Cellular In Vitro Responses Induced by Human Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles Obtained from Suspension Culture.

Mesenchymal stem/stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have been described to have important roles in tissue regeneration, including tissue repair, control of inflammation, enhancing angiogenesis, and regulating extracellular matrix remodeling. MSC-EVs have many advantages for use in regeneration therapies such as facility for dosage, histocompatibility, and low immunogenicity, thus possessing a lower possibility of rejection. In this work, we address the potential activity of MSC-EVs isolated from adipose-derived MSCs (ADMSC-EVs) cultured on cross-linked dextran microcarriers, applied to test the scalability and reproducibility of EV production. Isolated ADMSC-EVs were added into cultured human dermal fibroblasts (NHDF-1), keratinocytes (HaCat), endothelial cells (HUVEC), and THP-1 cell-derived macrophages to evaluate cellular responses (i.e., cell proliferation, cell migration, angiogenesis induction, and macrophage phenotype-switching). ADMSC viability and phenotype were assessed during cell culture and isolated ADMSC-EVs were monitored by nanotracking particle analysis, electron microscopy, and immunophenotyping. We observed an enhancement of HaCat proliferation; NHDF-1 and HaCat migration; endothelial tube formation on HUVEC; and the expression of inflammatory cytokines in THP-1-derived macrophages. The increased expression of TGF-ß and IL-1ß was observed in M1 macrophages treated with higher doses of ADMSC-EVs. Hence, EVs from microcarrier-cultivated ADMSCs are shown to modulate cell behavior, being able to induce skin tissue related cells to migrate and proliferate as well as stimulate angiogenesis and cause balance between pro- and anti-inflammatory responses in macrophages. Based on these findings, we suggest that the isolation of EVs from ADMSC suspension cultures makes it possible to induce in vitro cellular responses of interest and obtain sufficient particle numbers for the development of in vivo concept tests for tissue regeneration studies.

Indole-3-carbinol loaded-nanocapsules modulated inflammatory and oxidative damages and increase skin wound healing in rats.

This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.

I3C nanocapsules exhibited characteristics compatible with this kind of suspension;On 3rd day, I3C nanocapsules prevented the increase of wound area;I3C nanocapsules decreased oxidative damage in wound tissue;Inflammatory proteins were decreased in I3C nanocapsules treated group.

Early versus Delayed Vitrectomy for Open Globe Injuries: A Systematic Review and Meta-Analysis.

Background: Open globe injuries (OGIs) are a leading cause of monocular blindness worldwide and require prompt intervention to prevent proliferative vitreoretinopathy (PVR) and endophthalmitis when serious intraocular damage occurs. The management of OGIs involves initial wound closure within 24 hours, followed by vitrectomy as a secondary surgery. However, there is a lack of consensus regarding the optimal timing of vitrectomy for maximizing visual outcomes. This meta-analysis aimed to investigate whether early or delayed vitrectomy leads to better outcomes in patients with OGIs. Methods: This review was conducted based on PRISMA guidelines. The Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched (October 23, 2023). Clinical studies that used vitrectomy to manage OGIs as early (within 7 days) or delayed (8-14 days) interventions were included. Randomized controlled trials (RCTs) and non-RCTs were appraised using the Cochrane risk of bias and JBI tools, respectively. Results: Eleven studies met the inclusion criteria and were included in the quantitative analyses. There were 235 patients with OGIs who received early intervention and 211 patients who received delayed intervention. The retina was reattached in 91% and 76% of the patients after early and delayed intervention, respectively. Traumatic PVR was present in 9% and 41% of the patients in the early and delayed groups, respectively. The odds of retinal reattachment after vitrectomy were greater in the early group (OR = 3.42, p = 0.010, 95% CI=1.34-8.72), and the odds of visual acuity ≥ 5/200 were 2.4 times greater in the early group. The incidence of PVR was significantly greater in the delayed surgery group (OR = 0.16, p < 0.0001; 95% CI=0.06-0.39), which also required more than one vitrectomy surgery. Conclusion: Early vitrectomy results in better postoperative visual acuity, a greater proportion of retinal reattachment, and a decreased incidence of PVR.

Performance of multiple therapeutic approaches for palatal wound healing after soft tissue graft removal - an overview of systematic reviews.

OBJECTIVE: To overview the literature to answer the following question: "What is the performance of different therapies on wound healing and postoperative discomfort after palatal ASTG removal?" METHODS: SRs that evaluated the wound healing (WH), postoperative pain, bleeding, and analgesic consumption of patients submitted to de-epithelialized/free gingival grafts (FGG) or subepithelial connective tissue grafts (SCTG) removed from the palate were included. The searches were conducted on six white and two gray databases up to December 2023. Methodological quality was evaluated through AMSTAR 2. The synthesis of results was described as a narrative analysis. RESULTS: Ten SRs (involving 25 randomized clinical trials) related to low-level laser therapy (LLLT) (3), platelet-rich fibrin (PRF) (4), cyanoacrylate tissue adhesives (CTA) (2), and ozone therapy (OT) (1) were included in this overview. All techniques demonstrated improvements in WH. LLT, PRF, and CTA reduced pain and analgesic consumption. PRF and CTA reduced bleeding. Regarding methodological quality, the SRs were classified as critically low (2), low (5), moderate (2), or high quality (1). CONCLUSIONS: In SRs related to LLLT, PRF, CTA, and OT, the use of different therapies after palatal ASTG removal improved WH and postoperative discomfort. Due to the studies' low methodological quality and high heterogeneity, data should be interpreted with caution. CLINICAL RELEVANCE: The present overview compiles the evidence of SRs related to different therapies for WH and patients' postoperative experience and reveals that different treatments can significantly improve the clinical outcomes of patients who require ASTG removal for periodontal or peri-implant surgeries. REGISTRATION: PROSPERO registration number: CRD42022301257.

