Application of extracellular matrix cross-linked by microbial transglutaminase to promote wound healing.

One primary focus of skin tissue engineering has been the creation of innovative biomaterials to facilitate rapid wound healing. Extracellular matrix (ECM), an essential biofunctional substance, has recently been discovered to play a crucial role in wound healing. Consequently, we endeavored to decellularize ECM from pig achilles tendon and refine its mechanical and biological properties through modification by utilizing cross-linking agents. Glutaraldehyde (GA), 1-ethyl-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), double aldol starch (DAS), and microbial transglutaminase (MTG) were utilized to produce crosslinked ECM variants (GA-ECM, EDC/NHS-ECM, DAS-ECM, and MTG-ECM). Comprehensive assessments were conducted to evaluate the physical properties, biocompatibility, and wound healing efficacy of each material. The results indicated that MTG-ECM exhibited superior tensile strength, excellent hydrophilicity, minimal cytotoxicity, and the best pro-healing impact among the four modified scaffolds. Staining analysis of tissue sections further revealed that MTG-ECM impeded the transition from type III collagen to type I collagen in the wound area, potentially reducing the development of wound scar. Therefore, MTG-ECM is expected to be a potential pro-skin repair scaffold material to prevent scar formation.

Hyaluronic Acid-Dopamine-NCSN Hydrogel Combined With Extracellular Matrix Promotes Wound Healing.

The skin barrier is essential to prevent pathogenic invasion. When injury occurs, multiple biological pathways are promptly activated and wound repair processes are triggered. The effective healing of wounds is essential for survival, and dysfunction could result from aberrant wound repair. Preparation of many hydrogels, which involve the addition of growth/cell factors or mimic extracellular matrix (ECM) components, has not resulted in significant advances in tissue recovery. ECM contains a large number of biologically active molecules that activate a variety of cellular transduction pathways, which are essential for wound repair. Here, this work prepares hyaluronic acid-dopamine-thiourea (HA-DA-NCSN) hydrogels exhibiting ultrafast gelation in situ, following the methods of Xu et al., and subsequently designs a hydrogel containing ECM particles. In addition, the loaded ECM material, specifically decellularized ECM material, not only enhances the strength of the hydrogel network, but also delivers bioactive substances that make it a suitable platform for skin wound repair. The ECM hydrogel has great potential as an efficient bioactive wound dressing. This research suggests that this strategy is likely to improve skin wound closure in rat skin wound models.

CuS@TA-Fe Nanoparticle-Doped Multifunctional Hydrogel with Peroxide-Like Properties and Photothermal Properties for Synergistic Antimicrobial Repair of Infected Wounds.

Bacterial infection is a critical factor in wound healing. Due to the abuse of antibiotics, some pathogenic bacteria have developed resistance. Thus, there is an urgent need to develop a non-antibiotic-dependent multifunctional wound dressing for the treatment of bacteria-infected wounds. In this work, a multifunctional AOCuT hydrogel embedded with CuS@TA-Fe nanoparticles (NPs) through Schiff base reaction between gelatin quaternary ammonium salt - gallic acid (O-Gel-Ga) and sodium dialdehyde alginate (ADA) along with electrostatic interactions with CuS@TA-Fe NPs is prepared. These composite hydrogels possess favorable injectability, rapid shape adaptation, electrical conductivity, photothermal antimicrobial activity, and biocompatibility. Additionally, the doped NPs not only impart fast self-healing properties and excellent adhesion performance to the hydrogels, but also provide excellent peroxide-like properties, enabling them to scavenge free radicals and exhibit anti-inflammatory and antioxidant capabilities via photothermal (PTT) and photodynamic (PDT) effects. In an S. aureus infected wound model, the composite hydrogel effectively reduces the expression level of wound inflammatory factors and accelerates collagen deposition, epithelial tissue, and vascular regeneration, thereby promoting wound healing. This safe and synergistic therapeutic system holds great promise for clinical applications in the treatment of infectious wounds.

A pectin-based photoactivated bactericide nanosystem for achieving an improved utilization rate, photostability and targeted delivery of hematoporphyrin.

