Plant stem cell extract from Coffea canephora shows antioxidant, anti-inflammatory, and skin regenerative properties mediated by suppression of nuclear factor-κB

Plant cell cultures have become a promising production platform of bioactive compounds for biomedical and cosmetic uses in the last decades. However, the success so far has been limited. The study aimed to evaluate the effectiveness of this unique biotechnology process to obtain a bioactive stem cell extract of Coffea canephora (SCECC) with antioxidant, anti-inflammatory, and regenerative properties. Total phenolic and flavonoid contents were determined in the SCECC by spectrophotometry. The chemical composition of the extracts was characterized by mass spectrometry. Antioxidant activity was evaluated using the colorimetric methods of free radical scavenging 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and the ferric reducing ability of plasma (FRAP). The anti-inflammatory activity was determined in lipopolysaccharide-stimulated RAW 264.7 macrophages through the production of superoxide anion (O2•-), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and the activity of nuclear factor kappa B (NF-κB). Moreover, the ability of SCECC to stimulate the proliferation and migration of fibroblasts was assessed. Five compounds were tentatively identified, two flavonoids, two phenolic acids, and one sugar. High phenolic content and antioxidant activity were observed in the SCECC. SCECC promoted the proliferation and migration of fibroblasts and suppressed the pro-inflammatory mediators O2•-, NO, TNF-α, and IL-6 in a dose-dependent manner. Moreover, SCECC inhibited the NF-κB transcription factor. Therefore, we obtained evidence that the extract from C. canephora stem cells can be used as a natural agent against skin damage. Hence, it could be of interest in cosmetics for preventing skin aging.

Application of small molecular compounds in promoting the repair of dentin-pulp complex injury / 口腔医学

@#Dental caries, trauma, and iatrogenic stimulation can cause damage to the dentin-pulp complex. Preserving the viable pulp and promoting damage repair of the dentin-pulp complex is of great clinical significance at present. In recent years, studies have found that various small molecular compounds can regulate inflammation, promote the migration, proliferation, and differentiation of dental pulp stem cells, promote blood vessel, nerve regeneration and other biological processes by regulating key intracellular signaling pathways and metabolic pathways, and could thereby promote damage repair of the dentin-pulp complex. The objective of this paper is to review recent research on various small molecular compounds used in promoting the repair of dentin-pulp complex.

Review of the Benefits of Eggshell Content in Body Tissue Structure Repair

@#Eggshell (ES) is a waste material that cannot be consumed with low economic value. ES mainly contains calcium carbonate (CaCO3) and an organic matrix in the form of proteins, glycoproteins, and proteoglycans. Meanwhile, the eggshell membrane (ESM) contains osteopontin collagen, fibronectin, keratin, histones, avian beta defensins, ovocalyxin-36, apolipoproteins, protocadherin, chondroitin sulfate, ovotransferrin, hyaluronic acid, and sialic acid as well as various amino acids. Recently, ES has been widely used in industry, agriculture, food, and medical fields. The potential of ES in the medical field is interesting to discuss, especially in relation to tissue repair. Efforts to reduce the prevalence of wounds that generally originate from acute wounds but become chronic due to various factors that are neglected in their management. In particular, this review will describe the benefits of ES content in repairing body tissues. ES-derived active ingredients such as CaCO3, brushite, and hydroxyapatite exhibit osteoconductive properties that promote bone regeneration. Calcium ions can increase insulin and leptin sensitivity in the liver and can induce repair of acute kidney injury. Meanwhile, ESM contributes positively to neural tissue repair and plays an important role in wound healing, response to external stimuli, defense response, inflammatory response, cell-substrate adhesion, promoting cell growth, migration, differentiation, and tissue remodeling.

Eficácia e importância da patência foraminal em casos de dentes despolpados e em dentes com vitalidade pulpar / Efficacy and importance of apical foramen patency in procedures involving pulpless teeth and teeth with vital pulps

A ciência endodôntica possui um vasto conhecimento e com esse conhecimento os seus inúmeros questionamentos. Algumas teorias e conceitos mudam constantemente e trazem à tona contradições e divergências clínicas no âmbito biológico e prático. A patência foraminal é uma prática que permite que um instrumento de pequeno calibre ultrapasse o forame apical, com o intuito de limpar passivamente e prevenir o acúmulo de detritos e inibir a proliferação de microorganismos que podem causar infecções pós tratamento endodôntico. Essa prática gera discussão interna entre especialistas da área, mas as vantagens da técnica são inúmeras, principalmente no que diz respeito aos casos de polpa necrosada. Casos como esse não são solucionados com sucesso sem a utilização da patência apical. Por outro lado, existem contradições em relação aos casos em que a polpa está viva. Esse trabalho tem como objetivo analisar as vantagens e desvantagens da patência apical, bem como, se os benefícios excedem os possíveis danos que ela pode trazer(AU)