Polyphenolic Compounds Nanostructurated with Gold Nanoparticles Enhance Wound Repair.

Gold nanoparticles (AuNPs) have been used in a wide range of applications, conferring to bio-molecules diverse properties such as delivery, stabilization, and reduction of the adverse effects of drugs or plant extracts. Polyphenolic compounds from Bacopa procumbens (B. procumbens) (BP) can modulate proliferation, adhesion, migration, and cell differentiation, reducing the artificial scratch area in fibroblast cultures and promoting wound healing in an in vivo model. Here, chemically synthesized AuNPs conjugated with BP (AuNP-BP) were characterized using UV-Vis, ATR-FTIR, DLS, zeta-potential, and TEM analysis. The results showed an overlap of the FTIR spectra of the polyphenolic compounds from B. procumbens adhered to the surface of the AuNPs. UV-vis analysis indicated that the average size of the AuNP-BP was 28 nm, while DLS analysis showed a size of 44.58 nm and, by TEM, a size of 16.5 nm with an icosahedral morphology was observed. These measurements suggest an increase in the size of the nanoparticles after conjugation with BP, compared to the sizes of 9 nm, 44.51 nm, and 14.17 nm for the unconjugated AuNPs, respectively. Furthermore, the zeta potential of the AuNPs, which was originally -36.3 ± 12.3 mV shifted to -18.2 ± 7.02 mV after conjugation with BP, indicating improved stability of the nanoparticles. Enhancement of the wound healing effect was evaluated by morphometric, histochemical, and FTIR changes in a rat wound excision model. Results showed that the nanoconjugation process reduced the BP concentrations by 100-fold to have the same wound healing effect as BP alone. Besides, histological and FTIR spectroscopy analyses demonstrated that AuNP-BP treatment exhibited better macroscopical performance, showing a reduction in inflammatory cells and an increased synthesis and improved organization of collagen fibers.

Exploring the association between a standardized extract of pequi peels (Caryocar brasiliense Cambess) and blue light as a photodynamic therapy for treating superficial wounds.

Natural products derived from plants can be used as photosensitizers for antimicrobial photodynamic therapy (aPDT) combining key therapeutic strategies for tissue repair while controlling microorganisms' growth. We investigated a standardized extract of pequi peels (Caryocar brasiliense Cambess) as a brownish natural photosensitizer for aPDT using blue light. Three concentrations of the pequi extract (PE; 10, 30, or 90 µg/mL) were tested solely or associated with blue laser (445 nm, 100 mW, 138 J/cm2 , 6 J, 60 s). In vitro, we quantified reactive oxygen species (ROS), assessed skin keratinocytes (HaCat) viability and migration, and aPDT antimicrobial activity on Streptococcus or Staphylococcus strains. In vivo, we assessed wound closure for the most active concentration disclosed by the in vitro assay (30 µg/mL). Upon aPDT treatments, ROS were significantly increased in cell monolayers regardless of PE concentration. PE at low doses stimulates epithelial cells. Although PE stimulated cellular migration, aPDT was moderately cytotoxic to skin keratinocytes, particularly at the highest concentration. The antimicrobial activity was observed for PE at the lowest concentration (10 µg/mL) and mostly at PE 10 µg/mL and 30 µg/mL when used as aPDT photosensitizers. aPDT with PE 30 µg/mL presents antimicrobial activity without compromising the initial phases of skin repair.

Bioengineered skin constructs based on mesenchymal stromal cells and acellular dermal matrix exposed to inflammatory microenvironment releasing growth factors involved in skin repair.

