Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.

Dual Factor-Loaded Artificial Periosteum Accelerates Bone Regeneration.

In the clinic, inactivation of osteosarcoma using microwave ablation would damage the periosteum, resulting in frequent postoperative complications. Therefore, the development of an artificial periosteum is crucial for postoperative healing. In this study, we prepared an artificial periosteum using silk fibroin (SF) loaded with stromal cell-derived factor-1α (SDF-1α) and calcitonin gene-related peptide (CGRP) to accelerate bone remodeling after the microwave ablation of osteosarcoma. The prepared artificial periosteum showed a sustained release of SDF-1α and CGRP after 14 days of immersion. In vitro culture of rat periosteal stem cells (rPDSCs) demonstrated that the artificial periosteum is favorable for cell recruitment, the activity of alkaline phosphatase, and bone-related gene expression. Furthermore, the artificial periosteum improved the tube formation and angiogenesis-related gene expression of human umbilical vein endothelial cells (HUVECs). In an animal study, the periosteum in the femur of a rabbit was inactivated through microwave ablation and then removed. The damaged periosteum was replaced with the as-prepared artificial periosteum and favored bone regeneration. In all, the designed dual-factor-loaded artificial periosteum is a promising strategy to replace the damaged periosteum in the therapy of osteosarcoma for a better bone-rebuilding process.

Fracture risk assessment of vascularized medial femoral condylar bone graft: A finite element analysis.

BACKGROUND: Vascularized medial femoral condyle (MFC) bone graft is useful for pseudarthrosis and osteonecrosis, but has the risk of fracture as a complication. This study aimed to create multiple three-dimensional (3D) finite element (FE) femur models to biomechanically evaluate the fracture risk in the donor site of a vascularized MFC bone graft. METHODS: Computer tomography scans of the femurs of nine patients (four males and five females) with no left femur disease were enrolled in the study. A 3D FE model of the left femur was generated based on the CT images taken from the patients. The descending genicular artery (DGA), the main nutrient vessel in vascularized MFC bone grafts, divides into the proximal transversal branch (TB) and the distal longitudinal branch (LB) before entering the periosteum. Thirty-six different bone defect models with different sizes and locations of the harvested bone were created. RESULTS: The highest stress was observed in the proximal medial and metaphyseal portions under axial and external rotation, respectively. In the bone defect model, the stress was most elevated in the extracted region's anterior or posterior superior part. Stress increased depending on proximal location and harvested bone size. CONCLUSION: Increasing the size of the bone graft proximally raises the stress at the site of bone extraction. For bone grafting to non-load-bearing areas, bone grafting distally using LB can reduce fracture risk. If TB necessitates a larger proximal bone extraction, it is advisable to avoid postoperative rotational loads.

Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration.

The periosteum is known as the thin connective tissue covering most bone surfaces. Its extrusive bone regeneration capacity was confirmed from the very first century-old studies. Recently, pluripotent stem cells in the periosteum with unique physiological properties were unveiled. Existing in dynamic contexts and regulated by complex molecular networks, periosteal stem cells emerge as having strong capabilities of proliferation and multipotential differentiation. Through continuous exploration of studies, we are now starting to acquire more insight into the great potential of the periosteum in bone formation and repair in situ or ectopically. It is undeniable that the periosteum is developing further into a more promising strategy to be harnessed in bone tissue regeneration. Here, we summarized the development and structure of the periosteum, cell markers, and the biological features of periosteal stem cells. Then, we reviewed their pivotal role in bone repair and the underlying molecular regulation. The understanding of periosteum-related cellular and molecular content will help enhance future research efforts and application transformation of the periosteum.

Novel Sheep Model to Assess Critical-Sized Bone Regeneration with Periosteum for In Vivo Bioreactors.

