Genetic relationship between Chinese wild Vitis species and American and European Cultivars based on ISSR markers

Inter-simple sequence repeat (ISSR) markers were employed to detect the genetic diversity among 70 grape accessions including 52 clones of 17 Chinese wild grape species, seven interspecific hybrids, 10 Vitis vinifera L. cultivars, and one strain of Vitis riparia L. A total of 119 polymorphic bands with an average of 11.9 per primer were observed. The unweighted pair-group method (UPGMA) analysis indicated that the 70 clones or accessions had a similarity range from 0.08 to 0.93, indicating that abundant diversities exist among these accessions. Based on cluster analysis and principal coordinate analysis, all accessions could be divided into two major groups, the Chinese wild grape group, and the American and European cultivar group. The largest distance was found among V. riparia MichX, Vitis piasezkii, V. vinifera L. interspecific hybrid (Vitis binifera × V. labrusca) and the wild grapes native to China.     

Hydroalcoholic extract based-ointment from Punica granatum L. peels with enhanced in vivo healing potential on dermal wounds

The present study reports for the first time, the in vivo wound healing potential of Punica granatum L. peels. A 5% (w/w) methanolic extract based-ointment was formulated and evaluated for its wound healing in guinea pigs. The ointment was applied in vivo on the paravertebral area of twelve excised wounded models once a day for 10 consecutive days. The ointment significantly enhanced the wound contraction and the period of epithelialization as assessed by the mechanical (contraction rate, tensile strength), the biochemical (increasing of collagen, DNA and proteins synthesis) and the histopathological characteristics. Such investigation was encouraged by the efficiency of the methanolic extract as antimicrobial and antioxidant. Indeed, the extract showed antioxidant activity as strong as natural and synthetic compounds (Trolox, BHA, Quercetin). Furthermore, the extract exhibited significant antibacterial and antifungal activity against almost all tested bacteria: Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Klebsiella pneumoniae, Salmonella anatum, Salmonella typhimurium, Streptococcus pneumoniae, and fungi Candida albicans, Candida glabrata, Trichopyton rubrum and Aspergillus niger. The formulated ointment might well find use as skin repair agent without hazard to human health based on these results and on the fact that it has been well established that the extracts of pomegranate used in conditions similar to those applied by traditional medicine, showed no toxic effects.     

Wound healing Activities of the bioactive compounds from Micrococcus sp. OUS9 isolated from marine water

Marine species are increasingly important as a source of specific biological active metabolites. Marine species comprise almost half of global biodiversity. Oceans and sea are thus the biggest source of positive natural compounds that could be utilized in the pharmaceutical industry as functional constituents. In the present study was to find out the wound healing property of the bioactive compounds from Micrococcus sp. OUS9 isolated from marine source. The in vivo wound healing activity was studied using excision wound model. The KLUF 10 and KLUF13 ointment was prepared and used to determine wound healing activity in albino rats. Topical application of the ointment enhanced the contraction of wound in contrast with rat control group. KLUF13 had shown strong healing ability in wounds and had a positive influence on the various phases of wound repair.     

Identification of pterostilbene as a phytoalexin from Vitis vinifera leaves

An inducible antifungal compound in grapevine leaves (Vitis vinifera L., cv Cabernet-Sauvignon) has been identified as trans-pterostilbene (3,5-dimethoxy-4′-hydroxy stilbene). It is only a minor component of the phytoalexin response of V. vinifera but its antifungal activity is relatively high by comparison with resveratrol and the viniferins, stress metabolites which have been identified previously in grapevine. Methods for the quantitative analysis of pterostilbene, resveratrol, ε- and α-viniferins by HPLC are described.     

Copper-induced change in the ESR signal of hemoglobin nitrosyl complexes in wound by the action of copper nanoparticles

The results concerning changes in the ESR signal of hemoglobin nitrosyl complexes in wound tissues in the course of healing by the action of ointments with copper nanoparticles (patent N2460532, Russia) are presented. It is shown that the wound healing process modified by the influence of copper nanoparticles demonstrates the increase in the ESR signal amplitude for hemoglobin nitrosyl complexes as compared with controls (the ointment base without nanoparticles). Planimetric measurements of wound area through reparation course indicate an active process of wound healing for injuries treated with copper nanoparticles in the ointment, resulting in lessening half-reparation time up to 5.0 times as compared with controls (treatment with the ointment base). The paper discusses the role of copper nanoparticles, NO and their potential synergistic effect on the skin wound regeneration.     

