Full-thickness Skin Incisions Research Articles

Bioinspired Collagen Scaffold Loaded with bFGF-Overexpressing Human Mesenchymal Stromal Cells Accelerating Diabetic Skin Wound Healing via HIF-1 Signal Pathway Regulated Neovascularization.

The healing of severe chronic skin wounds in chronic diabetic patients is still a huge clinical challenge due to complex regeneration processes and control signals. Therefore, a single approach is difficult in obtaining satisfactory therapeutic efficacy for severe diabetic skin wounds. In this study, we adopted a composite strategy for diabetic skin wound healing. First, we fabricated a collagen-based biomimetic skin scaffold. The human basic fibroblast growth factor (bFGF) gene was electrically transduced into human umbilical cord mesenchymal stromal cells (UC-MSCs), and the stable bFGF-overexpressing UC-MSCs (bFGF-MSCs) clones were screened out. Then, an inspired collagen scaffold loaded with bFGF-MSCs was applied to treat full-thickness skin incision wounds in a streptozotocin-induced diabetic rat model. The mechanism of skin damage repair in diabetes mellitus was investigated using RNA-Seq and Western blot assays. The bioinspired collagen scaffold demonstrated good biocompatibility for skin-regeneration-associated cells such as human fibroblast (HFs) and endothelial cells (ECs). The bioinspired collagen scaffold loaded with bFGF-MSCs accelerated the diabetic full-thickness incision wound healing including cell proliferation enhancement, collagen deposition, and re-epithelialization, compared with other treatments. We also showed that the inspired skin scaffold could enhance the in vitro tube formation of ECs and the early angiogenesis process of the wound tissue in vivo. Further findings revealed enhanced angiogenic potential in ECs stimulated by bFGF-MSCs, evidenced by increased AKT phosphorylation and elevated HIF-1α and HIF-1β levels, indicating the activation of HIF-1 pathways in diabetic wound healing. Based on the superior biocompatibility and bioactivity, the novel bioinspired skin healing materials composed of the collagen scaffold and bFGF-MSCs will be promising for healing diabetic skin wounds and even other refractory tissue regenerations. The bioinspired collagen scaffold loaded with bFGF-MSCs could accelerate diabetic wound healing via neovascularization by activating HIF-1 pathways.

Etamsylate-loaded hydrogel composed of carboxymethyl chitosan and oxidized tannic acid for improved wound healing

Proper wound dressing is essential to facilitate skin wound healing, stop bleeding, and prevent infections. Herein, carboxymethyl chitosan (CMC) was crosslinked with oxidized tannic acid (OTA) to form an adhesive and self-healing OTA/CMC hydrogel, and etamsylate was loaded to enhance the hemostatic effect of the hydrogel dressing. The resultant OTA/CMC/E hydrogel exhibited a spectrum of noteworthy attributes including excellent cell compatibility, high antioxidant activity, effective anti-bacterium, and excellent hemorrhage control. Functionally, it mitigated intracellular ROS levels, hindered the proliferation of Staphylococcus aureus, while also significantly reducing hemostasis duration and total blood loss. In vivo full-thickness skin incision results showed that the OTA/CMC/E hydrogel could efficiently accelerate in vivo wound closure and healing, promising as an advanced wound healing material.

Tunneling nanotube-driven complete regeneration of murine fetal skin

This study investigated the three-dimensional (3D) cellular interactions and tunneling nanotubes (TNTs) during fetal mouse skin regeneration on embryonic days 13 (E13) and 15 (E15). We aimed to understand spatial relationships among cell types involved in skin regeneration and assess the potential role of TNTs. Full-thickness skin incisions were performed in E13 and E15 embryos. Wound sites were collected, embedded in epoxy resin, processed for 3D reconstruction (1 μm thickness sections), and subjected to whole-mount immunostaining. We conducted in vitro co-culture experiments with fetal macrophages and fibroblasts to observe TNT formation. To assess the effect of TNTs on skin regeneration, an inhibiting agent (cytochalasin B) was administered to amniotic fluid. Results revealed that E13 epidermal keratinocytes interacted with dermal fibroblasts and macrophages, facilitating skin regrowth. TNT structures were observed at the E13-cell wound sites, among macrophages, and between macrophages and fibroblasts, confirmed through in vitro co-culture experiments. In vitro and utero cytochalasin B administration hindered those formation and inefficient skin texture regeneration at E13 wound sites. This emphasizes the necessity of 3D cellular interactions between epidermal and dermal cells during skin regeneration in mouse embryos at E13. The prevalence of TNT structures indicated their involvement in achieving complete skin texture restoration.