Considerable research is being undertaken to develop novel biomaterials-based approaches for surgical reconstruction of bone defects. This extends to three-dimensional (3D) printed materials that provide stable, structural, and functional support in vivo. However, few preclinical models can simulate in vivo human biological conditions for clinically relevant testing. In this study we describe a novel ovine model that allows evaluation of in vivo osteogenesis via contact with bone and/or periosteum interfaced with printed polymer bioreactors loaded with biomaterial bone substitutes. The infraspinous scapular region of 14 Dorset cross sheep was exposed. Vascularized periosteum was elevated either attached to the infraspinatus muscle or separately. In both cases, the periosteum was supplied by the periosteal branch of the circumflex scapular vessels. In eight sheep, a 3D printed 4-chambered polyetheretherketone bioreactor was wrapped circumferentially in vascularized periosteum. In 6 sheep, 12 double-sided 3D printed 2-chambered polyetherketone bioreactors were secured to the underlying bone allowing direct contact with the bone on one side and periosteum on the other. Our model enabled simultaneous testing of up to 24 (12 double-sided) 10 × 10 × 5 mm bioreactors per scapula in the flat contact approach or a single 40 × 10 mm four-chambered bioreactor per scapula using the periosteal wrap. De novo bone growth was evaluated using histological and radiological analysis. Of importance, the experimental model was well tolerated by the animals and provides a versatile approach for comparing the osteogenic potential of cambium on the bone surface and elevated with periosteum. Furthermore, the periosteal flaps were sufficiently large for encasing bioreactors containing biomaterial bone substitutes for applications such as segmental mandibular reconstruction.

Tissue engineered periosteum: Fabrication of a gelatin basedtrilayer composite scaffold with biomimetic properties for enhanced bone healing.

The periosteum, a vascularized tissue membrane, is essential in bone regeneration following fractures and bone loss due to some other reasons, yet there exist several research gaps concerning its regeneration. These gaps encompass reduced cellular proliferation and bioactivity, potential toxicity, heightened stiffness of scaffold materials, unfavorable porosity, expensive materials and procedures, and suboptimal survivability or inappropriate degradation rates of the implanted materials. This research used an interdisciplinary approach by forming a new material fabricated through electrospinning for the proposed application as a layer-by-layer tissue-engineered periosteum (TEP). TEP comprises poly(ε-caprolactone) (PCL), PCL/gelatin/magnesium-doped zinc oxide (vascular layer), and gelatin/bioactive glass/COD liver oil (osteoconductive layer). These materials were selected for their diverse properties, when integrated into the scaffold formation, successfully mimic the characteristics of native periosteum. Scanning electron microscopy (SEM) was employed to confirm the trilayer structure of the scaffold and determine the average fiber diameter. In-vitro degradation and swelling studies demonstrated a uniform degradation rate that matches the typical recovery time of periosteum. The scaffold exhibited excellent mechanical properties comparable to natural periosteum. Furthermore, the sustained release kinetics of COD liver oil were observed in the trilayer scaffold. Cell culture results indicated that the three-dimensional topography of the scaffold promoted cell growth, proliferation, and attachment, confirming its non-toxicity, biocompatibility, and bioactivity. This study suggests that the fabricated scaffold holds promise as a potential artificial periosteum for treating periostitis and bone fractures.

Guided Bone Regeneration: Novel Use of Fixation Screws as an Alternative to Using the Buccoapical Periosteum for Membrane Stabilization With Sutures-Two Case Reports.

Guided bone regeneration (GBR) requires a stable graft-membrane complex. This article presents a novel technique that uses membrane fixation screws to serve as anchors for membrane stabilization sutures without the need for periosteal dissection and biting of the buccoapical periosteum. This technique may be a viable alternative when there is a preference to avoid the complexities of periosteal suturing and direct membrane fixation using tacks or screws. The technique, which utilizes anchoring screws as mooring lines, can be used at the time of tooth extraction as well as for ridge augmentation of an edentulous site in preparation for future dental implant placement. Two case reports are presented that illustrate the feasibility of the technique, in which the integrity and stability of a resorbable membrane is preserved prior to final closure, suggesting that screws used as anchors for stabilization sutures might be a predictable option when addressing challenging horizontal defects requiring GBR.