Photoactivated pesticides have many advantages, such as high activity, low toxicity, and no drug resistance. However, poor photostability and a low utilization rate limit their practical application. Herein, the photosensitizer hematoporphyrin (HP) was used as a photoactivated pesticide, covalently linked with pectin (PEC) via ester bonds, to prepare an amphiphilic polymer pro-bactericide, and subsequently self-assembled in aqueous solutions to obtain an esterase-triggered nanobactericide delivery system. The fluorescence quenching effect due to the aggregation of HP in nanoparticles (NPs) enabled the inhibition of photodegradation of HP in this system. Esterase stimulation could trigger HP release and increase its photodynamic activity. Antibacterial assays have shown that the NPs had potent antibacterial capacity, almost completely inactivating bacteria after 60 min of exposure to light. The NPs had good adherence to the leaves. Safety assessment indicated that the NPs have no obvious toxic effects on plants. Antibacterial studies on plants have shown that the NPs have excellent antibacterial effects on infected plants. These results provide a new strategy for obtaining a photoactivated bactericide nanosystem with a high utilization rate and good photostability and targeting ability.

M6A RNA Methylation Mediates NOD1/NF-kB Signaling Activation in the Liver of Piglets Challenged with Lipopolysaccharide.

N6-methyladenosine (m6A) is the most abundant internal modification that widely participates in various immune and inflammatory responses; however, its regulatory mechanisms in the inflammation of liver induced by lipopolysaccharide in piglets remain largely unknown. In the present study, piglets were intraperitoneally injected with 80 µg/kg LPS or an equal dose of sterile saline. Results indicated that LPS administration increased activities of serum alanine aminotransferase (ALT), induced M1 macrophage polarization and promoted secretion of inflammatory cytokines, and finally led to hepatic lesions in piglets. The NOD1/NF-κB signaling pathway was activated in the livers of the LPS group. Moreover, the total m6A level was significantly elevated after LPS treatment. MeRIP-seq showed that 1166 and 1344 transcripts contained m6A methylation in control and LPS groups, respectively. The m6A methylation sites of these transcripts mainly distributes in the 5' untranslated region (5'UTR), the coding sequence (CDS), and the 3' untranslated region (3'UTR). Interestingly, these genes were mostly enriched in the NF-κB signaling pathway, and LPS treatment significantly changed the m6A modification in NOD1, RIPK2, NFKBIA, NFKBIB, and TNFAIP3 mRNAs. In addition, knockdown of METTL3 or overexpression of FTO both changed gene levels in the NOD1/NF-κB pathway, suggesting that activation of this pathway was regulated by m6A RNA methylation. Moreover, the alteration of m6A RNA methylation profile may be associated with the increase of reactive oxygen species (ROS), HIF-1α, and MAT2A. In conclusion, LPS activated the NOD1/NF-κB pathway at post-transcriptional regulation through changing m6A RNA methylation, and then promoted the overproduction of proinflammatory cytokines, ultimately resulting in liver inflammation and damage.

Regulator of calcineurin 1 deletion attenuates mitochondrial dysfunction and apoptosis in acute kidney injury through JNK/Mff signaling pathway.

Ischemia-reperfusion (I/R) induced acute kidney injury (AKI), characterized by excessive mitochondrial damage and cell apoptosis, remains a clinical challenge. Recent studies suggest that regulator of calcineurin 1 (RCAN1) regulates mitochondrial function in different cell types, but the underlying mechanisms require further investigation. Herein, we aim to explore whether RCAN1 involves in mitochondrial dysfunction in AKI and the exact mechanism. In present study, AKI was induced by I/R and cisplatin in RCAN1flox/flox mice and mice with renal tubular epithelial cells (TECs)-specific deletion of RCAN1. The role of RCAN1 in hypoxia-reoxygenation (HR) and cisplatin-induced injury in human renal proximal tubule epithelial cell line HK-2 was also examined by overexpression and knockdown of RCAN1. Mitochondrial function was assessed by transmission electron microscopy, JC-1 staining, MitoSOX staining, ATP production, mitochondrial fission and mitophagy. Apoptosis was detected by TUNEL assay, Annexin V-FITC staining and Western blotting analysis of apoptosis-related proteins. It was found that protein expression of RCAN1 was markedly upregulated in I/R- or cisplatin-induced AKI mouse models, as well as in HR models in HK-2 cells. RCAN1 deficiency significantly reduced kidney damage, mitochondrial dysfunction, and cell apoptosis, whereas RCAN1 overexpression led to the opposite phenotypes. Our in-depth mechanistic exploration demonstrated that RCAN1 increases the phosphorylation of mitochondrial fission factor (Mff) by binding to downstream c-Jun N-terminal kinase (JNK), then promotes dynamin related protein 1 (Drp1) migration to mitochondria, ultimately leads to excessive mitochondrial fission of renal TECs. In conclusion, our study suggests that RCAN1 could induce mitochondrial dysfunction and apoptosis by activating the downstream JNK/Mff signaling pathway. RCAN1 may be a potential therapeutic target for conferring protection against I/R- or cisplatin-AKI.

Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial Function.

Endothelial dysfunction plays a pivotal role in the development and progression of diabetic vascular complications. Naringenin (Nar) is a flavanone bioactive isolated from citrus fruits known to have in vitro and in vivo antidiabetic properties. However, whether Nar affects endothelial function remains unclear in diabetes or under high-glucose (HG) condition. Using an in vitro model of hyperglycemia in human umbilical vein endothelial cells (HUVECs), we found that Nar administration markedly attenuated HG-induced alterations of endothelial function, evidenced by the mitigation of oxidative stress and inflammation, the reduction of cell adhesion molecular expressions, and the improvement of insulin resistance. We also found that HG exposure significantly reduced the levels of intracellular heat shock protein 70 (iHSP70 or iHSPA1A) and the release of HSP70 from HUVECs. HSP70 depletion mimicked and clearly diminished the protective effects of Nar on HG-induced alterations of endothelial function. In addition, Nar treatment significantly enhanced iHSP70 protein levels through a transcription-dependent manner. These results demonstrated that Nar could protect HUVECs against HG-induced alterations of endothelial function through upregulating iHSP70 protein levels. These findings are also helpful in providing new therapeutic strategies that are promising in the clinical use of Nar for the treatment of diabetes and diabetic complications.

Preparation and properties of carboxymethyl chitosan/oxidized hydroxyethyl cellulose hydrogel.

Hydrogel wound dressing is a type of hydrophilic polymer, which has been widely studied and applied in biomedical field. In this study, a simple and non-toxic method was developed to prepare a new type of composite hydrogel, which was formed through the Schiff-base reaction between the aldehyde of Oxidized Hydroxyethyl Cellulose (OHEC) and the amino of Carboxymethyl Chitosan (CMCS). Hence, a series of tests toward this new composite hydrogel which contained its structure and performance was applied. Statistics achieved from those tests showed that this composite hydrogel comprised of some high-quality properties such as suitable gelation time, good swelling ability, suitable water evaporation rate, good blood compatibility and biocompatibility. Considering these properties, this hydrogel has a potential to be explored as wound dressing.

Repair of Massive Bone Defects of the Proximal Femur Using Iliac Bone Flaps of the Ascending Branch of the Lateral Circumflex Femoral Artery: A Retrospective Report.

BACKGROUND AND OBJECTIVE: The management of bone defects is still a difficult problem. Local vascularized bone grafts represent an efficient and widely used method. In this retrospective report, iliac bone flaps of the ascending branch of the lateral circumflex femoral artery were used for the management of proximal femur bone defects. PATIENTS AND METHODS: The hospital information system and clinical data collected by surgeons were retrospectively reviewed. Patients with massive bone defects of the proximal femur reconstructed with iliac bone flaps of the ascending branch of the lateral circumflex femoral artery were included. Relevant data, including general information, perioperative treatment, and imaging data during follow-up, were retrieved for analysis. Five patients (4 males and 1 female) aged 18 to 42 years were included in this report. All patients were diagnosed with proximal femoral bone defects. The sizes of the bone defects ranged from 5 ×4 cm to 8 × 5 cm. Harris hip score was adopted to evaluate the functional outcomes. The adverse events were recorded. The mean follow-up time was 6.3 years. RESULTS: Iliac bone flaps of the ascending branch of the lateral circumflex femoral artery were transferred locally for the 5 patients. Bone flaps were fixed with plates in 4 cases and Kirschner wires in 1 case. The hospital stay was 12 to 27 days, with an average of 19.4 days. All cases achieved bony healing after 3 to 6 months postoperatively. The Harris hip scores ranged from 87 to 95 at final follow-up. All patients achieved good to excellent functional outcomes. One superficial infection occurred. No other adverse events or serious adverse events were noted. CONCLUSIONS: Local transfer of iliac bone flaps of the ascending branch of the lateral circumflex femoral artery represents a safe and effective method for the reconstruction of massive bone defects of the proximal femur.

