapitulate its mechanical properties. However, early bone repair is not characterized by immediate mechanical strength but rather by materials that highly promote osteogenesis. In this study, we present the fabrication and evaluation of composite scaffolds composed of bioactive glass nanoparticles (BGNPs), silk fibroin, gelatin, and alginate, designed to optimize the ratio of inorganic BGNPs to biological polymers to enhance both biocompatibility and osteogenic potential. Characterization of the scaffolds revealed that the balance between BGNP and polymer content significantly influenced their structural and functional properties. Thermogravimetric analysis (TGA) showed a positive correlation between polymer content and scaffold water retention, while differential TGA(DTG) indicated that BGNPs improved the thermal stability of the polymer matrix. Swelling and biodegradation studies demonstrated that scaffolds with higher polymer content absorbed more water and degraded faster, creating a more dynamic environment conducive to cell activity. Uniaxial compression testing demonstrated that scaffolds with balanced compositions exhibited mechanical properties resembling those of the soft callus. In vitro biocompatibility tests demonstrated that scaffolds with higher polymer content were noncytotoxic, whereas those with excessive BGNPs reduced cell viability. Scaffolds with balanced compositions (Polymer blend: BGNPs = 9:1 and 7:3) showed significantly enhanced cell viability and osteogenicity, as indicated by increased alkaline phosphatase activity. Surprisingly, the optimal ratios resembled those of the soft callus, rather than mature bone. Based on these findings, we propose that scaffold designs should mimic the inorganic-to-organic composition of the soft callus, formed in the early stages of bone repair, as this composition better promotes osteogenesis. Optimizing the BGNP-to-polymer ratio is crucial for creating biomaterials that will achieve long-term clinical success.

Association of transferred coracoid graft positioning and fixation screw angulation with early bone union after the arthroscopic Bristow-Bankart procedure.

Background: Low-intensity pulsed ultrasound (LIPUS) is a non-invasive biophysical modality shown to enhance bone healing through mechanotransduction. Its role in maxillofacial bone regeneration remains less clearly defined compared with orthopaedic applications. Methods: This systematic review was conducted in accordance with PRISMA guidelines, synthesizing clinical and translational evidence on the use of LIPUS in maxillofacial bone healing. Electronic databases were searched for studies published between 2000 and 2025 evaluating mandibular fractures, distraction osteogenesis, orthognathic surgery, and dental implant osseointegration treated with LIPUS. Outcomes relevant to bone union, mineralization, pain reduction, and functional recovery were narratively analyzed, and risk of bias was assessed using appropriate standardized tools. Results: Included studies demonstrated accelerated radiographic union, increased early bone density, enhanced callus maturation, improved peri-implant bone preservation, and reduced postoperative pain with LIPUS therapy.Several studies also reported earlier functional recovery and improved clinical stability compared with conventional treatment protocols. However, heterogeneity in study design, outcome measures, and treatment parameters was noted, highlighting the need for standardized protocols and high-quality randomized controlled trials. Conclusion: LIPUS appears to be a safe and promising adjunct for maxillofacial bone healing, although further high-quality randomized trials are required to establish standardized protocols and definitive clinical guidelines

This article details the 2025 consensus update from the Brazilian Group for Pediatric Bone Marrow Transplantation and the Brazilian Society for Pediatric Oncology regarding hematopoietic stem cell transplantation (HSCT) for pediatric acute lymphoblastic leukemia (ALL). Allogeneic HSCT is the standard treatment for high-risk or relapsed ALL. Key indications include, in first remission, very high risk patients defined by primary induction failure or positive minimal residual disease (MRD) after consolidation. In second remission, it is indicated for early bone marrow relapse, early isolated extramedullary B-cell relapse, and all T-cell ALL relapses. The consensus recommends myeloablative conditioning as standard, preferring total body irradiation based regimens for children over 2–3 years old. The preferred donor hierarchy is a matched sibling, followed by a matched unrelated donor, with bone marrow being the preferred cell source. Post-HSCT monitoring of MRD is critical for guiding interventions and identifying relapse. This document serves as an essential, updated guide for clinical decision-making in this field.

