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Echanism and thinking of Masquelet induced membrane technique in diabetic wound
Tao Ke, Cao Tao, Shao Luocheng
, Available online  , doi: 10.3760/cma.j.cn501225-20251125-00487
Abstract:
Diabetic wounds are hindered in the healing process due to chronic inflammation caused by the high sugar microenvironment, vascularization disorder, and imbalance in the secretion of growth factors. Masquelet induced membrane technique creates a bioactive membrane composed of various cellular components and rich in growth factors and microvessels by implanting bone cement into the wound. The membrane mainly promotes wound healing by remodeling the inflammatory microenvironment, promoting functional angiogenesis, and producing endogenous growth factors. This article briefly explains the mechanism by which the induced membrane technology improves wound healing and summarizes its clinical application in diabetic wounds. It is expected to provide new ideas and effective means for the clinical treatment of difficult-to-heal diabetic wounds. Future research needs to focus on the key molecular pathways of induced membrane therapy and the development of new membrane induction materials, so as to provide new strategies for the treatment of diabetic wounds.
Mechanism of Wnt9a regulating fibroblast function to promote chronic wound healing
Jia Yanhui, Yuan Yixuan, Hu Dahai, Guan Hao
, Available online  , doi: 10.3760/cma.j.cn501225-20241122-00457
Abstract:
  Objective  To investigate the expression changes, role, and its possible mechanism of Wnt9a in chronic wound healing.  Methods  This study was a group-designed experimental research.The chronic wound tissue and adjacent normal skin tissue were collected from 8 patients with diabetic foot ulcers, including 5 males and 3 females, aged 45-72 years. The expression of Wnt9a was detected by enzyme-linked immunosorbent assay (ELISA) method and immunofluorescence method. Eight male C57BL/6 mice aged 6-8 weeks were used to establish a full-thickness skin defect wound on the back and were divided into control group with no additional treatment and chronic wound group subcutaneously injected with M1 macrophage derived exosomes at the wound edge to construct a chronic wound model using a random number table method (the same grouping method below), with 4 mice in each group. At 7 days after modeling, the Wnt9a expressions in the wound tissue of mice in two groups was detected by ELISA method. Additional 16 male C57BL/6 mice aged 6-8 weeks were used to establish the chronic wound model as before and were divided into blank control group and Wnt9a overexpression group, with 8 mice in each group, which were injected subcutaneously at the wound edge with enhanced green fluorescent protein empty adenovirus (AV-eGFP) and Wnt9a gene recombinant adenovirus expressing enhanced green fluorescent protein (AV-Wnt9a-eGFP), respectively. At 3, 7, and 14 days after modeling, the percentages of residual wound area were calculated; at 14 days after modeling, the expressions of type Ⅰ and type Ⅲ collagen protein were detected by Western blotting. The collected human normal skin tissue was used to extract fibroblasts (Fbs), which were divided into empty control group infected with AV-eGFP and Wnt9a overexpression group infected with AV-Wnt9a-eGFP. The protein expression of Wnt9a at 72 h after infection was detected by Western blotting, and the cell migration rate at 48 h after scratching was detected by scratch test. Additional human normal skin Fbs were collected and divided into Wnt9a specific small interfering RNA (siRNA-Wnt9a) group and negative control small interfering RNA (siRNA-NC) group, which were transfected with corresponding small interfering RNA (siRNA). Scratch test was conducted to detect the cell migration rate at 48 h after scratching. Additional human normal skin Fbs were taken and divided into empty control group and Wnt9a overexpression group treated as before. At 72 h after infection, transcriptome sequencing was performed to screen for differentially expressed genes (DEGs); the gene ontology (GO) and Kyoto encyclopedia of genes and genomes enrichment analysis were performed on DEGs. The sample number in all cell experiments was 3.  Results  The results of ELISA method and immunofluorescence method showed that the expression level of Wnt9a in human chronic wound tissue was significantly lower than that in normal skin tissue (with t values of 7.68 and 10.25, respectively, P<0.05). At 7 days after modeling, the expression level of Wnt9a in the wound tissue of mice in chronic wound group was significantly lower than that in control group (t=5.12, P<0.05). The percentages of residual wound area of mice in Wnt9a overexpression group were significantly lower than those in empty control group at 3, 7, and 14 days after modeling (with t values of 3.90, 6.62, and 5.73, respectively, P<0.05). At 14 days after modeling, the protein expression levels of type Ⅰ and type Ⅲ collagen in the wound tissue of mice in Wnt9a overexpression group were significantly lower than those in empty control group (with t values of 6.25 and 5.48, respectively, P<0.05). The Wnt9a protein expression level in Fbs in Wnt9a overexpression group was significantly higher than that in empty control group (t=6.96, P<0.05). At 48 h after scratching, the cell migration rate in Wnt9a overexpression group was (71.6±6.4)%, which were significantly higher than (38.5±2.4)% in empty control group (t=8.31, P<0.05). The cell migration rate in siRNA-Wnt9a group was (15±3)%, which were significantly lower than (32±4)% in siRNA-NC group (t=5.93, P<0.05). At 72 h after infection, compared with that in empty control group, the significantly downregulated DEGs in Fbs in Wnt9a overexpression group included multiple collagen family genes, and DEGs in Fbs in Wnt9a overexpression group were significantly enriched in the non-classical Wnt signaling pathway.  Conclusions  Wnt9a expression is downregulated in chronic wound tissue of human and mice, and the overexpressed Wnt9a may promote migration of Fbs and collagen remodeling through non-classical Wnt signaling pathway, thereby accelerating chronic wound healing.
