Capacidade terapêutica da fitoterapia na odontologia: uma análise abrangente das proteínas antimicrobianas, anti-inflamatórias e reparadoras / Therapeutic capacity of phytotherapy in dentistry: a comprehensive analysis of antimicrobial, anti-inflammatory, and reparative properties

Introdução: A fitoterapia se baseia na utilização de plantas medicinais, através de diferentes formulações farmacêuticas com fins terapêuticos. Na Odontologia, os fitoterápicos têm sido alvo de estudos, devido suas propriedades benéficas, além de apresentarem biocompatibilidade, baixo custo e fácil acesso. Objetivo: Realizar um levantamento na literatura científica sobre a utilização da fitoterapia na Odontologia, com vistas aos efeitos antimicrobiano, anti-inflamatório e reparador. Material e Métodos: A busca ocorreu entre fevereiro a julho/2023, nas bases PubMed e LILACS, além de livre busca, cruzando-se os descritores "Phytotherapy", "Dentistry", "Anti-inflamatory Agents", "Anti-Infective Agents", "Wound Healing", "Fitoterapia", "Odontologia", "Anti-inflamatório", "Antimicrobiano" e "Cicatrização". Após leitura inicial, seguida da análise crítica com aplicação dos critérios estabelecidos, foram selecionadas 50 referências. Desenvolvimento: Diversas plantas são empregadas sob a forma de fitoterapia, como Aloe vera (babosa), Matricaria recutita (camomila), Copaifera (copaíba), Punica granatum (romã), Uncaria tomentosa (unha-de-gato), Malva sylvestris (malva), Althaea officinalis (malvaísco), Myracrodruon urundeuva (Aroeira), Lippia sidoides (Alecrim pimenta) e Glycyrrhiza glabra (Alcaçuz). Na Odontologia, pesquisas evidenciaram resultados satisfatórios para o tratamento de afecções da cavidade oral, especialmente com caráter inflamatório e infeccioso, além de aclerar a cicatrização. Esses achados apontam que a fitoterapia é um tratamento eficaz, acessível e com mínimos efeitos colaterais. Considerações finais: Com base na literatura revisada, a fitoterapia parece ser uma alternativa promissora no tratamento de afecções orais, devido aos seus notáveis efeitos cicatrizantes, antimicrobianos e anti-inflamatórios. Contudo, mais pesquisas com metodologias adequadas são necessárias para que se estabeleçam protocolos clínicos seguros e eficazes.

Introduction: Phytotherapy is based on the use of medicinal plants through different pharmaceutical formulations for therapeutic purposes. In Dentistry, phytotherapeutics have been the subject of studies due to their beneficial properties, as well as their biocompatibility, low cost, and easy accessibility. Objective: To conduct a literature review on the use of phytotherapy in Dentistry, focusing on antimicrobial, anti-inflammatory, and reparative effects. Materials and Methods: The search took place between February and July 2023, using PubMed and LILACS databases, in addition to a free search, crossing the descriptors "Phytotherapy," "Dentistry," "Anti-inflammatory Agents," "Anti-Infective Agents," "Wound Healing," "Fitoterapia," "Odontologia," "Anti-inflammatory," "Antimicrobial," and "Cicatrização." After an initial reading, followed by critical analysis with the application of established criteria, 50 references were selected. Development: Various plants are employed in phytotherapy, such as Aloe vera (aloe), Matricaria recutita (chamomile), Copaifera (copaiba), Punica granatum (pomegranate), Uncaria tomentosa (cat's claw), Malva sylvestris (mallow), Althaea officinalis (marshmallow), Myracrodruon urundeuva (Brazilian copaiba), Lippia sidoides (rosemary pepper), and Glycyrrhiza glabra (licorice). In Dentistry, research has shown satisfactory results for the treatment of oral cavity conditions, especially those with inflammatory and infectious characteristics, as well as accelerating healing. These findings suggest that phytotherapy is an effective, accessible treatment with minimal side effects. Final considerations: Based on the reviewed literature, phytotherapy appears to be a promising alternative in the treatment of oral conditions due to its notable healing, antimicrobial, and anti-inflammatory effects. However, more research with appropriate methodologies is necessary to establish safe and effective clinical protocols.

Follicular unit grafting in chronic ulcers: a valuable technique for integrated management

Abstract Chronic ulcers significantly affect the quality of life of patients and impose a high cost on the healthcare system. The therapeutic management should be comprehensive, taking into consideration the etiological diagnosis of the wound and the characteristics of the wound bed when deciding on a therapeutic proposal appropriate to the healing phase, correcting factors that delay healing. During the epithelialization phase, repair techniques with grafts are recommended to shorten re-epithelialization time, improve the quality of scar tissue, and achieve adequate pain management. Currently, due to the reported benefits of skin appendages, the technique of follicular unit auto-grafting obtained with a scalp punch is among the chosen strategies for wound repair. This is a minimally invasive, outpatient practice, whose technique has advantages over the donor site, patients recovery and well-being.

Tratamento de infecções localizadas em feridas de difícil cicatrização: uma revisão integrativa / Treatment of Localized Infections in Hard-to-Heal Wounds: An Integrative Review / Tratamiento de infecciones localizadas en heridas de difícil cicatrización: una revisión integrativa

Objetivo: Identificar la producción de conocimiento sobre el tratamiento de infecciones localizadas en heridas de difícil cicatrización. Método: Revisión integrativa de la literatura realizada en la Biblioteca Virtual en Salud; Base de datos de enfermería; Scientific Electronic Library; Web of Science; Biblioteca Cochrane; Catálogo de Tesis y Disertaciones de la Coordinación para el Perfeccionamiento del Personal de Educación Superior; y PubMed. Los artículos seleccionados no tienen límite de tiempo. Los estudios fueron exportados a la aplicación Rayyan y sometidos a evaluación doble ciego mediante la lectura del título y el resumen, según los criterios de inclusión y exclusión. La información fue analizada y sintetizada según el nivel de evidencia. Resultados: 19 estudios fueron incluidos para lectura completa. Se encontró como evidencia la higiene de la herida; la limpieza con ácido acético al 1%; la identificación y el tratamiento de biopelículas; el uso de cobertores y soluciones con acción antimicrobiana. Conclusión: La infección localizada de la herida ha sido objeto de varias investigaciones y las prácticas recomendadas se refieren a tratamientos tópicos. (AU)

