(+)4-cholesten-3-one has been proved to have potential wound healing effect in the process of wound regeneration. This study aimed to evaluate the effect of (+)4-cholesten-3-one/sodium alginate/gelatin on skin injury and reveal its potential molecular mechanism. First, we prepared sodium alginate/gelatin hydrogel (SA/Gel hydrogel) with different ratios and tested their characteristics. Based on these results, different concentrations of (+)4-cholesten-3-one were added into SA/Gel hydrogel. A full-thickness skin injury model was successfully established to evaluate wound healing activityin vivo. HE staining and Masson staining were used to evaluate the thickness of granulation tissue and collagen deposition level. Immunohistochemical staining and immunofluorescence staining were applied to detect the level of revascularization and proliferation in each group of wounds. Western blot, quantitative-PCR and immunofluorescence staining were used to detect the expression of proteins related to Wnt/β-catenin signaling pathway in each group of wounds.In vitroresults showed that the hydrogel not only created a 3D structure for cell adhesion and growth, but also exhibited good swelling ability, excellent degradability and favorable bio-compatibility. Most importantly,in vivoexperiments further indicated that (+)4-cholesten-3-one/SA/Gel hydrogel effectively enhanced wound healing. The effectiveness is due to its superior abilities in accelerating healing process, granulation tissue regeneration, collagen deposition, promoting angiogenesis, tissue proliferation, as well as fibroblast activation and differentiation. The underlying mechanism was related to the Wnt/β-catenin signaling pathway. This study highlighted that (+)4-cholesten-3-one/SA/Gel hydrogel holds promise as a wound healing dressing in future clinical applications.

Despite differing etiologies, acute thermal burn injuries and full-thickness (FT) skin defects are associated with similar therapeutic challenges. When not amenable to primary or secondary closure, the conventional standard of care (SoC) treatment for these wound types is split-thickness skin grafting (STSG). This invasive procedure requires adequate availability of donor skin and is associated with donor site morbidity, high healthcare resource use (HCRU), and costs related to prolonged hospitalization. As such, treatment options that can facilitate effective healing and donor skin sparing have been highly anticipated. The RECELL® Autologous Cell Harvesting Device facilitates preparation of an autologous skin cell suspension (ASCS) for the treatment of acute thermal burns and FT skin defects. In initial clinical trials, the approach showed superior donor skin-sparing benefits and comparable wound healing to SoC STSG among patients with acute thermal burn injuries. These findings led to approval of RECELL for this indication by the US Food and Drug Administration (FDA) in 2018. Subsequent clinical evaluation in non-thermal FT skin wounds showed that RECELL, when used in combination with widely meshed STSG, provides donor skin-sparing advantages and comparable healing outcomes compared with SoC STSG. As a result, the device received FDA approval in June of 2023 for treatment of FT skin defects caused by traumatic avulsion or surgical excision or resection. Given that health economic advantages have been demonstrated for RECELL ± STSG versus STSG alone when used for burn therapy, it is prudent to examine similarities in the burn and FT skin defect treatment pathways to forecast the potential health economic advantages for RECELL when used in FT skin defects. This article discusses the parallels between the two indications, the clinical outcomes reported for RECELL, and the HCRU and cost benefits that may be anticipated with use of the device for non-thermal FT skin defects.

