Bone Healing Research Articles

Impact of lateral cortical notching on biomechanical performance in cephalomedullary nailing for unstable pertrochanteric fractures.

In pertrochanteric femur fractures the risk for fracture healing complications increases with the complexity of the fracture. In addition to dynamization along the lag screw, successful fracture healing may also be facilitated by further dynamization along the shaft axis. The aim of this study was to investigate the mechanical stability of additional axial notch dynamization compared to the standard treatment in an unstable pertrochanteric femur fracture treated with cephalomedullary nailing. In 14 human cadaver femora, an unstable pertrochanteric fracture was stabilized with a cephalomedullary nail. Additional axial notch dynamization was enabled in half of the samples and compared against the standard treatment (n = 7). Interfragmentary motion, axial construct stiffness and load to failure were investigated in a stepwise increasing cyclic load protocol. Mean load to failure (1414 ± 234N vs. 1428 ± 149N, p = 0.89) and mean cycles to failure (197,129 ± 45,087 vs. 191,708 ± 30,490, p = 0.81) were equivalent for axial notch dynamization and standard treatment, respectively. Initial construct stiffness was comparable for both groups (axial notch dynamization 684 [593-775] N/mm, standard treatment 618 [497-740] N/mm, p = 0.44). In six out of seven specimens the additional axial dynamization facilitated interfragmentary compression, while maintaining its mechanical stability. After initial settling of the constructs, there were no statistically significant differences between the groups for either subsidence or rotation of the femoral head fragment (p ≤ 0.30). Axial notch dynamization provided equivalent mechanical stability compared to standard treatment in an unstable pertrochanteric fracture. Whether the interfragmentary compression generated by axial notch dynamization will promote fracture healing through improved fracture reduction needs to be evaluated clinically.

The application of proximal tibial anterior closing wedge osteotomy in anterior cruciate ligament reconstruction

IntroductionPosterior tibial slope (PTS) plays a vital role in knee stability. PTS of more than 12° may be considered with increased strain on the native anterior cruciate ligament (ACL) fibers. To handle the instability caused by changes in PTS degree, Proximal Tibial Anterior Closing Wedge Osteotomy (PT-ACWO) is adopted by surgeons. MethodsBetween October 2015 and October 2019, our department conducted a retrospective analysis of patients who experienced anterior cruciate ligament reconstruction (ACLR) graft failures, with a particular focus on pathological PTS. The time from initial ACLR to revision ranged from 1 to 10 years, with a mean of 2.5 years. Radiological assessments of PTS were conducted, and outcomes were quantified using the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity scale. The surgical technique and the use of 3D Patient-Specific Instrumentation (PSI) were outlined. Preoperative imaging included the use of Kirschner wires to establish tibial plateau reference points, and 3D-PSI was employed to guide the location and depth of the tibial osteotomy, which was performed obliquely. In a notable instance, a novel tibial tunnel was mapped out, and ortho-bridge system (OBS) fixation was utilized to ensure adequate space for the new tunnel. ResultsIn a cohort of seven patients with a mean follow-up of 28.1 months, a significant reduction in PTS was noted postoperatively (median [interquartile range, IQR], from 15.27° [13.46°, 16.60°] to 6.25° [5.89°, 6.78°]; P = 0.002). IKDC score improved to 85.10 (80.25, 88.10), P < 0.001; the Lysholm score to 88.00 (73.00, 90.50), P < 0.001; and the Tegner score to 8.00 (7.20, 8.05), P = 0.025 at final follow-up. Skin incision healing delays occurred in two instances, yet achieved closure by six weeks. Radiographs at three months demonstrated faster bone healing in oblique osteotomies than transverse ones. Knee joint stability was maintained, with no additional complications or evidence of instability noted. Magnetic resonance imaging (MRI) confirmed graft integrity in all patients, without signs of enlargement or mispositioning at last observation. ConclusionAn augmented PTS angle exceeding 12 may constitute a potential etiology for the failure of ACLR grafts. In such patients, the implementation of ACLR combined with PT-ACWO could mitigate the risk of surgical failure during initial ACLR or subsequent revision procedures.