Objective: To identify the knowledge production on the treatment of localized infections in hard-to-heal wounds. Method: An integrative literature review was conducted in the Virtual Health Library, Nursing Database, Scientific Electronic Library Online, Web of Science, Cochrane Library, Catalog of Theses and Dissertations of the Coordination for the Improvement of Higher Education Personnel, and PubMed. The selected articles had no time limit. The studies were exported to the Rayyan application and subjected to double-blind evaluation through title and abstract reading, based on inclusion and exclusion criteria. The information was analyzed and synthesized according to the level of evidence. Results: A total of 19 publications were fully analyzed. The evidence obtained on the topic includes wound hygiene, cleaning with 1% acetic acid, identification and treatment of biofilms, the use of dressings, and solutions with antimicrobial action. Conclusion: Localized wound infections have been the subject of various research studies, and the recommended practices refer to topical treatments. (AU)

Objetivo: Identificar a produção de conhecimento sobre o tratamento de infecções localizadas em feridas de difícil cicatrização. Método: Revisão integrativa da literatura realizada na Biblioteca Virtual em Saúde, Base de Dados de Enfermagem, Scientific Electronic Library Online, Web of Science, Biblioteca Cochrane, Catálogo de Teses e Dissertações da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior e Public Medline. Os artigos selecionados não possuem limite temporal. Os estudos foram exportados para o aplicativo Rayyan e submetidos à avaliação duplo-cega por meio da leitura do título e do resumo, com base nos critérios de inclusão e exclusão. As informações foram analisadas e sintetizadas de acordo com o nível de evidência. Resultados: Foram analisadas 19 publicações em sua totalidade. Obteve-se como evidências acerca do tema a higienização da ferida, a limpeza com ácido acético 1%, a identificação e o tratamento de biofilmes, o uso de coberturas e as soluções com ação antimicrobiana. Conclusão: A infecção localizada de feridas tem sido objeto de várias pesquisas e as práticas recomendadas referem-se a tratamentos tópicos. (AU)

Effectiveness of leukocyte- and platelet-rich fibrin in the management of medication-related osteonecrosis of the jaws ­ a systematic review / Efectividad de la fibrina rica en leucocitos y plaquetas en el tratamiento de osteonecrosis mandibular relacionada con medicamentos: una revisión sistemática

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but significant adverse event primarily associated with the intake of antiresorptive and antiangiogenic medications. Although antiresorptive and antiangiogenic the-rapies improve life expectancy, particularly in cancer patients, MRONJ may hamper the patient's quality of life due to pain, discomfort, anxiety, depression, speech impairment, difficulty in swallowing and eating, frequent medical and dental evaluations and treatments, and the possibility of treatment discontinuation. Leukocyte­ and Platelet-rich Fibrin (L-PRF) is an autologous platelet aggregate that promotes wound healing by stimulating re-epithelialization, angiogenesis, and extracellular matrix production. Aim: The present systematic review aimed to compare the results in the published literature on whether L-PRF is an effective and predictable adjuvant to surgical debridement of necrotic bone for improving the healing efficacy in patients with MRONJ. Materials and Methods: The PubMed, Scopus, Cochrane, Science Direct, LILACS, and Web of Science databases were searched using the predetermined MeSH terms and eligibility criteria, and the search yielded a total of five articles. Two studies were retrospective, and three studies were case series. Results: Seventeen participants received a combination of surgical debridement, L-PRF membrane, and antibiotics. Complete wound healing was observed in 70% of the participants, and most of them healed without any complications. Conclusions: L-PRF as an adjuvant to surgical debridement of necrosed bone appears to have a positive association with the healing outcome in patients with MRONJ.

Introducción: La osteonecrosis mandibular relacionada con medicamentos (ONMRM) es un evento adverso raro pero significativo asociado principalmente con la ingesta de medicamentos antirresortivos y antiangiogénicos. Aunque las terapias antirresortivas y antiangiogénicas mejoran la esperanza de vida, particularmente en pacientes con cáncer, la ONMRM puede obstaculizar la calidad de vida del paciente debido a dolor, incomodidad, ansiedad, depresión, discapacidad del habla, dificultad para tragar y comer, evaluaciones y tratamientos médicos y dentales frecuentes, y la posibilidad de interrupción del tratamiento. La fibrina rica en plaquetas y leucocitos (L-PRF) es un agregado de plaquetas autólogo que promueve la curación de heridas al estimular la reepitelización, la angiogénesis y la producción de la matriz extracelular. Objetivo: La presente revisión sistemática tuvo como objetivo comparar los resultados en la literatura publicada sobre si L-PRF es un adyuvante efectivo y predecible al desbridamiento quirúrgico del hueso necrótico para mejorar la eficacia curativa en pacientes con ONMRM. Materiales y Métodos: Las bases de datos de PubMed, Scopus, Cochrane, ScienceDirect, LILACS y Web of Science se registraron utilizando los términos DeCS/MeSH predeterminados y los criterios de elegibilidad, y la búsqueda arrojó un total de cinco artículos. Dos estudios fueron retrospectivos, y tres estudios fueron series de casos. Resultado: Diecisiete participantes recibieron una combinación de desbridamiento quirúrgico, membrana L-PRF y antibióticos. Se observó curación completa de heridas en el 70% de los participantes, y la mayoría de ellos se curaron sin ninguna complicación. Conclusión: L-PRF como adyuvante para el desbridamiento quirúrgico del hueso necrótico parece tener una asociación positiva con el resultado de curación en pacientes con ONMRM.