29Three-dimensional (3D)-printed bioactive scaffolds that can be produced rapidly could offer an individualized approach for treating full-thickness skin defects. Decellularized extracellular matrix (dECM) and mesenchymal stem cells have been proven to support wound healing. Adipose tissues obtained by liposuction are rich in adipose-derived dECM (adECM) and adipose-derived stem cells (ADSCs) and thus represent a natural source of bioactive materials for 3D bioprinting. Herein, ADSC-laden 3D-printed bioactive scaffolds consisting of gelatin methacryloyl (GelMA), hyaluronic acid methacryloyl (HAMA), and adECM were fabricated with dual properties of photocrosslinking in vitro and thermosensitive crosslinking in vivo. adECM was prepared by decellularization of human lipoaspirate and mixed as a bioactive material with GelMA and HAMA to form a bioink. Compared with the GelMA-HAMA bioink, the adECM-GelMA-HAMA bioink had better wettability, degradability, and cytocompatibility. Full-thickness skin defect healing in a nude mouse model showed that ADSC-laden adECM-GelMA-HAMA scaffolds accelerated wound healing by promoting faster neovascularization, collagen secretion, and remodeling. ADSCs and adECM collectively conferred bioactivity on the prepared bioink. This study represents a novel approach to enhancing the biological activity of 3D-bioprinted skin substitutes by adding adECM and ADSCs derived from human lipoaspirate and may provide a promising therapeutic option for full-thickness skin defects.

OBJECTIVE: To investigate the clinical outcomes of a novel soft tissue repair patch (porcine small intestinal submucosa patch, SIS patch) in the treatment of full-thickness hand skin defects.
METHODS: From January 2017 to July 2019, 80 patients with hand soft tissue defects, who met the inclusion criteria, were retrospectively reviewed and divided into two groups. After debridement, patients in group A were treated with the novel SIS patch to cover the wound, and patients in group B were treated with autologous skin graft. The dimensions of skin defect area and healing outcome were evaluated and recorded. Scar assessment was carried out using Scar Cosmesis Assessment and Rating Scale (SCAR scale) at the last follow-up postoperation, and the recovery of wound sensation was assessed at the same time using British Medical Research Council (BMRC) grading of sensorimotor recovery. All the data were collected and statistically analyzed.
RESULTS: A total of 80 patients were enrolled in the study with 40 patients in each group. Four patients in group A and 5 patients in group B were excluded due to wound infection and lost to follow-up. There were 36 patients in group A and 35 patients in group B finally got follow-up postoperation with mean interval of 12.75 ± 5.61 months in group A and 14.11 ± 5.42 months in group B. The dimensions of skin defect area in group A ranged from 7.5 to 87.5 cm2 (mean 25.97 ± 18.66 cm2) and in group B ranged from 7.5 to 86.25 cm2 (mean 33.61 ± 19.27 cm2) which have no significant difference (P > 0.05). SCAR scale results of group A and group B were 10.98 ± 0.33 and 9.49 ± 0.35, respectively, and the difference was statistically significant (P < 0.05). BMRC grading results showed 6 cases of S4, 11 cases of S3+, 5 cases of S3, 6 cases of S2, 6 cases of S1 and 2 cases of S0 in group A, and 8 cases of S4, 10 cases of S3+, 7 cases of S3, 4 cases of S2, 5 cases of S1, and 1 case of S0 in group B, which had no significant difference between them (P > 0.05).
CONCLUSIONS: The novel SIS patch is an applicable biological material in the treatment of hand skin defect, which could achieve a better cosmetic appearance of the newborn skin tissue.

Trauma, burns, and diabetes result in nonhealing wounds that can cause bone or tendon exposure, a significant health threat. The use of an artificial regeneration template combined with skin grafting as an alternative method to highly invasive flap surgery has been shown to be an effective way to cover full-thickness skin defects with bone or tendon exposure for both functional and aesthetic recovery. However, artificial regeneration templates, such as Pelnac, are overwhelmingly expensive, limiting their clinical use. Here, we demonstrate for the first time that polyurethane film combined with absorbable gelatine sponge, affordable materials widely used for haemostasis, are effective for dermal reconstruction in wounds with bone or tendon exposure. The absorbable gelatine sponge combined with polyurethane film was applied to eight patients, all resulting in adequate granulation that fully covered the exposed bone or tendon. The outcome of absorbable gelatine sponge combined with polyurethane film application indicates that this approach is a potential novel and cost-effective dermal reconstruction strategy for the treatment of severe wounds with bone or tendon exposure.