Neutrophil extracellular traps-inspired DNA hydrogel for wound hemostatic adjuvant

Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.

Pre-Incisional and Multiple Intradermal Injection of N-Acetylcysteine Slightly Improves Incisional Wound Healing in an Animal Model.

The objective of this study was to investigate if delivering multiple doses of N-acetylcysteine (NAC) post-surgery in addition to pre-incisional administration significantly impacts the wound healing process in a rat model. Full-thickness skin incisions were carried out on the dorsum of 24 Sprague-Dawley rats in six locations. Fifteen minutes prior to the incision, half of the sites were treated with a control solution, with the wounds on the contralateral side treated with solutions containing 0.015%, 0.03% and 0.045% of NAC. In the case of the NAC treated group, further injections were given every 8 h for three days. On days 3, 7, 14 and 60 post-op, rats were sacrificed to gather material for the histological analysis, which included histomorphometry, collagen fiber organization analysis, immunohistochemistry and Abramov scale scoring. It was determined that scars treated with 0.015% NAC had significantly lower reepithelization than the control at day 60 post-op (p = 0.0018). Scars treated with 0.045% NAC had a significantly lower collagen fiber variance compared to 0.015% NAC at day 14 post-op (p = 0.02 and p = 0.04) and a lower mean scar width than the control at day 60 post-op (p = 0.0354 and p = 0.0224). No significant differences in the recruitment of immune cells and histological parameters were found. The results point to a limited efficacy of multiple NAC injections post-surgery in wound healing.

Evaluation of Efficacy of 2 Extended-release Bupivacaine Products in a Porcine Model of Incisional Pain.

Extended-release (ER) local anesthetics are often incorporated in multi-modal analgesia or as an alternative when the effect of systemic analgesics may confound research. In this study, we compared the analgesic efficacy of 2 ER bupivacaine anesthetics with different ER mechanisms, a slow-release bupivacaine-meloxicam polymer (BMP) and a sucrose acetate isobutyrate bupivacaine (SABER-B) system. We used a full-thickness unilateral skin incision porcine model to evaluate the efficacy of these 2 ER bupivacaine analgesics. Eighteen male swine were randomized into 3 groups: control (saline; n = 6), bupivacaine:meloxicam (10 mg/kg, 0.3 mg/kg; n = 6), and SABER-B (10 mg/kg; n = 6). After surgery, pigs were assessed for changes in body weight, salivary cortisol level, and response to von Frey testing at 1, 3, 6, 24, 48, 72, 96, 120, and 168 h. Body weight and salivary cortisol levels were not significantly different between groups. Based on the von Frey testing, the pigs that received analgesics showed a significantly higher withdrawal threshold of nociceptive stimulus than those that received saline at 1, 3, 6, and 24 h after the surgery. At 48 h after surgery, the SABER-B group had a significantly higher withdrawal threshold than the saline group. The withdrawal threshold was not significantly different from the baseline measurement on intact skin at 3 and 6 h after surgery in the BMP group or 1 and 3 h for the SABERB group. The analgesic effects of BMP were greatest at 3 and 6 h after surgery and that of SABER-B as 1 and 3 h SABER-B provided an earlier onset of analgesia and longer analgesia duration than did BMP. This study demonstrates that ER bupivacaine can provide pigs with 24 to 48 h of analgesia for incisional pain.