Evidências clínicas do uso de plantas medicinais e fitoterápicos na cicatrização de feridas cutâneas: uma revisão integrativa / Evidencia clínica sobre el uso de plantas medicinales y medicinas a base de hierbas en la curación de heridas en la piel: una revisión integrativa / Clinical evidence on the use of medicinal plants and herbal medicine in healing skin wounds: an integrative review

Introdução: Plantas medicinais e fitoterápicos são tradicionalmente utilizados na cicatrização de diversos tipos de feridas. Muitas plantas contêm compostos bioativos com propriedades anti-inflamatórias, antimicrobianas e cicatrizantes. Objetivo: Reunir evidências clínicas do uso de plantas medicinais e fitoterápicos na cicatrização de feridas cutâneas. Metodologia: Trata-se de uma revisão integrativa da literatura. Os estudos foram coletados das bases de dados MEDLINE/PubMed e LILACS, utilizando como estratégia de busca os termos ((WoundHealing) ou (Inflammation)) e ((MedicinalPlants) ou (Phytotherapy)) com recorte temporal de 2011 a 2021. Resultados: 15 estudos foram incluídos na revisão. A maioria dos estudos foram do tipo ensaio clínico controlado randomizado. Foi investigada a eficácia de 15 espécies medicinais para o tratamento de feridas agudas e crônicas, sendo as mais recorrentes queimaduras de segundo grau, úlceras crônicas e feridas cirúrgicas. As espécies medicinais que apresentaram melhores resultados foram babosa (Aloevera), centela (Centellaasiatica),beldroega (Portulacaoleraceae), Arnebia euchroma, hipérico (Hypericum perforatum) emil-folhas (Achilleamillefolium), melhorando critérios como eritema, edema, tempodere-epitelização, tempo de cicatrização e a aparência geral da ferida. Conclusões: Plantas medicinais e fitoterápicos apresentam eficácia no processo de cicatrização, sendo, portanto, alternativa terapêutica para o tratamento de feridas cutâneas (AU).

Introduction: Medicinal plants and herbal medicines are traditionally used to heal various types of wounds. Many plants contain bioactive compounds with anti-inflammatory, antimicrobial, and wound-healing properties. Objective: Gathering clinical evidence on the use of medicinal plants and herbal medicine in the healing of skin wounds. Methodology:Thisisan integrative review of the literature. The studies were collected from the MEDLINE/PubMed and LILACS data bases, using the terms ((WoundHealing) or (Inflammation)) and ((MedicinalPlants) or (Phytotherapy)) as a search strategy, from 2011 to 2021. Results: Fifteen studies were included in the review. Most of them were of the randomized controlled clinical trial type. The effectiveness of 15 medicinal species was investigated for the treatment of acute and chronic wounds, the most common of which were second-degree burns, chronic ulcers,and surgical wounds. The species with the best results were Aloe vera, Centella asiatica, Portulaca oleraceae, Arnebia euchroma, Hypericum perforatum, and Achillea millefolium, improving criteria such as erythema, edema, re-epithelialization time, healing time, and the general appearance of the wound. Conclusions: Medicinalplants and herbal medicine are effective in the healing process, therefore being a therapeutic alternative for treating skin wounds (AU).

Introducción: Las plantas medicinales y las medicinas a base de hierbas se utilizan tradicionalmente para curar diversos tipos de heridas. Muchas plantas contienen compuestos bioactivos con propiedades antiinflamatorias, antimicrobianas y cicatrizantes. Objetivo: Recopilar evidencia clínica sobre el uso de plantas medicinales y medicinas a base de hierbas en la curación de heridas cutáneas. Metodología: Se trata de una revisión integradora de la literatura. Los estudios fueron obtenidos de las bases de datos MEDLINE/PubMed y LILACS, utilizando como estrategia de búsqueda los términos ((WoundHealing) o (Inflammation)) y ((MedicinalPlants) o (Phytotherapy)) con un marco temporal de 2011 a 2021. Resultados: Se incluyeron 15 estudios en la revisión. La mayoría de los estudios fueron del tipo ensayo clínico controlado aleatorio. Se investigó la eficacia de 15 especies medicinales para el tratamiento de heridas agudas y crónicas, las más comunes fueron quemaduras de segundo grado, úlceras crónicas y heridas quirúrgicas. Las especies medicinales con mejoresr esultados fueron Aloe vera, Centella asiatica, Portulaca oleraceae, Arnebia euchroma, Hypericum perforatum y Achillea millefolium, mejorando criterios como eritema, edema, tiempo de reepitelización, tiempo de cicatrización y aspecto general de la herida. Conclusiones: Plantas medicinales y medicinas a base de hierbas son efectivas en el proceso de cicatrización, siendo portanto un aalternativa terapéutica para el tratamiento de heridas en la piel (AU).

Small Molecules Accelerate Skin Wound Healing: Shikonin Efficacy and Mechanism of Action in Mice / Las Moléculas Pequeñas Aceleran la Curación de Heridas en la Piel: Eficacia de Shikonin y Mecanismo de Acción en Ratones

SUMMARY: The objective of this study was to investigate the therapeutic wound healing potential and molecular mechanisms of shikonin as small molecules in vitro. A mouse burn model was used to explore the potential therapeutic effect of shikonin; we traced proliferating cells in vivo to locate the active area of skin cell proliferation. Through the results of conventional pathological staining, we found that shikonin has a good effect on the treatment of burned skin and promoted the normal distribution of skin keratin at the damaged site. At the same time, shikonin also promoted the proliferation of skin cells at the damaged site; importantly, we found a significant increase in the number of fibroblasts at the damaged site treated with shikonin. Most importantly, shikonin promotes fibroblasts to repair skin wounds by regulating the PI3K/AKT signaling pathway. This study shows that shikonin can effectively promote the proliferation of skin cell, and local injection of fibroblasts in burned skin can play a certain therapeutic role.

El objetivo de este trabajo fue investigar el potencial terapéutico de cicatrización de heridas y los mecanismos moleculares de la shikonina como moléculas pequeñas in vitro. Se utilizó un modelo de quemaduras en ratones para explorar el posible efecto terapéutico de la shikonina; Rastreamos las células en proliferación in vivo para localizar el área activa de proliferación de células de la piel. A través de los resultados de la tinción para patología convencional, encontramos que la shikonina tiene un buen efecto en el tratamiento de la piel quemada y promueve la distribución normal de la queratina de la piel en el sitio dañado. Al mismo tiempo, la shikonina también promovió la proliferación de células de la piel en el sitio dañado. Es importante destacar que encontramos un aumento significativo en la cantidad de fibroblastos en el sitio dañado tratado con shikonina. Lo más importante es que la shikonina promueve la función reparadora de fibroblastos en las heridas de la piel regulando la vía de señalización PI3K/ AKT. Este estudio muestra que la shikonina puede promover eficazmente la proliferación de células de la piel y que la inyección local de fibroblastos en la piel quemada puede desempeñar un cierto papel terapéutico.