BACKGROUND: Skin tissue engineering is a rapidly evolving field of research that effectively combines stem cells and biological scaffolds to replace damaged tissues. Human Wharton's jelly mesenchymal stromal cells (hWJ-MSCs) are essential to generate tissue constructs, due to their potent immunomodulatory effects and release of paracrine factors for tissue repair. Here, we investigated whether hWJ-MSC grown on human acellular dermal matrix (hADM) scaffolds and exposed to a proinflammatory environment maintain their ability to produce in vitro growth factors involved in skin injury repair and promote in vivo wound healing. METHODS: We developed a novel method involving physicochemical and enzymatic treatment of cadaveric human skin to obtain hADM scaffold. Subsequently, skin bioengineered constructs were generated by seeding hWJ-MSCs on the hADM scaffold (construct 1) and coating it with human platelet lysate clot (hPL) (construct 2). Either construct 1 or 2 were then incubated with proinflammatory cytokines (IL-1α, IL-1ß, IL-6, TNF-α) for 12, 24, 48, 72 and 96 h. Supernatants from treated and untreated constructs and hWJ-MSCs on tissue culture plate (TCP) were collected, and concentration of the following growth factors, bFGF, EGF, HGF, PDGF, VEGF and Angiopoietin-I, was determined by immunoassay. We also asked whether hWJ-MSCs in the construct 1 have potential toward epithelial differentiation after being cultured in an epithelial induction stimulus using an air-liquid system. Immunostaining was used to analyze the synthesis of epithelial markers such as filaggrin, involucrin, plakoglobin and the mesenchymal marker vimentin. Finally, we evaluated the in vivo potential of hADM and construct 1 in a porcine full-thickness excisional wound model. RESULTS: We obtained and characterized the hADM and confirmed the viability of hWJ-MSCs on the scaffold. In both constructs without proinflammatory treatment, we reported high bFGF production. In contrast, the levels of other growth factors were similar to the control (hWJ-MSC/TCP) with or without proinflammatory treatment. Except for PDGF in the stimulated group. These results indicated that the hADM scaffold maintained or enhanced the production of these bioactive molecules by hWJ-MSCs. On the other hand, increased expression of filaggrin, involucrin, and plakoglobin and decreased expression of vimentin were observed in constructs cultured in an air-liquid system. In vivo experiments demonstrated the potential of both hADM and hADM/hWJ-MSCs constructs to repair skin wounds with the formation of stratified epithelium, basement membrane and dermal papillae, improving the appearance of the repaired tissue. CONCLUSIONS: hADM is viable to fabricate a tissue construct with hWJ-MSCs able to promote the in vitro synthesis of growth factors and differentiation of these cells toward epithelial lineage, as well as, promote in a full-thickness skin injury the new tissue formation. These results indicate that hADM 3D architecture and its natural composition improved or maintained the cell function supporting the potential therapeutic use of this matrix or the construct for wound repair and providing an effective tissue engineering strategy for skin repair.

Novel Studies in the Designs of Natural, Synthetic, and Compound Hydrogels with Biomedical Applications / Novedosos Estudios en el Diseño de Hidrogeles Naturales, Sintéticos y Compuestos con Aplicaciones Biomédicas

ABSTRACT Hydrogels are gaining widespread popularity in the biomedical field due to their extraordinary properties, such as biocompatibility, biodegradability, zero toxicity, easy processing, and similarity to physiological tissue. They have applications in controlled drug release, wound dressing, tissue engineering, and regenerative medicine. Among these applications, hydrogels as a controlled drug delivery system stands out, which releases active substances in precise amounts and at specific times. To explore the latest advances in the design of hydrogels, a literature review of articles published in indexed scientific journals, in Scopus and Science Direct, was carried out. This review aimed to discover and describe the most innovative hydrogel research with applications in the biomedical field; hydrogels synthesized with polymers of different origins were selected, such as; i. Natural (dextran, agarose, chitosan, etc.); ii. Synthetic (polyacrylamide, polyethylene glycol, polyvinyl alcohol, etc.); iii. Composites (interpenetrants, hybrid crosslinkers, nanocomposites, etc.). Comparative analysis revealed that hydrogels with composite materials show the most promise. These composite hydrogels combine the advantages of different polymers or incorporate additional components, offering enhanced properties and functionalities. In summary, hydrogels are versatile biomaterials with immense potential in biomedicine. Their unique properties make them suitable for diverse applications. However, innovative designs and formulations must continue to be explored to further advance the capabilities of hydrogels and expand their biomedical applications.

RESUMEN Los hidrogeles están ganando una extensa popularidad en el campo biomédico gracias a que presentan propiedades extraordinarias como biocompatibilidad, biodegradabilidad, nula toxicidad, fácil procesamiento, y similitud con el tejido fisiológico. tienen aplicaciones en la liberación controlada de fármacos, el vendaje de heridas, la ingeniería de tejidos y la medicina regenerativa. Entre estas aplicaciones, destaca el uso de hidrogeles como sistema de administración controlada de fármacos, que liberan sustancias activas en cantidades precisas y en momentos concretos. Para explorar los últimos avances en el diseño de hidrogeles, se realizó una revisión bibliográfica de artículos publicados en revistas científicas indexadas, en Scopus y Science Direct. El objetivo de esta revisión fue descubrir y describir las investigaciones de hidrogeles más innovadoras con aplicaciones en el campo biomédico, se seleccionaron hidrogeles sintetizados con polímeros de diferente índole como; i. Naturales (dextrano, agarosa, quitosano, etc.); ii. Sintéticos (poliacrilamida, polietilenglicol, alcohol polivinílico, etc); iii. Compuestos (interpenetrantes, reticulantes híbridos, nanocompuestos, etc.). El análisis comparativo reveló que los hidrogeles que utilizan materiales compuestos son los más prometedores. Estos hidrogeles compuestos combinan las ventajas de distintos polímeros o incorporan componentes adicionales, ofreciendo propiedades y funcionalidades mejoradas. En resumen, los hidrogeles son biomateriales versátiles con un inmenso potencial en biomedicina. Sus propiedades únicas los hacen adecuados para diversas aplicaciones, sin embargo, se debe seguir explorando diseños y formulaciones innovadores para seguir avanzando en las capacidades de los hidrogeles y ampliar sus aplicaciones biomédicas.

Red LED light therapy associated with epidermal growth factor on wound repair process in rats.