Tissue adhesive hydrogel based on upcycled proteins and plant polyphenols for enhanced wound healing

This study investigates the potential of keratin and silk as natural structural proteins for designing tissue adhesives for wound healing. The study demonstrates the silk-wool-tannic acid (SF-Wool-TA) complex as an in situ tissue adhesive through the utilization of polyphenol chemistry. Keratin is first isolated from coarse sheep wool using a green microwave treatment process. Due to the presence of functional groups such as tyrosine, carboxyl, and thiol groups; silk, and keratin can form multiple interactions with pyrogallol and catechol functional groups of TA to form an in situ adhesive hydrogel. The SF-Wool-TA hydrogel exhibits in situ gelation, recyclability, moldability, elasticity (G’>100 kPa), adhesiveness, self-healing properties, 3D printability, antibacterial activity, antioxidant properties, and biocompatibility. The inclusion of wool keratin also enhances the hydrophilicity of the hydrogel. The hydrogel was tested in vivo and enhanced wound healing in a full-thickness skin incision model. The keratin-polyphenol interaction represents an attractive hybrid material for advanced biomaterials applications, particularly in the field of skin wound healing.

Injectable, self-healing hydrogel adhesives with firm tissue adhesion and on-demand biodegradation for sutureless wound closure.

Tissue adhesives have garnered extensive interest as alternatives and supplements to sutures, whereas major challenges still remain, including weak tissue adhesion, inadequate biocompatibility, and uncontrolled biodegradation. Here, injectable and biocompatible hydrogel adhesives are developed via catalyst-free o-phthalaldehyde/amine (hydrazide) cross-linking reaction. The hydrogels demonstrate rapid and firm adhesion to various tissues, and an o-phthalaldehyde-mediated tissue adhesion mechanism is established. The hydrogel adhesives show controlled degradation profiles of 6 to 22 weeks in vivo through the incorporation of disulfide bonds into hydrogel network. In liver and blood vessel injury, the hydrogels effectively seal the incisions and rapidly stop bleeding. In rat and rabbit models of full-thickness skin incision, the hydrogel adhesives quickly close the incisions and accelerate wound healing, which exhibit efficacies superior to those of commercially available fibrin glue and cyanoacrylate glue. Thus, the hydrogel adhesives show great potential for sutureless wound closure, hemostasis sealing, and prevention of leakage in surgical applications.

Tissue factor-heparanase complex: intracellular nonhemostatic effects

BackgroundHeparanase, known to be involved in angiogenesis, cancer progression, and inflammation, was shown to form a complex with tissue factor (TF) via its procoagulant domain and to enhance the hemostatic system. ObjectivesTo reveal a potential role of heparanase procoagulant domain in nonhemostatic effects. MethodsEffects of peptides 16 and 16AC derived from the heparanase procoagulant domain, discovered by our group, were studied using the XTT proliferation assay, western blot analysis, and immunostaining in vitro and a mouse wound-healing model. ResultsProcoagulant peptides induced increased proliferation, release of heparanase, and upregulation of heparanase, TF, tissue factor pathway inhibitor (TFPI), and TFPI-2 in U87, T47D, and MCF-7 tumor cell lines and in endothelial cells. These results were reversed by a peptide derived from TFPI-2 that inhibited the heparanse procoagulant domain-TF complex. Thrombin had a similar effect on tumor cell proliferation and heparanase release, although the impact of thrombin on cell proliferation was mediated by the heparanase procoagulant domain. A mouse model of full-thickness skin incision exhibited higher levels of heparanase, TF, TFPI, and TFPI-2 in the healing skin, mainly in the blood vessel wall and lumen in animals injected with the procoagulant peptides compared to controls. The cells transfected to overexpress full-length TF or TF devoid of the cytoplasmic domain demonstrated that the procoagulant domain conveyed intracellular signaling via TF. ConclusionHeparanase procoagulant domain induces nonhemostatic effects via TF. The finding that TF serves as a receptor to heparanase supports the close direct relation between the hemostatic system and cancer progression.

Injectable antibacterial tissue-adhesive hydrogel based on biocompatible o-phthalaldehyde/amine crosslinking for efficient treatment of infected wounds

