Skin Wound Research Articles

Interleukin-37 promotes wound healing in diabetic mice by inhibiting the MAPK/NLRP3 pathway.

Diabetic foot ulcer (DFU) is a prevalent complication of diabetes characterized by heightened inflammation and impaired wound-healing processes. Interleukin-37 (IL-37) is a natural suppressor of innate inflammation. Here, we aim to investigate the potential of IL-37 in enhancing the healing process of diabetic wounds. The skin samples of DFU and non-diabetic patients during foot and ankle orthopedic surgery were collected. The IL-37 transgenic mice (IL-37Tg) were created using CRISPR/Cas-mediated genome engineering. Mice were administered streptozotocin (STZ, 150 mg/kg) to induce a diabetic model. After 4 weeks, an equidistant full-thickness excisional wound measuring 8 mm was created on the central back of each mouse and allowed to heal naturally. Body weight and blood glucose levels were measured weekly. The wound area was measured, and skin samples were collected on Day 10 for further Quantitative polymerase chain reaction (qPCR) and WB detection and RNA sequencing analysis. The proinflammation cytokines such as TNF-α and IL-1β and the MAPK signaling pathway were significantly increased in the wound margin of DFU patients. Compared with diabetic mice, diabetic IL-37Tg mice showed a significantly accelerated healing process. The enriched signaling pathways in RNA sequencing included cytokine-cytokine receptor interaction, TNF signaling pathway, and NOD-like receptor signaling pathway. Through QPCR and WB detection, we found that IL-37 could inhibit the activated MAPK and NOD-like signaling pathway, reducing TNF-α, IL-1β, and NLRP3 expression in the diabetic wound. IL-37 promotes skin wound healing in diabetic mice, providing a new possible target for treating diabetic wounds.

3D-Printed Hydrogel Scaffolds Loaded with Flavanone@ZIF-8 Nanoparticles for Promoting Bacteria-Infected Wound Healing

Bacterial-infected skin wounds caused by trauma remain a significant challenge in modern medicine. Clinically, there is a growing demand for wound dressings with exceptional antibacterial activity and robust regenerative properties. To address the need, this study proposes a novel multifunctional dressing designed to combine efficient gas exchange, effective microbial barriers, and precise drug delivery capabilities, thereby promoting cell proliferation and accelerating wound healing. This work reports the development of a 3D-printed hydrogel scaffold incorporating flavanone (FLA)-loaded ZIF-8 nanoparticles (FLA@ZIF-8 NPs) within a composite matrix of κ-carrageenan (KC) and konjac glucomannan (KGM). The scaffold forms a stable dual-network structure through the chelation of KC with potassium ions and intermolecular hydrogen bonding between KC and KGM. This dual-network structure not only enhances the mechanical stability of the scaffold but also improves its adaptability to complex wound environments. In mildly acidic wound conditions, FLA@ZIF-8 NPs release Zn2+ and flavanone in a controlled manner, providing sustained antibacterial effects and promoting wound healing. In vivo studies using a rat full-thickness infected wound model demonstrated that the FLA@ZIF-8/KC@KGM hydrogel scaffold significantly accelerated wound healing, showcasing its superior performance in the treatment of infected wounds.

HMGB1 Accelerates Wound Healing by Promoting the Differentiation of Epidermal Stem Cells via the "HMGB1-TLR4-Wnt/Notch" Axis.

Objective: Impairments in the differentiation and migratory capacity of epidermal stem cells (ESCs) are pivotal factors contributing to delayed wound healing. High mobility group box1 (HMGB1) has recently emerged as a potential target for tissue repair. Therefore, we aimed to investigate the role and molecular mechanisms of HMGB1 in ESCs during the wound-healing process. Approach: Initially, we examined the expression of HMGB1 and the differentiation of ESCs in normal skin, normal wounds and chronic wounds. Then, we assessed the ESC migration and differentiation, and the key markers in the Wnt/Notch signaling pathways, after treatment of HMGB1 and inhibitor, and the knockdown of toll-like receptor 4 (TLR4), using scratch assay, qPCR, western blotting, and immunofluorescence. Finally, we conducted mice models to analyze the healing rates and quality invivo. Results: HMGB1 was decreased across all epidermal layers, and the differentiation of ESCs was hindered in diabetic foot ulcer. In vitro, HMGB1 enhanced both the migration and differentiation of ESCs while stimulating the expression of the Wnt/Notch pathway within ESCs. However, the downregulation of TLR4 negated these effects. Finally, our invivo experiments provided evidence that HMGB1 facilitates wound healing and epidermis differentiation via TLR4 and Wnt/Notch signaling pathways. Innovation: This study innovatively introduces HMGB1 as a novel target for skin wound healing and elucidates its mechanisms of action. Conclusions: HMGB1 accelerated wound healing by promoting the differentiation of epidermal stem cells through the "HMGB1-TLR4-Wnt/Notch" axis, which reveals a new potential mechanism and target to expedite wound healing.