Augmenting Endogenous Wnt Signaling Improves Skin Wound Healing

Wnt signaling is required for both the development and homeostasis of the skin, yet its contribution to skin wound repair remains controversial. By employing Axin2^LacZ/+ reporter mice we evaluated the spatial and temporal distribution patterns of Wnt responsive cells, and found that the pattern of Wnt responsiveness varies with the hair cycle, and correlates with wound healing potential. Using Axin2^LacZ/LacZ mice and an ear wound model, we demonstrate that amplified Wnt signaling leads to improved healing. Utilizing a biochemical approach that mimics the amplified Wnt response of Axin2^LacZ/LacZ mice, we show that topical application of liposomal Wnt3a to a non-healing wound enhances endogenous Wnt signaling, and results in better skin wound healing. Given the importance of Wnt signaling in the maintenance and repair of skin, liposomal Wnt3a may have widespread application in clinical practice.     

Thymosin beta 4 improves dermal burn wound healing via downregulation of receptor of advanced glycation end products in db/db mice

BackgroundThe delay of dermal burn wound healing caused by vascular disorders is a critical problem for many diabetic patients. Thymosin β₄ (Tβ₄), identified by subtractive cloning of endothelial cells on plastic versus basement membrane substrates, has been found to promote angiogenesis and dermal wound repair in rats, aged mice, and db/db diabetic mice. However, previous studies involving the role of Tβ₄ in wound repair were limited to mechanical damage and dermal impairment. Thus, this study aimed to evaluate the improvement of healing of burn wounds by Tβ₄ in relation to advanced glycation end products (AGE), which are pathological factors in diabetes.MethodsWe adapted a dermal burn wound in vivo model in which the dorsal skin of db/db mice was exposed for 10 s to 100 °C heated water to produce a deep second-degree burn 10 mm in diameter. Five mg/kg of Tβ₄ was then injected intradermally near the burn wound twice a week for 2 weeks.ResultsAfter treatment, Tβ₄ improved wound healing markers such as wound closure, granulation, and vascularization. Interestingly, Tβ₄ reduced levels of receptor of AGE (RAGE) during the wound healing period.ConclusionsTβ₄ exerts effects to remedy burn wounds via downregulation of RAGE.General significanceOur results suggest the potential importance of Tβ₄ as a new therapy for impaired burn wound healing that is associated with diabetes.     

In vitro and in vivo evaluation of the wound healing properties and safety assessment of two seaweeds (Sargassum ilicifolium and Ulva lactuca)

Seaweeds have been regarded as a reservoir of biologically active molecules that are important in the pharmaceutical industry. The aim of the present study was to explore the wound healing properties and to assess the safety of the seaweed Sargassum ilicifolium and Ulva lactuca. Enhanced cell proliferation and cell migration activities were observed in L929 cells treated with S. ilicifolium extract compared to U. lactuca extract treated cells and the control group. In-vivo experiments were conducted using five groups (10 in each) of Albino mice (BALB/c). Mice in group I and group II were treated (Orally, 100 mg/kg BW/day) with aqueous extracts of S. ilicifolium and U. lactuca, respectively for 14 days. Treatment group III received a topical application of the aqueous extract of S. ilicifolium (25% w/w) and ointment base (75% w/w) (2 g/kg BW/day, for 14 days). Group IV (Control) received an equal amount of distilled water, orally and mice in group V kept without wounds. The extract from S. ilicifolium showed stronger wound healing properties than the one from Ulva lactuca. Histopathological findings also revealed that the healing process was significantly enhanced in the mice group treated orally with S. ilicifolium aqueous extract. These findings show that S. ilicifolium species possess promising wound healing properties in-vitro and in-vivo.     