Effect of Curcumin on Promoting Skin Wound Healing in Diabetes Mice / 医药导报

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

Effect of Qufu Shengji ointment combined with ulinastatin on postoperative wound healing and inflammatory factor levels in perianal surgery / 中国药师

Objective To investigate the effect of Qufu Shengji ointment combined with ulinastatin in the treatment of wound healing after perianal surgery and its effect on the level of inflammatory factors.Methods Patients who underwent perianal surgery in Guilin Hospital of Integrated Traditional Chinese and Western Medicine from July 2020 to January 2022 were randomly divided into control group and test group.The patients in both groups were treated with conventional debridement therapy and ulinastatin,and the test group was treated with Qufu Shengji ointment.The wound healing efficacy,TCM symptom score,inflammatory factor level,growth factor level and treatment safety of the two groups were compared.Results A total of 116 patients were included in the study,including 58 patients in the test group and 58 in the control group.The total effective rate of the test group(91.38％)was higher than that of the control group(75.86％),and the difference was statistically significant(P＜0.05).After treatment,the TCM syndrome score levels of interleukin-17A(IL-17A),C-reactive protein(CRP)and serum amyloid A(SAA)in the test group were lower than those in the control group(P＜0.05).The levels of vascular endothelial growth factor receptor 1(VEGFR1),fibroblast growth factor receptor(FGFR)and transforming growth factor-β1(TGF-β1)were higher than those in the control group(P＜0.05).The anal function index was higher than that of the control group(P＜0.05).The incidence of adverse reactions between the two groups was 13.79％and 8.62％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion The effect of Qufu Shengji ointment combined with ulinastatin in the treatment of wound healing after perianal surgery is significant,which can improve the TCM syndrome,reduce inflammatory factors,and upregulate growth factors,and has good safety.

Repair of skin defect with 3D-bioprinted organoid artificial skin derived from adult stem cells in mice / 中华创伤杂志

Objective:To construct 3D-bioprinted organoid artificial skin derived from adult stem cells and investigate their effects on repair of skin defect in mice.Methods:The cell suspension mixture was prepared with human skin keratinocytes, fibroblasts and vascular endothelial cells with a ratio of 2∶1∶1 and cultured in ultra-low attachment plates, and morphological changes of cell spheres were observed with an inverted phase contrast microscope. After 7 days of culture, cell spheres were collected and immunofluorescence staining was performed to characterize the expression and structural distribution of the epidermis, dermis and blood vessels. The artificial skin composed of skin organoids were printed through 3D printing and morphology of printed artificial skin and dressing was observed. Ten immunodeficient balb/c female mice were divided into hydrogel group and organoid group, with 5 mice in each group with the method of random number table. The full-thickness skin defect model with a diameter of 1 cm was established in all mice, and the wound was covered with the hydrogel dressings in hydrogel group and with 3D-printed skin organoids of the same size in organoid group. Wound healing and healing rate of the two groups were observed at 0, 4, 8, 12 and 16 days after modeling. At 16 days after modeling, HE staining was performed on wound skin samples to observe the epidermal keratosis and dermal epidermal junction of the wound surface and Masson staining to observe the density of collagen fibers and dermal fiber thickness of the wound surface.Results:(1) The cell suspension mixture of keratinocytes, fibroblasts and vascular endothelial cells could self-aggregate into cell spheres in the ultra-low attachment plates, and it was observed with the inverted phase contrast microscope that the volume of cell spheres gradually increased with the extension of culture time. (2) Immunofluorescence staining of the cell spheres showed that epidermal markers such as keratin (K)1, K10, and K14 were expressed in the outer layer of the cell spheres, and dermal markers such as vimentin (VIM) and vascular markers CD31 were expressed in the core, which indicated the epidermis was located in the outer layer of the sphere, and the dermis and blood vessels were located in the core of the sphere, with the same structural characteristics of the skin organoids. (3) The 3D-printed organoid artificial skin and hydrogel dressing were round and transparent, with a diameter of 10 mm and a thickness of 1 mm. (4) As shown in the general observation of the wound surface, the wound area of both groups decreased with the extension of treatment time. The wound of the organoid group healed faster, which showed obvious epithelization at 4 days after modeling and basic wound healing at 16 days after modeling. At 0 day after modeling, there was no obvious difference in the appearance of wound surface between the two groups. At 4 and 8 days after modeling, the wound healing rates were (31.7±1.0)% and (52.4±5.4)% in the organoid group, and (24.3±6.8)% and (45.4±7.0)% in the hydrogel group ( P>0.05). At 12 and 16 days after modeling, the wound healing rates were (78.6±8.0)% and (91.1±5.6)% in the organoid group, and were (58.5±5.4)% and (71.9±7.8)% in the hydrogel group ( P<0.01). (5) HE staining showed that in the organoid group epidermal keratinization was found better, with the epidermis being more intact and well attached to the dermis. Epidermal keratinization was not complete in hydrogel group and the epidermis and dermis were obviously separated. Masson staining showed the formation of collagen fiber structures in the wound surface of both groups, which were blue and reticular. The collagen fiber structure was more compact and the dermal fiber thickness was smaller in the organoid group, while the collagen fiber structure was loose and the dermal fiber thickness was greater in the hydrogel group. Conclusions:Adult stem cells of skin can successfully form skin organoids in 3D culture conditions and organoid artificial skin can be constructed with 3D bioprinting technology. Compared with hydrogel dressing, 3D-bioprinted organoid artificial skin can significantly improve the healing rate in mice, with better epidermal keratinization and closer attachment of the epidermis to the dermis. Moreover, the collagen fiber structure of the wound is more compact, with smaller dermal fiber in thickness.

Construction strategies of skin organoids: a review / 中华创伤杂志

Large skin defect caused by severe trauma is a common clinical problem with high incidence, great harm, difficult treatment and poor prognosis, which not only seriously affects the quality of patients′ life, but also threatens their lives. Large skin defects are difficult to heal by themselves and the main treatment is skin transplantation. However, the source of the autologous flap is limited and may cause secondary damage to patients. The artificial skin has poor mechanical integrity that cannot be integrated, causing formation of scars, and also has the risk of immune rejection. Skin organoid technology can extremely simulate the human skin tissue and its functions. Thus, it can overcome the shortcomings of the current skin wound treatment to a certain extent and provide a new treatment for the patients with large skin defects. At present, the construction methods of skin organoids are relatively mature, but each method has its advantages and disadvantages, and the best method has not been determined yet. Moreover, the structure and function of skin organoids are relatively simple, so there is still a relatively big gap between skin organoids and real human skin. Hence, the authors reviewed the research progress in skin organoid construction strategies from organoids′ skin organoid technology, and construction methods of skin organoids, hoping to provide a reference for the construction of skin organoids with more complex structures and functions in the future.