Epidermal growth factor (EGF) and light-emitting diode (LED) are currently deployed as promissory treatments for skin repair; however, the mechanisms of their association are not yet evidenced. Thus, the present study aimed to evaluate the effects of combined treatment with EGF and red LED on the wound healing processes in rats. Adult Wistar rats were randomized in control group (CG) wounds without treatment; wounds submitted to EGF treatment (EGF); wounds submitted to LED treatment (LED); wounds submitted to EGF associated with LED treatments (EGF/LED). Treatments were performed immediately after the surgical procedure and each 24 h, totaling 8 sessions. Moreover, LED was applied before EGF treatment at a single point in the center of the wound. Morphological characteristics and the immunoexpression of COX-2, VEGF, and TGF-ß were measured. The results demonstrated that EGF/LED group presented a higher wound healing index. Additionally, all experimental groups presented similar findings in the histological evaluation, the degree of inflammation, and the area of dermis-like tissue. However, for EGF-treated animals (with or without LED), neoepithelial length was higher. Furthermore, all the treated groups decreased COX-2 and increased VEGF immunoexpression, and only EGF/LED group enhanced the TGF-ß protein expression when compared to the untreated group. This research shows that EGF and LED modulate inflammatory process and increase the vascularity. In addition, treatment of EGF associated with LED promoted a more evident positive effect for increasing TGF-ß expression and may be promising resources in the clinical treatment of cutaneous wounds.

Evaluation of mesenchymal cells and dapsone for the treatment of dermonecrotic wounds caused by Loxosceles laeta venom in rabbits / Avaliação de células mesenquimais e dapsona para o tratamento de feridas dermonecróticas causadas pelo veneno de Loxosceles laeta em coelhos

This study aimed to evaluate the efficacy of mesenchymal stem cells (MSC), alone or associated with dapsone (DAP), in treating dermonecrotic wounds caused by Loxosceles laeta venom. Twenty-five male rabbits were distributed into five groups. Negative control received ultrapure water (C-), whilst all other groups were injected with 20 μg of L. laeta venom. After 4 hours, each group received one of the following treatments: PBS (C+), DAP, MSC, and DAP+MSC. Animals were evaluated daily and photographic records made for analysis of wound area. Twelve days after, animals were euthanized and skin samples removed for histological analysis. We observed that DAP showed the best percentage of wound contraction at day 3. In the treatments using MSCs, a negative value of wound contraction was observed for the isolated MSCs, as well as a lower contraction value for the association of the MSC + DAP when compared to PBS, probably, by the increase in initial infammation after the application of stem cells, due to the fact that MSCs secrete a broad spectrum of bioactive molecules such as cytokines and growth factors that favor regeneration. Histologically, it was observed that animals of C+ showed extensive areas of necrosis, ulcers, neutrophilic infiltrate, and mineralization. Collagen deposition showed increase in MSC+DAP treatment, however vascularization remained unchanged. This is the first report using MSC and MSC+DAP as a treatment for cutaneous loxoscelism and more studies are needed to determine its use as an alternative therapy for dermonecrotic lesions caused by Loxosceles spider.

Este estudo teve como objetivo avaliar a eficácia das células-tronco mesenquimais (CTMs), isoladas ou associadas à dapsona (DAP), no tratamento de feridas dermonecróticas causadas pelo veneno de Loxosceles laeta. Vinte e cinco coelhos machos foram distribuídos em cinco grupos. O controle negativo recebeu água ultrapura (C-), enquanto todos os outros grupos foram injetados com 20 μg de veneno de L. laeta. Após 4 horas, cada grupo recebeu um dos seguintes tratamentos: PBS (C+), DAP, CTMs e DAP + CTMs. Os animais foram avaliados diariamente durante 12 dias, e feitos registros fotográficos para análise da ferida e no 12º dia, foram eutanasiados e, retiradas amostras de pele para análise histológica. Observou-se que a DAP apresentou o melhor percentual de contração da ferida no terceiro dia. Nos tratamentos com CTMs, observou-se uma contração negativa da ferida tanto para as CTMs isoladas, bem como a associação CTMs + DAP em relação ao PBS, possivelmente, pelo aumento da infamação inicial após a aplicação de células-tronco. Isso é devido ao fato de que as CTMs secretam um amplo espectro de moléculas bioativas como citocinas e fatores de crescimento que favorecem a regeneração. Histologicamente, observou-se que os animais de C+ apresentaram extensas áreas de necrose, úlceras, infiltrado neutrofílico, além de mineralização. Houve aumento de deposição de colágeno no tratamento CTMs + DAP, no entanto, a vascularização permaneceu inalterada. Este é o primeiro relato usando CTMs e CTMs + DAP como tratamento para loxoscelismo cutâneo e mais estudos são necessários para determinar seu uso como terapia alternativa para lesões demonecróticas causadas pela aranha Loxosceles.

