High glucose-induced vascular endothelial cell injury serves as a primary pathological factor contributing to delayed healing of diabetic wounds. Effective wound vascularization remains a core challenge in tissue engineering research. Hydrogel-based injectable technology and three-dimensional (3D) bioprinting technology, through synergistic innovation of biomaterials and advanced manufacturing processes, enable precise construction of bionic tissue structures, laying the foundation for functional organ replacement. This review focuses on discussing the synergistic strategies of injectable hydrogels and 3D bioprinted hydrogels in tissue engineering vascularization, as well as the clinical translation of intraoperative bioprinting and its synergistic vascularization strategies, which is currently in urgent need of development. These advancements are expected to provide novel strategies for the repair of diabetic wounds.

Effective scar prevention and treatment remain a clinical challenge in the field of surgery, while concept innovation and technological progress will be the key to making the breakthrough. Although tissue remodeling is an important part of wound healing process, natural healing often results in scar formation. The fundamental reason is that the natural tissue remodeling is not effective enough. The author proposes that the strategy of interventional tissue remodeling can be used for scar prevention and treatment. This strategy involves artificially interfering the wound healing process using various feasible means such as laser and microplasma therapy, drugs, bioactive molecules as well as tissue regenerative methods. Therefore, the natural wound healing process can be transformed towards the process of tissue regeneration to a certain extent. As a result, it is likely to achieve better tissue remodeling effect that is not possible by the natural remodeling process. Based on reported literature and the author's own clinical experience, this article reviews the feasible application areas of interventional tissue remodeling strategies in the field of scar prevention and treatment along with clinical evidence of case report, and hopes to draw attention from peer colleagues to this clinical challenge in order to establish such an effective strategy with further clinical validation by additional evidence.

Objective:To explore the clinical effect of applying above-knee medial free-style perforator propeller flap in repairing deep wounds in and around the knee joint.Methods:This study was a retrospective observational study. From December 2020 to October 2023, the Department of Burns and Cutaneous Surgery of the First Affiliated Hospital of Air Force Medical University admitted 13 patients who met the inclusion criteria and had deep burn wounds in and around the knee joints, including 9 males and 4 females, aged 16-70 years. After debridement, the sizes of skin and soft tissue defects ranged from 5.0 cm×4.0 cm to 9.0 cm×7.0 cm. A free-style perforator propeller flap was designed and harvested from the medial supragenicular region, using a perforator vessel as the pedicle. The size of the flap ranged from 6.0 cm×4.0 cm to 15.0 cm×7.0 cm. The larger paddle of the flap was used to repair the wound in and around the knee joint, while the smaller paddle assisted in closing the donor site wound. After surgery, the survival status of the flap, wound healing at the donor and recipient sites, and complications such as infection, effusion, and necrosis were observed. During the follow-up, the appearance, color, and texture of the flap as well as the wound healing, scar contracture, and knee joint mobility at the recipient site were observed, and the scar condition, sensory recovery, and complications at the donor site were recorded.Results:Postoperatively, all 13 patients achieved successful flap survival. In one case, infection occurred at the edge of the flap but healed after appropriate treatment including drainage and dressing changes, and the donor site wound healed well; the remaining 12 patients showed uneventful healing at both donor and recipient sites without complications. During follow-up of 5 to 24 months, all 13 patients exhibited natural appearance, normal skin color, soft texture, and good elasticity. The recipient site wounds healed well without scar contracture or deformity, with full range of motion in the knee joint. A mild linear scar remained at the donor site on the inner thigh, with normal sensory function and no numbness.Conclusions:The above-knee medial free-style perforator propeller flap demonstrates simple harvest with minimal trauma for repairing deep wounds in and around the knee joint, providing satisfactory aesthetic and functional outcomes at both donor and recipient sites.