Development and evaluation of an injectable ChitHCl-MgSO4-DDA hydrogel for bone regeneration: In vitro and in vivo studies on cell migration and osteogenesis enhancement

Nonunion and delayed union of the bone are situations in orthopedic surgery that can occur even if the bone alignment is correct and there is sufficient mechanical stability. Surgeons usually apply artificial bone grafts in bone fracture gaps or in bone defect sites for osteogenesis to improve bone healing; however, these bone graft materials have no osteoinductive or osteogenic properties, and fit the morphology of the fracture gap with difficulty. In this study, we developed an injectable chitosan-based hydrogel with MgSO4 and dextran oxidative, with the purpose to improve bone healing through introducing an engineered chitosan-based hydrogel. The developed hydrogel can gelate and fit with any morphology or shape, has good biocompatibility, can enhance the cell-migration capacity, and can improve extracellular calcium deposition. Moreover, the amount of new bone formed by injecting the hydrogel in the bone tunnel was assessed by an in vivo test. We believe this injectable chitosan-based hydrogel has great potential for application in the orthopedic field to improve fracture gap healing.

Severe Maxillary Protrusion Treated with Surgically Assisted Rapid Maxillary Expansion

In this case, surgically assisted rapid maxillary expansion (SARME) was successfully adopted to treat a skeletal maxillary protrusion with large overjet and severe crowding. The female patient, aged 25 years and 11 months, was diagnosed with skeletal maxillary protrusion with severe crowding and excessive overjet associated with labially inclined maxillary central incisors. After achieving sufficient space for surgical incision between bilateral maxillary central incisors, the SARME was performed. A total of 8.0 mm lateral expansion of the maxilla was completed. At 48 days after surgery, the Hyrax appliance was replaced with an Anchor-Lock system used as an external surgical stent and skeletal anchorage for maxillary group distalization, and the distal movement of the maxillary molars was initiated without waiting for bone healing of the separated midpalatal suture by SARME. Twenty-five months’ treatment, including surgical preparation, achieved an acceptable and stable occlusion with adequate interincisal relationship. The occlusion was much more stable with a little relapse through more than 4 years’ retention period. In conclusion, SARME followed by the Anchor-Lock system might lead to favorable occlusal outcome in the long term without any relapses.

Vancomycin-Loaded Sol-Gel System for In Situ Coating of Artificial Bone to Prevent Surgical Site Infections.

Surgical site infections (SSIs) related to implants have always been a major challenge for clinical doctors and patients. Clinically, doctors may directly apply antibiotics into the wound to prevent SSIs. However, this strategy is strongly associated with experience of doctors on the amount and the location of antibiotics. Herein, an in situ constructable sol-gel system is developed containing antibiotics during surgical process and validated the efficacy against SSIs in beagles. The system involves chitosan (CS), β-glycerophosphate (β-GP) and vancomycin (VAN), which can be adsorbed onto porous hydroxyapatite (HA) and form VAN-CS/β-GP@HA hydrogel in a short time. The VAN concentration from VAN-CS/β-GP@HA hydrogel is higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) at the 21st day in vitro. In an in vivo canine model for the prevention of SSIs in the femoral condyle, VAN-CS/β-GP@HA exhibits excellent biocompatibility, antimicrobial properties, and promotion of bone healing. In all, the CS/β-GP instant sol-gel system is able to in situ encapsulate antibiotics and adhere on artificial bone implants during the surgery, effectively preventing SSIs related to implants.

Bone Fracture Healing under the Intervention of a Stretchable Ultrasound Array.