A framework map from grapevine V3125 (Vitis vinifera ‘Schiava grossa’?×?‘Riesling’)?×?rootstock cultivar ‘B?rner’ (Vitis riparia?×?Vitis cinerea) to localize genetic determinants of phylloxera root resistance

Grapevine rootstock cultivar ‘B?rner’ is a hybrid of Vitis riparia and Vitis cinerea Arnold that shows high resistance to phylloxera (Daktulosphaira vitifoliae Fitch). To localize the determinants of phylloxera root resistance, the susceptible grapevine V3125 (Vitis vinifera ‘Schiava grossa’ × ‘Riesling’) was crossed to ‘B?rner’. Genetic framework maps were built from the progeny. 235 microsatellite markers were placed on the integrated parental map. They cover 1,155.98 cM on 19 linkage groups with an average marker distance of 4.8 cM. Phylloxera resistance was scored by counting nodosities after inoculation of the root system. Progeny plants were triplicated and experimentally infected in 2 years. A scan of the genetic maps indicated a quantitative trait locus on linkage group 13. This region was targeted by six microsatellite-type markers newly developed from the V. vinifera model genome sequence. Two of these appear closely linked to the trait, and can be useful for marker-assisted breeding.     

Induction of defence mechanisms in grapevine leaves by emodin- and anthraquinone-rich plant extracts and their conferred resistance to downy mildew

The ability of two plant extracts, Rheum palmatum root extract (RPRE) and Frangula alnus bark extract (FABE), to protect Vitis vinifera leaves from Plasmopara viticola infection was evaluated. These natural products are toxic to the pathogen and induce defence reactions in a susceptible cultivar of V. vinifera (V. vinifera cv. Chasselas), including stilbenic phytoalexin accumulation, enhanced peroxidase (EC 1.11.1.7) activity, and a hypersensitive reaction. Inhibition of the first stage of biotrophic hyphal development of P. Viticola by the two plant extracts was observed. HPLC–DAD–MS analysis showed that these two natural extracts contain many phenolic compounds belonging to the anthraquinone family, such as rhein, frangulin A, emodin, aloe-emodin, chrysophanol, and physcion. Emodin alone is able to impair P. viticola development and to stimulate viniferins and the accumulation of pterostilbene.     

Wnt signaling induces epithelial differentiation during cutaneous wound healing

Background  

Cutaneous wound repair in adult mammals does not regenerate the original epithelial architecture and results in altered skin function. We propose that lack of regeneration may be due to the absence of appropriate molecular signals to promote regeneration. In this study, we investigated the regulation of Wnt signaling during cutaneous wound healing and the consequence of activating either the beta-catenin-dependent or beta-catenin-independent Wnt signaling on epidermal architecture during wound repair.     

Novel biosynthesis,characterization and bio-catalytic potential of green algae (Spirogyra hyalina) mediated silver nanomaterials

In recent years green nanotechnology gained significant importance to synthesize nanoparticles due to their cost effectiveness and biosafety. In the current study, silver nanoparticles were synthesized by using extract of Spirogyra hyalina as a capping and reducing agent. The synthesized nanoparticles were characterized by UV–Visible spectroscopy, Fourier transform infrared spectroscopy, Scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffractive analysis. Silver nanoparticles give a characteristic Surface Plasmon Resonance peak of 451 nm at 2.21 a.u (arbitrary unit). SEM micrograph revealed the spherical morphology and average grain size of 52.7 nm. Furthermore, antibacterial, antifungal, insecticidal, antioxidant and membrane damage activities were determined. The maximum antibacterial and antifungal activity was observed for Pseudomonas aeruginosa (18 ± 1.2 mm) and Fusarium solani (14.3 ± 0.6 mm), respectively. In membrane damage assay, Pseudomonas aeruginosa absorbed A₂₆₀ wavelength and gave maximum peak values of 0.286, 0.434 and 0.629 at 25, 35 and 45 µg/mL of silver nanoparticles. The membrane damage assay confirmed that nanoparticles are involved in bacterial cell membrane damage. At 500 ppm silver nanoparticles showed 30% mortality against Tribolium castaneum (a common grain pest). The silver nanoparticles also showed potent antioxidant activity and successfully scavenged the DPPH free radicals upto 53.43 ± 0.17, 43.26 ± 0.97, 31.39 ± 0.33, 24.62 ± 0.85, and 14.13 ± 0.12% at a concentration of 400, 200, 100, 50, and 25 µg/mL of nanoparticles, respectively. It is concluded that silver nanoparticles can easily be synthesized by using green algae Spirogyra hyalina as a capping and reducing agent. Silver nanoparticles showed potent biomedical activities and thus can be used for therapeutic applications invitro and invivo.     

Studies on wound healing potential of red pigment isolated from marine Bacterium Vibrio sp.