Pediatric orbital subperiosteal abscess outbreak in Iran: characteristics and causes.

PURPOSE: To evaluate demographics, characteristics, and management of pediatric patients with subperiosteal abscesses (SPA) secondary to orbital cellulitis and discuss the etiology of a dramatic rise in SPA. METHODS: Data were gathered by retrospective chart review of patients admitted to a tertiary referral eye hospital (Farabi Eye Hospital) diagnosed with orbital cellulitis with subperiosteal abscess from October 2022 to March 2023 (six months). Data on demographic information, clinical examination, radiographic evidence of sinusitis, orbital cellulitis, SPA, surgical and non-surgical management taken, isolated bacteria, and duration of hospital stay were gathered. RESULTS: 24 patients were admitted during these six months, with a diagnosis of orbital SPA secondary to paranasal sinusitis, confirmed by an orbital Computed Tomography (CT) scan. The age range was 11 months to 16 years. 75% of patients were male. All patients had a history of flu-like illness before developing orbital cellulitis. All patients had concurrent sinusitis, and 18 underwent initial surgical abscess drainage. The ethmoid sinus was the most involved, and most patients had a medially located SPA. Abscess volume ranged from 0.78 to 7.81 cm3 (mean: 3.52 cm3). One patient had concurrent central retinal artery occlusion due to orbital cellulitis. CONCLUSIONS: In this study, we report a dramatic increase in the incidence of SPA referred to our hospital. Larger abscess volumes and an increased number of cases that needed initial surgical drainage are also of note. An influenza outbreak in the autumn and winter, undiagnosed Corona Virus Disease 2019 (COVID-19) infection, increased antimicrobial resistance due to excessive off-label use of antibiotics during the COVID-19 pandemic, and more virulent bacterial infections are the most probable hypotheses to justify this observation.

A Self-Adaptive Biomimetic Periosteum Employing Nitric Oxide Release for Augmenting Angiogenesis in Bone Defect Regeneration.

The periosteum plays a vital role in the regeneration of critical-size bone defects and highly comminuted fractures, promoting the differentiation of osteoblasts, accelerating the reconstruction of the vascular network, and guiding bone tissue regeneration. However, the materials loaded with exogenous growth factors are limited by the release and activity of the elements. Therefore, the material structure must be carefully designed for the periosteal function. Here, a self-adaptive biomimetic periosteum strategy is proposed, which is a novel interpenetrating double network hydrogel consisting of diselenide-containing gelatin and calcium alginate (modified natural collagen and polysaccharide) to enhance the stability, anti-swelling, and delayed degradation of the hydrogel. The diselenide bond continuously releases nitric oxide (NO) by metabolizing endogenous nitrosated thiols (RSNO), activates the nitric oxide-cycle guanosine monophosphate (NO-cGMP) signal pathway, coordinates the coupling effect of angiogenesis and osteogenesis, and accelerates the repair of bone defects. This self-adaptive biomimetic periosteum with the interpenetrating double network structure formed by the diselenide-containing gelatin and calcium alginate has been proven to be safe and effective in repairing critical-size bone defects and is expected to provide a promising strategy for solving clinical problems.

Characterization of adult human skeletal cells in different tissues reveals a CD90+CD34+ periosteal stem/progenitor population.