Prospective study of three-dimensional-printed in vitro guide plates assisted hip arthroscopy in treatment of Cam-type femoroacetabular impingement

A prospective study was conducted to investigate the feasibility and effectiveness of three-dimensional printed in vitro guide plates assisted hip arthroscopy in the treatment of Cam-type femoroacetabular impingement (FAI). The clinical data of 25 patients with Cam-type FAI who met the selection criteria between December 2016 and September 2022 were collected. There were 13 males and 12 females with an average age of 42 years (range, 19-66 years). The disease duration ranged from 3 to 120 months, with an average of 22.2 months. The preoperative range of internal rotation-external rotation was (28.70±4.50)°, α angle was (69.04±0.99)°, visual analogue scale (VAS) score was 6.5±0.2, and modified Harris hip score (HHS) was 50.5±0.7. All patients were treated with hip arthroscopy assisted by three-dimensional printed in vitro guide plate. The occurrence of complications was observed postoperatively, α angle of the affected hip joint was measured on Dunn X-ray film, and the glenoid labrum injury was observed by MRI. The percentage of overlap between the Cam plasty area and the preoperative simulated grinding area was calculated by three-dimensional CT+reconstruction. The effectiveness was evaluated by VAS score and modified HHS score. Postoperative dorsalis pedis numbness occurred in 1 case, and the symptoms disappeared after 1 month of conventional drug treatment such as neurotrophy. Two cases of perineal skin injury occurred, and healed after symptomatic treatment. There was no male erectile dysfunction, deep incision infection, pulmonary embolism, or other serious complications occurred. The percentage of overlap between the Cam plasty area and the preoperative simulated grinding area was 81.6%-95.3%, with an average of 89.8%. All 25 patients were followed up 6-12 months, with an average of 8 months. At last follow-up, the range of internal rotation-external rotation was (40.10±2.98)°, α angle was (43.72±0.84)°, VAS score was 1.8±0.2, and the modified HHS score was 72.1±1.3, which significantly improved when compared with preoperative ones ( P<0.05). The treatment of Cam-type FAI with three-dimensional printed in vitro guide plates assisted hip arthroscopy is safe and feasible, and can achieve good effectiveness.

Haematological and serum biochemical responses following surgically created open skin wound healing in alloxan-induced diabetic rabbits

Haematological and serum biochemical responses following surgically created open skin wound healing in alloxan-induced diabetic rabbits

Comparison of Traditional Dressing Change Techniques and Vacuum Sealing Drainage Techniques in the Treatment of Skin and Soft Tissue Injuries

Objective: To analyze the therapeutic effects of traditional dressing change techniques and vacuum sealing drainage (VSD) techniques on skin and soft tissue injuries. Methods: 60 patients with skin and soft tissue injuries admitted to the hospital from October 2021 to October 2023 were selected. They were randomly divided into an observation group (30 cases) receiving VSD treatment and a control group (30 cases) receiving the traditional dressing change technique. The total effective rate, treatment indicators, inflammatory factors, and complication rate were compared between the two groups. Results: The total effective rate of the observation group was higher than that of the control group, and the treatment indicators were better than those of the control group (P &lt; 0.05). Before treatment, the levels of inflammatory factors were similar between the two groups (P &gt; 0.05). After four weeks of treatment, the levels of inflammatory factors in the observation group were lower than those in the control group (P &lt; 0.05). The complication rate of the observation group was lower than that of the control group (P &lt; 0.05). Conclusion: In the treatment of skin and soft tissue injuries, VSD can improve the total effective rate, shorten the treatment cycle, alleviate the degree of inflammatory reaction, and reduce the risk of complications.

