UNASSIGNED: With the introduction and continuous improvement in operative fracture fixation, even the most severe bone fractures can be treated with a high rate of successful healing. However, healing complications can occur and when healing fails over prolonged time, the outcome is termed a fracture non-union. Non-union is generally believed to develop due to inadequate fixation, underlying host-related factors, or infection. Despite the advancements in fracture fixation and infection management, there is still a clear need for earlier diagnosis, improved prediction of healing outcomes and innovation in the treatment of non-union.
UNASSIGNED: This review provides a detailed description of non-union from a clinical perspective, including the state of the art in diagnosis, treatment, and currently available biomaterials and orthobiologics.Subsequently, recent translational development from the biological, mechanical, and infection research fields are presented, including the latest in smart implants, osteoinductive materials, and in silico modeling.
UNASSIGNED: The first challenge for future innovations is to refine and to identify new clinical factors for the proper definition, diagnosis, and treatment of non-union. However, integration of in vitro, in vivo, and in silico research will enable a comprehensive understanding of non-union causes and correlations, leading to the development of more effective treatments.

Secondary healing of fractured bones requires an application of an appropriate fixator. In general, steel or titanium devices are used mostly. However, in recent years, composite structures arise as an attractive alternative due to high strength to weight ratio and other advantages like, for example, radiolucency. According to Food and Drug Administration (FDA), the only unidirectionally reinforced composite allowed to be implanted in human bodies is carbon fiber (CF)-reinforced poly-ether-ether-ketone (PEEK). In this work, the healing process of long bone assembled with CF/PEEK plates with cross- and angle-ply lay-up configurations is studied in the framework of finite element method. The healing is simulated by making use of the mechanoregulation model basing on the Prendergast theory. Cells transformation is determined by the octahedral shear strain and interstitial fluid velocity. The process runs iteratively assuming single load cycle each day. The fracture is subjected to axial and transverse forces. In the computations, the Abaqus program is used. It is shown that the angle-ply lamination scheme of CF/PEEK composite seems to provide better conditions for the transformation of the soft callus into the bone tissue.

This editorial explores the impact of non-steroidal anti-inflammatory drugs (NSAIDs) on postoperative recovery in hand fracture patients, amidst shifting pain management strategies away from opioids due to their adverse effects. With hand fractures being significantly common and postoperative pain management crucial for recovery, the potential of NSAIDs offers a non-addictive pain control alternative. However, the controversy over NSAIDs\' effects on bone healing-stemming from their Cyclooxygenase-2 inhibition and associated risks of fracture non-union or delayed union-necessitates further investigation. Despite a comprehensive literature search, the study finds a lack of specific research on NSAIDs in postoperative hand fracture management, highlighting an urgent need for future studies to balance their benefits against possible risks.