Wounds are common clinical entities of life which may be subacute or acute. Wound healing is a complex biochemical process where the cell structures are restored to normalcy, which depend on cell proliferation and migration, basically fibroblast cell. The present investigation was undertaken to evaluate the healing efficacy of red pigment isolated from marine isolate Vibrio sps on experimental wounds in albino rats. The red pigment was applied topically, twice daily for 14 days. Treatment with framycetin ointment was used as reference control. The red pigment treated group showed faster reduction in wound area in comparison with control and framycetin ointment treated groups. In conclusion, red pigment possesses significant healing potential in wounds and has a positive influence on the different phases of wound repair.     

SETD2 epidermal deficiency promotes cutaneous wound healing via activation of AKT/mTOR Signalling

ObjectivesCutaneous wound healing is one of the major medical problems worldwide. Epigenetic modifiers have been identified as important players in skin development, homeostasis and wound repair. SET domain–containing 2 (SETD2) is the only known histone H3K36 tri‐methylase; however, its role in skin wound healing remains unclear.Materials and MethodsTo elucidate the biological role of SETD2 in wound healing, conditional gene targeting was used to generate epidermis‐specific Setd2‐deficient mice. Wound‐healing experiments were performed on the backs of mice, and injured skin tissues were collected and analysed by haematoxylin and eosin (H&E) and immunohistochemical staining. In vitro, CCK8 and scratch wound‐healing assays were performed on Setd2‐knockdown and Setd2‐overexpression human immortalized keratinocyte cell line (HaCaT). In addition, RNA‐seq and H3K36me3 ChIP‐seq analyses were performed to identify the dysregulated genes modulated by SETD2. Finally, the results were validated in functional rescue experiments using AKT and mTOR inhibitors (MK2206 and rapamycin).ResultsEpidermis‐specific Setd2‐deficient mice were successfully established, and SETD2 deficiency resulted in accelerated re‐epithelialization during cutaneous wound healing by promoting keratinocyte proliferation and migration. Furthermore, the loss of SETD2 enhanced the scratch closure and proliferation of keratinocytes in vitro. Mechanistically, the deletion of Setd2 resulted in the activation of AKT/mTOR signalling pathway, while the pharmacological inhibition of AKT and mTOR with MK2206 and rapamycin, respectively, delayed wound closure.ConclusionsOur results showed that SETD2 loss promoted cutaneous wound healing via the activation of AKT/mTOR signalling.     

Immobilization of trypsin on polysaccharide film from Anacardium occidentale L. and its application as cutaneous dressing

Polysaccharide obtained from Anacardium occidentale L. gum was used for trypsin entrapment using cellulose (gaze) as a support and this preparation was applied as cutaneous wound healing. Trypsin release in vitro and the influence of pH and temperature on activity, stability and storage time of entrapped enzyme were evaluated. The preparation showed that it was still capable to release enzyme even after 48 h. Entrapped enzyme presented an optimal pH and temperature of 8.6 and 55 °C, respectively. Also, it was stable at high temperature (45 °C for 60 min) and wide range of pH, retaining 80% of its initial activity when stored for 28 days at 25 °C. Histopathological analysis of mice skin wound healing under the entrapped trypsin preparation treatment showed an acceleration of fibroblast proliferation, neovascularization of granulation tissue and stimulating effect on the epithelium formation compared to the skin wound under the treatment using preparations without trypsin. These results demonstrate that the trypsin–polysaccharide–cellulose preparation could be used in cutaneous dressing applications for wound healing.     

Stress-Mediated Increases in Systemic and Local Epinephrine Impair Skin Wound Healing: Potential New Indication for Beta Blockers

Background

Stress, both acute and chronic, can impair cutaneous wound repair, which has previously been mechanistically ascribed to stress-induced elevations of cortisol. Here we aimed to examine an alternate explanation that the stress-induced hormone epinephrine directly impairs keratinocyte motility and wound re-epithelialization. Burn wounds are examined as a prototype of a high-stress, high-epinephrine, wound environment. Because keratinocytes express the β2-adrenergic receptor (β2AR), another study objective was to determine whether β2AR antagonists could block epinephrine effects on healing and improve wound repair.