Rehabilitation therapy with insulin-like growth factor after acute skeletal muscle injury / Terapia de reabilitação com fator de crescimento semelhante à insulina após lesão muscular esquelética aguda / Terapia de rehabilitación con factor de crecimiento semejante a la insulina después de una lesión aguda del músculo esquelético

ABSTRACT Introduction Skeletal muscle injuries account for 10% to 50% of treadmill sports injuries. Insulin-like growth factor (IGF) is a family of polypeptides with both insulin-like anabolic and growth-promoting effects. Sports play a vital role in the recovery of skeletal muscle injuries. Objective The paper analyzes the ability of insulin-like growth factor 1 (IGF-1) to repair skeletal muscle injury caused by treadmill exercise. Method We injected drugs under the wound after exercise-induced injury in rats. The control group was injected with saline, and the experimental group was injected with an insulin-like growth factor. We conduct histological and electron microscopic structural analysis of rats, Results: After an injury, the experimental group formed a basal lamina protective film earlier than the control group, activated myoblasts, formed myofilaments, formed myotubes, and fused into muscle fibers earlier than the control group. The healing quality was also better. The experimental group was endogenous. The mRNA content of sex IGF-1 and IGF-2 both increased earlier than the control group. Conclusion Local injection of exogenous insulin-like growth factor-1 can stimulate the proliferation of myoblasts and accelerate the post-traumatic repair process of skeletal muscle caused by treadmill sports. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução As lesões do músculo esquelético representam de 10% a 50% das lesões em esteira esportiva. O fator de crescimento semelhante à insulina (IGF) é uma família de polipeptídeos com efeitos anabólicos e de promoção do crescimento semelhantes à insulina. Os esportes desempenham um papel vital na recuperação de lesões musculares esqueléticas. Objetivo o artigo analisa a capacidade do fator de crescimento semelhante à insulina 1 (IGF-1) em reparar lesões musculares esqueléticas causadas por exercícios em esteira. Método Injetamos drogas sob a ferida após lesão induzida por exercício em ratos. O grupo controle foi injetado com solução salina e o grupo experimental foi injetado com um fator de crescimento semelhante à insulina. Realizamos análises histológicas e microscópicas eletrônicas estruturais de ratos. Resultados Após a lesão, o grupo experimental formou um filme protetor da lâmina basal mais cedo do que o grupo controle, mioblastos ativados, miofilamentos formados, miotubos formados e fundidos em fibras musculares mais cedo do que o grupo controle. A qualidade da cura também foi melhor. O grupo experimental era endógeno. O conteúdo do sexo IGF-1 e IGF-2 mRNA aumentou mais cedo do que no grupo de controle. Conclusão A injeção local de fator de crescimento semelhante à insulina 1 exógeno pode estimular a proliferação de mioblastos e acelerar o processo de reparo muscular esquelético pós-traumático causado por esportes em esteira. Nível de evidência II; Estudos terapêuticos: investigação dos resultados do tratamento.

RESUMEN Introducción Las lesiones del músculo esquelético representan del 10% al 50% de las lesiones deportivas en cinta. El factor de crecimiento semejante a la insulina (IGF) es una familia de polipéptidos con efectos anabólicos y estimulantes del crecimiento semejantes a la insulina. Los deportes juegan un papel vital en la recuperación de las lesiones del músculo esquelético. Objetivo El artículo analiza la capacidad del factor de crecimiento semejante a la insulina 1 (IGF-1) para reparar la lesión del músculo esquelético causada por el ejercicio en cinta. Método inyectamos drogas debajo de la herida después de una lesión inducida por el ejercicio en ratas. Al grupo de control se le inyectó solución salina y al grupo experimental se le inyectó un factor de crecimiento semejante a la insulina. Realizamos análisis estructurales histológicos y microscópicos electrónicos de ratas, Resultados: Después de una lesión, el grupo experimental formó una película protectora de la lámina basal antes que el grupo de control, activó mioblastos, formó miofilamentos, formó miotubos y se fusionó en fibras musculares antes que el grupo de control. La calidad de curación también fue mejor. El grupo experimental fue endógeno. El contenido de ARNm de IGF-1 e IGF-2 de sexo aumentaron antes que en el grupo de control. Conclusión La inyección local de factor de crecimiento semejante a la insulina 1 exógeno puede estimular la proliferación de mioblastos y acelerar el proceso de reparación postraumático del músculo esquelético causado por los deportes en cinta. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

The complexity of TGFß/activin signaling in regeneration.

The role of transforming growth factor ß TGFß/activin signaling in wound repair and regeneration is highly conserved in the animal kingdom. Various studies have shown that TGF-ß/activin signaling can either promote or inhibit different aspects of the regeneration process (i.e., proliferation, differentiation, and re-epithelialization). It has been demonstrated in several biological systems that some of the different cellular responses promoted by TGFß/activin signaling depend on the activation of Smad-dependent or Smad-independent signal transduction pathways. In the context of regeneration and wound healing, it has been shown that the type of R-Smad stimulated determines the different effects that can be obtained. However, neither the possible roles of Smad-independent pathways nor the interaction of the TGFß/activin pathway with other complex signaling networks involved in the regenerative process has been studied extensively. Here, we review the important aspects concerning the TGFß/activin signaling pathway in the regeneration process. We discuss data regarding the role of TGF-ß/activin in the most common animal regenerative models to demonstrate how this signaling promotes or inhibits regeneration, depending on the cellular context.

Full- versus partial-thickness sutures: experimental models of corneal injury repair.