Injectable antibacterial hydrogels have attracted considerable attention in wound management. However, the development of injectable hydrogels with excellent antibacterial activity, good biocompatibility, and strong tissue adhesion remains a challenge. In this study, an antibacterial tissue-adhesive hydrogel was developed based on a catalyst-free o-phthalaldehyde (OPA)/amine reaction by simply mixing OPA-terminated four-arm poly(ethylene glycol) (4aPEG-OPA) and ε-poly-l-lysine (ε-PLL) solutions. The hydrogel showed tunable gelation time, storage moduli, and degradation rate depending on the polymer concentration and 4aPEG-OPA/ε-PLL mass ratio. The hydrogel exhibited nearly 100% bacterial inhibition rates in-vitro against Gram-negative E. coli and Gram-positive S. aureus, while maintaining good biocompatibility. The hydrogel matched well in shape and tightly adhered to the tissue after in-situ formation at the wound sites. Following the treatment of rat models of full-thickness skin incisions and round wounds, the hydrogel effectively closed the wounds and promoted wound healing. Moreover, after administering to S. aureus infected full-thickness skin wounds, the hydrogel exhibited remarkable efficacy in inhibiting wound infection with a bacterial inhibition rate over 99.94%, achieving a significantly accelerated wound healing compared with the commercially available Prontosan® gel. Therefore, the hydrogel exhibits great potential as a wound dressing for infection prevention and promotion of healing.

Copper-deposited diatom-biosilica enhanced osteogenic potential in periodontalligamentstemcellsand rat cranium.

This study aimed to establish that copper-deposited Diatom-biosilica have the potential and possibility for clinical applications in repairing bone defects in a state of inflammation, such as periodontitis. Treatment of alveolar bone defects caused by periodontitis is a major challenge for clinicians. To achieve better repair results, the material should not only be bone conductive but also have the ability to stimulate osteogenesis and angiogenesis at the lesion site. Copper (II) and silicon (IV) ions could react to form basic copper silicate, which promoted both osteogenesis and angiogenesis. The mineralized diatom (Cu-DBs) loaded with copper (II) ions were synthesized by processing diatom shells using a hydrothermal method. Periodontal ligament stem cells (PDLSCs) are used to detect the osteogenic properties of Cu-DBs at the gene and protein levels. Using a rat cranial defect model and a full-thickness skin incision model to test the osteogenic properties of Cu-DBs in vivo. Compared with untreated diatoms (DBs), Cu-DBs extractsignificantly promoted the expression of osteogenesis-related factors like ALP, RUNX2, BSP, OCN, and OPN in PDLSCs. In vivo experiments further confirmed that Cu-DBs could effectively stimulate the osteogenesis of a rat skull defect and promote angiogenesis, significantly inhibit the inflammatory responses to bone damages, and reduce the infiltration of inflammatory immune cells to the lesion site. Due to the unique chemical characteristics of Si4+ and Cu2+ ions, the Cu-DBs composite biomaterial could enhance the osteogenic differentiation of PDLSCS in vitro, as well as stimulate the osteogenesis of the rat in vivo.

Temporal evaluation of efficacy and quality of tissue repair upon laser-activated sealing.

Injuries caused by surgical incisions or traumatic lacerations compromise the structural and functional integrity of skin. Immediate approximation and robust repair of skin are critical to minimize occurrences of dehiscence and infection that can lead to impaired healing and further complication. Light-activated skin sealing has emerged as an alternative to sutures, staples, and superficial adhesives, which do not integrate with tissues and are prone to scarring and infection. Here, we evaluate both shorter- and longer-term efficacy of tissue repair response following laser-activated sealing of full-thickness skin incisions in immunocompetent mice and compare them to the efficacy seen with sutures. Laser-activated sealants (LASEs) in which, indocyanine green was embedded within silk fibroin films, were used to form viscous pastes and applied over wound edges. A hand-held, near-infrared laser was applied over the incision, and conversion of the light energy to heat by the LASE facilitated rapid photothermal sealing of the wound in approximately 1 min. Tissue repair with LASEs was evaluated using functional recovery (transepidermal water loss), biomechanical recovery (tensile strength), tissue visualization (ultrasound [US] and photoacoustic imaging [PAI]), and histology, and compared with that seen in sutures. Our studies indicate that LASEs promoted earlier recovery of barrier and mechanical function of healed skin compared to suture-closed incisions. Visualization of sealed skin using US and PAI indicated integration of the LASE with the tissue. Histological analyses of LASE-sealed skin sections showed reduced neutrophil and increased proresolution macrophages on Days 2 and 7 postclosure of incisions, without an increase in scarring or fibrosis. Together, our studies show that simple fabrication and application methods combined with rapid sealing of wound edges with improved histological outcomes make LASE a promising alternative for management of incisional wounds and lacerations.