Ultrasound treatment has been recognized as an effective and noninvasive approach to promote fracture healing. However, traditional rigid ultrasound probe is bulky, requiring cumbersome manual operations and inducing unfavorable side effects when functioning, which precludes the wide application of ultrasound in bone fracture healing. Here, we report a stretchable ultrasound array for bone fracture healing, which features high-performance 1-3 piezoelectric composites as transducers, stretchable multilayered serpentine metal films in a bridge-island pattern as electrical interconnects, soft elastomeric membranes as encapsulations, and polydimethylsiloxane (PDMS) with low curing agent ratio as adhesive layers. The resulting ultrasound array offers the benefits of large stretchability for easy skin integration and effective affecting region for simple skin alignment with good electromechanical performance. Experimental investigations of the stretchable ultrasound array on the delayed union model in femoral shafts of rats show that the callus growth is more active in the second week of treatment and the fracture site is completely osseous healed in the sixth week of treatment. Various bone quality indicators (e.g., bone modulus, bone mineral density, bone tissue/total tissue volume, and trabecular bone thickness) could be enhanced with the intervention of a stretchable ultrasound array. Histological and immunohistochemical examinations indicate that ultrasound promotes osteoblast differentiation, bone formation, and remodeling by promoting the expression of osteopontin (OPN) and runt-related transcription factor 2 (RUNX2). This work provides an effective tool for bone fracture healing in a simple and convenient manner and creates engineering opportunities for applying ultrasound in medical applications.

A new fluoroscopic view to evaluate the medial and lateral articular reduction quality in patella fractures during internal fixation

To introduce a new fluoroscopic method for assessing the quality of medial and lateral joint surface reduction during internal fixation of patellar fractures and to summarize the clinical outcomes of patients treated using this method. A retrospective analysis was conducted on the clinical data of 52 patients with patellar fractures treated between January 2018 and January 2022 who met the inclusion criteria. There were 27 male and 25 female patients, aged 21-75 years, with an average age of 62 years. The types of patellar fractures included 9 transverse fractures, 37 comminuted fractures, and 6 longitudinal fractures. According to the AO/Orthopaedic Trauma Association (AO-OTA)-2018 fracture classification, there were 21 cases of type 34A, 6 cases of type 34B, and 25 cases of type 34C. The time from injury to operation ranged from 1 to 5 days, with an average of 2.3 days. Treatments included internal fixation with hollow screws or hollow screw tension bands, with or without anchor repair. During operation, the medial and lateral joint surfaces of the patella were observed using the tangential fluoroscopic method to assess the smoothness of reduction of the median ridge, lateral joint surface, medial joint surface, and lateral joint edge. Patients were followed up regularly, and X-ray films were taken to observe fracture healing. Knee joint range of motion, Böstman score, and Lysholm score were used to evaluate functional recovery. The tangential fluoroscopic method for the medial and lateral joint surfaces of the patella during operation showed satisfactory reduction of the joint surfaces and good positioning of the implants. All patients were followed up 12-16 months, with an average of 13.4 months. During the follow-up, fracture displacement occurred in 1 case and titanium cable breakage in 1 case. All patella fractures healed successfully, with a healing time of 8-16 weeks (mean, 11.4 weeks). At last follow-up, knee joint range of motion ranged from 120° to 140°, with an average of 136°. The Böstman score ranged from 20 to 30, with an average of 28, yielding excellent results in 45 cases and good results in 7 cases. The Lysholm score ranged from 88 to 100, with an average of 93, yielding excellent results in 40 cases and good results in 12 cases. The intraoperative application of the tangential fluoroscopic method for the medial and lateral joint surfaces of the patella can quickly determine the fluoroscopic plane of the patella, accurately assess the quality of fracture reduction and the position of internal fixator, thereby improving effectiveness.

Anatomic variability of the human femur and its implications for the use of artificial bones in biomechanical testing.

Aside from human bones, epoxy-based synthetic bones are regarded as the gold standard for biomechanical testing os osteosyntheses. There is a significant discrepancy in biomechanical testing between the determination of fracture stability due to implant treatment in experimental methods and their ability to predict the outcome of stability and fracture healing in a patient. One possible explanation for this disparity is the absence of population-specific variables such as age, gender, and ethnicity in artificial bone, which may influence the geometry and mechanical properties of bone. The goal of this review was to determine whether commercially available artificial bones adequately represent human anatomical variability for mechanical testing of femoral osteosyntheses. To summarize, the availability of suitable bone surrogates currently limits the validity of mechanical evaluations of implant-bone constructs. The currently available synthetic bones neither accurately reflect the local mechanical properties of human bone, nor adequately represent the necessary variability between various populations, limiting their generalized clinical relevance.