Endodontic science has vast knowledge and with this knowledge its countless questions. Some theories and concepts are constantly changing and bring to light clinical contradictions and divergences in the biological and practical scope. Foraminal patency is a practice that allows a small-caliber instrument to go beyond the apical foramen, in order to passively clean and prevent the accumulation of debris in the region and inhibit the proliferation of microorganisms that can cause infections after endodontic treatment. This practice generates internal discussion among specialists in the field, but the advantages of the technique are numerous, especially with regard to cases of necrotic pulp. Cases like this are not successfully resolved without the use of apical patency. On the other hand, there are contradictions regarding the cases where the pulp is alive. This work aims to analyze the advantages and disadvantages of apical patency, as well as whether the benefits exceed the harm it can bring(AU)

Eletrofiação aplicada a cicatrização de feridas: revisão de literatura / Electrospinning applied to wound healing: literature review / Electroalambre aplicado a la cicatrización de heridas: revisión de la literatura

feridas correspondem a interrupção da continuidade da pele, com a perda de uma ou mais camadas do tecido cutâneo. Curativos tradicionalmente aplicados em feridas cutâneas buscam principalmente fornecer uma barreira de proteção e permitir o desenvolvimento dos eventos celulares e bioquímicos que compreendem a cicatrização. Objetivou-se com este estudo apresentar sob a forma de revisão de literatura narrativa os principais eventos relacionados ao processo de reparo tecidual da pele, bem como abordar a aplicabilidade da técnica de eletrofiação no desenvolvimento de curativos funcionais biocompatíveis. Foram selecionados artigos voltados à caracterização dos eventos chave ocorridos a nível tecidual durante a cicatrização e, na sequência, buscou-se artigos voltados à produção, caracterização e aplicação de filmes nanoeletrofiados com ênfase na utilização de biopolímeros e substâncias bioativas. Observou-se que a maioria dos trabalhos recentes, voltados a pesquisa de base, descrevem a resposta vascular como o principal evento do processo cicatricial, sendo responsável pelas etapas que se desenrolam a seguir, que compreendem as fases inflamatória, proliferativa e de remodelamento, classicamente já descritas. Os curativos funcionais baseados em polímeros eletrofiados apresentam resultados superiores quanto testados in vitro e in vivo. As características morfoestruturais mimetizam a matriz extracelular e podem atuar em tecidos alvo como dispositivos de entrega de substâncias. Conclui-se que a atualização e reorganização de conceitos relativos à cicatrização podem contribuir no desenvolvimento de inovações, como os curativos produzidos por eletrofiação. Embora promissora, as desvantagens da técnica encontram-se principalmente no processo de obtenção e disponibilidade, que limitam a aplicação clínica em escala comercial.

Wounds correspond to the interruption of skin continuity, with the loss of one or more layers of skin tissue. Dressings traditionally applied to cutaneous wounds mainly seek to provide a protective barrier and allow the development of cellular and biochemical events that comprise healing. The objective of this study was to present, in the form of a narrative literature review, the main events related to the skin tissue repair process, as well as to address the applicability of the electrospinning technique in the development of biocompatible functional dressings. Articles focused on the characterization of the key events that occurred at the tissue level during healing were selected and, subsequently, articles focused on the production, characterization and application of nanoelectrospun films with emphasis on the use of biopolymers and bioactive substances were sought. It was observed that most recent works, focused on basic research, describe the vascular response as the main event of the healing process, being responsible for the steps that follow, which include the inflammatory, proliferative and remodeling phases, classically already described. Functional dressings based on electrospun polymers show superior results when tested in vitro and in vivo. The morphostructural features mimic the extracellular matrix and can act in target tissues as substance delivery devices. It is concluded that the updating and reorganization of concepts related to healing can contribute to the development of innovations, such as dressings produced by electrospinning. Although promising, the technique's disadvantages lie mainly in the process of obtaining and availability, which limit clinical application on a commercial scale.