Mechanism of Wenyang Shengji Ointment in treating diabetic wounds based on network pharmacology and animal experiments / 数字中医药（英文）

Objective @#To explore the mechanism of Wenyang Shengji Ointment (温阳生肌膏, WYSJO) in the treatment of diabetic wounds from the perspective of network pharmacology, and to verify it by animal experiments.@*Methods@#The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and related literature were used to screen active compounds in WYSJO and their corresponding targets. GeneCards, Online Mendelian Inheritance in Man (OMIM), DrugBank, PharmGkb, and Therapeutic Target Database (TTD) databases were employed to identify the targets associated with diabetic wounds. Cytoscape 3.9.0 was used to map the active ingredients in WYSJO, which was the diabetic wound target network. Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) platform was utilized to construct protein-protein interaction (PPI) network. Kyoto Encyclopedia of Genes and Genomes (KEGG) andGene Ontology (GO) enrichment analyses were performed to identify signaling pathways between WYSJO and diabetic wounds. AutoDock 1.5.6 was used for molecular docking of core components in WYSJO to their targets. Eighteen rats were randomly divided into control, model, and WYSJO groups (n = 6). The model and WYSJO groups were used to prepare the model of refractory wounds in diabetes rats. The wound healing was observed on day 0, 5, 9, and 14 after treatment, and the wound tissue morphology was observed by hematoxylin-eosin(HE) staining. The expression levels of core genes were detected by quantitative real-timepolymerase chain reaction (qPCR).@*Result@#A total of 76 active compounds in WYSJO, 206 WYSJO drug targets, 3 797 diabetic wound targets, and 167 diabetic wound associated WYSJO targets were screened out through network pharmacology. With the use of WYSJO-diabetic wound target network, core targets of seven active compounds encompassing quercetin, daidzein, kaempferol, rhamnetin, rhamnocitrin, strictosamide, and diisobutyl phthalate (DIBP) in WYSJO were found. GO enrichment analysis showed that the treatment of diabetes wounds with WYSJO may involve lipopolysaccharide, bacteria-derived molecules, metal ions, foreign stimuli, chemical stress, nutrient level, hypoxia, and oxidative stress in the biological processes. KEGG enrichment analysis showed that the treatment of diabetes wounds with WYSJO may involve advanced glycation end products (AGE-RAGE), p53, interleukin (IL)-17, tumor necrosis factor (TNF),hypoxia inducible factor-1 (HIF-1), apoptosis, lipid, atherosclerosis, etc. The results of animal experiments showed that WYSJO could significantly accelerate the healing process of diabetic wounds (P < 0.05), alleviate inflammatory response, promote the growth of granulation tissues, and down-regulate the expression levels of eight core genes [histone crotonyltransferase p300 (EP300), protoc gene-oncogene c-Jun (JUN), myelocytomatosis (MYC), hypoxia inducible factor 1A (HIF1A), mitogen-activated protein kinase 14 (MAPK14), specificity protein 1 (SP1), tumor protein p53 (TP53), and estrogen receptor 1 (ESR1)] predicted by the network pharmacology (P < 0.05).@*Conclusion@#The mechanism of WYSJO in treating diabetes wounds may be closely related to AGE-RAGE, p53, HIF-1, and other pathways. This study can provide new ideas for the pharmacological research of WYSJO, and provide a basis for its further transformation and application.

Effect of oral fish oil on wound healing in patients with diabetic foot ulcers:a randomized,double-blind,placebo-controlled study / 重庆医学

Objective To investigate the effect of oral fish oil on wound healing and related indexes in patients with diabetic foot ulcer(DFU).Methods A randomized,double-blind,placebo-controlled design was used to recruit 68 patients with DFU aged 18-80 years old in the hospital,and the baseline clinical data of the patients were collected.The patients were randomly divided into experimental group(32 cases,fish oil soft capsule,3 g/d)and control group(33 cases,corn oil soft capsule,3 g/d)by random number generated by Ex-cel,and the intervention lasted for 12 weeks.The primary endpoints included the proportion of complete wound healing and healing area≥50%.The secondary endpoints included wound area,healing time,inflamma-tion index,glucose metabolism index,nutrition related index and wound reinfection.Additionally,the influen-cing factors of wound healing were analyzed.Results After intervention,the proportion of complete wound healing and healing area≥50%in the experimental group was significantly higher than that in the control group(P=0.007,0.039).In the subjects with complete wound healing,the mean healing time in the experi-mental group was shorter than that in the control group,but the difference was not statistically significant(P=0.132).The reduction area of wound area in the experimental group was significantly larger than that in the control group(P=0.045).The decrease of interleukin(IL)-6 and IL-8 in the experimental group was significantly higher than that in the control group(P<0.05).There was no significant difference in the reduc-tion of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),neutrophil-to-lymphocyte ratio(NLR),glycated hemoglobin A1c(HbA1c)and platelet-to-lymphocyte ratio(PLR)between the two groups(P>0.05).The improvement of prealbumin(PA)in the experimental group was higher than that in the control group,but the difference was not statistically significant(P>0.05).Multivariate logistic regression analysis showed that oral fish oil intervention(OR=6.771,95%CI:1.787-25.652),HbA1c(OR=4.149,95%CI:1.026-16.770)and ulcer type(OR=4.319,95%CI:1.026-18.173)were the influencing factors of wound healing(P<0.05).Conclusion Oral fish oil promotes wound healing in patients with DFU,which may be re-lated to improving the level of chronic inflammation in the body.