Simultaneous correction of leg length discrepancy and angular deformity of the distal femur with retrograde Precice nails: a retrospective analysis of 45 patients.

Magnetically controlled motorized intramedullary lengthening nails (ILNs) can be employed for simultaneous correction of angular deformities of the distal femur and leg length discrepancy. This spares typical complications of external fixators but requires precise preoperative planning and exact intraoperative execution. To date, its results are insufficiently reported. We aimed to elucidate the following questions: (i) Is acute angular deformity correction and gradual femoral lengthening via a retrograde ILN a reliable and precise treatment option? (ii) What are the most common complications of treatment? Acute angular deformity correction and subsequent gradual lengthening of the distal femur with retrograde ILN was retrospectively analyzed in 45 patients (median patient age: 15 years, interquartile range [IQR] 13-19 and median follow-up: 40 months, IQR 31-50). Outcome parameters were accuracy, precision, reliability, bone healing, and complications of treatment. The median distraction was 46 mm (IQR 29-49), median distraction and consolidation index 0.9 mm/day (IQR 0.7-1.0) and 29 days/cm (IQR 24-43), respectively. The median preoperative mechanical axis deviation (MAD) was 30 mm (IQR 23-39) in the varus cohort and -25 mm (IQR -29 to -15) in the valgus cohort and reduced to a mean of 8 mm (standard deviation [SD] 8) and -3 (SD 10), respectively. Accuracy, precision, and reliability of lengthening were 94%, 95% and 96%, respectively. Accuracy and precision of deformity correction were 92% and 89%, respectively. In total, 40/45 of patients achieved distraction with a difference of less than 1 cm from the initial plan and a postoperative MAD ranging from -10 mm to +15 mm. In 13/45 patients unplanned additional surgeries were conducted to achieve treatment goal with nonunion being the most frequent (4/45) and knee subluxation (3/45) the most severe complication. Acute deformity correction and subsequent lengthening of the distal femur with retrograde ILN is a reliable and accurate treatment achieving treatment goal in 89% but unplanned additional surgeries in 29% of patients should be anticipated.

Evaluation of the clinical efficacy of using an inverted triangular cannulated compression screw in combination with positive or negative buttress reduction for the healing of femoral neck fractures

ObjectiveWe aimed to compare the clinical efficacy of inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction in the healing of femoral neck fractures.MethodsBetween October 2017 and March 2021, 55 patients with femoral neck fractures underwent treatment using inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction. Among these patients, 29 received inverted triangular cannulated compression screws combined with Gotfried positive buttress reduction treatment. This group consisted of 16 males and 13 females, with an average age of 43.45 ± 8.23 years. Additionally, 26 patients received inverted triangular cannulated compression nails combined with Gotfried negative buttress reduction treatment. This group included 14 males and 12 females, with an average age of 41.96 ± 8.69 years. Postsurgery, various measurements were taken, including the degree of shortening of the femoral neck, degree of bone nonunion, degree of fixation failure, degree of ischemic necrosis of the femoral head, and Harris score of the hip joint.ResultsAll patients were followed up for a minimum of 18 months. The group that underwent treatment with an inverted triangular cannulated compression screw combined with Gotfried positive buttress reduction did not experience any cases of bone nonunion, fixation failure, or ischemic necrosis of the femoral head. In the group that received treatment with inverted triangle cannulated compression screws combined with Gotfried negative buttress reduction, there was one case of bone nonunion, three cases of early fixation failure, and one case of ischemic necrosis. Ultimately, five patients (19.23% of the total) underwent joint replacement surgery. The average shortening lengths in the vertical plane were 4.07 ± 1.98 mm and 8.08 ± 3.54 mm, respectively. In the horizontal plane, the average shortening lengths were 3.90 ± 1.57 mm and 7.77 ± 3.31 mm, respectively. At the last follow-up, the group that received Gotfried positive buttress reduction had a greater Harris hip joint score.ConclusionThe success rate of combining inverted triangular cannulated compression screws with Gotfried positive buttress reduction surgery is relatively high. This surgical approach effectively prevents femoral neck shortening and improves hip joint function. Moreover, it is crucial to avoid negative buttress reduction when managing femoral neck fractures.