PURPOSE: To evaluate the performance of full-thickness (FT) versus partial-thickness (PT) sutures in a full-thickness corneal wound in an animal model. METHODS: This is a prospective, experimental, comparative, longitudinal study. A 6-mm linear, full-thickness corneal incision was performed on the right eye of eight domestic pigs. Eyes were randomly assigned for repair with interrupted PT (80-90% depth) sutures or FT 10-0 nylon sutures. Anterior segment OCT, corneal pachymetry and clinical photographs were obtained 1, 4 and 8 weeks postoperatively. Corneal thickness, depth of suture placement, perilesional edema, coaptation of wound edges and complications were noted. Histopathologic examination was performed at 8 weeks. RESULTS: 100% of the eyes with FT sutures developed a linear, less opaque scar. 100% of the eyes with PT developed a dense, opaque stromal scar (p = 0.02). Vascularization of the cornea was present in 75% of PT group and 25% in the FT group (p = 0.50). As the corneas healed, there was a marked trend toward thicker corneas in the PT group versus FT group with a median difference of - 63 µm at week 1 [median 788 µm vs. 725 µm, (p = 0.11)], - 38 µm at week 4, (724 µm vs. 686 µm, (p = 0.63)) and - 47 µm median difference at week 8 with (670 µm vs. 623 µm, (p = 0.06)). Histopathology showed disorganization of the collagen fibers and the formation of a retrocorneal fibrous membrane in the PT group. CONCLUSIONS: The FT group presented less corneal edema at week 8 with a more linear and less opaque scar. Histopathology showed a better-organized scar and endothelialization without the formation of a fibrous membrane.

Membrana de látex natural de Hevea brasiliensis auxilia no processo de reparação tecidual em bovinos / Natural latex rubber from Hevea brasiliensis aids tissue repair of bovine

Feridas cutâneas em bovinos são um constante desafio clínico cirúrgico por desencadearem perdas econômicas bastante significativas. O látex proveniente da seiva da seringueira (Hevea brasiliensis) apresenta potencial terapêutico para incrementar o processo de reparação tecidual. Portanto, pretendeu-se com esse estudo avaliar o tipo de reação tecidual e os possíveis mecanismos de angiogênese desencadeados pelo implante de uma membrana de látex natural em bovinos. Para tal, foram utilizados seis bovinos da raça Nelore, submetidos ao implante subcutâneo experimental de três fragmentos de membranas de látex natural. Foram coletadas amostras de tecido e da membrana aos 15, 30 e 45 dias após a implantação, para avaliações histológicas, ultraestruturais por microscopia eletrônica de varredura e imunoistoquímicas com anticorpos antimarcador de macrófagos (MAC), CYR 61 e VEGF. O implante de látex proporcionou aumento da angiogênese e reparação tecidual em bovinos, não mediada pela expressão do VEGF e CYR 61.(AU)

Cattle wounds are a constant surgical and clinical challenge, leading to important economical losses. The latex from the sap of the rubber tree (Hevea brasiliensis) has therapeutic potential to enhance tissue repair process. Therefore, we evaluated the type of tissue reaction and possible mechanisms of angiogenesis triggered by implanting natural latex rubber in bovine species. Six Nelore bovines were subjected to subcutaneous experimental implant of three fragments of natural rubber latex membranes. Tissue and rubber membrane samples were harvested at 15, 30 and 45 days implantation for histology, scanning electron microscopy and immunohistochemical evaluation with anti macrophage marker (MAC), anti CYR 61, anti VEGF antibodies. The latex membrane estimulates tissue reaction and repair and significant angiogenesis stimuli without activating CYR 61 and VEGF pathways.(AU)

Photobiomodulation of a flowable matrix in a human skin ex vivo model demonstrates energy-based enhancement of engraftment integration and remodeling.

The use of dermal substitutes to treat skin defects such as ulcers has shown promising results, suggesting a potential role for skin substitutes for treating acute and chronic wounds. One of the main drawbacks with the use of dermal substitutes is the length of time from engraftment to graft take, plus the risk of contamination and failure due to this prolonged integration. Therefore, the use of adjuvant energy-based therapeutic modalities to augment and accelerate the rate of biointegration by dermal substitute engraftments is a desirable outcome. The photobiomodulation (PBM) therapy modulates the repair process, by stimulating cellular proliferation and angiogenesis. Here, we evaluated the effect of PBM on a collagen-glycosaminoglycan flowable wound matrix (FWM) in an ex vivo human skin wound model. PBM resulted in accelerated rate of re-epithelialization and organization of matrix as seen by structural arrangement of collagen fibers, and a subsequent increased expression of alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor A (VEGF-A) leading to an overall improved healing process. The use of PBM promoted a beneficial effect on the rate of integration and healing of FWM. We therefore propose that the adjuvant use of PBM may have utility in enhancing engraftment and tissue repair and be of value in clinical practice.

Reconstrucción de extensa úlcera por presión lumbar -glútea grado IV con colgajo lumbar bipediculado / Reconstruction of extensive ulcer by lumbar pressure - gluteal grade IV with bipedicled lumbar flap