Clinical application effects of the "three-source and four-line method" in the design and harvest of anterolateral lower leg perforator flaps
Wu Chenglong, Zhang Yan, Cheng Junnan, Liu Yucheng, Cao Yang, Wang Guiyang, Wang Shi, Dong Shuai, Liu Yuefei, Ju Jihui
, Available online  , doi: 10.3760/cma.j.cn501225-20250328-00148
Abstract:
  Objective  To explore the clinical application effects of the "three-source and four-line method" in the design and harvest of anterolateral lower leg perforator flaps.  Methods  This study was a retrospective study of case series. From August 2023 to July 2024, the patients with hand or foot wounds who met the inclusion criteria were admitted to Suzhou Ruihua Orthopedic Hospital, including 24 patients from the Department of Hand Surgery and 6 patients from the Department of Foot and Ankle Surgery. There were 22 males and 8 females, aged 18 to 58 years. After debridement, the single wound area ranged from 2.0 cm×1.5 cm to 15.0 cm×4.5 cm. By applying the "three-source and four-line method", the line connecting the fibular head and the tip of the lateral malleolus was defined as Line C, representing the surface landmark line of the fibula; Line B was defined as Line C shifted 1.5 cm anteriorly, representing the axis of the superficial peroneal artery perforator flap; Line A was defined as Line C shifted 3.0 cm anteriorly, representing the axis of the anterior tibial artery perforator flap; Line D was defined as Line C shifted 1.5 cm posteriorly, representing the axis of the peroneal artery perforator flap. Then the color Doppler ultrasound detector was employed to identify perforators from the three vascular origins along Lines A, B, and D, respectively. Accordingly, anterolateral lower leg perforator flaps were designed and harvested to repair the wounds. A total of 35 flaps were harvested, with the single flap area ranging from 2.5 cm×2.0 cm to 16.0 cm×5.0 cm. All the donor site wounds were closed by direct suturing. During surgery, the total number of actually used perforators, as well as the number, caliber, and vascular pedicle length of perforators from different sources were recorded; the vertical distances from the perforators' skin entry points to their corresponding axes were measured. After surgery, flap survival was observed. During follow-up, the color, texture, and appearance of the flaps and the scar condition of donor sites were recorded. At the final follow-up, the flap repair outcome was evaluated using the flap comprehensive rating scale, and the excellent and good rate of flap repair outcome was calculated.  Results  During surgery, a total of 38 perforators were actually used. Among them, 6 perforators originated from the anterior tibial artery, with a mean caliber of 0.47 mm, a mean vascular pedicle length of 4.33 cm, and a mean vertical distance from the perforators' skin entry point to the Line A of 0.48 cm. Twenty perforators originated from the superficial peroneal artery, with a mean caliber of 0.51 mm, a mean vascular pedicle length of 5.25 cm, and a mean vertical distance from the perforators' skin entry point to the Line B of 0.54 cm. Twelve perforators originated from the peroneal artery, with a mean caliber of 0.72 mm, a mean vascular pedicle length of 4.13 cm, and a mean vertical distance from the perforators' skin entry point to the Line D of 0.43 cm. After surgery, all flaps survived smoothly. Follow up for 6-15 months showed the flaps exhibited favorable color, soft texture, and no obvious bulkiness; only linear scars were left at the donor sites. At the final follow-up, the scores of flap comprehensive rating scale ranged from 82 to 94 points and the excellent and good rate of flap repair outcome was 100% (35/35).  Conclusions  The "three-source and four-line method" has the advantages of simple operation and accurate perforator localization. It is helpful for flexible preoperative design and safe intraoperative harvest of the anterolateral lower leg perforator flaps with high clinical application value.