UNASSIGNED: Acute skin wounds may compromise the skin barrier, posing a risk of infection. Small intestinal submucosa (SIS) is widely used to treat acute and chronic wounds. However, the efficacy of SIS to accelerate wound healing still needs to be improved to meet clinical demands. To tackle this problem, platelet-rich plasma (PRP) is used due to its potency to promote proliferation, migration and adhesion of target cells. In this study, we applied PRP and SIS to skin wounds to explore their effects on wound healing by evaluating re-epithelialization, collagen production, angiogenesis and the inflammatory response.
UNASSIGNED: A 1 × 1-cm full-thickness skin defect was established in mice. Sixty mice were divided into four treatment groups: PRP + SIS, PRP, SIS and control. On days 3, 5, 7, 10 and 14 post-surgery, tissue specimens were harvested. Haematoxylin and eosin, Masson\'s trichrome, immunohistochemical and immunofluorescence double staining were used to visualize epidermal thickness, collagen and vascular regeneration and inflammation.
UNASSIGNED: Wound contraction in the PRP and PRP + SIS groups was significantly greater, compared with the other groups, on days 3 and 5 post-surgery. A histological analysis showed higher collagen expression in the PRP and PRP + SIS groups on day 7, which was associated with a thicker epidermal layer on day 14. In addition, immunohistochemical staining showed that CD31-positive blood vessels and vascular endothelial growth factor expression in the PRP + SIS and PRP groups were significantly higher, compared with the control group. Furthermore, immunofluorescence double staining showed that the number of M1 and M2 macrophages in the PRP + SIS and PRP groups was higher, compared with the control and SIS groups alone, on day 3. However, on day 7, the number of M1 macrophages dramatically decreased in the PRP + SIS and PRP groups. The ratio of M2 to M1 macrophages in the PRP + SIS and PRP groups was 3.97 and 2.93 times that of the control group and 4.56 and 3.37 times that of the SIS group, respectively.
UNASSIGNED: Co-administration of SIS and PRP has a better effect on promoting angiogenesis, re-epithelialization and collagen regeneration in managing acute wound healing than either agent alone.

To overcome limited donor-site availability in patients with extensive burns, split-thickness skin grafts (STSGs) are sometimes minced into micrografts (MGs) to improve the expansion ratio of the grafts, but this may reduce wound healing. We aimed to produce a novel hydrogel as an overlay of minced STSGs to improve wound healing. The new hydrogel was produced using recombinant human collagen type III powder as a raw material. Morphological and physical characteristics (degradation and swelling rate), cytotoxicity, and cell viability of the hydrogel were evaluated in vitro. A full-thickness in vivo skin defect model was constructed with male Sprague-Dawley rats. The animals were randomly assigned to experimental and control groups in which the new hydrogel and Vaseline gauze, respectively, were overlaid on minced STSGs to repair and regenerate skin wound. The healing rates and recovery status were compared between the two groups. The hydrogels exhibited good water retention properties and a suitable degradation rate, which can promote the proliferation and migration of wound healing-related cells in vitro. Further, using the hydrogel as an overlay accelerated wound closure and angiogenesis, increased dermal tissue and basement membrane formation, enhanced collagen synthesis and wound healing-related growth factor expression, while reducing scar formation compared to the Vaseline gauze group. In conclusion, the novel, low-cost recombinant human collagen hydrogel can accelerate wound closure and improve wound healing when used as an overlay of minced STSGs. The new hydrogel could become a new treatment option for traumatic skin wounds caused by burns or injuries.