Objective:To explore the clinical efficacy of layered thinning superficial circumflex iliac artery perforator (SCIP) flap based on color Doppler ultrasound (CDU) positioning.Methods:The study was a retrospective observational study. From February 2023 to February 2024, 14 patients who met the inclusion criteria were admitted to the Department of Hand Surgery of Beijing Jishuitan Hospital Affiliated to Capital Medical University, including 11 males and 3 females, aged 15 to 60 years. The wound area was from 7 cm×4 cm to 14 cm×11 cm. Before the flap transplantation surgery, CDU was used to accurately locate the deep fascial exit point of the superficial branch of the superficial circumflex iliac artery. During the surgery, the SCIP flap was thinned in layers to repair the hand and forearm wounds of 11 patients and foot wounds of 3 patients. The flap incision area ranged from 8 cm×5 cm to 15 cm×12 cm. The donor area wounds of flaps were sutured directly. During the surgery, the deep fascial exit point of the superficial branch of the superficial circumflex iliac artery in the flap donor area was observed and compared with the result of CDU positioning before the surgery, and the flap thickness was measured. The flap survival and occurrence of adverse reactions were observed after the surgery. During follow-up, the appearance and texture of flaps, and the wound healing in the donor area was observed. At the last follow-up, the function of the wrist and hand in the affected limbs was evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association, and the function of the foot and ankle in the affected limbs was evaluated according to the scoring standard of American Orthopaedic Foot and Ankle Society.Results:During the surgery, the deep fascial exit point of the superficial branch of the superficial circumflex iliac artery in the flap donor area was consistent with the result of CDU positioning before the surgery, and the distance between them was less than 10 mm. The flap thickness was 5 to 8 mm with an average of 6.2 mm. All the flaps survived after surgery. During the follow-up of 5 to 12 months, the flaps had good appearance and texture, all the wounds in the donor areas healed with only linear scar left. At the last follow-up, the function of the wrist and hand in the affected limbs was evaluated as excellent in 9 cases, good in one case, and fair in one case; the function of the foot and ankle in the affected limbs was evaluated as excellent in one case and good in two cases.Conclusions:CDU examination can provide precise preoperative perforator positioning for layered thinning of SCIP flap and contribute to the optimization of flap design, so as to avoid the problem of flap necrosis caused by improper preoperative design to some extent and improve the safety of surgery. In addition, the layered thinning SCIP flap results in less damage to the donor area and is beneficial for the recovery of the affected limb function, which is worthy of clinical promotion.

Objective:To investigate the clinical application effects of free transplantation of lobulated inguinal flaps.Methods:This study was a retrospective observational study. From July 2019 to April 2024, 34 patients with skin defect wounds whose wounds in one part met the inclusion criteria were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 28 males and 6 females, aged 26 to 59 years. The wound area in the recipient area ranged from 3.0 cm×2.0 cm to 25.0 cm×20.0 cm. The lobulated inguinal flap pedicled with the branch of the superficial circumflex iliac artery were obtained in 19 patients, and the lobulated inguinal flap pedicled with the main artery of the superficial circumflex iliac artery and the superficial inferior epigastric artery were obtained in 15 patients. The total area of the flaps ranged from 6.0 cm×2.2 cm to 27.0 cm×23.0 cm. The flaps were divided into 2 to 4 lobes, and the area of each lobe ranged from 2.0 cm×1.0 cm to 17.0 cm×12.0 cm. Each lobe of the flaps was reassembled, spliced, or directly transplanted onto the wounds, and the donor wounds were sutured in layers. The survival of each lobe of the flaps and wound healing in the recipient and donor areas were observed, and the wound recovery in the recipient and donor areas were followed up. At the last follow-up, the patient's satisfaction with the efficacy was assessed by 5-grade Likert scale.Results:A small amount of necrosis appeared in the tip of one lobe of the flaps in 4 patients after surgery, which healed after trimming. The flaps of the remaining 30 patients survived. The wounds in the recipient areas healed smoothly. There was a small amount of necrosis at the suture edge of the donor areas in 3 patients, which healed after local trimming and dressing change. The donor wounds healed well in the remaining 31 patients. During the follow-up of 6 to 42 months, all the recipient wounds were well repaired, and the shape of the donor areas was good. At the last follow-up, 15 patients were very satisfied with the efficacy, 15 were relatively satisfied, and 4 were generally satisfied.Conclusions:Through preoperative ultrasonic examination and positioning, the inguinal flap is designed according to the course of blood vessels and lobulated with the branch of the superficial circumflex iliac artery or the main artery of the superficial circumflex iliac artery and the superficial inferior epigastric artery as the pedicles. The anatomical process is reliable and the blood flow of the flap after being lobulated is rich, which can meet the repair needs of various skin defect wounds. The repair effect is good, and the damage in the donor area is small, which is worthy of promotion.