Initial stages of bone colonization by breast cancer cells are critical for metastasis, but current in vitro models cannot decipher the microenvironmental cues involved. Therefore, a biphasic hydrogel model system is designed that recapitulates structural, biophysical, and biochemical components of the bone microenvironment to replicate early metastasis events. Breast cancer cells embedded within a glycosaminoglycan-based nanoporous hydrogel phase are traced as they colonize a directly adjacent macroporous cryogel compartment, precisely and selectively equipped with specific bone-like biomolecular signals and/or solution-deposited mineral crystals. Microscopic monitoring of the spatiotemporal cancer cell distributions yields colonization profiles that display the correlated effects of cell invasion, matrix interaction, and proliferation. MDA-MB-231 cells, but not MCF-7 cells, rapidly infiltrate the cryogel compartment at rates depending on the cross-linking degree of the hydrogel phase. Cryogel functionalization with adhesion-mediating peptide ligands enhances matrix interactions and survival/proliferation of the MDA-MB-231 cells. When combined with cryogel-released stromal cell-derived factor 1 (SDF-1), survival/proliferation are further amplified and additionally MDA-MB-231 cell invasion is promoted. The presence of deposited bone-like mineral strongly impedes these responses and is accompanied by characteristic alterations in distinct cellular gene-expression programs. The reported methodology may not only provide further mechanistic insights into early bone metastasis, but also facilitate the screening of anti-metastatic drugs.

Alveolar bone loss challenges tooth retention and implant placement. Freeze-dried bone allograft (FDBA) is widely used for alveolar ridge preservation but has limitations in resorption rate and healing time. In this proof-of-concept study, we tested whether pro-mineralization enzyme, tissue-nonspecific alkaline phosphatase (TNAP) enhances bone healing. Seven-week-old mice (n=4-6/group; equal numbers of males and females) underwent maxillary molar extraction and standardized alveolar defect creation. Mice were assigned to sham, FDBA with saline (BGS) or FDBA with mineral-targeted TNAP-Fc-D10 (BGT). Healing was assessed using microcomputed tomography (micro-CT), serum alkaline phosphatase (ALP) levels, histology, and immunohistochemistry, between 14- and 60-days post-procedure (dpp). Intergroup comparisons were analyzed by one-way ANOVA and post-hoc Tukey test (α=0.05) RESULTS: At 14 dpp, the BGT group demonstrated significantly greater bone volume fraction (BV/TV) and bone mineral density (BMD) compared with BGS (p<0.01, p<0.05) and sham groups (p<0.001). Alveolar bone volume was greater than sham (p<0.001). Alveolar bone dimension (height and width) was significantly more stable in the BGT group (p<0.05). Although BV/TV at 60 dpp showed no significant differences, BGT maintained higher BMD and alveolar bone width stability (p<0.01). Histological and immunohistochemical analyses revealed increased new bone formation and greater bone marker expression in the short-term BGT group (p<0.05). No changes in serum ALP levels were detected. TNAP-Fc-D10 with FDBA significantly enhances early alveolar bone healing and dimensional stability. While long-term volumetric gains were not observed, sustained improvements in mineral density and ridge preservation support TNAP as a promising biologic for alveolar ridge preservation. When people lose teeth, keeping enough bone in the jaw is critical for future treatments like dental implants. A common material used to rebuild bone is called freeze-dried bone allograft (FDBA), but it does not always heal quickly or completely. In this study, we tested whether adding a special enzyme called TNAP, which helps build bones naturally, could make FDBA work better. After extracting teeth and creating bone defects in mice, we compared healing between three groups: control (sham), FDBA + saline, and FDBA + engineered TNAP-Fc-D10. After 2 weeks, the group that received FDBA+TNAP-Fc-D10 showed more new bone formation and better preservation of the size of the jawbone. Even after 2 months, their bone remained denser and more stable compared with the other groups. Importantly, we found no signs of unwanted side effects in the blood. These results suggest that adding TNAP-Fc-D10could make bone grafts more effective early on, helping preserve jaw structure better over time. More research is needed to fine-tune the treatment and see how well it works in humans.