Effectiveness of minimally invasive treatment of hallux valgus with small incision external articular osteotomy

To compare the effectiveness of small incision external articular minimally invasive osteotomy and traditional Chevron osteotomy in the treatment of hallux valgus. A retrospective analysis was conducted on the clinical data of 58 patients (58 feet) with hallux valgus who were admitted between April 2019 and June 2022 and met the selection criteria. Among them, 28 cases were treated with small incision external articular minimally invasive osteotomy (minimally invasive group), and 30 cases were treated with traditional Chevron osteotomy (traditional group). There was no significant difference in baseline data such as age, gender, disease duration, Mann classification, and preoperative inter metatarsal angle (IMA), hallux valgus angle (HVA), distal metatarsal articular angle (DMAA), forefoot width, tibial sesamoid position (TSP) score, American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score, visual analogue scale (VAS) score, psychological score (SF-12 MCS score) and physiological score (SF-12 PCS score) of short-form 12 health survey scale, and range of motion (ROM) of metatarsophalangeal joint between the two groups ( P>0.05). The incision length, operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, weight-bearing walking time, fracture healing time, and incidence of complications were recorded and compared between the two groups; as well as the changes of imaging indexes at last follow-up, and the clinical function score and ROM of metatarsophalangeal joint before operation, at 6 weeks after operation, and at last follow-up. All patients were followed up 11-31 months, with an average of 22 months. The incision length and intraoperative blood loss in the minimally invasive group were significantly less than those in the traditional group ( P<0.05), and the intraoperative fluoroscopy frequency and operation time in the minimally invasive group were significantly more than those in the traditional group ( P<0.05); but no significant difference was found in weight-bearing walking time and fracture healing time between the two groups ( P>0.05). There was 1 case of skin injury in the minimally invasive group and 3 cases of poor incision healing in the traditional group; all patients had good healing at the osteotomy site, and no complication such as infection, nerve injury, or metatarsal head necrosis occurred. At last follow-up, the imaging indexes of the two groups significantly improved when compared with those before operation ( P<0.05). The changes of DMAA and TSP score in the minimally invasive group were significantly better than those in the traditional group ( P<0.05), and there was no significant difference in the changes of IMA, HVA, and forefoot width between the two groups ( P>0.05). The clinical scores and ROM of metatarsophalangeal joint significantly improved in the two groups at 6 weeks after operation and at last follow-up when compared with preoperative ones ( P<0.05), and the indicators in the minimally invasive group were significantly better than those in the traditional group ( P<0.05). Compared with traditional Chevron osteotomy, small incision external articular minimally invasive osteotomy can effectively improve HVA, IMA, and forefoot width, correct foot deformities, and has less trauma. It can better correct the first metatarsal pronation deformity and restore the anatomical position of the sesamoid bone, resulting in better effectiveness.

Macrophage membrane-reversibly camouflaged nanotherapeutics accelerate fracture healing by fostering MSCs recruitment and osteogenic differentiation

The fracture healing outcome is largely dependent on the quantities as well as osteogenic differentiation capacities of mesenchymal stem cells (MSCs) at the lesion site. Herein, macrophage membrane (MM)-reversibly cloaked nanocomplexes (NCs) are engineered for the lesion-targeted and hierarchical co-delivery of short stromal derived factor-1α peptide (sSDF-1α) and Ckip-1 small interfering RNA (Ckip-1 siRNA, siCkip-1) to promote bone repair by concurrently fostering recruitment and osteogenic differentiation of endogenous MSCs. To construct the NCs, a membrane-penetrating α-helical polypeptide first assembles with siCkip-1, and the cationic NCs are sequentially coated with catalase and an outer shell of sSDF-1α-anchored MM. Due to MM-assisted inflammation homing, intravenously injected NCs could efficiently accumulate at the fractured femur, where catalase decomposes the local hydrogen peroxide to generate oxygen bubbles that drives the shedding of sSDF-1α-anchored MM in the extracellular compartment. The exposed, cationic inner core thus enables robust trans-membrane delivery into MSCs to induce Ckip-1 silencing. Consequently, sSDF-1α-guided MSCs recruitment cooperates with siCkip-1-mediated osteogenic differentiation to facilitate bone formation and accelerate bone fracture healing. This study provides an enlightened strategy for the hierarchical co-delivery of macromolecular drugs into different cellular compartments, and it also renders a promising modality for the management of fracture healing.