Reconstruction of a Distal Foot Skin Defect Using an Intermediate Dorsal Neurocutaneous Flap.

OBJECTIVE: To present the use of an intermediate dorsal neurocutaneous flap for the reconstruction of defects on the distal foot. METHODS: From September 2016 to October 2018, five patients (mean age at operation 33.8 years; range, 7-70 years; female/male = 2/3) with skin defects on one of their feet caused by road-traffic accidents, electrical injury, and syndactyly correction were retrospectively reviewed. The size of the defects ranged from 2.0 cm × 1.0 cm to 5.0 cm × 3.5 cm. All patients had undergone a reconstruction surgery using intermediate dorsal neurocutaneous flap. One patient underwent a syndactyly correction, and four patients first experienced aggressive debridement. The sizes of the flaps were between 5.0 cm × 2.0 cm and 6.0 cm × 4.0 cm. The function, appearance, and pain of the injured foot were assessed using the Chinese Manchester Foot Pain and Disability Index and visual analogue scale. RESULTS: These five patients were systematically followed up for a mean of 15.8 months (range, 12-20 months). The donor sites were closed primarily in two cases, and skin grafts were performed in three cases. All the flaps survived with a success rate of 100%; the wounds healed well, and the color matches were excellent. Partial superficial flap necrosis occurred in one of five flaps, which was treated by dressing change using a hypertonic saline gauze. No significant problems were found at the donor site in any patient immediately afterwards or at follow-up. There were no problems in any patients associated with wearing shoes. Based on the Chinese Manchester Foot Pain and Disability Index, four patients were strongly satisfied and one was satisfied with the recovery of physical function; all the patients were strongly satisfied with the appearance of the injured foot; all five patients had an excellent score of pain intensity subscale. Except for one patient who reported mild pain, all the other patients reported no pain based on the visual analogue scale. Two typical cases are presented in this paper. CONCLUSIONS: The intermediate dorsal neurocutaneous flap is an alternative and effective technique that can reliably cover minor- to medium-sized defects on the distal foot, toes, and web spaces. This surgical method leads to satisfactory functional recovery with minimal donor site morbidity, and no major vessels need to be sacrificed. This procedure offers an advisable option for orthopaedic surgeons to treat defects on the distal foot.

Preparation and characterization of carboxymethyl chitosan/collagen peptide/oxidized konjac composite hydrogel.

Medical dressings are used to protect damaged skin from external factors and provide a good healing environment. Hydrogels are aggregates of hydrophilic polymers and water that have a three-dimensional space and can absorb large amounts of water. It has been widely studied in the field of biomedical materials. In this study, we prepared a novel composite hydrogel combined carboxymethyl chitosan, collagen peptide and oxidized konjac, all three materials have been shown to be biocompatible. Then, we set up different hydrogels and tested hydrogels with different proportions. The structures of CMCS (carboxymethyl chitosan)/COP (collagen peptide)/OKGM (oxidized konjac) hydrogels were characterized by IR, NMR, X-ray diffraction and SEM. The effects of hydrogels on the growth of NS-FB and HS-FB cells were studied in vitro. The results of these tests show that the composite hydrogel has excellent mechanical properties and biological activity, and has potential application in wound dressing field.

[Application of composite tissue flaps pedicled with distal perforating branch of posterior tibial artery for repairing distal leg defects].