Las heridas corresponden a la interrupción de la continuidad de la piel, con la pérdida de una o más capas de tejido cutáneo. Los apósitos aplicados tradicionalmente a las heridas cutáneas buscan principalmente proporcionar una barrera protectora y permitir el desarrollo de los eventos celulares y bioquímicos que comprenden la curación. El objetivo de este estudio fue presentar en forma de revisión bibliográfica narrativa los principales acontecimientos relacionados con el proceso de reparación tisular de la piel, así como abordar la aplicabilidad de la técnica de electrodeposición en el desarrollo de apósitos funcionales biocompatibles. Se seleccionaron artículos dirigidos a la caracterización de los eventos chave ocurridos a nivel técnico durante la cicatrización y, a continuación, se buscaron artículos dirigidos a la producción, caracterización y aplicación de películas nanoelectrofíricas con énfasis en el uso de biopolímeros y sustancias bioativas. Se observa que la mayoría de los trabajos recientes, realizados en la investigación de base, describen la respuesta vascular como el principal evento del proceso cicatricial, siendo responsable de las etapas que se desarrollan a continuación, que comprenden las fases inflamatoria, proliferativa y de remodelación, clásicamente descritas. Los apósitos funcionales basados en polímeros electro-tejidos presentan resultados superiores cuando se prueban in vitro e in vivo. Las características morfoestruturales mimetizan la matriz extracelular y pueden actuar en tejidos alvos como dispositivos de entrega de sustancias. Se concluye que la actualización y la reorganización de los conceptos relativos a la cicatrización pueden contribuir al desarrollo de innovaciones, como las curativas producidas por la electrofagia. Aunque es prometedora, las desventajas de la técnica radican principalmente en el proceso de obtención y la disponibilidad, que limitan la aplicación clínica a escala comercial.

Extracts of Portulaca oleracea promote wound healing by enhancing angiology regeneration and inhibiting iron accumulation in mice / 中草药·英文版

Objective: To investigate the role of Portulaca oleracea (POL) in promoting revascularization and re-epithelization as well as inhibiting iron aggregation and inflammation of deep tissue pressure injury (DTPI). Methods: The hydroalcoholic extract of POL (P) and aqueous phase fraction of POL (PD) were prepared based on maceration and liquid–liquid extraction. The number of new blood vessels and VEGF-A expression level were assessed using H&E stain and Western blot on injured muscle to examine the role of POL different extracts in vascularization. The iron distribution and total elemental iron of injured muscle were detected using laser ablation inductively coupled plasma mass spectrometry (ICP-MS) and Perls’ staining to determine whether POL extracts can inhibit the iron accumulation. Besides, the ability of POL extracts to promote wound healing by combining re-epithelization time, inflammation degree and collagen deposition area were comprehensively evaluated. Results: In vitro, we observed a significant increase in HUVEC cell viability, migration rate and the number of the tube after P and PD treatment (P < 0.05). In vivo, administration of P and PD impacted vascularization and iron accumulation on injured tissue, evident from more new blood vessels, higher expression of VEGF-A and decreased muscle iron concentration of treatment groups compared with no-treatment groups (P < 0.05). Besides, shorter re-epithelization time, reduced inflammatory infiltration and distinct collagen deposition were associated with administration of P and PD (P < 0.05). Conclusion: POL extract administration groups have high-quality wound healing, which is associated with increased new blood vessels, collagen deposition and re-epithelization, along with decreased iron accumulation and inflammatory infiltration. Our results suggest that that POL extract is beneficial to repair injured muscle after ischemia–reperfusion, highlighting the potential of POL in the DTPI treatment.

Pouteria ramiflora leaf extract on emulgel in wound healing activity in diabetic rats / Ação do extrato de folhas de Pouteria ramiflora em emulgel na atividade de cicatrização de feridas em ratos diabéticos

The genus Pouteria has been studied because it presents various activities, among which is its anti-inflammatory potential. The effects of Pouteria ramiflora Carbopol gel on the healing of skin wounds in diabetic rats were evaluated by microscopic imaging. Streptozotocin was administered intraperitoneally in animals that had fasted for 12 hours, a situation confirmed by the glycemic index (> 240 mg dL-1). An excision on the back of the animals was performed and three groups were formed: Control (Gel), Ethanolic extract (Ext) and Gel + extract 2% (Ext+gel); the histopathological evaluation occurred on the 7th, 14th, 21st and 30th days after the post-operative period. The results of the phytochemical prospecting of P. ramiflora extract demonstrated the major presence of phenolic compounds and flavonoids; the assessment of the inflammatory infiltrate on the 7th day was higher on group Ext and Ext+gel when compared to group Control; on the 14th day control and Ext (p<0.05). The quantification of fibroblasts was higher on the 7th day among the three treatments, control and Ext (p<0.05), on the 21st day. Angiogenesis showed a higher number of vessels in Ext+gel group (p<0.05) on the 7th day; in Control, Ext and Ext+gel (p<0.05) on the 14th day; and Control and Ext (p<0.05)on the 21st day. The histopathological results showed that the formulation Ext+gel was efficient in tissue reparation and decrease in inflammatory cells on the diabetic's animals.