The periosteum plays a crucial role in bone healing and is an important source of skeletal stem and progenitor cells. Recent studies in mice indicate that diverse populations of skeletal progenitors contribute to growth, homeostasis and healing. Information about the in vivo identity and diversity of skeletal stem and progenitor cells in different compartments of the adult human skeleton is limited. In this study, we compared non-hematopoietic populations in matched tissues from the femoral head and neck of 21 human participants using spectral flow cytometry of freshly isolated cells. High-dimensional clustering analysis indicated significant differences in marker distribution between periosteum, articular cartilage, endosteum and bone marrow populations, and identified populations that were highly enriched or unique to specific tissues. Periosteum-enriched markers included CD90 and CD34. Articular cartilage, which has very poor regenerative potential, showed enrichment of multiple markers, including the PDPN+CD73+CD164+CD146- population previously reported to represent human skeletal stem cells. We further characterized periosteal populations by combining CD90 with other strongly expressed markers. CD90+CD34+ cells sorted directly from periosteum showed significant colony-forming unit fibroblasts (CFU-F) enrichment, rapid expansion, and consistent multi-lineage differentiation of clonal populations in vitro. In situ, CD90+CD34+ cells include a perivascular population in the outer layer of the periosteum and non-perivascular cells closer to the bone surface. CD90+ cells are also highly enriched for CFU-F in bone marrow and endosteum, but not articular cartilage. In conclusion, our study indicates considerable diversity in the non-hematopoietic cell populations in different tissue compartments within the adult human skeleton, and suggests that periosteal progenitor cells reside within the CD90+CD34+ population.

Effect of Intact Periosteum on Alveolar Ridge Contour Stability after Horizontal Guided Bone Regeneration in the Posterior Region: a Retrospective and Radiographical Cohort Study.

OBJECTIVE: To radiographically evaluate the effect of intact periosteum in guided bone regeneration (GBR) for the treatment of peri-implant ridge defects in posterior region. METHODS: Twenty-eight patients who satisfied the criteria were included in this study. Buccal dehiscence defects were regenerated using demineralised bovine bone mineral (DBBM). Subjects were divided into two groups: the control group (conventional GBR, buccal trapezoidal flap and DBBM with collagen membrane coverage, n = 14) and the test group (modified GBR, buccal pouch and DBBM with collagen membrane coverage, n = 14). CBCT images obtained immediately after and 3 to 7 months following GBR were used to assess buccal bone thickness (BBT) at a level of 0, 2, 4 and 6 mm below the implant platform. RESULTS: Immediately after surgery, BBT at 0 mm and 2 mm below the implant platform presented a significant difference between the two groups (P < 0.05) with significantly thicker buccal bone in the control group in terms of BBT-0 (3.83 ± 1.01 mm) and BBT-2 (4.88 ± 1.15 mm) than in the test group (2.33 ± 0.66 mm and 3.60 ± 1.10 mm, P = 0.000 and P = 0.008, respectively). After 3 to 7 months of healing, the BBT at all levels showed no significant difference between the two groups (P > 0.05), but more bone graft resorption (BBR) in the control group in terms of BBR-0 (2.45 ± 1.14 mm), BBR-2 (2.09 ± 0.94 mm) and BBR-0% (65.37% ± 26.62%) than the test group (BBR-0 1.07 ± 0.51 mm, P = 0.001; BBR-2, 1.22 ± 0.63 mm, P = 0.008; BBR-0% 45.70% ± 15.52%, P = 0.024). CONCLUSION: In the short term, all treatment modalities achieved similar coronal BBT and the intact periosteum had a positive effect on keeping ridge dimensions even.

Spatiotemporal Immunomodulation and Biphasic Osteo-Vascular Aligned Electrospun Membrane for Diabetic Periosteum Regeneration.