Objective:To establish a three-dimensional navigation process for design and resection of perforator flaps based on multi-detector computed tomography angiography (MDCTA) and to explore its clinical application effects.Methods:This study was a retrospective observational study. From January 2021 to October 2023, 7 patients and 6 patients with post-traumatic skin and soft tissue defects in extremity and conformed to the inclusion criteria were admitted to the Affiliated Hospital of Jiangsu University and Wuxi No. 9 People's Hospital, respectively. There were 8 males and 5 females, aged 21 to 68 years. Nine patients had wounds on the hand and 4 patients had wounds on the foot. The wound area after debridement ranged from 8.0 cm×6.0 cm to 18.0 cm×17.0 cm. Through the three-dimensional navigation process based on MDCTA, 14 perforator flaps were designed and resected, including 11 free anterolateral thigh perforator flaps and 3 pedicled peroneal artery perforator flaps with sural nerve nutritional vessel chain, with flap size ranging from 9.0 cm×6.0 cm to 20.0 cm×15.0 cm. Six wounds in the flap donor sites were directly sutured, and eight wounds in the flap donor sites were transplanted with skin grafts. The consistency of the location, type, and source of the perforators was compared between the preoperative navigation display and actual intraoperative detection. Immediately after surgery, the coverage of wound by the flap was evaluated according to the self-made criteria. The postoperative flap survival was observed. The occurrence of complications was observed during follow-up. At the last follow-up, the appearance of the flaps was observed, the blood supply of the flaps and the hand function of the 9 patients with hand trauma were evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association, and the foot function of the 4 patients with foot trauma was assessed using the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scoring System.Results:The location, type, and source of the perforators displayed in preoperative navigation were consistent with the actual intraoperative detection. Immediately after surgery, the coverage of the wounds by 11 flaps was rated as excellent, and that of 3 flaps was rated as moderate. Postoperatively, 13 flaps survived completely, and 1 flap had partial necrosis, which healed after a full-thickness skin grafting from the thigh. Patients were followed up for 4 to 24 months postoperatively, one patient developed a hematoma under the flap, and one patient had local infection. At the last follow-up, the flaps of all patients were good in color and texture, and 5 patients with bloated flaps post operation had good appearance after thinning surgery; the blood supply was excellent in 12 flaps and was good in 2 flaps; among patients with hand trauma, the hand function was rated as excellent in 2 cases, good in 4 cases, and poor in 3 cases; among patients with foot trauma, the foot function was rated as excellent in 3 cases and good in 1 case.Conclusions:The three-dimensional navigation process for design and resection of perforator flaps based on MDCTA realizes precise evaluation of perforator vessels in flap donor sites and skin and soft tissue defects in the recipient sites. Guided by the three-dimensional navigation process, the application of free anterolateral thigh perforator flaps and pedicled peroneal artery perforator flaps with sural nerve nutritional vessel chain in repairing skin and soft tissue defects in extremity realizes precise surgery, reducing flap donor site injury and achieving excellent clinical outcomes.