Comparison of the predictive efficacy of the Wagner, SINBAD, and WIfI grading systems for short-term wound non-healing and amputation in patients with diabetic foot ulcers
Xu Zihui, Duan Weizhe, Xie Weiguo, Tan Qin, Fu Xiuli, Wang Pei, Li Na, Liu Saiji, Xu Jinling, Wang Zhongjing
, Available online  , doi: 10.3760/cma.j.cn501225-20251129-00494
Abstract:
  Objective  To compare the predictive efficacy of the Wagner grading system, site, ischemia, neuropathy, bacterial infection, area, depth (SINBAD) grading system, and wound, ischemia and foot infection (WIfI) grading system for short-term wound non-healing and amputation in patients with diabetic foot ulcers (DFUs).  Methods  This study was a retrospective study of case series. From January 2023 to December 2024, 400 patients with DFUs who met the inclusion criteria were admitted to the Diabetic Foot Center of the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology. All patients were assessed with Wagner grade, SINBAD score, and WIfI stage within 48 hours of admission. There were 232 males and 168 females, aged 44 to 84 years. Based on whether the wound had healed at 3 months after the first hospitalization, patients were divided into healing group (194 cases) and non-healing group (206 cases); based on amputation, patients who underwent major or minor amputation were included in amputation group (255 cases), while the remaining patients were included in non-amputation group (145 cases); the Wagner grades, SINBAD scores, and WIfI stages of patients in each group were recorded. The amputation and non-healing wound at 3 months after the first admission in patients with different Wagner grades, SINBAD scores, or WIfI stages were compared. Spearman correlation analysis was used to assess the correlation between the Wagner grades, SINBAD scores, WIfI stages and the wound healing time in patients with DFUs. The receiver operating characteristic curves were plotted to evaluate the predictive efficacy of each grading system for non-healing wound at 3 months after the first admission and amputation in patients with DFUs, and the DeLong test was used to compare the differences in the area under the receiver operating characteristic curve (AUROC) among the grading systems.  Results  The patients in non-healing group and amputation group had significantly higher Wagner grades, SINBAD scores, and WIfI stages than those in healing group and non-amputation group, respectively (with t values of 8.25, 19.78, and 9.87, 14.05, 11.73, and 16.45, P<0.05). There were statistically significant differences among the numbers of patients who underwent amputation and the numbers of patients with non-healing wounds at 3 months after the first admission in patients with different Wagner grades, SINBAD scores, or WIfI stages (with χ2 values of 150.35 and 73.97, 133.84 and 221.10, 187.63 and 83.37, P<0.05). The Wagner grades, SINBAD scores, and WIfI stages were all significantly positively correlated with the wound healing time in patients with DFUs (with rs values of 0.52, 0.70, and 0.52, respectively, P<0.05). With wounds unhealed at 3 months after the first admission as the prognostic outcome, the SINBAD grading system had the highest AUROC of 0.96 (with 95% CI of 0.94-0.98) and a maximum Youden index of 0.80; the Wagner grading system showed an AUROC of 0.66 (with 95% CI of 0.61-0.72) and a maximum Youden index of 0.28; the WIfI grading system showed an AUROC of 0.69 (with 95% CI of 0.64-0.74) and a maximum Youden index of 0.33. The DeLong test indicated that the predictive efficacy of the SINBAD grading system for short-term wound non-healing in patients with DFUs was significantly superior to that of the Wagner grading system and WIfI grading system (with Z values of 12.52 and 12.97, P values both <0.05). With amputation as the prognostic outcome, the WIfI grading system had the highest AUROC of 0.89 (95% CI 0.85-0.93) and a maximum Youden index of 0.75; the Wagner grading system showed an AUROC of 0.87 (with 95% CI of 0.83-0.91) and a maximum Youden index of 0.55; the SINBAD grading system showed an AUROC of 0.80 (with 95% CI of 0.76-0.84) and a maximum Youden index of 0.43. The DeLong test showed that the predictive efficacy of both the WIfI grading system and Wagner grading system for amputation in patients with DFUs was significantly superior to that of the SINBAD grading system (with Z values of 3.76 and 2.96, P<0.05).  Conclusions  The Wagner grading system, SINBAD grading system, and WIfI grading system can all effectively predict the risk of short-term wound non-healing and amputation in patients with DFUs. The SINBAD grading system performs the best in predicting short-term wound non-healing, while the WIfI grading system has an advantage in predicting amputation. Although the Wagner grading system has poorer predictive efficacy for short-term wound non-healing, it still demonstrates good predictive efficacy for amputation. In clinical practice, different grading systems can be used in combination based on the focus of assessment.