Under diabetic conditions, blood glucose fluctuations and exacerbated immunopathological inflammatory environments pose significant challenges to periosteal regenerative repair strategies. Responsive immune regulation in damaged tissues is critical for the immune microenvironment, osteogenesis, and angiogenesis stabilization. Considering the high-glucose microenvironment of such acute injury sites, a functional glucose-responsive immunomodulation-assisted periosteal regeneration composite material-PLA（Polylactic Acid）/COLI(Collagen I）/Lipo(Liposome）-APY29 (PCLA)-is constructed. Aside from stimulating osteogenic differentiation, owing to the presence of surface self-assembled type I collagen in the scaffolds, PCLA can directly respond to focal area high-glucose microenvironments. The PCLA scaffolds trigger the release of APY29-loaded liposomes, shifting the macrophages toward the M2 phenotype, inhibiting the release of inflammatory cytokines, improving the bone immune microenvironment, and promoting osteogenic differentiation and angiogenesis. Bioinformatics analyses show that PCLA enhances bone repair by inhibiting the inflammatory signal pathway regulating the polarization direction and promoting osteogenic and angiogenic gene expression. In the calvarial periosteal defect model of diabetic rats, PCLA scaffolds induce M2 macrophage polarization and improve the inflammatory microenvironment, significantly accelerating periosteal repair. Overall, the PCLA scaffold material regulates immunity in fluctuating high-glucose inflammatory microenvironments, achieves relatively stable and favorable osteogenic microenvironments, and facilitates the effective design of functionalized biomaterials for bone regeneration therapy in patients with diabetes.

Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function.

We have previously reported that the cortical bone thinning seen in mice lacking the Wnt signaling antagonist Sfrp4 is due in part to impaired periosteal apposition. The periosteum contains cells which function as a reservoir of stem cells and contribute to cortical bone expansion, homeostasis, and repair. However, the local or paracrine factors that govern stem cells within the periosteal niche remain elusive. Cathepsin K (Ctsk), together with additional stem cell surface markers, marks a subset of periosteal stem cells (PSCs) which possess self-renewal ability and inducible multipotency. Sfrp4 is expressed in periosteal Ctsk-lineage cells, and Sfrp4 global deletion decreases the pool of PSCs, impairs their clonal multipotency for differentiation into osteoblasts and chondrocytes and formation of bone organoids. Bulk RNA sequencing analysis of Ctsk-lineage PSCs demonstrated that Sfrp4 deletion down-regulates signaling pathways associated with skeletal development, positive regulation of bone mineralization, and wound healing. Supporting these findings, Sfrp4 deletion hampers the periosteal response to bone injury and impairs Ctsk-lineage periosteal cell recruitment. Ctsk-lineage PSCs express the PTH receptor and PTH treatment increases the % of PSCs, a response not seen in the absence of Sfrp4. Importantly, in the absence of Sfrp4, PTH-dependent increase in cortical thickness and periosteal bone formation is markedly impaired. Thus, this study provides insights into the regulation of a specific population of periosteal cells by a secreted local factor, and shows a central role for Sfrp4 in the regulation of Ctsk-lineage periosteal stem cell differentiation and function.

Cell sheet-basedin vitrobone defect model for long term evaluation of bone repair materials.

Development of tissue-engineeredin vitrohuman bone defect models for evaluation of bone repair materials (BRMs) is a promising approach for addressing both translational and ethical concerns regarding animal models. In this study, human bone marrow mesenchymal stem cell sheets were stacked to form a periosteum like tissue. HE staining showed a cell-dense, multilayered structure. BRMs were implanted in the defect area of the three-dimensional (3D) model. The CCK-8 test demonstrated that the 3D model was stronger in resisting the cytotoxicity of three kinds of commercial BRMs than the 2D culture model, which was consistent within vivoresults. After 28 d implantation in the 3D model, western blot and RT-qPCR showed that three materials induced increased expressions of RUNX2, OSX, OCN, OPN, while Materials B and C seemed to have stronger osteoinductivity than A.In vivoexperiments also confirmed the osteoinductivity of the BRMs after 28 and 182 d implantation. Alizarin red staining proved that the mineralized nodules of Materials B and C were more than that of A. The differences of osteogenic properties among three BMRs might be attributed to calcium ion release. This cell sheet-based bone tissue model can resist cytotoxicity of BRMs, demonstrating the priority of long-term evaluation of osteoinductivity of BRMs. Further, the osteoinduction results of the 3D model corresponded to that ofin vivoexperiments, suggesting this model may have a potential to be used as a novel tool for rapid, accurate evaluation of BRMs, and thus shorten their research and development process.