Introduction of a LAT gel and low-dose midazolam sedo-analgesia protocol for pediatric skin suture in the emergency department: simpler is better.

skin lacerations are one of the main causes of children's referral to the emergency department (ED). We introduced in our general ED a pediatric sedo-analgesia protocol (SAP) for suturing skin wounds using LAT gel, a local anesthetic solution of lidocaine, adrenaline and tetracaine, with or without low-dose oral midazolam according to patient's age, to improve the experience of laceration repair. Primary outcomes were improvement of suturing experience for ED operators (as a reduction in the desire to avoid the procedure) and of the adequacy of sedo-analgesia provided, investigated through two different surveys administered to the ED staff before and after the introduction of the SAP. Children's parents were asked about satisfaction with the sedo-analgesia provided. Data were collected prospectively. The analysis included 85 and 60 healthcare professionals involved in the suture of skin wounds in children, respectively before and after the introduction of our SAP. The introduction of the SAP reduced ED operators' stress and improved the entire suturing experience. The pre-post analysis showed a statistically significant improvement in the perceived adequacy of the provided sedo-analgesia (p < 0.0001) and a significant reduction of operators who would have avoided the procedure (p < 0.0001). The great majority of children's parents expressed a high level of satisfaction. The introduction of a LAT gel and low-dose oral midazolam SAP allows an improvement of both the sedo-analgesia provided and the ED operators' suturing experience of skin lacerations in children. Our SAP appeared to be safe and effective, with low cost and high tolerability.

Effectiveness of spinal cord stimulation in diabetic patients with chronic limb-threatening ischemia: small cohort study

BackgroundChronic limb-threatening ischemia (CLTI) is the most severe form of peripheral artery disease (PAD). Patients with diabetes mellitus (DM) have a faster progression of PAD and a fourfold increased risk of CLTI compared to patients without DM. Epidural spinal cord stimulation (SCS) has been used as a method to improve microcirculation, relieve ischemic pain and reduce the number of amputations in patients with PAD. This is a retrospective small cohort analysis of patients with diabetes and the long-term treatment effect of spinal cord stimulation.MethodsAs the main outcome of the study, we evaluated the survival and amputation of 13 diabetic patients with chronic lower-limb ischemia who were not eligible for surgical or interventional therapy. Secondary outcomes included ankle-brachial index (ABI), ischemic pain intensity, quality of life, use of analgesic medications and skin wound outcomes analyzed during long-term follow-up.ResultsBetween January 2010 and January 2017, 13 patients underwent SCS implantation in our vascular center. At 1-year follow-up, the limb salvage rate was 92.3% (12 of 13 patients), and limb ulcers healed in 75% of patients (6/8). No patient died during the one-year follow-up. A total of 4 of patients (31%) experienced major amputation during long-term follow-up, all of them were Fontaine stage IV. Pain intensity and quality of life improved significantly at 6-month follow-up (p &amp;lt; 0.05). ABI measurements were unaffected by SCS treatment. There were no complications related to the procedure or device.ConclusionsSCS is a promising treatment option for diabetic patients unsuitable for endovascular or surgical revascularization. The method improves limb survival in diabetic patients with critical limb ischemia, provides significant pain control, and improves patients' quality of life. However, more studies are needed to clarify the indications for SCS and clarify its effects on the vascular system.

Investigating the Healing Potential of Fresh Amniotic Membranes in Full-Thickness Canine Skin Wounds

Investigating the Healing Potential of Fresh Amniotic Membranes in Full-Thickness Canine Skin Wounds

Attenuation of skin injury by a MARCO targeting PLGA nanoparticle

Cutaneous exposure to the DNA alkylating class of chemotherapeutic agents including nitrogen mustard (NM) leads to both skin injury and systemic inflammation. Circulating myeloid subsets recruited to the skin act to further exacerbate local tissue damage while interfering with the wound healing process. We demonstrate herein that intravenous delivery of poly(lactic-co-glycolic acid) immune-modifying nanoparticles (PLGA-IMPs) shortly after NM exposure restricts accumulation of macrophages and inflammatory monocytes at the injury site, resulting in attenuated skin pathology. Furthermore, PLGA-IMPs induce an early influx and local enrichment of Foxp3+ regulatory T cells (Treg) in the skin lesions critical for the suppression of myeloid cell-pro-inflammatory responses via induction of IL-10 and TGF-β in the cutaneous milieu. Functional depletion of CD4+ Tregs ablates the efficacy of PLGA-IMPs accompanied by a loss of local accumulation of anti-inflammatory cytokines essential for wound healing. Thus, in severe skin trauma, PLGA-IMPs may have therapeutic potential via modulation of inflammatory myeloid cells and regulatory T lymphocytes.