O gênero Pouteria apresenta várias aplicações terapêuticas e, dentre elas, grande potencial antiflamatório. Os efeitos do gel de Pouteria ramiflora sobre a cicatrização de feridas na pele de ratos diabéticos foram avaliados pela histomorfometria. A estreptozotocina foi administrada por via intraperitoneal em animais após jejum de 12 horas, a confirmação de indução da diabetes foi confirmada pelo índice glicêmico (> 240 mg dL-1). Foi realizada uma incisão no dorso do animal e foram criados 3 grupos de tratamento: controle (gel carbopol), extrato etanólico (Ext) e Gel + extrato etanólico à 2% (Ext+gel); a avaliação histopatológica foi realizada no 7º, 14º, 21º e 30º dias após o período pós operatório. Os resultados da prospecção fitoquímica dos extratos de P. ramiflora demonstraram majoritariamente a presença de compostos fenólicos e flavonóides; o infiltrado inflamatório avaliado no 7º dia foi maior para animais do grupo controle em relação aos grupos Ext (p<0.05) e Ext+gel 2% (p<0.05); no 14º dia o controle e Exp (p<0.05) apresentaram aumento significativo dos infiltrados inflamatórios. A presença de fibroblastos foi elevada no 7º dia em todos os tratamentos. O processo da angiogênese mostrou um maior número de vasos sanguíneos entre os grupos Ext e Ext+gel (p<0.05) no 7º dia; no 14º dia o grupo controle, Ext (p<0.05), Control e Ext+gel (p<0.05) apresentaram aumento de vascularização, e no 21º dia apenas os grupos controle e Ext (p<0.05). Os resultados histopatológicos mostraram que a formulação gel carbopol + extrato etanólico a 2% foi eficiente na reparação de tecidos e na diminuição de células inflamatórias nos animais diabéticos.

Pouteria ramiflora leaf extract on emulgel in wound healing activity in diabetic rats / Ação do extrato de folhas de Pouteria ramiflora em emulgel na atividade de cicatrização de feridas em ratos diabéticos

The genus Pouteria has been studied because it presents various activities, among which is its anti-inflammatory potential. The effects of Pouteria ramiflora Carbopol gel on the healing of skin wounds in diabetic rats were evaluated by microscopic imaging. Streptozotocin was administered intraperitoneally in animals that had fasted for 12 hours, a situation confirmed by the glycemic index (> 240 mg dL-¹). An excision on the back of the animals was performed and three groups were formed: Control (Gel), Ethanolic extract (Ext) and Gel + extract 2% (Ext+gel); the histopathological evaluation occurred on the 7th, 14th, 21st and 30th days after the post-operative period. The results of the phytochemical prospecting of P. ramiflora extract demonstrated the major presence of phenolic compounds and flavonoids; the assessment of the inflammatory infiltrate on the 7th day was higher on group Ext and Ext+gel when compared to group Control; on the 14th day control and Ext (p<0.05). The quantification of fibroblasts was higher on the 7th day among the three treatments, control and Ext (p<0.05), on the 21st day. Angiogenesis showeda higher number of vessels in Ext+gel group (p<0.05) on the 7th day; in Control, Ext and Ext+gel (p<0.05) on the 14th day; and Control and Ext (p<0.05)on the 21st day. The histopathological results showed that the formulation Ext+gel was efficient in tissue reparation and decrease in inflammatory cells on the diabetic's animals.

O gênero Pouteria apresenta várias aplicações terapêuticas e, dentre elas, grande potencial antiflamatório. Os efeitos do gel de Pouteria ramiflora sobre a cicatrização de feridas na pele de ratos diabéticos foram avaliados pela histomorfometria. A estreptozotocina foi administrada por via intraperitoneal em animais após jejum de 12 horas, a confirmação de indução da diabetes foi confirmada pelo índice glicêmico (> 240 mg dL-1). Foi realizada uma incisão no dorso do animal e foram criados 3 grupos de tratamento: controle (gel carbopol), extrato etanólico (Ext) e Gel + extrato etanólico à 2% (Ext+gel); a avaliação histopatológica foi realizada no 7º, 14º, 21º e 30º dias após o período pós operatório. Os resultados da prospecção fitoquímica dos extratos de P. ramiflora demonstraram majoritariamente a presença de compostos fenólicos e flavonóides; o infiltrado inflamatório avaliado no 7º dia foi maior para animais do grupo controle em relação aos grupos Ext (p<0.05) e Ext+gel 2% (p<0.05); no 14º dia o controle e Exp (p<0.05) apresentaram aumento significativo dos infiltrados inflamatórios. A presença de fibroblastos foi elevada no 7º dia em todos os tratamentos. O processo da angiogênese mostrou um maior número de vasos sanguíneos entre os grupos Ext e Ext+gel (p<0.05) no 7º dia; no 14º dia o grupo controle, Ext (p<0.05), Control e Ext+gel (p<0.05) apresentaram aumento de vascularização, e no 21º dia apenas os grupos controle e Ext (p<0.05). Os resultados histopatológicos mostraram que a formulação gel carbopol + extrato etanólico a 2% foi eficiente na reparação de tecidos e na diminuição de células inflamatórias nos animais diabéticos.