Frailty and survival in the 1918 influenza pandemic.

One of the most well-known yet least understood aspects of the 1918 influenza pandemic is the disproportionately high mortality among young adults. Contemporary accounts further describe the victims as healthy young adults, which is contrary to the understanding of selective mortality, which posits that individuals with the highest frailty within a group are at the greatest risk of death. We use a bioarchaeological approach, combining individual-level information on health and stress gleaned from the skeletal remains of individuals who died in 1918 to determine whether healthy individuals were dying during the 1918 pandemic or whether underlying frailty contributed to an increased risk of mortality. Skeletal data on tibial periosteal new bone formation were obtained from 369 individuals from the Hamann-Todd documented osteological collection in Cleveland, Ohio. Skeletal data were analyzed alongside known age at death using Kaplan-Meier survival and Cox proportional hazards analysis. The results suggest that frail or unhealthy individuals were more likely to die during the pandemic than those who were not frail. During the flu, the estimated hazards for individuals with periosteal lesions that were active at the time of death were over two times higher compared to the control group. The results contradict prior assumptions about selective mortality during the 1918 influenza pandemic. Even among young adults, not everyone was equally likely to die-those with evidence of systemic stress suffered greater mortality. These findings provide time depth to our understanding of how variation in life experiences can impact morbidity and mortality even during a pandemic caused by a novel pathogen.

Analysis of Cellular Crosstalk and Molecular Signal between Periosteum-Derived Precursor Cells and Peripheral Cells During Bone Healing Process Using a Paper-Based Osteogenesis-On-A-Chip Platform.

Periosteum-derived progenitor cells (PDPCs) are highly promising cell sources that are indispensable in the bone healing process. Adipose-derived stem cells (ADSCs) are physiologically close to periosteum tissue and release multiple growth factors to promote the bone healing process. Co-culturing PDPCs and ADSCs can construct periosteum-bone tissue microenvironments for the study of cellular crosstalk and molecular signal in the bone healing process. In the current work, a paper-based osteogenesis-on-a-chip platform was successfully developed to provide an in vitro three-dimensional coculture model. The platform was a paper substrate sandwiched between PDPC-hydrogel and ADSC-hydrogel suspensions. Cell secretion could be transferred through the paper substrate from one side to another side. Growth factors including BMP2, TGF-ß, POSTN, Wnt proteins, PDGFA, and VEGFA were directly analyzed by a paper-based immunoassay. Cellular crosstalk was studied by protein expression on the paper substrate. Moreover, osteogenesis of PDPCs was investigated by examining the mRNA expressions of PDPCs after culture. Neutralizing and competitive assays were conducted to understand the correlation between growth factors secreted from ADSCs and the osteogenesis of PDPCs. In vitro periosteum-bone tissue microenvironment was established by the paper-based osteogenesis-on-a-chip platform. The proposed approach provides a promising assay of cellular crosstalk and molecular signal in 3D coculture microenvironment that may potentially lead to the development of effective bone regeneration therapy.

BMP-9 Improves the Osteogenic Differentiation Ability over BMP-2 through p53 Signaling In Vitro in Human Periosteum-Derived Cells.