Objective:To explore the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the microcirculatory perfusion of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns.Methods:This study was an experimental study. Thirty-two male big ear white rabbits aged 6-8 months were assigned into electric burn group of 20 rabbits with high-voltage electric burns in the right lower limb and control group of 12 rabbits with sham injury in the right lower limb using the random number table method. At 0.5, 24.0, 48.0, and 72.0 h post injury, the lower limbs of rabbits in the two groups underwent axial fast spin echo T1-weighted imaging, fast spin echo T2-weighted imaging, and DCE-MRI examination. A reference region-based hemodynamic model was applied to obtain the blood perfusion parameters of skeletal muscle in the injured limbs, including the volume transfer constant K trans value and rate constant K ep value. The skeletal muscle tissue from the electric burn group of rabbits at 0.5, 24.0, 48.0, and 72.0 h post injury and the control group of rabbits at 0.5 h post injury was harvested for immunohistochemical staining to observe the microvascular changes and calculate the microvascular density (MVD). The correlation between the K trans and K ep values and the MVD of skeletal muscle tissue in electric burn group of rabbits at 0.5-72.0 h post injury was analyzed. The number of samples was 5 in the electric burn group, and the number of samples was 3 in the control burn group. Results:From 0.5-72.0 h post injury, the K trans and K ep values in skeletal muscle tissue of electric burn group of rabbits exhibited the trends of increase first and decrease then, both of which reached peak values at 24.0 h post injury. The K trans values at 0.5, 24.0, 48.0, and 72.0 h post injury (with t values of -15.77, -14.91, -40.35, and -40.25, respectively, P<0.05) and the K ep values at 0.5, 24.0, and 48.0 h post injury (with t values of -5.39, -6.82, and -6.83, respectively, P<0.05) in skeletal muscle tissue in electric burn group of rabbits were significantly higher than those in control group. The MVD in skeletal muscle tissue in control group of rabbits at 0.5 h post injury and in electric burn group of rabbits at 0.5, 24.0, 48.0, and 72.0 h post injury was (24.7±3.5), (21.8±2.2), (40.8±9.1), (16.4±2.4), and (9.8±0.8) per mm2, respectively. The MVD in skeletal muscle tissue in electric burn group of rabbits at 24.0 h post injury was significantly higher than that in control group at 0.5 h post injury ( t=2.89, P<0.05), and the MVD in skeletal muscle tissue at 48.0 and 72.0 h post injury was significantly lower than that in control group at 0.5 h post injury (with t values of 4.01 and 9.52, respectively, P<0.05). The K trans and K ep values of skeletal muscle tissue in rabbits in electric burn group were significantly positively correlated with microvascular density at 0.5 to 72.0 h post injury (with both r values of 0.95, P<0.05). Conclusions:The quantitative perfusion parameters K trans and K ep values of DCE-MRI can effectively reflect the microcirculatory perfusion changes of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns.

Objective:To investigate the influence and mechanism of bone marrow mesenchymal stem cells (BMSCs) overexpressing growth arrest specific 6, i.e. GAS6/BMSCs on full-thickness skin defect wounds in diabetic mice.Methods:This study was an experimental study. Twelve 8-week-old male C57BL/6J mice were divided into a control wound group with only full-thickness skin defects and a diabetic wound group with diabetic full-thickness skin defects according to the random number table method, with 6 mice in each group. The wound healing rates were calculated at 3, 7, 14, and 21 days after injury. At 21 days after injury, wound tissue specimens were collected for hematoxylin-eosin staining to observe the histopathological conditions; Masson staining was performed to detect collagen deposition; immunohistochemical staining was performed to detect the number of proliferating cell nuclear antigen (PCNA)-positive cells and CD31-positive cells, representing cell proliferation and capillary density, respectively; immunofluorescence staining