INTRODUCCIÓN: La literatura cita numerosas técnicas quirúrgicas para la cobertura de defectos en región lumbar- glútea, complejos secundario a complicaciones neurológicas, como: colgajo de rotación, colgajos de transposición, colgajos musculocutáneos (dorsal ancho, glúteo mayor, vasto lateral, entre otros). Un severo compromiso en la extensión del defecto lumbar-glúteo hace difícil su reconstrucción total con resolución inmediata. OBJETIVO: Buscar alternativas de cobertura en extensas pérdidas de sustancia en base a los tejidos circundantes y demostrar la utilidad de los colgajos para cobertura de pérdida de sustancia, en reconstrucción de úlceras por presión extensas en la zona lumbar. PRESENTACIÓN DEL CASO: Presentamos el caso de una paciente cuadripléjica con pérdida de tejido en la zona lumbar y glútea de gran extensión que fue reconstruida con un colgajo lumbar transverso bi-pedunculado con vascularización tipo aleatorio. RESULTADOS: Se realizó una cirugía reconstructiva que la que se utilizó un colgajo lumbar transverso bi-pedunculado con vascularización tipo aleatoria, empleando un colgajo dermograso capaz de cerrar defectos lumbosacros severos, amplios y complejos, con satisfactorios resultados estéticos. CONCLUSIONES: El colgajo lumbar transverso es una opción quirúrgica confiable y recomendable con destacadas ventajas en virtud de notable amplitud de extensión para cobertura de defectos en la región lumbosacra como en la úlcera por presión de la presente paciente. Este tipo de colgajo tiene una adecuada vascularización que se integra apropiadamente a los tejidos adyacentes. El riesgo quirúrgico por la extensión del colgajo hace un reto y desafío para el cirujano.

INTRODUCTION: The literature cites numerous surgical techniques for the coverage of defects in the lumbar-gluteal region, complexes secondary to neurological complications, such as: rotation flap, transposition flaps, musculocutaneous flaps (latissimus dorsi, gluteus maximus, vastus lateralis, among others). A severe compromise in the extension of the lumbar-gluteal defect makes it difficult to fully reconstruct it with immediate resolution. There are several surgical techniques to repair gluteus-lumbar skin defects caused by pressure ulcers related to chronic neurologic disorders including rotation flap, transposition flap, muscle cutaneous flap (latissimus dorsa flap, gluteus maximus flap, vastus lateralis flap). OBJECTIVE: Search for alternative coverage in extensive losses of substance based on the surrounding tissues and demonstrate the usefulness of the flaps for coverage of loss of substance, in reconstruction of extensive pressure ulcers in the lumbar area. CASE PRESENTATION: We present the case of a quadriplegic patient with loss of tissue in the lumbar and gluteal area of ​​great extension that was reconstructed with a transverse lumbar bi-pedunculated flap with random type vascularization. RESULTS: Reconstructive surgery was performed using a transverse lumbar bi-pedunculated flap with random-type vascularization, using a dermofat flap capable of closing severe, wide and complex lumbosacral defects, with satisfactory aesthetic results. CONCLUSIONS: The transverse lumbar flap is a reliable and recommendable surgical option with outstanding advantages by virtue of a remarkable amplitude of extension for coverage of defects in the lumbosacral region as in the pressure ulcer of the present patient. This type of flap has an adequate vascularity that is properly integrated into adjacent tissues. The surgical risk due to the extension of the flap makes it a challenge and challenge for the surgeon.

Membrana de látex natural de Hevea brasiliensis auxilia no processo de reparação tecidual em bovinos / Natural latex rubber from Hevea brasiliensis aids tissue repair of bovine

Feridas cutâneas em bovinos são um constante desafio clínico cirúrgico por desencadearem perdas econômicas bastante significativas. O látex proveniente da seiva da seringueira (Hevea brasiliensis) apresenta potencial terapêutico para incrementar o processo de reparação tecidual. Portanto, pretendeu-se com esse estudo avaliar o tipo de reação tecidual e os possíveis mecanismos de angiogênese desencadeados pelo implante de uma membrana de látex natural em bovinos. Para tal, foram utilizados seis bovinos da raça Nelore, submetidos ao implante subcutâneo experimental de três fragmentos de membranas de látex natural. Foram coletadas amostras de tecido e da membrana aos 15, 30 e 45 dias após a implantação, para avaliações histológicas, ultraestruturais por microscopia eletrônica de varredura e imunoistoquímicas com anticorpos antimarcador de macrófagos (MAC), CYR 61 e VEGF. O implante de látex proporcionou aumento da angiogênese e reparação tecidual em bovinos, não mediada pela expressão do VEGF e CYR 61.(AU)

Cattle wounds are a constant surgical and clinical challenge, leading to important economical losses. The latex from the sap of the rubber tree (Hevea brasiliensis) has therapeutic potential to enhance tissue repair process. Therefore, we evaluated the type of tissue reaction and possible mechanisms of angiogenesis triggered by implanting natural latex rubber in bovine species. Six Nelore bovines were subjected to subcutaneous experimental implant of three fragments of natural rubber latex membranes. Tissue and rubber membrane samples were harvested at 15, 30 and 45 days implantation for histology, scanning electron microscopy and immunohistochemical evaluation with anti macrophage marker (MAC), anti CYR 61, anti VEGF antibodies. The latex membrane estimulates tissue reaction and repair and significant angiogenesis stimuli without activating CYR 61 and VEGF pathways.(AU)

El rol de la miel en los procesos morfofisiológicos de reparación de heridas / Rol of the miel in the morphophysiologic process of the reparation wounds

Los beneficios de la miel de abeja (Apis mellifera) se conocen desde hace miles de años y ha sido utilizada en la antigüedad por su valor nutritivo y medicinal siendo "redescubierta" por la medicina moderna debido a sus importantes propiedades anti-bacterianas en heridas infectadas. Nuevos estudios han argumentado a favor de la capacidad de la miel para interactuar con la compleja maquinaria celular y llevar a cabo la reparación de los tejidos. Por este motivo, se realizó una revisión de los contenidos actuales de las propiedades de la miel y su rol en los procesos morfofisiológicos de reparación de heridas. De esta manera se abarcó la acción anti-bacteriana, anti-oxidante y anti-inflamatoria de sus componentes. Así mismo, se revisaron las propiedades físicas y de desbridamiento, la importancia del origen floral y ubicación geográfica en el valor medicinal de los diferentes tipos de miel. Los estudios sugieren que los efectos de la miel son el resultado de una actividad combinada, donde sus componentes interactúan de manera sinérgica para lograr su función terapéutica. Su acción la realiza en todas las etapas del proceso morfofisiológico de reparación logrando acelerar la cicatrización de heridas. El origen florar y ubicación geográfica de la miel son factores importantes a considerar, ya que ésta varía en su composición y, por lo tanto, también su valor medicinal.