Safety and efficacy of a 3D-printed external cranial protection device in preventing complications after unilateral supratentorial decompressive craniectomy: A retrospective cohort study.

The objective was to clarify the feasibility and clinical effect of 3D-printed external cranial protection devices (ECPD) in preventing complications following unilateral supratentorial decompressive craniectomy (DC). A retrospective cohort study was conducted on post-DC patients meeting inclusion and exclusion criteria. In the experimental group, head computed tomography data were collected after DC, and the ECPD were 3D-printed with photosensitive resin materials, and fixed to the bone window defect for continuous wear. The control group received similar postoperative treatment and procedures but did not place the ECPD. Clinical data were collected and analyzed. Forty-four patients were enrolled, 24 in the experimental and 20 in the control group. The incidence of postoperative complications of DC was 84.09%. The median time to initial use of the 3D-printed ECPD was 13.5 days. No patients had skin pressure ulcers, allergies, or wound infections. There were no statistically significant differences between the groups in pre-DC Glasgow Coma Scale scores, post-DC complication rates, or Glasgow Outcome Scale scores at discharge (P > .05). Whereas, there was a statistically significant difference in pre-cranioplasty DC-related complications (P = .027), with a notable reduction in the incidence of subdural effusion in the experimental group (P = .004). The 2 groups had no significant differences in modified Rankin Scale scores after cranioplasty. The clinical use of the 3D-printed ECPD is safe and reliable, effectively reducing the incidence of complications following DC, particularly in the prevention and treatment of subdural effusion. However, it does not significantly improve the prognosis of patients after DC, warranting further research.

Ceasing or gradually reducing incubator humidity after 7days for extremely preterm infants: a randomised clinical trial.

Ceasing or gradually reducing incubator humidification after day 7 of life had no effect on the number of episodes of hypothermia or hyperthermia in this cohort of extremely preterm infants (EPTI). There was also no effect on the number of episodes of hyponatraemia or hypernatraemia. ANZCTR.org.au (Australia New Zealand Clinical Trials Registry). ACTRN 1261 9000 266167 Registered 21/2/2019. • Incubator humidification is a widely accepted and routine practice in the management of EPTI as it influences transepidermal water loss (TEWL) and supports thermoregulation. However, weaning practices remain varied and inconsistent across the globe. • There remains a paucity of data to inform specific evidenced-based humidification practices. • Ceasing or gradually reducing incubator humidification after 7days had no effect on temperature stability, serum sodium levels, or frequency of skin injury in this cohort of EPTI between day 8 and day 14. • There is no apparent benefit in prolonging incubator humidity beyond day 7 of life in these EPTI.

Nanodrug-Engineered Exosomes Achieve a Jointly Dual-Pathway Inhibition on Cuproptosis.

Cuproptosis, caused by an intracellular overload of copper (Cu) ions and overexpression of ferredoxin 1 (FDX1), is identified for its regulatory role in the skin wound healing process. This study verifies the presence of cuproptosis in skin wound beds and reactive oxygen species-induced cells model. To address the two pathways leading to cell cuproptosis, a nanodrug-engineered exosomes is proposed. A Cu-chelator (Clioquinol, CQ) polydopamine (PDA)-modified stem cell exosome loaded with siRNA-FDX1, named EXOsiFDX1-PDA@CQ, is designed to efficiently inhibit the two cuproptosis pathways. The functionalized exosomes are loaded into an injectable hydrogel and applied to treat diabetic wounds in mice and acute skin wounds in pigs. The local and controlled release of EXOsiFDX1-PDA@CQ ensures the retention of the therapeutic agent at wound beds, effectively promoting wound healing. The strategy of engineered exosomes with functional nanoparticles (NPs) proposed in this study offers an efficient and scalable new approach for regulating cuproptosis.

Wound Healing in External Rhinoplasty-The Effect of Fibrin Glue on Dead Space Closure: A Retrospective Propensity Score-Matched Study.