was performed to detect the number of F4/80 and myeloperoxidase (MPO) double-positive cells, indicating efferocytosis. Two 4-week-old male C57BL/6J mice were used to extract BMSCs, and GAS6/BMSCs were constructed through adenovirus transfection and successfully identified. Eighteen 8-week-old male C57BL/6J mice were used to create diabetic full-thickness skin defect wound models and divided into phosphate buffered solution (PBS) group, BMSC group, and GAS6/BMSC group (with 6 mice in each group) according to the random number table method. Immediately after injury, PBS, BMSC single-cell suspension, and GAS6/BMSC single-cell suspension were injected locally into the wounds of the three groups of mice, respectively. The wound healing rates were calculated, and the cell proliferation, capillary density, and efferocytosis were detected at the same time points as the previous experiments.Results:At 3, 7, 14, and 21 days after injury, the wound healing rates of mice in diabetic wound group were significantly lower than those in control wound group (with t values of 7.99, 8.62, 9.80, and 5.85, respectively, P<0.05). Compared with those in control wound group, the wound tissue of mice in diabetic wound group showed the infiltration of a large number of inflammatory cells and reduced collagen deposition at 21 days after injury. At 21 days after injury, the number of PCNA-positive cells and CD31-positive cells in the wound tissue of mice in diabetic wound group were significantly less than that in control wound group (with t values of 6.61 and 5.38, respectively, P<0.05). At 21 days after injury, the number of F4/80 and MPO double-positive cells in the wound tissue of mice in diabetic wound group was 3.3±0.8, which was significantly less than 12.7±1.8 in control wound group ( t=11.00, P<0.05). At 14 and 21 days after injury, the wound healing rates of mice in BMSC group were significantly higher than those in PBS group ( P<0.05); at 3, 7, 14, and 21 days after injury, the wound healing rates of mice in GAS6/BMSC group were significantly higher than those in BMSC group ( P<0.05). At 21 days after injury, the number of PCNA-positive cells in the wound tissue of mice in BMSC group was significantly higher than that in PBS group ( P<0.05), and the number of PCNA-positive cells and CD31-positive cells in the wound tissue of mice in GAS6/BMSC group were significantly higher than that in BMSC group ( P<0.05). At 21 days after injury, the number of F4/80 and MPO double-positive cells in the wound tissue of mice in BMSC group was 4.2±1.2, which was similar to 3.5±1.1 in PBS group ( P>0.05); the number of F4/80 and MPO double-positive cells in the wound tissue of mice in GAS6/BMSC group was 8.2±1.2, which was significantly more than that in BMSC group ( P<0.05). Conclusions:Dysfunctional efferocytosis of macrophage exists in the full-thickness skin defect wounds of diabetic mice, while GAS6/BMSC can promote wound healing by restoring the efferocytosis of macrophages.

Objective:To explore the causal relationship between human immune cell phenotypes and keloids.Methods:This study was based on a two-sample Mendelian randomization (MR) analysis. Human immune cell phenotypes were considered as the exposure factors, and keloid was the outcome. Data on immune cell phenotypes (3 757 samples) and keloids (668 samples) were obtained from the genome-wide association study database. Using single nucleotide polymorphisms (SNPs) significantly associated with immune cell phenotypes as instrumental variables with the influence of weak instrumental variables being excluded, two-sample MR analysis was employed to evaluate the causal relationship between 731 human immune cell phenotypes and keloids. The inverse variance weighted (IVW) method was used to infer causal relationships, and the MR-Egger, weighted median, and weighted mode methods were used for validation. For SNPs of immune cell phenotypes meeting the hypothesis, the Cochran Q test was used to assess heterogeneity, and the MR-Egger regression and MR-PRESSO outlier tests were used to evaluate horizontal pleiotropy.Results:A total of 18 204 SNPs meeting the significant threshold ( P<1×10??) were