Actin cable formation and epidermis–dermis positional relationship during complete skin regeneration

Up to a certain developmental stage, a fetus can completely regenerate wounds in the skin. To clarify the mechanism of fetal skin regeneration, identifying when the skin switches from fetal-type wound regeneration to adult-type wound repair is necessary. We hypothesized that this switch occurs at several time points and that complete skin regeneration requires epidermal–dermal interactions and the formation of actin cables. We compared normal skin and wound morphology at each developmental stage. We examined two parameters: epidermal texture and dermal structure. We found that the three-dimensional structure of the skin was completely regenerated in full-thickness skin incisions made before embryonic day (E) 13. However, the skin texture did not regenerate in wounds made after E14. We also found that the dermal structure regenerates up to E16, but wounds created after E17 heal as scars with dermal fibrosis. By controlling the activity of AMP-activated protein kinase and altering actin cable formation, we could regulate scar formation in utero. These findings may contribute to therapies that allow complete skin regeneration without scarring.

Preparation and characterization of polyethylene glycol/chitosan composite water-based wound healing lubricant.

The proportion of pregnant women giving birth through cesarean section is increasing annually worldwide. However, post-cesarean section scar diverticulum is a common condition that occurs and requires better surgical strategies than the methods currently used. We hypothesized that using biological lubricant topically on the incision area during C-section could be an option to minimize the scar. This water-based polyethylene glycol (PEG)/chitosan (CS) composite lubricant was prepared via ultrasonic blending. The product was characterized using scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and Raman spectroscopy. The thermal stability of the materials and their heat absorption and release during heating were analyzed using thermogravimetric analysis and differential scanning calorimetry. Tribological tests proved that the PEG/CS composite had a better lubrication effect than either the PEG or CS lubricant alone, and the cell viability experiments verified that it had good biocompatibility. Finally, application of the composite lubricant onto the backs of mice modeling full-thickness skin incisions further confirmed that the product improved both the re-epithelialization and the collagen levels of the wounded skin. In conclusion, we expect our newly formulated PEG/CS composite lubricant to be useful not only for managing post-cesarean section scar diverticulum but also for healing skin wounds in general.

Supramolecular Thermo-Contracting Adhesive Hydrogel with Self-Removability Simultaneously Enhancing Noninvasive Wound Closure and MRSA-Infected Wound Healing.

Conventional wound closure and dressing are two crucial, time-consuming but isolated principles in wound care. Even though tissue adhesive opens a new era for wound closure, the method and biomaterial that can simultaneously achieve noninvasive wound closure and promote wound healing are highly appreciated. Herein, a novel supramolecular poly(N-isopropylacrylamide) hybrid hydrogel dressing composed of quaternized chitosan-graft-β-cyclodextrin, adenine, and polypyrrole nanotubes via host-guest interaction and hydrogen bonds is developed. The hydrogel demonstrates thermal contraction of 47% remaining area after 2 h at 37℃ and tissue adhesion of 5.74kPa, which are essential for noninvasive wound closure, and multiple mechanical and biological properties including suitable mechanical properties, self-healing, on-demand removal, antioxidant, hemostasis, and photothermal/intrinsic antibacterial activity (higher 99% killing ratio within 5 min after irradiation). In both full-thickness skin incision and excision wound models, the hydrogel reveals significant wound closure after 24 h post-surgery. In acute and methicillin-resistant Staphylococcus aureus-infected wound and photothermal/intrinsic antibacterial activity assays, wounds treated with the hydrogel demonstrate enhanced wound healing with rapid wound closure rate, mild inflammatory response, advanced angiogenesis, and well-arranged collagen fibers. Altogether, the results indicate the hydrogel is promising in synchronously noninvasive wound closure and enhanced wound healing.