Pouteria ramiflora leaf extract on emulgel in wound healing activity in diabetic rats

Abstract The genus Pouteria has been studied because it presents various activities, among which is its anti-inflammatory potential. The effects of Pouteria ramiflora Carbopol gel on the healing of skin wounds in diabetic rats were evaluated by microscopic imaging. Streptozotocin was administered intraperitoneally in animals that had fasted for 12 hours, a situation confirmed by the glycemic index ( 240 mg dL-1). An excision on the back of the animals was performed and three groups were formed: Control (Gel), Ethanolic extract (Ext) and Gel + extract 2% (Ext+gel); the histopathological evaluation occurred on the 7th, 14th, 21st and 30th days after the post-operative period. The results of the phytochemical prospecting of P. ramiflora extract demonstrated the major presence of phenolic compounds and flavonoids; the assessment of the inflammatory infiltrate on the 7th day was higher on group Ext and Ext+gel when compared to group Control; on the 14th day control and Ext (p 0.05). The quantification of fibroblasts was higher on the 7th day among the three treatments, control and Ext (p 0.05), on the 21st day. Angiogenesis showed a higher number of vessels in Ext+gel group (p 0.05) on the 7th day; in Control, Ext and Ext+gel (p 0.05) on the 14th day; and Control and Ext (p 0.05)on the 21st day. The histopathological results showed that the formulation Ext+gel was efficient in tissue reparation and decrease in inflammatory cells on the diabetics animals.

Resumo O gênero Pouteria apresenta várias aplicações terapêuticas e, dentre elas, grande potencial antiflamatório. Os efeitos do gel de Pouteria ramiflora sobre a cicatrização de feridas na pele de ratos diabéticos foram avaliados pela histomorfometria. A estreptozotocina foi administrada por via intraperitoneal em animais após jejum de 12 horas, a confirmação de indução da diabetes foi confirmada pelo índice glicêmico ( 240 mg dL-1). Foi realizada uma incisão no dorso do animal e foram criados 3 grupos de tratamento: controle (gel carbopol), extrato etanólico (Ext) e Gel + extrato etanólico à 2% (Ext+gel); a avaliação histopatológica foi realizada no 7º, 14º, 21º e 30º dias após o período pós operatório. Os resultados da prospecção fitoquímica dos extratos de P. ramiflora demonstraram majoritariamente a presença de compostos fenólicos e flavonóides; o infiltrado inflamatório avaliado no 7º dia foi maior para animais do grupo controle em relação aos grupos Ext (p 0.05) e Ext+gel 2% (p 0.05); no 14º dia o controle e Exp (p 0.05) apresentaram aumento significativo dos infiltrados inflamatórios. A presença de fibroblastos foi elevada no 7º dia em todos os tratamentos. O processo da angiogênese mostrou um maior número de vasos sanguíneos entre os grupos Ext e Ext+gel (p 0.05) no 7º dia; no 14º dia o grupo controle, Ext (p 0.05), Control e Ext+gel (p 0.05) apresentaram aumento de vascularização, e no 21º dia apenas os grupos controle e Ext (p 0.05). Os resultados histopatológicos mostraram que a formulação gel carbopol + extrato etanólico a 2% foi eficiente na reparação de tecidos e na diminuição de células inflamatórias nos animais diabéticos.

Research progress in role and mechanism of neutrophils in tissue repair / 中华创伤杂志

Damage to skin, muscle, bone and nerve tissues can result in various degrees of damage to the body, leading to organ dysfunction even life-threatening. To restore the structure and function of the damaged tissues, various immune cells and histocytes have successively participated in the tissue repair process. As the terminally differentiated white blood cells, neutrophils can remove necrotic tissue, debris and pathogens via phagocytosis and release of antimicrobial peptides after tissue injury to provide conditions for subsequent tissue repair process. However, enhanced neutrophils recruitment as well as excessive inflammatory response may also aggravate tissue damage. In recent years, more and more evidences indicate that neutrophils display plasticity and heterogeneity and that play critical roles in the initiation of tissue repair, promotion of angiogenesis, regulation of cell proliferation and so on. Herein, the authors review the recruitment, phenotype and function, role and outcome of neutrophils during tissue repair so as to provide references for future studies.