OBJECTIVE: This study aims to observe the clinical effect of bone plate reduction in combination with a resorbable plate on large mandibular cysts.
METHODS: Between October 2017 and September 2022, patients with large mandibular cysts in the presence of labial and buccal cortical bone were involved in the study. Intraoral approach was performed for bone plate reduction. Cone beam computed tomography (CBCT) scan was reviewed at 3, 6, and 9 months postoperatively to observe postoperative complications. Osteogenic results were assessed at these times to determine the clinical outcomes of this procedure.
RESULTS: Eleven cases with large mandibular cysts in the presence of cortical bone were evaluated. The average thickness of the cortical bone on the labial and buccal sides was measured to be about (1.98±0.37) mm before surgery, with a mean value of (0.73±0.17) mm at the thinnest part of the plate and up to 0.51 mm at the thinnest part of the plate. The cystic cavities were well revealed during the surgeries, which were completed successfully. Postoperatively, the wounds healed in one stage without infection. The percentages of cyst shrinkage were 20.01%, 41.76%, and 73.41% at 3, 6, and 9 months after surgery, respectively. Quantitative measurement of bone mineral density in the jaws by CBCT with MIMICS software. The bone mineral densities of the adult bone were 313.78, 555.85, and 657.45 HU at the 3, 6, and 9 month time intervals, respectively. No significant change in the patient\'s maxillofacial appearance were observed from the preoperative period as assessed by the patient\'s and observer\'s visual analog scale.
CONCLUSIONS: Bone plate reduction is an effective treatment for large mandibular cysts of the oral and maxillofacial region with the presence of cortical bone.
目的: 观察骨板翻盖术联合可吸收板治疗口腔颌面部大型下颌骨囊肿的临床效果。方法: 选取2017年10月—2022年9月在中国人民解放军总医院第一医学中心口腔颌面外科诊治的唇（颊）侧皮质骨存在的大型下颌骨囊肿患者为研究对象，口内入路行骨板翻盖术，术后3、6和9个月定期随访进行锥形束计算机断层扫描（CBCT），观察术后患者恢复情况及影像学检查，评估该术式的临床效果。结果: 对11例唇（颊）侧皮质骨存在的下颌骨大型囊肿进行了评估。术前测量唇（颊）侧皮质骨的平均厚度约为（1.98±0.37）mm，骨板最薄处厚度平均为（0.73±0.17）mm，骨板最薄处约0.51 mm。术中囊腔均显露良好，手术顺利完成。术后创口一期愈合无感染，术后3、6、9个月的囊肿缩小率分别约为20.01%、41.76%、73.41%。用CBCT和MIMICS软件测量颌骨的骨质密度，术后3、6、9个月囊肿区成骨密度约为313.78、555.85、657.45 HU。患者和观察者视觉模拟量表评估患者颌面部外形较术前无明显变化。结论: 骨板翻盖术是治疗唇（颊）侧皮质骨存在的口腔颌面部大型下颌骨囊肿的有效方法。.

Long bone fractures are common orthopedic conditions. There are numerous ways to repair these fractures. Bone grafting becomes necessary when a broken bone has a significant gap. However, due to insufficient donor volume and donor site morbidity, substitutes are required. In veterinary orthopaedics, calcium carbonate from cockle shells could be used as a bone biomaterial. We investigated its efficacy as a bone biomaterial repair for goat femoral fractures. The study included 10 healthy adult male Black Bengal goats weighing 8 kg and aged 12-13 months. The study includes control and treatment groups. Intramedullary pinning stabilized an 8-mm right femur diaphyseal fracture in the treatment and control groups. The treated group received 2 ml of bone paste in the fractured gap, whereas the control group left it empty. We examined all goats with X-rays on the 7th, 45th, and 60th days, followed by gross and histological findings. Due to callus bridging, radiographs revealed faster bone growth in the treated group than in the control group. Gross examination demonstrates the treated group had a larger fracture callus than the control group. Histopathology showed that bone formed faster and included more osteocytes, osteoblasts, osteoclasts, and bony spicules than in the control group. The treated group had more periosteum osteoblasts, while the control group had fibroblasts. These results showed that the treated group had more osteogenic activity than the control group. This study demonstrates the potential of cockle shell-based calcium carbonate bone paste as a synthetic biomaterial for healing long bone fractures in goats.

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.

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 SIGNIFICANCE: Titanium 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.

Platelet-derived growth factor receptor α (PDGFRα) is often considered as a general marker of mesenchymal cells and fibroblasts, but also shows expression in a portion of osteoprogenitor cells. Within the skeleton, Pdgfrα+ mesenchymal cells have been identified in bone marrow and periosteum of long bones, where they play a crucial role in participating in fracture repair. A similar examination of Pdgfrα+ cells in calvarial bone healing has not been examined. Here, we utilize Pdgfrα-CreERTM;mT/mG reporter animals to examine the contribution of Pdgfrα+ mesenchymal cells to calvarial bone repair through histology and single-cell RNA sequencing (scRNA-Seq). Results showed that Pdgfrα+ mesenchymal cells are present in several cell clusters by scRNA-Seq, and by histology a dramatic increase in Pdgfrα+ cells populated the defect site at early timepoints to give rise to healed bone tissue overtime. Notably, diphtheria toxin-mediated ablation of Pdgfrα reporter+ cells resulted in significantly impaired calvarial bone healing. Our findings suggest that Pdgfrα-expressing cells within the calvarial niche play a critical role in the process of calvarial bone repair.