Engineering a photosynthetic bacteria-incorporated hydrogel for infected wound healing

Treating wounds with multidrug-resistant bacterial infections remains a huge and arduous challenge. In this work, we prepared a “live-drug”-encapsulated hydrogel dressing for the treatment of multidrug-resistant bacterial infections and full-thickness skin incision repair. Our live dressing was comprised of photosynthetic bacteria (PSB) and extracellular matrix (ECM) gel with photothermal, antibacterial and antioxidant properties, as well as good cytocompatibility and blood compatibility. More interestingly, live PSB could be regarded as not only photothermal agents but also as anti-inflammatory agents to promote wound healing owing to their antioxidant metabolites. In vitro and in vivo studies showed that the PSB hydrogel not only had a high killing rate against methicillin-resistant Staphylococcus aureus (MRSA) but it also accelerated collagen deposition and granulation tissue formation by promoting cell proliferation and migration, which significantly promoted skin tissue regeneration and wound healing. We believe that the large-scale production of PSB Gel-based therapeutic dressings has the advantages of easy use and promising clinical applications. Statement of significanceRapid wound healing and the treatment of bacterial infections have always been the two biggest challenges in the field of wound care. We prepared a “live drug” dressing by encapsulating photosynthetic bacteria into an extracellular matrix hydrogel to sterilize the wound and promote wound healing.First, photosynthetic bacteria are not only a photothermal agent for photothermal wound sterilization, but also possess the anti-inflammatory capacity to enhance wound healing due to their antioxidant metabolites. Second, the extracellular matrix hydrogel is rich in a variety of growth factors and nutrients to promote cell migration and accelerate wound healing. Third, photosynthetic bacteria are not only green and non-toxic, but also can be obtained on a large scale, which facilitates manufacturing and clinical transformation.

Highly Efficient Self-Healing Multifunctional Dressing with Antibacterial Activity for Sutureless Wound Closure and Infected Wound Monitoring.

Wound healing represents a major clinical and public healthcare problem that is frequently challenged by infection risks, detrimental consequences on the surrounding tissues, and difficulties to monitor the healing process. Here wereport on a novel self-healing, antibacterial, and multifunctional wound dressing for sutureless wound closure and real-time monitoring of the healing parameters. The self-healing elastomer contains cetyltrimethylammonium bromide (CTAB) and has high mechanical toughness (35MJ m-3 ), biocompatibility, and outstanding antibacterial activity (bactericidal rate is ≈90% in 12 h), enabling the wound dressing to effectively inhibit bacterial growth and accelerate infected wound healing. In vivo tests based on full-thickness skin incision model shows that the multifunctional wound dressing can help in contracting wound edges and facilitate wound closure and healing, as could be evidenced by notably dense and well-organized collagen deposition. The test provides an evidence that the integrated sensor array within the multifunctional wound dressing can monitor temperature, pH, and glucose level of the wound area in real-time, providing reliable and timely information of the condition of the wound. Ultimately, the reported multifunctional dressing would be of high value in managing the burden associated with wound healing via personalised monitoring and treatment approaches, digital and other people-centred solutions for health care.

Comparative healing of swine skin following incisions with different surgical devices.

BackgroundElectrosurgical technology is widely used in surgical dissection and hemostasis, but the generated heat creates thermal injury to adjacent tissues and delays wound healing. The plasma blade (PB) applies pulsed radiofrequency (RF) to generate electrical plasma along the edge of a thin, flat, insulated electrode, minimizing collateral tissue damage. This study aimed to evaluate wound healing in swine skin following incision with a new surgical system that applies low-temperature plasma (NTS-100), a foreign PB, conventional electrosurgery (ES), and a scalpel blade.MethodsIn vitro porcine skin and an in vivo porcine skin model were used in this study. Full-thickness skin incisions 3 cm in length were made on the dorsum of each animal for each of the 5 surgical procedures at 0, 21, 28, 35, and 42 days. The timing of the surgical procedures allowed for wound-healing data points at 1, 2, 3, and 6 weeks accordingly. Local operating temperature and blood loss were quantified. Wounds were harvested at designated time points, tested for wound tensile strength, and examined histologically for scar formation and tissue damage.ResultsLocal operating temperature was reduced significantly with NTS-100 (cut mode 83.12±23.55 °C; coagulation mode 90.07±10.6 °C) compared with PB (cut mode 94.46±11.48 °C; coagulation mode 100.23±6.58 °C, P<0.05) and ES (cut mode 208.99±34.33 °C, P<0.01; coagulation mode 233.37±28.69 °C, P<0.01) in vitro. Acute thermal damage from NTS-100 was significantly less than ES incisions (cut mode: 247.345±42.274 versus 495.295±103.525 µm, P<0.01; coagulation mode: 351.419±127.948 versus 584.516±31.708 µm, P<0.05). Bleeding, histological scoring of injury, and wound strength were equivalent for the NTS-100 and PB incisions.ConclusionsThe local operating temperature of NTS-100 was lower than PB, and NTS-100 had similarly reliable safety and efficacy.