Preparation technology of platelet-rich-plasma lysate combined with hyaluronic acid microneedles and wound healing effect / 中国输血杂志

【Objective】 To investigate the application prospect of platelet-rich plasma lysate (PL) microneedles in the treatment of wound healing by optimizing the preparation process and evaluating the activity of platelet growth factor. 【Methods】 Firstly, hyaluronic acid (HA) was used as needle matrix material, and the concentration of HA was preliminarily determined by investigating the fluidity of HA solution, shape of needle, pressure change performance and puncture performance.Combined with the results of HA dissolution in PL, mechanical properties of PL microneedles and skin puncture, the preparation process of platelet-rich plasma lysis microneedles (PLMN) was optimized to investigate the growth factor activity of PLMN and evaluate the effect of PLMN on wound healing in rats. 【Results】 When the concentration of HA was 30 mg/mL, the solution had good fluidity.The HA microneedles could pierce three layers of sealing film, with the puncture rate at 70%, and the solution had good mechanical properties.When HA was dissolved in PL at a concentration of 30 mg/mL at 4℃, the solution had no crystallization and was with good fluidity.The prepared PLMN showed good needle shape and no bending under HD microscope and scanning electron microscope.In vitro transdermal simulation results showed that PLMN could penetrate 4 layers of sealing membrane, and the puncture rate of the first three layers was more than 85%.In vivo lysis experiment showed that PLMNs could be completely dissolved within 10 min after being inserted into the body.Forty minutes later, the micropores left after the insertion of the microneedle were almost closed, without redness, swelling, erythema and other adverse reactions.In vitro and in vivo transdermal experiments showed that clear blue holes were visible after PLMNs penetrated the skin stain, indicating that the microneedles could pierce the skin barrier.Growth factor detection results showed that the content of platelet-derived growth factor (PDGF-BB) and transforming growth factor (TGFβ1) in platelet lysate were (17.67±1.23) ng/mL and (105.95±2.16) ng/mL, respectively.After PLMNs were prepared and stored at room temperature for 1 week, the content of PDGF-BB(ng/mL) and TGFβ1(ng/mL) were 15.48±2.12 and 56.26±1.53, respectively.Compared with PL(vs 17.67±1.23 and 105.95±2.16), the content of PDGF-BB and TGFβ1 decreased, but still maintained the activity of growth factors.The results of wound healing experiment in rats showed that the wound healing rate (%) of PLMN group on the third day was significantly different from that of the control group(52.51±6.15 vs 33.31±3.60, P<0.05). 【Conclusion】 The PLMN prepared in this experiment has good mechanical properties and can successfully pierce the skin cuticle.It can also maintain the activity of growth factors, and has a good effect on wound healing in rats, which provides a new idea for minimally invasive treatment in the field of tissue repair.

Gracilis musculocutaneous flap in repair of perineal soft tissue defect with open pelvic fracture / 中华显微外科杂志

Objective:To investigate the clinical effect of gracilis musculocutaneous flap in repair of perineal soft defect with open pelvic fracture.Methods:From June 2009 to June 2019, 11 cases of open pelvic fracture associated with perineal injury were treated in the Department of Trauma and Orthopaedic of 521 Hospital of Norinco Group. There were 4 males and 7 females aged 16-56 (33 in average) years old. Cause of injuries: 6 cases by traffic accident, 4 by falling from height, and 1 by crushing. All the patients had open pelvic fractures. According to Tile classification, 1 case was rated as type A, 7 as type B and 3 as type C. All the patients were accompanied with perineal injury and soft tissue defect. The wound sizes ranged from 5 cm×5 cm to 8 cm×12 cm. The defects were repaired with gracilis musculocutaneous flap. The size of gracilis myocutaneous flaps was 6 cm×5 cm to 9 cm×13 cm. All donor areas of the flap were sutured directly. After surgery, 11 patients treated with strengthened nutritional support, keep supine position to avoid abduction, and appropriately raise the lower limbs. Follow-ups were conducted regularly after surgery.Results:All patients entered 6 to 30 (22 in average) months of follow-up. All of 11 myocutaneous flaps survived, besides 1 had a few necrosis at the distal surface of the myocutaneous flap, and healed after change of dressing. All the incisions at donor site had stage I healing. The colour, texture and flexibility of the gracilis myocutaneous flap were good. There was a scar at the donor sites without causing obvious dysfunction. Over the follow-up period, there was no failure of flap in either the recipient and donor sites. The patients were satisfied with the appearance and function.Conclusion:Gracilis musculocutaneous flap is one of the ideal methods in repair of perineal soft tissue defect with open pelvic fracture.