Objective: To investigate the clinical application and effectiveness of the composite tissue flaps pedicled with perforating branch of posterior tibial artery for repairing distal leg defects. Methods: Between September 2014 and August 2017, 12 patients with skin and bone defects of distal leg were repaired with the composite tissue flaps pedicled with perforating branch of posterior tibial artery. There were 8 males and 4 females with an average age of 41.3 years (range, 25-66 years). The causes of injury included traffic accident injury in 7 cases, heavy crushing injury in 2 cases, tibial osteomyelitis with soft tissue ulcer and necrosis in 2 cases, and bone and soft tissue defect after resection of bone tumor in 1 case. Eight patients underwent primary repair, and 4 patients underwent second-stage repair. The size ranged from 6 cm×4 cm to 10 cm×7 cm in skin flap, from 4.0 cm×2.5 cm to 8.0 cm×6.0 cm in muscle flap, and from 4 cm×2 cm×2 cm to 5 cm×4 cm×4 cm in tibial bone flap. Tibial defects of the donor region were repaired by autologous iliac bone grafting, and the wounds were sutured directly in 7 cases and repaired by autologous skin grafting in 5 cases. Results: All composite tissue flaps survived and both the recipient and the donor wounds healed primarily. All patients were followed up 6-12 months, with an average of 10.8 months. The appearance, color, texture of the composite tissue flaps and ankle function were satisfactory. X-ray films showed that the bone flap at the tibia defect and the ilium graft at the donor site both healed well at 6 months after operation. Conclusion: The composite tissue flaps pedicled with perforating branch of posterior tibial artery has abundant blood, and it is a good donor region for repairing the distal leg defects combined with circumscribed bone defect.

[Treatment of severe distal humeral bone defects with three-dimensional printing technology].

Objective: To explore the application of three-dimensional (3D) printing technology in precise and individualized surgical treatment of severe distal humeral bone defect. Methods: Five patients with severe distal humeral bone defects were treated with customized 3D printing prostheses between December 2010 and December 2015. There were 4 males and 1 female, with an age of 23-57 years (mean, 35 years); and the length of the bone defect was 5-12 cm (mean, 8 cm). The cause of injury was mechanical injury in 2 cases and strangulation in 3 cases. All of them were the open fracture of Gustilo type Ⅲ. There were 2 cases of radial fracture, 1 case of cubital nerve injury, and 3 cases of radial nerve injury. The time from injury to one-stage operation was 6-18 hours (mean, 10 hours). The operation time, intraoperative blood loss, and intraoperative fluoroscopy were recorded. During follow-up, the anteroposterior and lateral X-ray films of the elbow joints were performed to identify whether there was prosthesis loosening; Mayo Elbow Performance Score (MEPS) and upper extremity Enneking score were used to evaluate limb function. Results: The operation time was 140-190 minutes (mean, 165 minutes). The intraoperative blood loss was 310-490 mL (mean, 415 mL). The intraoperative fluoroscopy was 1-3 times (mean, 1.6 times). Five patients were followed up 14-38 months (mean, 21 months). The wound exudate occurred in 1 case and cured after anti-inflammatory local dressing change; the subcutaneous hematoma occurred in 1 case, and improved after color Doppler ultrasound guided puncture and drainage. The MEPS scores and the Enneking scores were all significantly improved when compared with preoperative ones ( P<0.05). Except MEPS score between 6 and 12 months after operation had no significant difference ( P>0.05), there were significant differences in MEPS scores and Enneking scores between the other time points ( P<0.05). During the follow-up, no prosthetic loosening or joint dislocation occurred. Conclusion: 3D printing technology can achieve personalized treatment of severe distal humeral bone defects, obtain relatively good elbow joint function, and has less postoperative complications and satisfactory effectiveness.

α-hemihydrate calcium sulfate/octacalcium phosphate combined with sodium hyaluronate promotes bone marrow-derived mesenchymal stem cell osteogenesis in vitro and in vivo.