Chinese Medicine Intervention in Signaling Pathways Related to Diabetic Ulcer： A Review / 中国实验方剂学杂志

Diabetic ulcer （DU） wound is one of the chronic and serious complications of diabetes characterized by prolonged wound healing， and it is more common in foot and lower extremity ulcers. DU has brought great economic and psychological pressure to patients and seriously affected the quality of life of patients because of its great difficulty in treatment， long treatment process， and high morbidity and mortality. Therefore， how to help the rapid healing of DU wounds， reduce the disability rate and mortality rate， protect limb function， and improve the quality of life is an important topic and hot spot in the field of medical research. The pathogenesis of DU is complex， mainly including microcirculation disorder， peripheral neuropathy， inflammation and infection， and excessive apoptosis of cells， involving physiological processes such as wound inflammation， granulation tissue hyperplasia and re-epithelialization. A large number of previous studies have found that Chinese medicine can regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Notch， nuclear factor E2-related factor 2 （Nrf2）， transforming growth factor-β （TGF-β）/Smad， and other signaling pathways， regulate abnormal glucose metabolism， improve microcirculation， inhibit inflammation and oxidative stress， regulate cell proliferation and excessive apoptosis， and promote wound tissue growth to promote the rapid healing of DU wounds under the guidance of treatment based on traditional Chinese medicine （TCM） syndrome differentiation and internal and external treatment. Therefore， this paper reviewed Chinese medicinal monomers or Chinese medicinal compounds in recent years in regulating the above signaling pathways and the expression of key protein molecules and promoting the rapid healing of DU wounds， aiming to provide ideas and a theoretical basis for the in-depth study and clinical application of Chinese medicine in promoting the healing of DU wounds.

Self-assembled Cross-linking Based Hydrogels for Skin Injury Applications / 生物化学与生物物理进展

When skin injuries are healing, complex wound environments can be easily created, which can result in wound infection, excessive inflammation caused by neutrophil accumulation and inflammatory factors, and excessive reactive oxygen species, resulting in high levels of oxidative stress. As a result of these factors, cell membranes, proteins, DNA, etc. may become damaged, which adversely affects the repair function of normal cells around the wound, resulting in the formation of chronic wounds. The effectiveness of wound dressings as a treatment is well known. They can offer temporary skin damage protection, prevent or control wound infection, create an environment that is conducive to mending skin damage, and speed wound healing. Traditional dressings like gauze, cotton balls, and bandages, however, have the drawbacks of having no antimicrobial properties, having weak adhesive properties, having poor mechanical properties, being susceptible to inflammation, obstructing angiogenesis, needing frequent replacement, and being unable to create an environment that is conducive to wound healing. As an innovative bandage, self-assembled hydrogel has great water absorption, high water retention, superior biocompatibility, biodegradability and three-dimensional (3D) structure. With properties including hemostasis, antibacterial, anti-inflammatory, and antioxidant, the synthesized raw material itself and the loaded active compounds have a wide range of potential applications in the treatment of skin injuries and wound healing. This research begins by examining and discussing the mechanism of cross-linking in self-assembled hydrogels. The cross-linking modes include non-covalent consisting of physical interaction forces such as electrostatic interactions, π-stacking, van der Waals forces, hydrophobic interactions, and metal-ligand bonds, covalent cross-linking formed by dynamic covalent bonding such as disulfide bonding and Schiff bases. And hybrid cross-linking with mixed physical forces and dynamic covalent bonding. The next part describes the special structure and excellent functions of self-assembled hydrogels, which include an extracellular matrix-like structure, the removal of exogenous microorganisms, and the mitigation of inflammation and oxidative stress. It goes on to explain the benefits of using self-assembled hydrogels as dressings for skin injuries. These dressings are capable of controlling cell proliferation, loading active ingredients, achieving hemostasis and coagulation, hastening wound healing, and controlling the regeneration of the injured area. The development of self-assembly hydrogels as dressings is summarized in the last section. The transition from purely non-covalent or covalent cross-linking to hybrid cross-linking with multiple networks, from one-strategy action to multi-strategy synergy in exerting antimicrobial, anti-inflammatory, and antioxidant effects and from single-function to multi-functioning in a single product. Additionally, it is predicted that future developments in self-assembled hydrogels will focus on creating biomimetic gels with multi-strategy associations linkage from naturally self-assembling biomolecules peptides, lipids, proteins and polysaccharides; improving the properties and cross-linking of raw materials to enhance the storage capabilities of hydrogels and cross-linking techniques, realizing the recycling of hydrogels; conducting additional research and exploration into the cross-linking process of hydrogels; and realizing the gel’s controllable rate of degradation. Furthermore, combining 3D printing and 3D microscopic imaging technology to design and build one-to-one specialized gel dressings; using computer simulation and virtual reality to eliminate the time factor, resulting in self-assembled hydrogels that perfectly fit the ideal dressing.

Exploring the Therapeutic Potential: Malaysian Channa striatus Water Extract Enriched with Arachidonic Acid for Wound Healing in Human Foetal Lung Cells (IMR-90) (Meneroka Potensi Terapeutik: Ekstrak Air Channa striatus Malaysia yang Diperkaya dengan Asid Arachidonic untuk Penyembuhan Luka dalam Sel Paru-paru Janin Manusia (IMR-90)) / Jurnal Sains Kesihatan Malaysia

@#Channa striatus, also known as haruan, is traditionally used in Malaysia for its wound-healing properties. This study evaluated the wound healing potential of Channa striatus water extract (CSWE) and identified key compounds promoting fibroblast cell growth. Channa striatus were deboned to maximize fillet retention. CSWE was obtained through aqueous extraction, and its physicochemical properties were analyzed, including pH, rheological characteristics, moisture content, amino acid composition, and arachidonic acid presence. The effective concentration (EC50) of the sample was determined using a 2-D cell culture system with human fibroblast cells (IMR-90) over three days. Results showed CSWE had a near-neutral pH (6.34 ± 0.01) and high moisture content (97.3 ± 0.01%). The extract displayed Newtonian fluid behavior with a viscosity of 1.50 ± 0.31 mPa.s. CSWE contained essential amino acid glycine and arachidonic acid, important for wound healing, but in low concentrations. These low concentrations did not significantly promote IMR-90 cell growth (p>0.05) compared to the control. Consequently, EC50 values for CSWE were invalid due to over-dilution from a high fish weight-to-solvent ratio. Despite this, IMR-90 cell growth rates remained consistent across different CSWE concentrations, with no observed mortality during the three-day incubation. Overall, IMR-90 cells exhibited insignificant growth, even with arachidonic acid and glycine at low concentrations during treatment.