Epidemiological characteristics of adult inpatients with diabetes-related chronic non-healing wounds in Hainan province
Yao Jiangling, Li Jiaxuan, Ming Xingchen, Gu Yuntao, Jiang Tao, Yang Jian, Bian Yangyang, Zheng Linyang, Wang Rong, Zeng Yunfu, Cheng Shaowen
, Available online  , doi: 10.3760/cma.j.cn501225-20250606-00257
Abstract:
  Objective  To analyze the epidemiological characteristics of adult inpatients with diabetes-related chronic non-healing wounds in Hainan province.  Methods  This study was a retrospective cohort study. From July 2019 to July 2024, 1 372 adult inpatients with diabetes-related chronic non-healing wounds and conformed to the inclusion criteria were admitted to three hospitals in Hainan Province, including 951 cases in the First Affiliated Hospital of Hainan Medical University, 287 cases in the Second Affiliated Hospital of Hainan Medical University, and 134 cases in Hainan Sino-German Orthopedic Hospital. The patients aged 18-96 years, with 889 males and 483 females. The medical records of patients were collected, including age, gender, occupation, type and disease duration of diabetes mellitus, comorbidities, formation causes, locations, types, and number of wounds, pathogen culture results of wound secretion specimens, treatment modalities and outcomes, and hospitalization duration and hospitalization costs of patients with different types of wounds.  Results  The majority of patients was ≥60 years old, males, and agricultural workers. Most of patients had type 2 diabetes mellitus, with disease duration of diabetes mellitus of 10 (5,18) years. Patients with diabetes mellitus were often combined with hypertension (678 cases), arterial disease (300 cases), and stroke (220 cases). The primary cause of wound formation was infection. The predominant type of wounds was diabetic foot ulcer (809 cases), followed by other wounds (232 cases), pressure ulcers (187 cases), and traumatic ulcers (144 cases). The wounds were primarily located on foot and lower legs with single wound. The results of pathogen culture of wound secretion specimens from 540 patients were positive, with a total of 606 strains of pathogens detected, predominantly Gram-negative bacteria (324 strains). The main pathogens were Staphylococcus aureus (125 strains), Pseudomonas aeruginosa (71 strains), and Escherichia coli (71 strains). Fungal detection ration was high of 6.11% (37/1 372). Treatment modalities primarily included simple debridement and debridement combined with vacuum sealing drainage. After treatment, the wounds in 84.62% (1 161/1 372) patients showed improvement, 11.30% (155/1 372) patients achieved wound healing, 3.28% (45/1 372) patients experienced wound exacerbation, and 0.80% (11/1 372) patients died. Patients with diabetic foot ulcer exhibited significantly longer hospitalization duration (18 (10, 29) d) and higher hospitalization costs (3.9 (2.1, 6.0) ten thousand yuan) compared with the pressure ulcer (14 (7, 21) d and 2.8 (1.5, 4.2) ten thousand yuan), the traumatic ulcer (12 (6, 18) d and 2.3 (1.2, 3.5) ten thousand yuan), and other wounds (16 (8, 25) d and 3.1 (1.8, 5.0) ten thousand yuan), (P<0.05).  Conclusions  The adult inpatients with diabetes-related chronic non-healing wounds in Hainan province are predominantly elderly male agricultural workers with comorbidities. The detected predominant pathogens in wounds are Gram-negative bacteria, and fungal detection ratio is high. Diabetic foot ulcers pose greater treatment burden, and patients with diabetic foot ulcers had significantly longer hospitalization duration and higher hospitalization costs compared with those of other wounds.