PURPOSE: The aims of this research were to combine α-hemihydrate calcium sulfate/octacalcium phosphate (α-CSH/OCP) with sodium hyaluronate (SH) or SH sulfate (SHS) to determine whether these composites can be used as a new type of bone repair material. This study may provide a theoretical basis and new ideas for the construction of active bone repair materials and their clinical application. METHODS: In this study, we combined α-CSH/OCP with SH or SHS. Scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and the wettability test were performed, and porosity, setting time, in vitro degradation, and the mechanical properties of these composite materials were analyzed to evaluate the ultrastructural and physicochemical properties. We evaluated the histocompatibility of these composites by MTT assay, hemolysis, acute toxicity, and pyrogenic and intracutaneous stimulation tests. In addition, the osteogenic differentiation ability of these materials was detected in vitro using Western blot analysis and in vivo using an animal model of bone defect. RESULTS: The α-CSH/OCP/SH composite had a compressive strength of 13.72 MPa, a porous rate of 27.45%, and the 28-day degradation rate of 64%. The MTT assay results showed that the relative proliferation rates of the α-CSH/OCP/SH group were greater than 90%. The results of the α-CSH/OCP/SH composite in the hemolysis, acute toxicity, pyrogenic, and intracutaneous stimulation tests were within the normal range. Western blot analysis indicated that the expression of bone extracellular matrix (ECM) proteins was notably upregulated and always higher in the α-CSH/OCP/SH group than in the other groups. XRD of the rabbit radius-defect model indicated that bone healing in the area implanted with α-CSH/OCP/SH was excellent approximately 9 weeks after repair. CONCLUSION: α-CSH/OCP/SH has very good biocompatibility and exhibits clear advantages in the induction of bone regeneration and self-repair, and this compound shows promise in the field of bone tissue engineering.

Long-term follow-up of fibular graft for the reconstruction of bone defects.

The use of fibular graft for the reconstruction of bone defects has been demonstrated to be a reliable method. The aim of this study was to assess the clinical outcome of graft union, functional outcome (hypertrophy of the graft bones) and complications of both non-vascularized and vascularized grafts.From 1981 to 2015, 10 patients were treated using non-vascularized fibular graft or free vascularized fibular graft. The outcomes were bony union time, graft hypertrophy and complications based on radiograph and functional outcomes according to the Musculoskeletal Tumor Society (MSTS) score. Mobility of the ankle at the donor site was evaluated using the Kofoed ankle score system.This study included 10 patients with an average follow-up of 6.8 years. The union rate for all patients was 100%. The mean union time was 21.3 weeks for vascularized fibular grafts and 30.5 weeks for non-vascularized fibular grafts (P = .310). There was a significant difference between the upper limbs and the lower limbs regarding hypertrophy of the grafts in 5 patients (P = .003). The mean MSTS score in 10 patients was 84% (range 53%-97%). Stress fracture of the graft occurred in 1 patient. Donor site complications, including valgus deformity and length discrepancy, between 2 legs occurred in 2 patients who were under 18 years of age at the time of operation (P = .114). The mean Kofoed score was 96.8 (range 88-100).A greater increase in hypertrophy of grafts was observed with reconstruction in the lower limbs. There was no difference in MSTS score between these 2 types of grafts. Children were more likely to experience the valgus deformity at the donor site after harvesting the fibula. Keeping at least the distal 1/4 of the fibula intact during the surgery is a valid means of ensuring ankle stability at the donor site, and children should be considered for prophylactic distal tibiofibular synostosis creation to prevent the valgus deformity of the ankle at the donor site.

Preparation and characterization of chitosan - collagen peptide / oxidized konjac glucomannan hydrogel.

In this paper, the microbial transglutaminase (MTGase) was used as a catalyst to graft the collagen peptide (COP) molecules on the amino group of chitosan to obtain water-soluble chitosan-collagen peptide (CS-COP) derivatives. The preparation of composite hydrogel was via the Schiff-base reaction between the amino of CS-COP and the aldehyde of oxidized konjac glucomannan (OKGM). The hydrogels were characterized by various techniques including Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The results of SEM showed that the hydrogel sample had a clear and stable three-dimensional network structure. Meanwhile, these effects of the addition of OKGM on gelation time, swelling behaviors, water evaporation rate and blood coagulation capacity were investigated. The shortest gelation time for hydrogels was 99.3s. The hydrogels showed a good swelling ability and appropriate water retention capacity. The maximum swelling ratio of the hydrogel was 265%. Dynamic blood clotting test showed that the hydrogels materials had good blood coagulation capacity. Moreover, The biocompatibility of hydrogels was evaluated with NIH-3T3 cells by MTT method. The results indicated that the hydrogels exhibited better biocompatibility. Therefore, this hydrogel has a promising potential to be applied as wound dressing.