Modulation Agents of Wound Healing in Ocular Surgeries

@#Wound healing is a complex process that includes haemostasis and inflammation, followed by a proliferation period and repair and finally remodelling. Ocular surgeries, particularly in glaucoma cases, aim at minimal fibrosis to preserve the function of trabeculectomy as an alternative pathway for aqueous drainage. Hence, it is important to find an agent to modulate the wound healing process. This review presents compilation of wound modulation agents that have been tested in vitro, in vivo, or clinically on patients undergoing ocular surgeries, particularly for glaucoma. We identified agents into four groups, mostly for glaucoma filtration operations: anti-metabolites, anti-growth factors, mechanical barriers and rho kinases. The effect of these agents is highlighted in this review. In conclusion, despite recognized drawbacks of antimetabolites, they are still regarded as the gold standard and the most efficient treatment as anti-scarring agents use in ocular surgeries. More studies are needed to inquire agents that efficient yet has minimal adverse effects both in short and long term.

Effect and mechanism of Panax notoginseng saponins on wound healing after anal fistula surgery in rats / 中国药房

OBJECTIVE To investigate the effect and mechanism of Panax notoginseng saponins （PNS） on wound healing after anal fistula surgery in rats by regulating the hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF）/ vascular endothelial growth factor receptor-2 （VEGFR2） signaling pathway. METHODS SD rats were selected to establish a postoperative rat model of anal fistula by infecting wound with Escherichia coli. The model rats were randomly grouped into model group， PNS low-dose and high-dose groups （15， 30 mg/cm2）， high-dose of PNS+2-methoxyestradiol （2ME2） group （PNS 30 mg/cm2+HIF-1α inhibitor 2ME2 4 mg/kg）， with 10 rats in each group. Another 10 normal rats were selected for back hair removal treatment as the control group. Each drug group was injected with the corresponding drug solution intramuscularly or （and） intraperitoneally， once a day， for 3 weeks. After the last administration， the wound healing rate （excluding the control group）， microvascular density （MVD）， the expression of collagen Ⅰ and fibronectin （FN） in the wound tissue were detected in each group； the levels of angiogenic factors [VEGF， E-mail：842710813@qq.com angiopoietin-Ⅰ （Ang-Ⅰ）， Ang-Ⅱ] in serum， the levels of inflammatory factors [interleukin-6 （IL-6） and IL-2] in serum binggui7183@163.com and wound tissue as well as the expressions of the related proteins of HIF-1α/VEGF/VEGFR2 signaling pathway in the wound tissue of rats were also detected in each group. RESULTS The MVD， the expression of collagen Ⅰ and FN in the wound tissue， and the levels of IL-6 and IL-2 in serum and wound tissue of rats increased significantly in the model group， compared to the control group （P＜0.05）， while the serum levels of VEGF， Ang- Ⅰ and Ang-Ⅱ decreased significantly （P＜0.05）. The wound healing rate， the MVD in wound tissue， the serum levels of VEGF， Ang-Ⅰ and Ang-Ⅱ， the expressions of collagen Ⅰ and FN in the wound tissue， and protein expressions of HIF-1α， VEGF and VEGFR2 in the PNS low-dose and high-dose groups increased significantly， compared to the model group （P＜0.05）， while the levels of IL-6 and IL-2 in serum and wound tissue decreased significantly （P＜0.05）； the high-dose PNS had a stronger effect （P＜ 0.05）. 2ME2 could weaken the effect of PNS on above indicators of rats after anal fistula surgery （P＜0.05）. CONCLUSIONS PNS can promote the production of angiogenic factors and inhibit the production of pro-inflammatory factors， thereby promoting wound healing in rats after anal fistula surgery. The above effects are related to the activation of HIF-1α/VEGF/VEGFR2 signaling pathway.

Huangqi Yanghe Decoction regulates PI3K/AKT/NF-κB signaling pathway to promote wound healing in diabetes foot ulcer rats / 天津医药

Objective To explore the effect of Huangqi Yanghe Decoction on wound healing of diabetic foot ulcer(DFU)rats based on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/nuclear factor-κB(NF-κB)signal pathway.Methods DFU rat model was constructed,and 48 rats successfully modeled were randomly divided into the model group,the Huangqi Yanghe Decoction low(8.5 g/kg)group,the Huangqi Yanghe Decoction high(17 g/kg)dose group and the Huangqi Yanghe Decoction high dose(17 g/kg)+LY294002(PI3K/AKT pathway inhibitor,0.3 mg/kg)group.There were 12 rats in each group.Another 12 rats were selected as the control group.Rats in each group were given corresponding drug intervention for 4 weeks.After the 14th and 28th day-administration,the general state and wound changes of rats were observed,and the wound healing rate was calculated.The fasting blood glucose(FBG)level of rats was measured,and the percutaneous partial pressure of oxygen(TcpO2)of tissue around the wound was detected.Serum levels of vascular endothelial growth factor(VEGF),hypoxia inducible factor-1α(HIF-1α),C-reactive protein(CRP)and interleukin(IL)-6 were determined by enzyme linked immunosorbent assay.Histopathological changes of the wound were observed by hematoxylin-eosin staining.Immunohistochemical staining was used to measure the microvascular density of rat wound tissue.The protein expression levels of PI3K,phosphorylated PI3K(p-PI3K),AKT,phosphorylated AKT(p-AKT),NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65)and NF-κB inhibitory protein α(IκB-α)in rat wound tissue were determined by Western blot assay.Results Rats in the control group had smooth hair color,normal diet,drinking water and excretion,more active,wound healing fast,less inflammatory reaction in wound tissue,and there were more new blood vessels.Fibroblasts and collagen matrix were abundant in granulation tissue.In the model group,the fur color of rats was dull and matte,and the activity was reduced.The symptoms of polydipsia,polyphagia and polyuria were appeared in the model group,the wound color was dark,and edema and ulcer appeared in the surrounding tissue,a large number of inflammatory cells infiltrated in the wound tissue,accompanied by tissue necrosis and exudation,fewer neovascularization and fibroblasts were observed.Wound healing rate,TcpO2 in wound surrounding tissue,serum VEGF,HIF-1α,microvascular density,p-PI3K,p-AKT and IκB-α protein expression levels in wound tissue were decreased,and FBG,serum CRP,IL-6,p-NF-κB p65 protein expression in wound tissue were increased(P＜0.05).Compared with the model group,the state of rats was gradually improved in the Huangqi Yanghe Decoction low and high dose groups,and the lesion degree of wound tissue was reduced successively,wound healing rate,TcpO2 in wound surrounding tissue,serum VEGF,HIF-1α,microvascular density,p-PI3K,p-AKT and IκB-α protein expression levels in wound tissue were increased in turn(P＜0.05).The FBG,serum CRP,IL-6 and p-NF-κB p65 protein expression in wound tissue were decreased in turn(P＜0.05).LY294002 could partially reverse the therapeutic effect of high-dose Huangqi Yanghe Decoction on DFU rats(P＜0.05).Conclusion Huangqi Yanghe Decoction can regulate PI3K/AKT/NF-κB pathway,inhibit inflammatory response in DFU rats,promote angiogenesis and thus promote wound healing.