Photosynthetic Bacterial Band-Aids for Enhanced Wounds Healing

Treating wounds with multidrug-resistant bacterial infections remains a huge and arduous challenge. In this work, we prepared a “live-drug”-encapsulated hydrogel dressing for the treatment of multidrug-resistant bacterial infections and full-thickness skin incision repair. Our live dressing was composed of photosynthetic bacteria (PSB) and extracellular matrix (ECM) gel with excellent photothermal, antibacterial and antioxidant properties, as well as good cytocompatibility and blood compatibility. More interestingly, the live PSB could be regarded as not only photothermal agents but also anti-inflammatory agents to promote wound healing owing to their antioxidant metabolites. In vitro and in vivo studies showed the PSB hydrogel not only had a high killing rate against methicillin-resistant staphylococcus aureus (MRSA) but also accelerated collagen deposition and granulation tissue formation by promoting cell proliferation and migration, which significantly promoted skin tissue regeneration and wound healing. We believe that these large-scale production of PSB Gel-based therapeutic band-aids possess the advantage of easy-to-use and promising clinical applications. Funding Information: This work was supported by the National Natural Science Foundation of China (21977024, 21601046 and 31971304), the Beijing-Tianjin-Hebei Basic Research Cooperation Project (19JCZDJC64100), Cross-Disciplinary Project of Hebei University (DXK201916). One Hundred Talent Project of Hebei Province (E2018100002). Science Fund for Creative Research Groups of Nature Science Foundation of Hebei Province(B2021201038). Declaration of Interests: The authors have no competing interests to declare. Ethics Approval Statement: Animal experiments conducted in the work are in accordance with the Medical Comprehensive Experimental Center of Hebei University (Approval No. 2018004).

Both fumigation and heating of moxibustion promote wound healing and tissue repair in rats with full-thickness skin incision

To investigate the effect of moxibustion on wound healing, new capillaries and tissue repair in rats with full thickness skin excision. SD rats were randomly divided into control, moxa-fumigating and moxa-heating groups, with 24 rats in each group. The full-thickness skin excision injury model was replicated according to Balaji's and colleague's methods. Rats in the moxa-fumigating group received fumigation of moxa-smog at the wound surface (25 min/time) immediately after modeling through a smoke-heat separation device, and those of the moxa-heating group received conventional thermal stimulation of the ignited moxa over the wound (25 min/time) without moxa smog, once a day for 10 consecutive days. The wound color, pus, carrion, granulation, and healing status of the rats were observed. H.E. staining and Masson staining were used to observe the local tissues and collagen fibers of the wound on the 3rd and 7th days. Newly born capillaries at the wound surface were observed on the 10th day. Following modeling, the wound area of the moxa-fumigating group on the 1st and 7th day, and those of both moxa-fumigating and moxa-heating groups on the 3rd and 5th day were significantly reduced compared with the model group (P<0.001), and the wound area of the moxa-fumigating group was obviously smaller than that of the moxa-hea-ting group (P<0.01，P<0.001). On the 3rd and 7th day after modeling, the re-epithelialization rates were significantly increased (P<0.001), and the amounts of inflammatory cells were significantly reduced in both moxa-fumigating and moxa-heating groups (P<0.001). At the same time, the re-epithelialization rate of the moxa-fumigating group was higher than that of the moxa-heating group (P<0.05，P<0.001), and the inflammatory cell count of the moxa-fumigating group was lower than that of the moxa-hea-ting group (P<0.001). On the 10th day after the modeling, the number of new capillaries and capillary density in the wound basal layer were significantly increased in both moxa-fumigating and moxa-heating groups (P<0.05, P<0.001, P<0.01), and were notably higher in the moxa-fumigating group than in the moxa-heating group (P<0.01, P<0.05). Both fumigation and heating of moxibustion can promote wound healing in rats with full-thickness skin excision injury，which may be related to their effects in controlling the inflammatory response and promoting the production of collagen fibers, granulation tissue and capillaries.