Medium- and long-term clinical efficacy of tibial transverse transport in the treatment of diabetic foot ulcers
Liu Siwen, Jia Zhongwei, Zhang Zihang, Guo Zhao, Zhang Xiangxiang, Luo Qian
, Available online  , doi: 10.3760/cma.j.cn501225-20241028-00417
Abstract:
  Objective  To investigate the medium- and long-term clinical efficacy of tibial transverse transport (TTT) in the treatment of diabetic foot ulcers (DFU).  Methods  This study was a retrospective cohort study. From January 2015 to December 2022, 87 patients with diabetic foot ulcers who met the inclusion criteria were admitted to the Department of Orthopedics of Shanxi Provincial People's Hospital and were treated with TTT. Due to amputation, death, or loss to follow-up of patients, the number of cases was 85, 82, 77, 73, and 62 at 3 months, 6 month, 1 year, 2 years, and 3 years postoperatively. The ankle brachial index (ABI), Michigan Neuropathy Screening Instrument (MNSI) physical examination score, 10 g monofilament test results, visual analogue scale (VAS) score, toe oxygen saturation was recorded preoperatively and at 1 month, 3 months, 6 months, 1 year, 2 years, and 3 years postoperatively. The occurrence of complications, wound healing, and amputation were recorded during 3 years postoperatively.  Results  The levels of ABI were 0.70 (0.65, 0.76), 0.93 (0.83, 1.01), 0.96 (0.86, 1.06), 0.93 (0.88, 1.01), 0.91 (0.86, 0.97), and 0.90 (0.81, 0.97) at 1 month, 3 months, 6 months, 1 year, 2 years, and 3 years postoperatively, which were significantly higher than 0.55 (0.47, 0.62) preoperatively (P<0.05). At 1 month, 3 months, 6 months, 1 year, 2 years, and 3 years postoperatively, the 10 g monofilament test scores were significantly more than those preoperatively (P<0.05), the VAS scores and MNSI physical examination scores were significantly lower than those preoperatively (P<0.05), and the levels of toe oxygen saturation were significantly higher than those preoperatively (P<0.05). During 3 years postoperatively, 3 patients experienced fractures at the bone transport site, and 4 patients developed infections at the pin tract and incision, all of whom recovered with conservative treatment. The wounds healed in 80 patients, and limbs were salvaged in 80 patients.  Conclusions  Patients with DFU and treated with TTT can significantly improve lower limb blood supply and foot microcirculation, alleviate pain, and enhance nerve conduction function and foot sensation, with few complications and remarkable results in wound healing and limb salvage. Besides, the overall efficacy within 3 years postoperatively was good.
Clinical application effects of the "novel three-vertical five-horizontal method" for perforator localization in anterolateral thigh chimeric flaps
Wu Xiangkui, Li Hai, Wu Bihua, Wei Zairong, Deng Chengliang
, Available online  , doi: 10.3760/cma.j.cn501225-20240520-00188
Abstract:
  Objective  To evaluate the clinical application effects of the "novel three-vertical five-horizontal method" for perforator localization in anterolateral thigh chimeric flaps.  Methods  This study was a retrospective study of case series. From June 2021 to June 2023, 15 patients with destructive limb wounds who met the inclusion criteria were admitted to the Affiliated Hospital of Zunyi Medical University. The wounds were located on the upper limbs in 5 cases and the lower limbs in 10 cases, with a post-debridement area ranging from 12 cm×5 cm to 22 cm×7 cm. The "novel three-vertical five-horizontal method" was employed. The anterior superior iliac spine was defined as Point P, the superolateral border of patella was defined as Point A, and the lateral femoral epicondyle was defined as Point B, then Lines PA and PB were drawn, respectively. The point C, the midpoint between Point A and Point B, was connected with Point P to form line PC. A perpendicular line was drawn from the midpoint of Line PA as Line E. Line E was translated 5 cm proximally to form Line D, while Lines F, G, and H were drawn 5, 10, and 15 cm distally, respectively. The intersections of Lines PA and PB with Lines D, E, F, G, and H were defined as Zones Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. These zones served as the guide for designing and harvesting the anterolateral thigh chimeric flaps to repair the wounds. The area of harvested flap ranged from 13.0 cm×6.0 cm to 23.0 cm×8.0 cm. The donor site wounds were closed directly. During surgery, the number and origin of perforators observed in each zone, as well as the vertical distance from the perforator's skin entry point to Line PC, were recorded. After surgery, flap survival was observed. During follow-up, the color, texture, appearance, and occurrence of complications of flaps were observed.  Results  During surgery, a total of 75 perforators was identified. Their distribution by zone was as follows: 18 perforators in Zone Ⅰ (3 originating from the oblique branch of anterolateral thigh artery and 15 originating from the descending branch of anterolateral thigh artery), 17 perforators in Zone Ⅱ (all originating from the descending branch of anterolateral thigh artery), 21 perforators in Zone Ⅲ (all originating from the descending branch of anterolateral thigh artery), and 19 perforators in Zone Ⅳ (12 originating from the descending branch of anterolateral thigh artery and 7 originating from the peripheral vessels in distal thigh). The 24 perforators' skin entry points were located directly on Line PC, while 51 perforators' skin entry points were located adjacent to it, with the vertical distances to Line PC all less than 1.0 cm. After surgery, one patient developed distal flap bruising, and two patients had minor exudation at the flap margin, which all healed after dressing change. The flaps in the remaining patients survived smoothly. During the follow-up period of 6 to 40 months, all flaps demonstrated favorable color, texture, and appearance, with no complications observed; the scars in donor sites were mild, with no muscle herniation.  Conclusions  The "novel three-vertical five-horizontal method" method can effectively locate anterolateral thigh chimeric flap perforators. The method is simple and reliable. The anterolateral thigh chimeric flaps designed and harvested based on this method have good clinical effect in repairing destructive limb wounds, which is worthy of promotion.