Hydrogel loaded with platelet-rich plasma promotes wound healing in diabetic rats / 中国组织工程研究

BACKGROUND:Diabetic wounds have complicated conditions such as infection,ischemia,peripheral neuropathy,and vascular disease.Ordinary hydrogel dressings with single structure and function cannot meet the needs of diabetic wound healing. OBJECTIVE:To explore the effect of a hydrogel loaded with platelet-rich plasma on wound healing of full-thickness skin defects in diabetic rats. METHODS:The blood of SD rats was extracted to prepare platelet-rich plasma.Carboxymethyl chitosan/oxychondroitin sulfate hydrogel and carboxymethyl chitosan/oxychondroitin sulfate hydrogel loaded with platelet-rich plasma were prepared separately.Streptozotocin was used to induce diabetes model in adult male SD rats.A round full-thickness skin wound with a diameter of 2 cm was made on the back of diabetic rats.The rats were randomly divided into four groups(n=10 per group).The blank group was applied with gauze on the wound.The hydrogel group,platelet-rich plasma group,and composite hydrogel group were respectively applied with the corresponding hydrogel,platelet-rich plasma and hydrogel loaded with platelet-rich plasma.The wound healing was observed within 20 days after treatment. RESULTS AND CONCLUSION:(1)On day 20 after treatment,the wound healing rate of the hydrogel group,platelet-rich plasma group and composite hydrogel group was significantly higher than that of the blank group(P<0.05).The wound healing rate of the composite hydrogel group was significantly higher than that of the platelet-rich plasma group(P<0.05).(2)The results of hematoxylin-eosin staining on day 5 after treatment showed that compared with the blank group,hydrogel group and platelet-rich plasma group,there were a large number of inflammatory cell infiltration,new granulation tissue and capillary formation in the wound tissue of the composite hydrogel group.(3)On day 5 after treatment,the results of immunohistochemical staining and western blot assay showed that the expression levels of tumor necrosis factor α and interleukin 1β in wound tissue in the composite hydrogel group were significantly lower than those in the blank group,hydrogel group and platelet-rich plasma group(P<0.05).(4)Masson staining results on day 15 after treatment showed that compared with the blank group,hydrogel group and platelet-rich plasma group,there were more collagen fibers in the wound tissue of the composite hydrogel group,which were orderly,evenly distributed and dense.(5)CD31 immunofluorescence staining showed that on day 15 after treatment,the expression of CD31 in wound tissue of the composite hydrogel group was significantly higher than that of the blank group,hydrogel group and platelet-rich plasma group(P<0.05).(6)These results suggest that the hydrogel loaded with platelet-rich plasma can promote the healing of full-thickness skin defect wounds in diabetic rats by promoting granulation tissue,collagen fiber and angiogenesis,and reducing the inflammatory response.

Prussian blue nanoparticles promote wound healing of diabetic skin / 中国组织工程研究

BACKGROUND:Inflammation,oxidative stress and bacterial infection are the main causes of delayed wound healing in diabetes.In recent years,various inorganic nanomaterials have been widely used in the treatment of skin wound healing due to their antibacterial activities,but their effects on anti-oxidation and anti-inflammation are limited. OBJECTIVE:To investigate the effect of Prussian blue nanoparticles on the wound repair of diabetes in terms of antioxidant,anti-inflammatory and photothermal antibacterial activities. METHODS:Prussian blue nanoparticles were prepared and characterized.(1)In vitro:The biocompatibility of Prussian blue nanoparticles with different concentrations was detected by MTT assay.The cytoprotective effect of Prussian blue nanoparticles and the intracellular reactive oxidative species level were examined under the condition of hydrogen peroxide.The ability of Prussian blue nanoparticles to decompose hydrogen peroxide and superoxide anion radicals was tested;the effect of Prussian blue nanoparticles on lipopolysaccharide-induced macrophage inflammation was investigated.The photothermal antibacterial activity of Prussian blue nanoparticles was detected by the plate colony counting method.(2)In vivo:ICR mice were intraperitoneally injected with streptozotocin to establish a diabetes mouse model.After the model was successfully established,a 6 mm wound was created on the back with a hole punch.There were the control group(no treatment),the Prussian blue group and the Prussian blue with light group.The wound healing and histomorphological changes were observed. RESULTS AND CONCLUSION:(1)In vitro:Prussian blue nanoparticles in 25-200 μg/mL were non-toxic to cells.Prussian blue nanoparticles had the extremely strong antioxidant capacity and mitigated the intracellular reactive oxidative species at a high oxidative stress environment,resulting in a pronounced cytoprotective effect.The Prussian blue nanoparticles not only exhibited hydrogen peroxide degradation activity but also showed strong superoxide scavenging ability.Prussian blue nanoparticles also displayed significant anti-inflammatory activity and extremely strong antibacterial ability after light irradiation.(2)In vivo:After 14 days,the wound sizes of the Prussian blue group and Prussian blue with light group were significantly reduced,and the healing speed of Prussian blue with light group was the fastest.Hematoxylin-eosin and Masson staining showed a lot of granulation tissue formation and collagen deposition in the Prussian blue group and the Prussian blue with light group,of which the Prussian blue with light group was the most.Immunofluorescence staining displayed that,compared with the control group,the expressions of α-SMA and CD31 were increased significantly in Prussian blue group and Prussian blue with light group(P<0.05),but F4/80 expression was decreased significantly in Prussian blue group and Prussian blue with light group(P<0.05),indicating more obvious improvement in the Prussian blue with light group.(3)These results showed that Prussian blue nanoparticles could promote the skin wound healing of the diabetes mouse model by exerting anti-inflammatory,antioxidant and antibacterial effects.