selected as instrumental variables for 731 immune cell phenotypes, and none of these SNPs were weak instrumental variables (with F values all >10). According to the IVW method, 21 immune cell phenotypes were identified with potential causal relationships to keloids, among which the CD62L - monocyte absolute count, CD19 on naive-mature B cell, CD19 on IgD + B cell, CD27 on plasma blast-plasma cell, CD86 on CD62L + myeloid dendritic cell, CD45 on natural killer T cell, CD25 on CD39 + CD4 + regulatory T cell, CD45 on monocytic myeloid-derived suppressor cells, CD8 on effector memory CD8 + T cell, and CD45RA on resting CD4 + regulatory T cell showed significant positive correlations with keloids (with odds ratios of 1.12, 1.09, 1.08, 1.21, 1.13, 1.12, 1.17, 1.11, 1.10, and 1.07, respectively, 95% confidence intervals of 1.03-1.23, 1.02-1.16, 1.01-1.15, 1.06-1.38, 1.02-1.25, 1.01-1.24, 1.03-1.33, 1.00-1.23, 1.00-1.20, and 1.01-1.13, respectively, P<0.05), while the activated and secreted CD4 + regulatory T cell absolute count, CD25 on unswitched memory B cell, plasmacytoid dendritic cell absolute count, CD14 on monocytic myeloid-derived suppressor cells, CD8 on natural killer T cell, CD20 on IgD + CD38 + B cell, CD11c + CD62L - monocyte absolute count, CD66b ++ myeloid cell absolute count, CD11c on granulocytes, CD14 on CD14 + CD16 + monocyte, and CD3 on central memory CD8 + T cell showed significant negative correlations with keloids (with odds ratios of 0.95, 0.93, 0.93, 0.93, 0.91, 0.89, 0.89, 0.88, 0.87, 0.86, and 0.85, respectively, 95% confidence intervals of 0.90-1.00, 0.87-0.99, 0.88-0.99, 0.87-0.99, 0.84-1.00, 0.81-0.98, 0.81-0.98, 0.79-0.99, 0.78-0.96, 0.75-0.99, and 0.74-0.96, respectively, P<0.05). MR-Egger method confirmed the potential causal relationship existing respectively between CD25 on CD39 + CD4 + regulatory T cell, CD86 on CD62L + myeloid dendritic cell, CD19 on IgD + B cell, CD45RA on resting CD4 + regulatory T cell, CD3 on central memory CD8 + T cell and keloids (with odds ratios of 1.32, 1.22, 1.11, 1.09, and 0.73, respectively, 95% confidence intervals of 1.03-1.70, 1.04-1.44, 1.02-1.21, 1.01-1.19, and 0.55-0.95, respectively, P<0.05). The weighted median method confirmed the potential causal relationship existing respectively between CD45 on natural killer T cell, activated and secreted CD4 + regulatory T cells absolute count, CD20 on IgD + CD38 + B cell, CD66b ++ myeloid cell absolute count and keloids (with odds ratios of 1.15, 0.93, 0.87, and 0.83, respectively, 95% confidence intervals of 1.01-1.31, 0.86-1.00, 0.77-0.98, and 0.71-0.96, respectively, P<0.05). Among them, the potential causal relationship between CD20 on IgD + CD38 + B cell and keloids was further verified by the weighted mode method (with odds ratio of 0.86, 95% confidence interval of 0.77-0.97, P<0.05). According to the aforementioned IVW method analysis results, the SNPs associated with the 21 immune cell phenotypes that had a significant causal relationship with keloids showed no significant heterogeneity ( P>0.05) or significant horizontal pleiotropy ( P>0.05). Conclusions:From a genetic perspective, the potential causal relationships between 21 human immune cell phenotypes and keloids have been revealed, of which 10 immune cell phenotypes may be risk factors for keloids, while 11 immune cell phenotypes may act as protective factors for keloids.

Over the course of more than 60 years of development, microsurgical techniques have entered the era of intelligence and digitization. This article focuses on the development of microsurgical techniques in the field of tissue repair in China, provides a detailed analysis of the application of microsurgical techniques in the repair of destructive burn wounds and the reconstruction of post-burn scar contracture deformity, and systematically introduces the flap repair strategies in various tissue forms. With advances of science and technology, and breakthroughs in emerging fields such as tissue engineering, regenerative medicine and gene editing, microsurgical techniques have demonstrated tremendous potential in the area of tissue repair, with broad prospects for future applications.