Methods and Findings

Migratory rates of normal human keratinocytes exposed to physiologically relevant levels of epinephrine were measured. To determine the role of the receptor, keratinocytes derived from animals in which the β2AR had been genetically deleted were similarly examined. The rate of healing of burn wounds generated in excised human skin in high and low epinephrine environments was measured. We utilized an in vivo burn wound model in animals with implanted pumps to deliver β2AR active drugs to study how these alter healing in vivo. Immunocytochemistry and immunoblotting were used to examine the up-regulation of catecholamine synthetic enzymes in burned tissue, and immunoassay for epinephrine determined the levels of this catecholamine in affected tissue and in the circulation. When epinephrine levels in the culture medium are elevated to the range found in burn-stressed animals, the migratory rate of both cultured human and murine keratinocytes is impaired (reduced by 76%, 95% confidence interval [CI] 56%–95% in humans, p < 0.001, and by 36%, 95% CI 24%–49% in mice, p = 0.001), and wound re-epithelialization in explanted burned human skin is delayed (by 23%, 95% CI 10%–36%, p = 0.001), as compared to cells or tissues incubated in medium without added epinephrine. This impairment is reversed by β2AR antagonists, is absent in murine keratinocytes that are genetically depleted of the β2AR, and is reproduced by incubation of keratinocytes with other β2AR-specific agonists. Activation of the β2AR in cultured keratinocytes signals the down-regulation of the AKT pathway, accompanied by a stabilization of the actin cytoskeleton and an increase in focal adhesion formation, resulting in a nonmigratory phenotype. Burn wound injury in excised human skin also rapidly up-regulates the intra-epithelial expression of the epinephrine synthesizing enzyme phenylethanolamine-N-methyltransferase, and tissue levels of epinephrine rise dramatically (15-fold) in the burn wounded tissue (values of epinephrine expressed as pg/ug protein ± standard error of the mean: unburned control, 0.6 ± 0.36; immediately postburn, 9.6 ± 1.58; 2 h postburn, 3.1 ± 1.08; 24 h post-burn, 6.7 ± 0.94). Finally, using an animal burn wound model (20% body surface in mice), we found that systemic treatment with βAR antagonists results in a significant increase (44%, 95% CI 27%–61%, p < 0.00000001) in the rate of burn wound re-epithelialization.

Conclusions

This work demonstrates an alternate pathway by which stress can impair healing: by stress-induced elevation of epinephrine levels resulting in activation of the keratinocyte β2AR and the impairment of cell motility and wound re-epithelialization. Furthermore, since the burn wound locally generates epinephrine in response to wounding, epinephrine levels are locally, as well as systemically, elevated, and wound healing is impacted by these dual mechanisms. Treatment with beta adrenergic antagonists significantly improves the rate of burn wound re-epithelialization. This work suggests that specific β2AR antagonists may be apt, near-term translational therapeutic targets for enhancing burn wound healing, and may provide a novel, low-cost, safe approach to improving skin wound repair in the stressed individual.     

Cold Atmospheric Plasma (CAP) Changes Gene Expression of Key Molecules of the Wound Healing Machinery and Improves Wound Healing In Vitro and In Vivo

Cold atmospheric plasma (CAP) has the potential to interact with tissue or cells leading to fast, painless and efficient disinfection and furthermore has positive effects on wound healing and tissue regeneration. For clinical implementation it is necessary to examine how CAP improves wound healing and which molecular changes occur after the CAP treatment. In the present study we used the second generation MicroPlaSter ß® in analogy to the current clinical standard (2 min treatment time) in order to determine molecular changes induced by CAP using in vitro cell culture studies with human fibroblasts and an in vivo mouse skin wound healing model. Our in vitro analysis revealed that the CAP treatment induces the expression of important key genes crucial for the wound healing response like IL-6, IL-8, MCP-1, TGF-ß1, TGF-ß2, and promotes the production of collagen type I and alpha-SMA. Scratch wound healing assays showed improved cell migration, whereas cell proliferation analyzed by XTT method, and the apoptotic machinery analyzed by protein array technology, was not altered by CAP in dermal fibroblasts. An in vivo wound healing model confirmed that the CAP treatment affects above mentioned genes involved in wound healing, tissue injury and repair. Additionally, we observed that the CAP treatment improves wound healing in mice, no relevant side effects were detected. We suggest that improved wound healing might be due to the activation of a specified panel of cytokines and growth factors by CAP. In summary, our in vitro human and in vivo animal data suggest that the 2 min treatment with the MicroPlaSter ß® is an effective technique for activating wound healing relevant molecules in dermal fibroblasts leading to improved wound healing, whereas the mechanisms which contribute to these observed effects have to be further investigated.     