The benefits of honey bee honey (Apis mellifera) have been known for thousands of years and it has been used since ancient times for its nutritional and medicinal values. It was "rediscovered" by modern medicine as a result of its important anti-bacterial properties in infected wounds. New studies have argued for the ability of honey to interact with the complex cellular machinery and achieve tissue repair. Therefore, a review was carried out of current contents of the properties of honey and their role in the morphophysiological processes of wound repair. Hence, antibacterial action, anti-oxidant and anti-inflammatory components of its properties were evaluated. At the same time, we reviewed physical and wound debridement benefits, the importance of floral origin and geographical location in the medicinal value of different types of honey. The studies suggest that the effects of honey are the result of a combined activity, where its components interact synergistically to achieve therapeutic function. Its action is realized in all stages of the morphophysiological repair process, accomplishing accelerated wound healing. The floral origin and geographical location of the honey are important factors to consider since the composition of honey is variable, as is its medicinal value.

Is it possible to use autologous adipose graft for wound repair in patients with coagulation disorders?

INTRODUCTION: Wound healing is an intricate process whereby the skin repairs itself after injury according to a specific sequence: haemostasis, inflammation, proliferation and remodelling. Cell therapy has the potential to improve wound healing conditions and can be applied in both acute and chronic wounds. Normal healing requires adequate haemostatic function. Patients with coagulation disorders whose haemostatic function is altered may not heal naturally. AIM: The aim of this study was to show a simple, safe and inexpensive minimally invasive technique for wound repair in patients with coagulation disorders which involves the use of concentrated autologous adipose cells. PATIENTS AND METHOD: Six patients were enrolled in this study at the Foundation of Haemophilia, in Buenos Aires, Argentina. Five patients had severe haemophilia type A and one had severe von Willebrand diseases. The average age was 37.5 years old. One patient had a retractile scar (RS) and five patients had cutaneous fistulas (CF). Suction was used to obtain autologous adipose graft from subcutaneous abdominal tissue. The graft was centrifuged and, the adipose cell concentrate was transferred to a syringe and injected in the edge of the lesion. RESULTS: One adipose suction in each patient was performed. There were no intraoperative or postoperative complications in any of the six patients. CONCLUSIONS: The application of autologous adipose graft is a simple and safe treatment for complicated wound repair in patients with coagulation disorders.

Perfil de proteases de lesões cutâneas experimentais em camundongos tratadas com a lectina isolada das sementes de Canavalia brasiliensis / Proteases profile of skin wounds treated with lectin from Canavalia brasiliensis seeds

O objetivo deste estudo foi determinar o perfil de proteases em lesões cutâneas experimentais tratadas com a lectina isolada das sementes da Canavalia brasiliensis (ConBr) livre e conjugada com o seu açúcar específico. Lesões cirúrgicas foram produzidas assepticamente na região dorsal de camundongos (n=120), divididos de acordo com o tratamento empregado: Grupo NaCl (NaCl 150mM), Grupo manose (manose 100mM), Grupo ConBr (ConBr 100µg mL-1) e Grupo ConBr/manose (solução contendo ConBr 100µg mL-1 preparada em manose 100mM). Amostras da área lesada foram coletadas para determinação do perfil de proteases e atividade colagenolítica no 2°, no 7° e no 12° dia de pós-operatório. O perfil das proteínas realizado através de eletroforese SDS-PAGE demonstrou a presença de proteínas com massa molecular de 67kDa em todos os grupos. O Grupo ConBr/manose apresentou a maior atividade colagenolítica no 12° dia de pós-operatório. A lectina isolada das sementes da Canavalia brasiliensis influenciou a expressão de proteases com atividade colagenolítica podendo assim interferir no processo cicatricial das lesões cutâneas em camundongos.

The objective of the present study was determining the proteases profile of cutaneous healings treated with free and conjugated lectin of Canavalia brasiliensis (ConBr) and their specific sugar. An aseptic wound was produced in the thoracic area of the mice (n=120), divided according to the employed treatment: NaCl Group (150mM NaCl), manose Group (100mM manose), ConBr Group (100µg mL-1 ConBr) and ConBr/manose Group (solution containing 100µg mL-1 ConBr prepared in 100mM manose). Samples of the injured area were collected for determination of proteases profile and collagenolytic activity on 2nd, 7th e 12th days after the surgery. Electrophoresis SDS-PAGE demonstrated proteins with molecular mass of 67kDa in all groups. Group IV presented the highest collagenolytic activity on the 12th day post surgery. ConBr lectin influenced proteases expression with collagenolytic activity thus being able to intervene on skin wound healing in mice.