Finite element solution of coupled multiphysics reaction-diffusion equations for fracture healing in hard biological tissues

This study proposes a computational framework to investigate the multi-stage process of fracture healing in hard tissues, e.g., long bone, based on the mathematical Bailon-Plaza and Van der Meulen formulation. The goal is to explore the influence of critical biological factors by employing the finite element method for more realistic configurations. The model integrates a set of variables, including cell densities, growth factors, and extracellular matrix contents, managed by a coupled system of partial differential equations. A weak finite element formulation is introduced to enhance the numerical robustness for coarser mesh grids, complex geometries, and more accurate boundary conditions. This formulation is less sensitive to mesh quality and converges smoothly with mesh refinement, exhibiting superior numerical stability compared to previously available strong-form solutions. The model accurately reproduces various stages of healing, including soft cartilage callus formation, endochondral and intramembranous ossification, and hard bony callus development for various sizes of fracture gap. Model predictions align with the existing research and are logically coherent with the available experimental data. The developed multiphysics simulation clarifies the coordination of cellular dynamics, extracellular matrix alterations, and signaling growth factors during fracture healing.

Titanium versus plasma electrolytic oxidation surface-modified magnesium miniplates in a forehead secondary fracture healing model in sheep

Magnesium as a biodegradable material offers promising results in recent studies of different maxillo-facial fracture models. To overcome adverse effects caused by the fast corrosion of pure magnesium in fluid surroundings, various alloys, and surface modifications are tested in animal models. In specified cases, magnesium screws already appeared for clinical use in maxillofacial surgery. The present study aims to compare the bone healing outcome in a non-load-bearing fracture scenario of the forehead in sheep when fixed with standard-sized WE43 magnesium fixation plates and screws with plasma electrolytic oxidation (PEO) surface modification in contrast to titanium osteosynthesis. Surgery was performed on 24 merino mix sheep. The plates and screws were explanted en-bloc with the surrounding tissue after four and twelve weeks. The outcome of bone healing was investigated with micro-computed tomography, histological, immunohistological, and fluorescence analysis. There was no significant difference between groups concerning the bone volume, bone volume/ total volume, and newly formed bone in volumetric and histological analysis at both times of investigation. The fluorescence analysis revealed a significantly lower signal in the magnesium group after one week, although there was no difference in the number of osteoclasts per mm2. The magnesium group had significantly fewer vessels per mm2 in the healing tissue. In conclusion, the non-inferiority of WE43-based magnesium implants with PEO surface modification was verified concerning fracture healing under non-load-bearing conditions in a defect model. Statement of SignificanceTitanium implants, the current gold standard of fracture fixation, can lead to adverse effects linked to the implant material and often require surgical removal. Therefore, degradable metals like the magnesium alloy WE43 with plasma electrolytic oxidation (PEO) surface modification gained interest. Yet, miniplates of this alloy with PEO surface modification have not been examined in a fracture defect model of the facial skeleton in a large animal model. This study shows, for the first time, the non-inferiority of magnesium miniplates compared to titanium miniplates. In radiological and histological analysis, bone healing was undisturbed. Magnesium miniplates can reduce the number of interventions for implant removal, thus reducing the risk for the patient and minimizing the costs.

Spatial transcriptomics implicates impaired BMP signaling in NF1 fracture pseudarthrosis in murine and patient tissues.