Interleukin (IL)-19 promoted skin wound healing by increasing fibroblast keratinocyte growth factor expression

BackgroundInterleukin (IL)-19, a member of the IL-10 cytokine family, is involved in keratinocyte proliferation in psoriasis.ObjectivesWe investigated the role of IL-19 in the wound-healing process in vivo and in vitro.MethodsTwo full-thickness circular wounds (4 mm in diameter) were punched into the skin of BALB/C mice. IL-19 and keratinocyte growth factor (KGF) mRNA in wounded skin were determined using real-time PCR. The wounds were treated with PBS, vehicle, IL-19 (400 ng/mL), or IL-20 (400 ng/mL) (n = 6 in each group) twice daily and the percentage of wound healing was measured daily for 7 days. In vitro, human skin fibroblast CCD966-SK cells and keratinocyte HaCaT cells were treated with IL-19 or KGF. Cell proliferation and migration were determined using bromodeoxyuridine (BrdU) and transwell assays, respectively. The expression of IL-19 and KGF mRNA was also analyzed.ResultsIn wounded mouse skin, IL-19 mRNA was upregulated at 12 h, and KGF at 24 h after the injury. Both increases in gene expression declined 72 h after the skin had been wounded. The percentage of wound healing in IL-19-treated mice was higher than in control mice. In vitro, IL-19 upregulated KGF expression in the CCD966-SK cells; IL-19 was upregulated in KGF-treated HaCaT cells. KGF but not IL-19 promoted HaCaT cell proliferation. However, IL-19 significantly increased the migration of HaCaT cells. HaCaT cells treated with the cultured supernatants of IL-19-stimulated CCD966-SK cells showed significantly more proliferation than in controls.ConclusionsIL-19 is important for cutaneous wound healing because it upregulates KGF expression.     

Novel Biodegradable Porous Scaffold Applied to Skin Regeneration

Skin wound healing is an important lifesaving issue for massive lesions. A novel porous scaffold with collagen, hyaluronic acid and gelatin was developed for skin wound repair. The swelling ratio of this developed scaffold was assayed by water absorption capacity and showed a value of over 20 g water/g dried scaffold. The scaffold was then degraded in time- and dose-dependent manners by three enzymes: lysozyme, hyaluronidase and collagenase I. The average pore diameter of the scaffold was 132.5±8.4 µm measured from SEM images. With human skin cells growing for 7 days, the SEM images showed surface fractures on the scaffold due to enzymatic digestion, indicating the biodegradable properties of this scaffold. To simulate skin distribution, the human epidermal keratinocytes, melanocytes and dermal fibroblasts were seeded on the porous scaffold and the cross-section immunofluorescent staining demonstrated normal human skin layer distributions. The collagen amount was also quantified after skin cells seeding and presented an amount 50% higher than those seeded on culture wells. The in vivo histological results showed that the scaffold ameliorated wound healing, including decreasing neutrophil infiltrates and thickening newly generated skin compared to the group without treatments.     

Sus Scrofa immune tissues as a new source of bioactive substances for skin wound healing

Influence of a new protein-peptide complex on promoting skin wound healing in male BALB/c mice was studied. Protein-peptide complex, extracted from Sus scrofa immune organs, was percutaneously administered using two methods: by lecithin gel-like liquid crystals and by liquid microemulsion. On the fifth day, wound closure in mice with a linear wound model become faster in group (less 2 days comparison to other ones), which was treated with lecithin liquid crystals carrying the protein-peptide complex. This promoting healing can be caused by resorption of bioactive high-molecular compounds the animal skin. In mice with the linear wound model, the tensile strength of the scars were respectively higher both in mice, treated using lecithin liquid crystals with protein-peptide complex, and in mice, treated using microemulsion containing protein-peptide complex, by 215.4% and 161.5% relative to the animals, which did not receive bioactive substances for wound treatment. It was associated with the regeneratory effects of tissue- and species-specific protein-peptide complexes, including α-thymosin Sus scrofa (C3VVV8_PIG, m/z 3802.8) and other factors, which were described as parts of the new extracted complex. This reveals that percutaneous administration of the complex reliably activates local regenerative processes in animals.