The BMP/GDF branch of TGF-β signaling regulates diverse aspects of skeletal biology, from skeletal development to maintenance and repair. However, the complexity, redundancy, and pleiotropy of BMP/GDF signaling have hamstrung a genetic dissection of its activities in different cell types over time. Here, we tested the feasibility of a three-transgene system using CRISPR/Cas9 to conditionally mutate six target sites, two each in the receptor-mediated Smad1, Smad5, and Smad8 transcriptional effectors of BMP/GDF signaling. Briefly, we used Prx1-cre to activate a conditional Cas9 transgene by recombination in early limb bud mesenchyme; this endonuclease then complexes with gRNAs expressed from a polycistronic tRNA-gRNA array for targeted mutagenesis. Slower than expected accumulation of gRNA-directed mutations in each Smad produced an unexpected postnatal skeletal phenotype. Beginning around one month after birth, all animals developed hyperostosis on the surface of all long limb bones, which progressively worsened with age. This woven bone expansion occurred through proliferation of RUNX2+ osteoprogenitor cells in the cambium layer of the periosteum, producing an abundance of periosteal osteoblasts. Endosteal osteoblasts did not increase in number but increased their mineralizing activity. As a result, the marrow cavities narrowed, and the patella and carpal elements, which have no periosteum, increased internal bone mass without altering shape and size. Thus, while BMP/GDF signaling is known to promote early postnatal bone growth, these data support an additional homeostatic role during late postnatal osteogenesis by regulating both periosteal and endosteal osteoblasts. Although this genetically simple approach requires further optimization to improve efficiency, combining three transgenes produced more than 160 conditionally mutagenized animals with a fully penetrant and reproducible phenotype. This is an advance over traditional cre/lox systems that scale in complexity with the number of target loci, and it highlights the potential to model a wide range of genetically complex traits and disorders.

Introduction: The one-step membrane technique, derived from the Masquelet induced membrane technique, uses human acellular dermal matrix (hADM) that is wrapped around the bone defect to bypass membrane induction, reducing treatment time. Pre-colonization of hADM with bone marrow cells (BMC), particularly after CD8+ T cell depletion, enhances bone regeneration. This study examined how CD8+ T cell depletion alters the proteins accumulated in the hADM during early healing. Materials and Methods: Eighteen male Sprague-Dawley rats received 5 mm femoral defects filled with autologous bone chips and wrapped with hADM, hADM + BMC, or hADM + BMC-CD8. hADMs were recovered on days 3 and 7 (n = 3/group/timepoint), incubated ex vivo, and conditioned medium analyzed with a proteome profiler detecting 79 proteins. Results: The protein content of the hADM evolved dynamically. At day three, 41 proteins were detected, rising to 47 by day seven, with RGM-A, osteoprotegerin, LIF, IL-6, CCL20, and CCL17 emerging late, consistent with increased regenerative activity. CD8+ T cell depletion suppressed early inflammatory and pro-osteogenic mediators (e.g., CCL2, IGF-I, IL-1RA) while upregulating LIX. By day seven, regenerative mediators (CCL20, GDF-15, RGM-A) were enriched, whereas inflammatory factors (CCL21, IL-1a, WISP-1) declined. MMP-9, Galectin-1, and GDF-15 increased exclusively in the CD8-depleted group. Conclusions: The hADM protein content transitions from pro-inflammatory to pro-regenerative within one week after surgery. CD8+ T cell depletion accelerates this shift, highlighting hADM as a dynamic scaffold that contributes to the immune–regenerative crosstalk in bone healing.

Does Early Bone Conduction Hearing Device Use Offer Benefit in Unilateral Congenital Aural Atresia?

There has been an increasing trend in using piezoelectric devices in craniofacial surgery to selectively cut bone and reduce collateral soft tissue trauma. Although the benefits of piezosurgery have been well demonstrated for osteotomies, its impact on bone healing during rasping remains understudied. This study evaluated bone regeneration following medial maxillary rasping performed with a manual rasp (MR) compared with piezotome-assisted rasping (PR) in a skeletally mature sheep model. Bilateral defects (rasps: ∼2cm x ∼2cm) were created along the coronal plane on the anterodorsal aspect of the nasal bone, with PR used on the anatomic right side and MR on the anatomic left side. Nondecalcified histologic processing and analysis was performed on the nasomaxillary bone at 3 and 12 weeks postoperatively (n=6 sheep/timepoint). At 3 weeks, MR-treated defects showed smoother, intact bone defect margins with minimal bone deposition. PR-treated defects displayed more irregular margins with scattered bone fragments, consistent with ultrasonic microfracturing. By 12 weeks, both techniques demonstrated comparable healing patterns with a regenerating nasal bone contour, maturation of bone architecture, visible osteocytes, and no evidence of bone fragments or inflammatory infiltrates. Semiquantitative scoring of osteogenesis revealed statistically homogenous findings between MR and PR usage (p=0.63 at 3weeks; p=1.00 at 12weeks). Within the limits of this model, piezotome-assisted rasping altered early bone surface topography but did not impair long-term bone regeneration compared with manual rasping. This provides preclinical support for piezotome use as an alternative bone-modifying technique in rhinoplasty.