The presence of "dead space" in external rhinoplasty creates a welcoming environment for erratic soft tissue contraction. Poor redraping of the skin over the underlying osseocartilaginous framework at the end of the surgery may result in its creation. If surgeons can control and reliably predict skin contraction and wound healing, septorhinoplasty results would undoubtedly improve. Fibrin glue application has previously demonstrated a reduction in adverse events in plastic surgery. Several potential advantages have been attributed to the application of fibrin glue, such as reducing downtime, improving patient satisfaction and reducing complication rates. To evaluate the effectiveness of homologous fibrin glue on the long-term healing process in external rhinoplasty. We performed a retrospective propensity score-matched analysis in 154 patients enrolled for external septorhinoplasty. An aesthetic evaluation was performed with the FACE-Q nose and nostrils, the Utrecht Questionnaire including VAS score and the NOSE. Assessments were conducted prior to surgery and post-operatively at 3, 6 and 12months. After propensity score matching, two equal groups of 66 patients were retained. The first cohort of 66 patients underwent a rhinoplasty without the application of fibrin glue; in the second cohort of 66 patients, human fibrin glue was used to achieve better adherence of the skin to the underlying skeletal framework. All patients had a statistically highly significant improvement on all PROMs post-operatively. The post-operative results remained stable over the different time points. However, no statistically significant difference in the aesthetic outcome was discovered whether fibrin glue was used or not during surgery. Obliteration of dead space is a key component in septorhinoplasty as it minimizes soft tissue contraction, resulting in a more predictable outcome. Although fibrin glue has been used successfully in different medical fields, no long-term positive effects on patient satisfaction could be detected in the present study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Native and cationic cellulose nanofibril films enriched with avocado seed compounds as a green alternative for potential wound care applications

Cellulose nanofibrils (CNF) show great potential for skin wound care and healing due to their biocompatibility, non-cytotoxicity, and high swelling with good mechanical stability. In the presented study, for the first time native and cationized cellulose nanofibrils were used in combination with avocado seeds extracts obtained with different extraction methods (ASE), as an alternative to a well-known antibiotic, Clindamycin, to produce films with high and long-lasting antimicrobial efficacy. The swelling capacity of prepared films and extracts/antibiotic release kinetics were studied at different pH values to evaluate pH response behavior.All developed films exhibited high bacteriostatic and bactericidal activity against Gram-negative Escherichia coli and G-positive Staphylococcus aureus, resulting in up to 100 % bacterial reduction with the log reduction factor up to 5.64 or 6.50, at 14.2 mg of avocado seed extract or clindamycin integrated in the 1 cm2 of CNF film. The high swelling capacity (up to 65.67 %) and stability of avocado seed extracts-enriched CNF films provide a suitable moisture environment and a sustainable release (up to 40.98 % in 48 h) of bioactive compounds. The prepared antibacterial films' chemical and morphological characteristics and pH-responsive behavior proved the potential applications in the cosmetics, biomedicine, and pharmaceutical industry.

Expression of concern: An 'on-demand' photothermal antibiotic release cryogel patch: evaluation of efficacy on an ex vivo model for skin wound infection.

Expression of concern for 'An 'on-demand' photothermal antibiotic release cryogel patch: evaluation of efficacy on an ex vivo model for skin wound infection' by Léa Rosselle, et al., Biomater. Sci., 2020, 8, 5911-5919, https://doi.org/10.1039/D0BM01535K.

SCALES FOR ASSESSMENT OF SKIN SCARS. CLINICAL SIGNIFICANCE. SYSTEMATIC REVIEW.

Having a skin scar is a serious psychosocial problem for a person. Scar and cicatrices are synonymous concepts. Interpretation of scar characteristics is necessary for monitoring purposes and, if necessary, determining treatment tactics. Subjective characteristics of the scar (pain, itching, etc.) are very important for the formation of a comprehensive assessment. Healing of skin wounds can lead to the formation of different types of scars: from minor lines to keloids. The physical and psychosocial aspects of having a skin scar can lead to a decrease in the patient's quality of life. Today, the question remains controversial which criteria for assessing a scar should be included in a particular tool (scale) for its comprehensive assessment. The ideal scar rating scale should not be difficult to complete, and the measurement results are easily reproducible and interpretable. It is important to determine the impact of the scar on psychosocial parameters (quality of life, self-esteem, social function of the patient). This literature review included 19 full-text articles containing information on ten developed skin scar rating scales. The literature review was carried out based on a search in the PubMed, Web of Science, Google Scholar and Elibrary.

A Vaccine Against Fibroblast Activation Protein Improves Murine Cardiac Fibrosis by Preventing the Accumulation of Myofibroblasts.