A compulsory course in clinical treatment in burn patients: pain and analgesia
Nie Fachuan
, Available online  , doi: 10.3760/cma.j.cn501225-20251014-00428
Abstract:
Based on the advancements in anesthesiology and pain medicine in recent years in addressing acute and chronic pain, this article expounds on the issues of pain and analgesia in burn clinical practice and provides systematic recommendations. It introduces knowledge related to neuropathic pain in burn patients, the risks and strategies of deep analgesia and sedation, as well as the respective advantages and disadvantages of non-steroidal anti-inflammatory drugs and opioids. Special emphasis is placed on the specificity of pain management in elderly and pediatric patients. A relatively specific implementation plan is proposed for the construction of a " pain-free burn unit," which is an important issue that benefits both patients and facilitates the development of the discipline.
Effects of polyvinyl alcohol-boric acid-based functionalized hydrogels on human skin fibroblasts and HaCaT cells
Song Wei, Zhang Chao, Kong Yue, He Muchun, Ren Kehao, Li Kejia, Li Zhao, Yu Bingyang, Tian Feng, Zhu Meng, Ju Xiaoyan, Tian Ye, Huang Sha, Niu Zhongwei
, Available online  , doi: 10.3760/cma.j.cn501225-20250825-00365
Abstract:
  Objective  To investigate the effects of polyvinyl alcohol-boric acid (PVA-BA)-based functionalized hydrogels on human skin fibroblasts (HSFs) and HaCaT cells, providing experimental evidences for subsequent in vivo studies on wound repair and clinical translation of this hydrogel system.  Methods  This study was designed as a grouped and factorial experimental investigation. Based on PVA-BA, a freeze-thaw cycling method was employed to prepare PVA-BA hydrogel, PVA-BA-S hydrogel loaded with a final molarity of 5 μmol/L SB431542, and PVA-BA-B hydrogel loaded with a final molarity of 1 μmol/L BML-284. Fourier transform infrared spectroscopy and X-ray diffraction were employed to characterize the characteristic absorption peaks and diffraction patterns of the above-mentioned hydrogels. The drug release of PVA-BA-S hydrogel and PVA-BA-B hydrogel in phosphate-buffered saline (PBS) with pH values of 5.5 and 7.4 was detected using a liquid chromatography, and the cumulative drug release rate at 48 hours of immersion was calculated. According to the random number table method, HSFs were divided into control group with conventional culture, activation-only group with conventional culture after treatment with recombinant human transforming growth factor-β1 (TGF-β1) protein for 24 hours, as well as PVA-BA group and PVA-BA-S group cultured with PVA-BA hydrogel extract and PVA-BA-S hydrogel extract, respectively, after treatment with recombinant human TGF-β1 protein for 24 hours. After 24 hours of culture, mRNA expression levels of TGF-β pathway-related factors α-smooth muscle actin (α-SMA), TGF-β, Smad2, Smad3, type Ⅰ collagen (COL Ⅰ), COL Ⅲ in HSFs were detected using real-time fluorescence quantitative reverse transcription polymerase chain reaction. Protein expression levels of COL Ⅰ and COL Ⅲ in HSFs were assessed via the immunofluorescence method. According to the random number table method, HaCaT cells were divided into control group with conventional culture, PVA-BA group cultured with PVA-BA hydrogel extract, and PVA-BA-B group cultured with PVA-BA-B hydrogel extract. After 24 hours of culture, mRNA expression levels of Wnt pathway-related factors β-catenin, matrix metalloproteinase-9 (MMP-9), E-cadherin, N-cadherin in HaCaT cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. The protein expression level of keratin 5 was evaluated by the immunofluorescence method. Except for characterization, the sample size for each experiment was 3.  