Decellularized extracellular matrix mediates tissue construction and regeneration / 医学前沿

Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide tissue with three-dimensional (3D) structural integrity and cellular-function regulation. Containing the crucial traits of the cellular microenvironment, ECM substitutes mediate cell-matrix interactions to prompt stem-cell proliferation and differentiation for 3D organoid construction in vitro or tissue regeneration in vivo. However, these ECMs are often applied generically and have yet to be extensively developed for specific cell types in 3D cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular ECM improves 3D culture development in vitro and tissue remodeling during wound healing after implantation into the host as well. Gaining better insight into ECM derived from either tissue or cells that regulate 3D tissue reconstruction or organ regeneration helps us to select, produce, and implant the most suitable ECM and thus promote 3D organoid culture and tissue remodeling for in vivo regeneration. Overall, the decellularization methodologies and tissue/cell-derived ECM as scaffolds or cellular-growth supplements used in cell propagation and differentiation for 3D tissue culture in vitro are discussed. Moreover, current preclinical applications by which ECM components modulate the wound-healing process are reviewed.

Clinical management of endo-perio lesion through guided tissue regeneration: a 5 year follow-Up / Manejo clínico de una lesión endo-perio a través de la regeneración tisular guiada: control post-operatorio de 5 años

ABSTRACT: Progressive periodontal disease causes loss of supporting structures of teeth resulting in deep bony defects. In this case a report of 22-year old female patient is being presented with clinical findings of vertical bone loss in two adjacent teeth, on distal surface of 2nd upper right premolar and mesial surface of upper right 1st molar. Root canal treatment, non-surgical periodontal therapy followed by guided tissue regeneration was carried out using decalcified freeze-dried bone allograft (DFDBA) and collagen membrane. Analysis of clinical and radiographic findings showed marked reduction in pocket depth up to 12mm with hard tissue repair on 3-month, 2-year and 5- year follow ups.

RESUMEN: La enfermedad periodontal progresiva provoca la pérdida de las estructuras de soporte de los dientes, lo que resulta en defectos óseos profundos. En este caso clínico se presenta un informe de una paciente de 22 años con pérdida ósea vertical en la superficie distal del segundo premolar superior derecho y en la superficie mesial del primer molar superior derecho. El tratamiento del conducto radicular, la terapia periodontal no quirúrgica seguida de la regeneración tisular guiada se llevó a cabo utilizando aloinjerto óseo liofilizado descalcificado (DFDBA) y membrana de colágeno. El análisis de los hallazgos clínicos y radiográficos mostró una marcada reducción en la profundidad de la bolsa de hasta 12 mm con reparación de tejido duro en seguimientos de 3 meses, 2 años y 5 años.

Investigação de pericitos e fotobiomodulação no reparo tecidual em modelo murino diabético / Investigation of pericytes under effect of photobiomodulation in tissue repair in a diabetic murine mice

Em indivíduos com diabetes mellitus (DM) o reparo tecidual cutâneo atrasado representa um desafio para o sistema de saúde. Evidências recentes mostram o potencial da fotobiomodulação (PBM, do inglês, photobiomodulation) em induzir a diferenciação de células-tronco em múltiplos tecidos. Os pericitos são células-tronco perivasculares com ampla plasticidade, podendo ser considerados alvos potenciais para a PBM durante o reparo tecidual. Assim, o objetivo deste estudo foi investigar o efeito da PBM na modulação de células indiferenciadas em feridas de camundongos em condição sistêmica análoga ao DM tipo-II. Trata-se de um estudo in vivo (CEUA#62/2019) utilizando camundongos transgênicos diabéticos induzidos artificialmente e com marcação endógena para pericitos (NG2+/DsRed+; Nestina+/GFP+ & NG2+/DsRed+) e células mesenquimais indiferenciadas (Nestina+/GFP+). Foram realizadas bilateralmente feridas no dorso dos camundongos, e as mesmas foram submetidas ou não a PBM e avaliadas nos tempos experimentais 1, 3 e 7 dias. O reparo tecidual foi acompanhado por morfometria, avaliação de fluxo sanguíneo, análises histológicas nos tempos 1, 3 e 7 dias, além de identificação dos pericitos por microscopia confocal ao final de 3 e 7 dias. Os dados obtidos foram submetidos à análise estatística. As análises morfométricas e histológicas mostraram maior efeito de reparo nas feridas submetidas a PBM, onde a média de área remanescente após 1 de PBM foi 73% da medida de área total inicial no grupo PBM e 86,21% no controle (p=0,0257); aos 3 dias, foram 66,98% e 87,49% respectivamente (p=0,026) e aos 7 dias, 25,54% no grupo PBM e 39,43% no controle (p<0,05). A perfusão sanguínea foi maior nas áreas das feridas quando comparadas a pele íntegra, no entanto, não foram observadas diferenças entre as feridas submetidas ou não a PBM. Por outro lado, foram observadas nestas (PBM), maiores quantidades de células mesenquimais indiferenciadas (Nestina+/GFP+) e de pericitos tipo-I (NG2+/DsRed+) após 7 dias. A utilização de PBM em processos de reparo tecidual em modelo diabético de feridas demostraram resultados significativos tanto clínicos com a nível celular, envolvendo em grande parte as células mesenquimais (nestina+/GFP+) e pericitos (NG2+/DsRed+). Conhecer os mecanismos celulares de ação da PBM em feridas de modelo diabético permite controlar esse processo, além de explorar essa técnica e abrir caminhos para investigação de outras ferramentas e protocolos úteis para o tratamento de feridas nestes indivíduos afetados.