The Neurofibromatosis Type 1 (NF1) RASopathy is associated with persistent fibrotic nonunions (pseudarthrosis) in human and mouse skeletal tissue. Here, we first performed spatial transcriptomics to define the molecular signatures across normal endochondral healing following fracture in mice. Within the control fracture callus, we observed spatially restricted activation of morphogenetic pathways, such as TGF-β, WNT, and BMP. To investigate the molecular mechanisms contributing to Nf1-deficient delayed fracture healing, we performed spatial transcriptomic analysis on a Postn-cre;Nf1flox/- (Nf1Postn) fracture callus. Transcriptional analyses, subsequently confirmed through p-SMAD1/5/8 immunohistochemistry, demonstrated a lack of BMP pathway induction in Nf1Postn mice. To further inform the human disease, we performed spatial transcriptomic analysis of fracture pseudarthrosis tissue from a NF1 patient. Analyses detected increased MAPK signaling at the fibrocartilaginous-osseus junction. Similar to the Nf1Postn fracture, BMP pathway activation was absent within the pseudarthrosis tissue. Our results demonstrate the feasibility to delineate the molecular and tissue-specific heterogeneity inherent in complex regenerative processes, such as fracture healing, and to reconstruct phase transitions representing endochondral bone formation in vivo. Furthermore, our results provide in situ molecular evidence of impaired BMP signaling underlying NF1 pseudarthrosis, potentially informing the clinical relevance of off-label BMP2 as a therapeutic intervention.

Contribution of initial lymphatics to oral wound healing after tooth extraction.

Lymphatics are involved in the resolution of inflammation and wound healing, but their role in the oral wound healing process after tooth extraction has never been investigated. We therefore sought to evaluate the healing process following the extraction of maxillary molars in two transgenic mouse models: K14-VEGFR3-Ig mice, which lack initial mucosal lymphatic vessels, and K14-VEGFC mice, which have hyperplastic mucosal lymphatics. Maxillary molars were extracted from both transgenic mouse types and their corresponding wild-type (WT) controls. Mucosal and alveolar bone healing were evaluated. A delayed epithelialization and bone regeneration were observed in K14-VEGFR3-Ig mice compared with their WT littermates. The hampered wound closure was accompanied by decreased levels of epidermal growth factor (EGF) and persistent inflammation, characterized by infiltrates of immune cells and elevated levels of pro-inflammatory markers in the wounds. Hyperplastic mucosal lymphatics did not enhance the healing process after tooth extraction in K14-VEGFC mice. The findings indicate that initial mucosal lymphatics play a major role in the initial phase of the oral wound healing process.

Injectable hydrogel scaffold incorporating microspheres containing cobalt-doped bioactive glass for bone healing.

Injectable in situ-forming scaffolds that induce both angiogenesis and osteogenesis have been proven to be promising for bone healing applications. Here, we report the synthesis of an injectable hydrogel containing cobalt-doped bioactive glass (BG)-loaded microspheres. Silk fibroin (SF)/gelatin microspheres containing BG particles were fabricated through microfluidics. The microspheres were mixed in an injectable alginate solution, which formed an in situ hydrogel by adding CaCl2. The hydrogel was evaluated for its physicochemical properties, in vitro interactions with osteoblast-like and endothelial cells, and bone healing potential in a rat model of calvarial defect. The microspheres were well-dispersed in the hydrogel and formed pores of >100 μm. The hydrogel displayed shear-thinning behavior and modulated the cobalt release so that the optimal cobalt concentration for angiogenic stimulation, cell proliferation, and deposition of mineralized matrix was only achieved by the scaffold that contained BG doped with 5% wt/wt cobalt (A-S-G5Co). In the scaffold containing higher cobalt content, a reduced biomimetic mineralization on the surface was observed. The gene expression study indicated an upregulation of the osteogenic genes of COL1A1, ALPL, OCN, and RUNX2 and angiogenic genes of HIF1A and VEGF at different time points in the cells cultured with the A-S-G5Co. Finally, the in vivo study demonstrated that A-S-G5Co significantly promoted both angiogenesis and osteogenesis and improved bone healing after 12 weeks of follow-up. These results show that incorporation of SF/gelatin microspheres containing cobalt-doped BG in an injectable in situ-forming scaffold can effectively enhance its bone healing potential through promotion of angiogenesis and osteogenesis.