BACKGROUND: The formation of normal bone and bone healing requires the cAMP-responsive element binding protein 3-like-1 (Creb3l1) transmembrane transcription factor, as deletion of the murine CREB3L1 results in osteopenic animals with limited capacity to repair bone after a fracture. Creb3l1 undergoes regulated intramembrane proteolysis (RIP) to release the N-terminal transcription activating (TA) fragment that enters the nucleus and regulates the expression of target genes.
METHODS: To expand our understanding of Creb3l1\'s role in skeletal development and skeletal patterning, we aimed to generate animals expressing only the TA fragment of Creb3l1 lacking the transmembrane domain and thereby not regulated through RIP. However, the CRISPR/Cas9-mediated genome editing in zebrafish Danio rerio caused a frameshift mutation that added 56 random amino acids at the C-terminus of the TA fragment (TA+), making it unable to enter the nucleus. Thus, TA+ does not regulate transcription, and the creb3l1TA+/TA+ fish do not mediate creb3l1-dependent transcription.
RESULTS: We document that the creb3l1TA+/TA+ fish exhibit defects in the patterning of caudal fin lepidotrichia, with significantly distalized points of proximal bifurcation and decreased secondary bifurcations. Moreover, using the caudal fin amputation model, we show that creb3l1TA+/TA+ fish have decreased regeneration and that their regenerates replicate the distalization and bifurcation defects observed in intact fins of creb3l1TA+/TA+ animals. These defects correlate with altered expression of the shha and ptch2 components of the Sonic Hedgehog signaling pathway in creb3l1TA+/TA+ regenerates.
CONCLUSIONS: Together, our results uncover a previously unknown intersection between Creb3l1 and the Sonic Hedgehog pathway and document a novel role of Creb3l1 in tissue patterning.

BACKGROUND: Iliac crest autograft is frequently used to fill in bone defects after osteotomies. Nonetheless, surgery for bone autograft procurement is associated with morbidity and pain at the donor site. Alternatives to it have been explored, but there is no consensus to guide their application as a routine practice in several orthopedic procedures. Thus, this study was designed to compare the efficacy and safety between iliac crest autograft and allograft in medial opening wedge high tibial osteotomy.
METHODS: Forty-seven patients with a symptomatic unilateral genu varum and an indication for high tibial osteotomy were randomly assigned to receive either autograft or allograft to fill the osteotomy site. Operative time, bone healing, and complication rates (delayed union, nonunion, superficial and deep infection, loss of correction, and hardware failure) were recorded after a one-year follow-up. Data were expressed as Mean ± Standard Deviation and considered statistically significant when p < 0.05.
RESULTS: The time to radiologic union was similar between both groups (Allograft: 2.38 ± 0.97 months vs. Autograft: 2.45 ± 0.91 months; p = 0.79). Complication rates were also similar in both groups, with one infection in the allograft group and two in the autograft group, two delayed unions in the allograft group, and three in the autograft group. The operative time differed by 11 min between the groups, being lower in the allograft group (Allograft: 65.4 ± 15.1 min vs. Autograft: 76.3 ± 15.2 min; p = 0.02).
CONCLUSIONS: Iliac crest allografts can be safely and effectively used in medial opening wedge high tibial osteotomy as it promotes the same rates of bone union as those achieved by autologous grafts, with the benefits of a shorter operative time.
BACKGROUND: U1111-1280-0637 1 December 2022, retrospectively registered.