OBJECTIVE: To investigate the function of miR-126-3p loaded on adipose stem cell (ADSC)-derived exosomes (ADSC-Exos) in wound healing of full-thickness skin defects.
METHODS: ADSCs transfected with miR-126-3p mimic, miR-126-3p inhibitor or pcDNA3.1-PIK3R2, or PKH26-marked ADSC-Exos were cultured with fibroblasts or human umbilical vein endothelial cells (HUVECs). The proliferation and migration rates of fibroblasts and angiogenesis of HUVECs were measured. Rats with full-thickness skin defects were injected with ADSC-Exos or exosomes extracted from ADSCs transfected with miR-126-3p inhibitor and the wound healing rates were measured. The wound bed, collagen deposition and angiogenesis in injured rats were assessed.
RESULTS: ADSC-Exos could be ingested by fibroblasts and HUVECs. Co-incubation with ADSCs or ADSC-Exos promoted the proliferation and migration of fibroblasts and angiogenesis of HUVECs, which was further enhanced by miR-126-3p overexpression. Inhibition of ADSC-Exos or miR-126-3p or PIK3R2 overexpression suppressed the proliferation and migration of fibroblasts and angiogenesis of HUVECs. ADSC-derived exosomal miR-126-3p increased wound healing rate, collagen deposition and newly formed vessels in injured rats.
CONCLUSIONS: ADSC-derived exosomal miR-126-3p promotes wound healing of full-thickness skin defects by targeting PIK3R2.

Vacuum sealing drainage (VSD) and epidermal growth factor (EGF) both play an important role in the treatment of wounds. This study aims to explore the effects of the combination of VSD and EGF on wound healing and the optimal concentration and time of EGF.
We tested the proliferation and migration capacity of HaCaT and L929 cells at different EGF concentrations (0, 1, 5, 10, and 100 ng/ml) and different EGF action times (2, 10, and 30 min). A full-thickness skin defect model was established using male, 30-week-old Bama pigs. The experiment included groups as follows: routine dressing change after covering with sterile auxiliary material (Control), continuous negative pressure drainage of the wound (VSD), continuous negative pressure drainage of the wound and injection of EGF 10 min followed by removal by continuous lavage (V + E 10 min), and continuous negative pressure drainage of the wound and injection of EGF 30 min followed by removal by continuous lavage (V + E 30 min). The wound healing rate, histological repair effect and collagen deposition were compared among the four groups.
An EGF concentration of 10 ng/ml and an action time of 10 min had optimal effects on the proliferation and migration capacities of HaCaT and L929 cells. The drug dispersion effect was better than drug infusion after bolus injection effect, and the contact surface was wider. Compared with other groups, the V + E 10 min group promoted wound healing to the greatest extent and obtained the best histological score.
A recombinant human epidermal growth factor (rhEGF) concentration of 10 ng/ml can promote the proliferation and migration of epithelial cells and fibroblasts to the greatest extent in vitro. VSD combined with rhEGF kept in place for 10 min and then washed, can promote wound healing better than the other treatments in vivo.

Although employed to release growth factors (GFs) for regenerative medicine, platelet-rich plasma (PRP) has been hindered by issues like burst effect. Based on collagen sponge scaffolds (CSSs) modified with polydopamine (pDA), a novel dermal regeneration template (DRT) was designed. However, whether it could efficiently deliver PRP and even foster wound healing remained unclear. In this work, after PRP was prepared and pDA-modified CSSs (pDA-CSSs) were fabricated, microscopic observation, GFs release assay and in-vitro biological evaluations of pDA-CSSs with PRP (pDA-CSS@PRP) were performed, followed by BALA-C/nu mice full-thickness skin defects implanted with pDA-CSS@PRP covered by grafted skins (termed as a One-step strategy). As a result, scanning electron microscope demonstrated more immobilized platelets on pDA-CSS\' surface with GFs\' controlled release via enzyme-linked immunosorbent assay, compared with CSSs. In line with enhanced in-vitro proliferation, adhesion and migration of keratinocytes & endothelial cells, pDA-CSS@PRP were histologically revealed to accelerate wound healing with less scar via rapid angiogenesis, arrangement of more mature collagen, guiding cells to spread, etc. In conclusion, pDA-CSSs have potential to serve as a novel DRT capable of delivering PRP, which may foster full-thickness skin defect healing by means of a One-step strategy.