Pediatric Diaphyseal Forearm Fracture Management with Biodegradable Poly-L-Lactide-Co-Glycolide (PLGA) Intramedullary Implants: A Longitudinal Study

Background: Pediatric forearm fractures represent a substantial proportion of childhood injuries, requiring effective and minimally invasive treatments. Our study investigated the mid-term outcomes of biodegradable poly-L-lactide-co-glycolide (PLGA) intramedullary implants in managing diaphyseal forearm fractures in children. Methods: A follow-up cohort study was conducted with 38 patients treated with PLGA implants. Control examinations were performed one year post-operation, assessing bone healing through radiographic evaluations and functional outcomes using injured and uninjured limb range of motion (ROM) comparisons. Scarring was evaluated employing the Vancouver Scar Scale (VSS), and satisfaction via a questionnaire. Results: Children were predominantly female (76.4%), with a mean age of 9.71 (SD: 2.69) years. Effective fracture stabilization and bone healing were found in all patients, with a minor reduction (mean difference of −1.5°, p = 0.282) in elbow flexion on the operated side (139.3°) compared to the intact (140.8°). Elbow extension presented negligible average changes (0.2°, p = 0.098). Forearm movements were slightly reduced on the operated side (mean pronation: 80.8° vs. 83.7°, p = 0.166; average supination: 83.5° vs. 85.7°, p = 0.141). Wrist palmar flexion and dorsiflexion showed no significant differences. VSS ratings indicated minimal scarring (mean guardian and doctor scores were 1.13 and 0.55, respectively, p = 0.020), and all patients reported satisfaction with the treatment outcomes. Conclusions: Biodegradable implants are effective for pediatric forearm fractures, providing stable bone healing while preserving functional ROM with minimal scarring and high patient satisfaction. PLGA proved to be a viable alternative to traditional metal implants, eliminating secondary removal surgeries.

Graphene Oxide Nanosheets for Bone Tissue Regeneration

Bone tissue engineering is a promising alternative to repair wounds caused by cellular or physical accidents that humans face daily. In this sense, the search for new graphene oxide (GO) nanofillers related to their degree of oxidation is born as an alternative bioactive component in forming new scaffolds. In the present study, three different GOs were synthesized with varying degrees of oxidation and studied chemically and tissue-wise. The oxidation degree was determined through infrared (FTIR), X-ray diffraction (XRD), X-ray photoelectron (XPS), and Raman spectroscopy (RS). The morphology of the samples was analyzed using scanning electron microscopy (SEM). The oxygen content was deeply described using the deconvolution of RS and XPS techniques. The latter represents the oxidation degree for each of the samples and the formation of new bonds promoted by the graphitization of the material. In the RS, two characteristic bands were observed according to the degree of oxidation and the degree of graphitization of the material represented in bands D and G with different relative intensities, suggesting that the samples have different crystallite sizes. This size was described using the Tuinstra–Koenig model, ranging between 18.7 and 25.1 nm. Finally, the bone neoformation observed in the cranial defects of critical size indicates that the F1 and F2 samples, besides being compatible and resorbable, acted as a bridge for bone healing through regeneration. This promoted healing by restoring bone and tissue structure without triggering a strong immune response.

A Janus Microsphere Delivery System Orchestrates Immunomodulation and Osteoinduction by Fine-tuning Release Profiles.

Bone regeneration is a well-orchestrated process synergistically involving inflammation, angiogenesis, and osteogenesis. Therefore, an effective bone graft should be designed to target multiple molecular events and biological demands during the bone healing process. In this study, a biodegradable gelatin methacryloyl (GelMA)-based Janus microsphere delivery system containing calcium phosphate oligomer (CPO) and bone morphogenetic protein-2 (BMP-2) is developed based on natural biological events. The exceptional adjustability of GelMA facilitates the controlled release and on-demand application of biomolecules, and optimized delivery profiles of CPO and BMP-2 are explored. The sustained release of CPO during the initial healing stages contributes to early immunomodulation and promotes mineralization in the late stage. Meanwhile, the administration of BMP-2 at a relatively high concentration within the therapeutic range enhances the osteoinductive property. This delivery system, with fine-tuned release patterns, induces M2 macrophage polarization and creates a conducive immuno-microenvironment, which in turn facilitates effective bone regeneration in vivo. Collectively, this study proposes a bottom-up concept, aiming to develop a user-friendly and easily controlled delivery system targeting individual biological events, which may offer a new perspective on developing function-optimized biomaterials for clinical use.