Results  The Fourier transform infrared spectroscopy spectra of the PVA-BA hydrogel, PVA-BA-S hydrogel, and PVA-BA-B hydrogel all exhibited stretching vibration peaks corresponding to C-O and B-O bonds within the B-O-C group at wavenumbers of 1 100 and 1 450 cm⁻¹, and X-ray diffraction patterns all showed a sharp diffraction peak at around 20°. At 48 hours of immersion, the cumulative drug release rate of PVA-BA-S hydrogel in PBS at pH 5.5 was (70.9±2.3)%, which was significantly higher than (60.0±2.2)% in PBS at pH 7.4 (t=6.02, P<0.05); the cumulative drug release rate of PVA-BA-B hydrogel in PBS at pH 5.5 was (83.9±2.2)%, which was significantly higher than (65.2±1.7)% in PBS at pH 7.4 (t=11.63, P<0.05). After 24 hours of culture, the mRNA expression levels of TGF-β, COL Ⅰ, COL Ⅲ, and Smad3 of HSFs in PVA-BA-S group were significantly higher than those in control group (P<0.05), the mRNA expression levels of TGF-β, COL Ⅰ, COL Ⅲ, α-SMA, Smad2, and Smad3 were significantly lower than those in activation-only group and PVA-BA group (P<0.05), and the protein expression levels of COL Ⅰ and COL Ⅲ of HSFs in PVA-BA-S group were significantly lower than those in activation-only group and PVA-BA group (P<0.05). After 24 hours of culture, compared with those in control group and PVA-BA group, the PVA-BA-B group showed significantly increased mRNA expression levels of β-catenin, MMP-9, and N-cadherin (P<0.05) and a significantly decreased mRNA expression level of E-cadherin (both P values <0.05) in HaCaT cells; the protein expression level of keratin 5 of HaCaT cells in PVA-BA-B group was significantly higher than that in control group and PVA-BA group (both P values <0.05).  Conclusions  PVA-BA-S hydrogel and PVA-BA-B hydrogel based on the PVA-BA can effectively inhibit the fibrotic phenotype of activated HSFs and enhance the migratory ability of HaCaT cells by regulating the TGF-β pathway and Wnt pathway, respectively, providing a novel drug delivery strategy for functional wound healing.
Efficacy of turbocharged medial sural artery perforator flap in repairing skin and soft tissue defects of hands and feet
Zhang Yan, Jin Guangzhe, Cao Yang, Wu Chenglong, Wang Guiyang, Wang Shi, Dong Shuai, Zhang Yuji, Liu Yucheng, Ju Jihui
, Available online  , doi: 10.3760/cma.j.cn501225-20241029-00419
Abstract:
  Objective  To explore the efficacy of turbocharged medial sural artery perforator flap in repairing skin and soft tissue defects of hands and feet.  Methods  This study was a retrospective case series study. From September 2022 to November 2023, 12 patients with skin and soft tissue defects of hands and feet who met the inclusion criteria were admitted to Suzhou Ruihua Orthopaedic Hospital, including 8 males and 4 females, aged 32-69 years. After debridement, the wound defect area ranged from 5.5 cm×3.5 cm to 13.5 cm×5.5 cm. The defects were repaired with turbocharged medial sural artery perforator flaps with an area of 6.0 cm×4.0 cm to 14.0 cm×6.0 cm, and the donor site wounds were directly closed by suturing. The flap harvesting status, postoperative survival, occurence of vascular crisis, and healing of donor site wounds were recorded. During follow-up, the appearance and texture of the flaps, as well as the scarring and pain of the donor site wounds were observed. At the last follow-up, a comprehensive evaluation scale was used to assess the flap transplantation effect, and the British Medical Research Council sensory function grading standard was adopted to evaluate the sensory function of the flaps.  Results  All flaps were harvested successfully and survived well postoperatively without vascular crisis; all donor site wounds healed smoothly. Follow-up for 6-15 months showed that the flaps had a good appearance and excellent texture, and the donor site wounds only were left with linear scars without scar contracture, pain, or other discomfort. At the last follow-up, 9 cases were rated as excellent and 3 cases as good in terms of flap transplantation effect; the sensory function of the flaps was graded as grade S1 in 1 case, grade S2 in 8 cases, and grade S3 in 3 cases.  Conclusions  The application of turbocharged medial sural artery perforator flap for repairing skin and soft tissue defects of hands and feet achieves good postoperative appearance and function recovery of both donor and recipient sites, making it one of the effective repair methods of this kind of defect.