Myofibroblasts are primary cells involved in chronic response-induced cardiac fibrosis. Fibroblast activation protein (FAP) is a relatively specific marker of activated myofibroblasts and a potential target molecule. This study aimed to clarify whether a vaccine targeting FAP could eliminate myofibroblasts in chronic cardiac stress model mice and reduce cardiac fibrosis. We coadministered a FAP peptide vaccine with a CpG K3 oligonucleotide adjuvant to male C57/BL6J mice and confirmed an elevation in the anti-FAP antibody titer. After continuous angiotensin II and phenylephrine administration for 28 days, we evaluated the degree of cardiac fibrosis and the number of myofibroblasts in cardiac tissues. We found that cardiac fibrosis was significantly decreased in the FAP-vaccinated mice compared with the angiotensin II and phenylephrine control mice (3.45±1.11% versus 8.62±4.79%; P=4.59×10-3) and that the accumulation of FAP-positive cells was also significantly decreased, as indicated by FAP immunohistochemical staining (4077±1746 versus 7327±1741 cells/mm2; FAP vaccine versus angiotensin II and phenylephrine control; P=6.67×10-3). No systemic or organ-specific inflammation due to antibody-dependent cell cytotoxicity induced by the FAP vaccine was observed. Although the transient activation of myofibroblasts has an important role in maintaining the structural robustness in the process of tissue repair, the FAP vaccine showed no adverse effects in myocardial infarction and skin injury models. Our study demonstrates the FAP vaccine can be a therapeutic tool for cardiac fibrosis.

Adipose-mesenchymal stem cell-derived extracellular vesicles enhance angiogenesis and skin wound healing via bFGF-mediated VEGF expression.

This study aimed to investigate whether extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ASCs) promote skin wound healing by delivering basic fibroblast growth factor (bFGF) to enhance vascular endothelial growth factor (VEGF) expression. ASCs were isolated and transfected with either a bFGF knockdown lentivirus (Lv-sh-bFGF) or a control lentivirus (Lv-sh-NC). EVs were extracted from ASCs cultures and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting for surface markers. EVs were extracted from the conditioned mediums of ASCs and subjected to different treatments. These EVs or control treatments were injected at the wound edges. Wound healing was assessed using histological techniques, including H&E and Masson's trichrome staining to evaluate tissue regeneration, collagen organization, and immunohistochemistry for CD31 to quantify microvessel density. Protein expression of bFGF and VEGF was measured by Western blotting. ASC-derived EVs significantly promoted angiogenesis and improved skin wound healing. EVs encapsulating bFGF enhanced VEGF expression in the wound tissue, while knockdown of bFGF reduced both bFGF and VEGF expression, leading to delayed wound healing. Further knockdown of VEGF partially reversed the pro-angiogenic and wound-healing effects of bFGF-encapsulated EVs. This study demonstrates that ASC-derived EVs promoted skin wound repair by enhancing angiogenesis and accelerating tissue regeneration through the bFGF/VEGF axis. These findings highlight the therapeutic potential of ASCs-derived EVs in improving skin wound healing.

Novel cocktail therapy based on multifunctional supramolecular hydrogel targeting immune-angiogenesis-nerve network for enhanced diabetic wound healing

Diabetes-associated chronic skin wounds present a formidable challenge due to inadequate angiogenesis and nerve regeneration during the healing process. In the present study, we introduce a groundbreaking approach in the form of a novel cocktail therapy utilizing a multifunctional supramolecular hydrogel. Formulated through the photo-crosslinking of gelatinized aromatic residues and β-cyclodextrin (β-CD), this injectable hydrogel fosters weak host-guest interactions, offering a promising solution. The therapeutic efficacy of the hydrogel is realized through its integration with adipose-derived stem cells (ADSCs) and lipid nanoparticles encapsulating ginsenoside RG1 and Stromal cell-derived factor-1 (SDF-1). This strategic combination directs ADSCs to the injury site, guiding them toward neurogenic specialization while establishing an advantageous immunomodulatory environment through macrophage reprogramming. The synergistic effects of the newly differentiated nerve cells and the regenerative cytokines secreted by ADSCs contribute significantly to enhanced angiogenesis, ultimately expediting the diabetic wound healing process. To summarize, this innovative hydrogel-based therapeutic system represents a novel perspective for the management of diabetic wounds by concurrently targeting immune response, angiogenesis, and nerve regeneration—a pivotal advancement in the quest for effective solutions in diabetic wound care.