Bone morphogenetic proteins (BMPs) have tremendous therapeutic potential regarding the treatment of bone and musculoskeletal disorders due to their osteo-inductive ability. More than twenty BMPs have been identified in the human body with various functions, such as embryonic development, skeleton genesis, hematopoiesis, and neurogenesis. BMPs can induce the differentiation of MSCs into the osteoblast lineage and promote the proliferation of osteoblasts and chondrocytes. BMP signaling is also involved in tissue remodeling and regeneration processes to maintain homeostasis in adults. In particular, growth factors, such as BMP-2 and BMP-7, have already been approved and are being used as treatments, but it is unclear as to whether they are the most potent BMPs that induce bone formation. According to recent studies, BMP-9 is known to be the most potent inducer of the osteogenic differentiation of mesenchymal stem cells, both in vitro and in vivo. However, its exact role in the skeletal system is still unclear. In addition, research results suggest that the molecular mechanism of BMP-9-mediated bone formation is also different from the previously known BMP family, suggesting that research on signaling pathways related to BMP-9-mediated bone formation is actively being conducted. In this study, we performed a phosphorylation array to investigate the signaling mechanism of BMP-9 compared with BMP-2, another influential bone-forming growth factor, and we compared the downstream signaling system. We present a mechanism for the signal transduction of BMP-9, focusing on the previously known pathway and the p53 factor, which is relatively upregulated compared with BMP-2.

[Effects of low position lateral supramalleolar flap carrying periosteum and proximal leg propeller flap in relay repair of electric burn wounds of forefoot].

Objective: To explore the effects of low position lateral supramalleolar flap carrying periosteum and proximal leg propeller flap in relay repair of electric burn wounds of forefoot. Methods: A retrospective observational study was conducted. From January 2019 to January 2022, 12 patients with electric burn wounds of forefoot meeting the inclusion criteria were admitted to the Sixth Hospital of Shanxi Medical University, including 10 males and 2 females, aged 23-65 years. After debridement, the wound with an area of 6.0 cm×3.0 cm to 15.0 cm×7.0 cm was repaired with the lateral supramalleolar flap carrying part of the periosteum of the distal tibia and fibula with the rotation point moved down to the front of the ankle joint. The area of the cutted flap was 6.5 cm×3.5 cm-15.5 cm×7.5 cm. At the same stage, the donor site wound of lateral supramalleolar flap was repaired with peroneal artery or superficial peroneal artery perforator propeller flap in relay, with the relay flap area of 3.0 cm×1.5 cm-15.0 cm×4.0 cm. After operation, the survival of the lateral supramalleolar flap and relay flap, and the wound healing of the relay flap donor site were observed. During follow-up, the shapes of the lateral supramalleolar flap and its donor site were observed. Results: After operation, one patient developed secondary blisters in the superficial skin distal to the lateral supramalleolar flap, which healed after dressing change, and the lateral supramalleolar flap and relay flaps survived well in the other patients; the donor site wound of the relay flap healed well. During follow-up of 12-18 months, the lateral supramalleolar flaps were in good shape and not bloated, with only linear scar left in the donor site of the flap. Conclusions: The low position lateral supramalleolar flap carrying periosteum can repair electric burn wounds of forefoot with advantages including reliable blood supply, low rotation point, and better repair effects. The use of relay flap to repair the donor site of lateral supramalleolar flap can reduce the damage to the appearance and function of the donor site.

Cadaveric Split-Thickness Skin Graft With Partial Guiding Closure for Scalp Defects Extending to the Periosteum.

A scalp defect that extends to or below the periosteum often poses a reconstructive conundrum. Achieving the level of tissue granulation necessary for secondary-intention healing is challenging without an intact periosteum; surgeons often resort to complex rotational flap closures in this scenario. For tumors at high risk for recurrence and in cases in which adjuvant therapy is necessary, tissue distortion with a complex rotational flap can make monitoring for recurrence difficult. Similarly, for elderly patients with substantial skin atrophy or those in poor health, extensive closure may be undesirable or more technically challenging and poses a higher risk for adverse events. Additional strategies are necessary to optimize wound healing and cosmesis. Granulation and epithelialization of wounds can be expedited using a cadaveric split-thickness skin graft (STSG) of biologically active tissue. We describe this technique and show its utility in cases in which there is concern for delayed or absent tissue granulation, or when monitoring for recurrence is essential.