Functional thenar eminence myocutaneous flap for reconstruction of thumb volar defect.

This case report describes the use of a Functional Thenar Eminence myocutaneous flap for reconstruction of volar defect of distal right thumb of a 25-year-old male who sustained a twisting injury while working. Part of bone and tendon were exposed and the tip of the distal phalanx was crushed, with bony defect.

Mutation screening in candidate genes in four Chinese brachydactyly families.

Autosomal dominant brachydactyly (BD) is a skeletal disorder with several subtypes, including brachydactyly type A1 (BDA1) and brachydactyly type B1 (BDB1). Mutations in Indian hedgehog (IHH) are usually associated with BDA1, whereas heterozygous mutations in receptor tyrosine kinase-like orphan receptor 2 (ROR2) are mainly responsible for BDB1. On the basis of the clinical phenotype identification, we screened IHH and ROR2 by the candidate gene approach using PCR direct sequencing. We found three known mutations of IHH (c.283_285delGAG, p.E95del; c.298 G>A, p.D100N; c.300C>G, p.D100E) in three Chinese families with BDA1, and a novel heterozygous nonsense mutation of ROR2 (c.2273C>A, p.S758X) in a BDB1 family. It was noted that c.300C>G mutation was a new nucleotide substitution compared to the reported c.300C>A, which led to the same amino acid change (p.D100E). The novel nonsense mutation p.S758X was verified by absence in the unaffected family members and the 100 randomly-selected controls. In this paper, we report three recurrent mutations with a new nucleotide substitution of IHH in three Chinese families with BDA1 and a novel nonsense mutation in BDB1 pedigree. We therefore recommend the approach of candidate gene screening as the first choice for genetic testing for BD.

Vacuum assisted closure therapy for treatment of complex wounds in replanted extremities.

The object of this study was to compare the outcomes of the vacuum assisted closure (VAC) therapy and conventional wound care with dressing change for treatment of complex wounds in patients with replantation of amputated upper and lower extremities. Data of 43 patients with replantation of amputated extremities from May 2004 to December 2011 were reviewed. There were 18 wounds of 18 patients with replantation, which were treated by dressing change and 26 wounds of 25 patients by VAC therapy. The outcomes were evaluated by the survival rate of replanted extremities, growth of granulation tissue, interval between wound treatment and secondary procedure and eventual secondary wound coverage methods. Vascular thromboses were found in 3 patients with wound treatment by dressing change and 5 by VAC. All replants of two groups of patients survived after salvage procedures. The wound score was 3.6 ± 0.7 in the conventional dressing change group and 5.8 ± 0.7 in the VAC group at the sixth day after treatment, respectively. The intervals between wound treatment and secondary wound coverage procedure were 12.0 ± 1.7 days in the dressing change group and 6.1 ± 0.7 days in the VAC group. Flaps were applied for wound coverage in 9 out of 18 (50.0%) wounds in the dressing change group and 5 out of 26 (19.2%) in the VAC group (P < 0.05), when the wounds of rest of patients were covered by the skin graft. The results showed that VAC could promote the growth of granulation tissue of wound, decrease the need of flap for wound coverage, and did not change the survival of replantation.

Preparation of carboxymethyl chitosan sulfate for improved cell proliferation of skin fibroblasts.

Carboxymethyl chitosan (CMC) was chemically modified by sulfating agent N(SO(3)Na)(3). The product carboxymethyl chitosan sulfate (CMCS) was characterized by Fourier transform infrared spectroscopy (FT-IR) and carbon-13 nuclear magnetic resonance spectroscopy ((13)C NMR). And the optimal reaction conditions were also studied by means of single factor experiment. MTT method was applied to evaluate the effects of CMCS on proliferation of skin fibroblasts. The results revealed the CMCS with sulfate content of 26.26% at the concentration of 100 µg/ml best promoted the proliferation of skin fibroblasts.