Effects of sequential treatment of diabetic calcaneal osteomyelitis wounds with antibiotic bone cement and VSD combined with free chimeric anterolateral thigh perforator myocutaneous flaps
Zhong Yuhui, Cui Xu, Zhou Situo, Guo Le, Huang Mitao, He Zhiyou, Yang Haolin, Zeng Jizhang, Liang Pengfei, Zhang Pihong, Zhou Jie
, Available online  , doi: 10.3760/cma.j.cn501225-20251129-00493
Abstract:
  Objective  To explore the effect of sequential treatment of diabetic calcaneal osteomyelitis wounds with antibiotic bone cement and vacuum sealing drainage (VSD) combined with free chimeric anterolateral thigh perforator myocutaneous flaps.  Methods  This study was a retrospective case series study. From June 2019 to June 2024, 12 patients with diabetic calcaneal osteomyelitis wounds meeting the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University, including 7 males and 5 females, aged 40 to 65 years. There were 8 cases of Wagner grade Ⅲ wounds and 4 cases of Wagner grade Ⅳ wounds. In stage Ⅰ, debridement+temporary antibiotic bone cement filling and coverage+VSD treatment was performed, in which the wound area after debridement was 6 cm×5 cm to 18 cm×8 cm, and the bone defect volume was 1.0 cm×0.8 cm×0.5 cm to 1.8 cm×1.5 cm×0.8 cm. In stage Ⅱ, free chimeric anterolateral thigh perforator myocutaneous flaps were used to repair the wounds, in which the area of the perforator flap was 10.0 cm×5.0 cm to 20.0 cm×10.0 cm, and the area of the muscle flap was 3.0 cm×2.5 cm to 7.0 cm×6.0 cm. The wound at the flap donor site was directly sutured or repaired by split-thickness skin graft from the thigh. The white blood cell count, neutrophil, high-sensitivity C-reactive protein level, and microbial culture of wound secretion specimens at admission and 7 days after stage Ⅰ treatment, and the growth of wound bed granulation tissue 7 days after stage Ⅰ treatment were recorded. After stage Ⅱ surgery, the flap survival and the wound healing in the donor and recipient areas were observed. During follow-up, the blood supply, appearance, and texture of the recipient area flaps, whether ulcers and osteomyelitis recurred, the recovery of the donor areas, and the function of the affected limbs were observed.  Results  Seven days after stage Ⅰ treatment, the white blood cell count, neutrophil, and high-sensitivity C-reactive protein level of the patients were 7.15 (6.73, 8.70)×10⁹/L, 0.65 (0.63, 0.72), and 15.50 (12.48, 25.50) mg/L, respectively, which were significantly lower than 12.30 (11.28, 13.48)×10⁹/L, 0.80 (0.78, 0.83), and 73.20 (57.25, 93.75) mg/L at admission (with Z values of -2.905, -2.825, and -3.059, respectively, P values all <0.05). At admission, the microbial culture results of the wound secretion specimens were all positive, and the redness and swelling around the wound were obvious; 7 days after stage Ⅰ treatment, the microbial culture results of the wound secretion specimens were all negative, there was no obvious redness or swelling around the wound, and the wound bed granulation tissue grew well. After stage II surgery, only two patients had a small area of ischemic epidermal necrosis at the distal end of the flap, and the wounds achieved delayed healing after dressing changes; the flaps of the other patients all survived well and the wounds in the recipient areas all healed smoothly; the donor area wounds of all patients healed well. Follow-up for 6 to 18 months showed that the blood supply and appearance of the flaps were good, and the texture was soft; no recurrence of ulcers was observed, and no obvious signs of recurrence of osteomyelitis were shown by X-ray examination; the donor areas recovered well without obvious scar hyperplasia, and the affected limbs were all able to perform weight-bearing activities.  Conclusions  Sequential repair of diabetic calcaneal osteomyelitis wounds with antibiotic bone cement and VSD combined with free chimeric anterolateral thigh perforator myocutaneous flaps, on the basis of thorough removal of infected lesions, achieves effective closure of deep calcaneal dead space and soft tissue coverage. The short-term follow-up effect is good, and it is worthy of clinical promotion.