In individuals with diabetes mellitus (DM) delayed cutaneous tissue repair represents a challenge for the health system. Recent evidence shows the potential of photobiomodulation (PBM) to induce stem cell differentiation in multiple tissues. Pericytes, in turn, are perivascular stem cells with wide plasticity and can be considered potential targets for PBM during tissue repair. The objective of this study was to investigate the role of PBM in stem cell modulation in wounds of mice under systemic condition analogous to type-II DM. This is an in vivo study (Ethical protocol: CEUA#62/2019) using artificially induced transgenic diabetic mice with endogenous labeling for pericytes (NG2+/DsRed+; Nestin+/GFP+ & NG2+/DsRed+) and undifferentiated mesenchymal cells (Nestin+/GFP+). Wounds on the mice's back were bilaterally performed, and then submitted or not to laser therapy and evaluated at experimental times 1, 3 and 7 days. Tissue repair was followed by periodic measurements of wound diameter, blood flow assessment, histological analysis and screening of pericytes by confocal microscopy at the end of each experimental time. The data obtained were submitted to statistical analysis. The histologic and morphometric analysis showed a greater repair effect in wounds submitted to PBM, where the average area remaining after 1 day of laser application was 73% of the initial total area measurement in the PBM group, and 86.21% in the control (p= 0.0257); at 3 days, they were 66.98% and 87.49% respectively (p= 0. 026), and at 7 days, 25.54% in the PBM group and 39.43% in the control (p<0.05). Blood perfusion was greater in wound areas when compared to intact skin, however, no statistical differences were observed between wounds submitted or not to PBM. On the other hand, larger amounts of undifferentiated mesenchymal cells (Nestin+/GFP+) and type-I pericytes (NG2+/DsRed+) were observed in these wounds after 7 days. The use of PBM in tissue repair processes in a diabetic wound healing model showed significant clinical and cellular results, involving mostly mesenchymal cells (nestin+/GFP+) and pericytes (NG2+/DsRed+). Knowing the cellular mechanisms of action of PBM in wounds of diabetic, allows better management of the therapy, also it opens paths for the investigation of other tools and protocols useful for the treatment of wounds in DM individuals.

Matriz extracelular de la submucosa de intestino delgado (mec- sid; sid) como biomaterial versátil en medicina regenerativa basada en ingeniería de tejidos / Extracellular matrix of small intestine submucose (mec-sid; sid) as a versatile biomaterial in regenerative medicine based on tissue engineering

Resumen Durante las últimas décadas, la submucosa del intestino delgado (SID), una matriz extracelular descelularizada (MEC) de origen natural, ha atraído atención en la reparación de tejidos porque puede proporcionar abundantes factores bioactivos y un microambiente biomimético de tres dimensiones para inducir las funciones celulares deseadas. En este artículo se revisan las últimas investigaciones sobre SID, que se centran en los siguientes aspectos: superioridad principal como una notable bioactividad, baja inmunogenicidad, reabsorbibilidad y capacidad de recelularización. Se reporta como la adhesión, proliferación, migración y diferenciación de las células se ve influenciada cuando son depositadas sobre este soporte, debido a sus características. Se presenta el gran potencial de este biomaterial para resolver los problemas de cuello de botella que se encuentran en la reparación de varios tejidos, convirtiéndola en un excelente biomaterial para uso en medicina regenerativa basada en ingeniería de tejidos. Palabras clave: Reparación de tejidos, matriz extracelular, Biomateriales, Ingeniería de tejidos, Propiedades fisicoquímicas.

Over the past decades, the small intestine submucosa (SID), a naturally occurring decellularized extracellular matrix (ECM), has attracted attention in tissue repair because it can provide abundant bioactive factors and a three-dimensional biomimetic microenvironment to induce the functions desired cell phones. This article reviews the latest research on SID, which focuses on the following aspects: main superiority as remarkable bioactivity, low immunogenicity, resorbability and recellularization capacity. It is reported how the adhesion, proliferation, migration and differentiation of cells is influenced when they are deposited on this support, due to its characteristics. The great potential of this biomaterial is presented to solve the bottleneck problems found in the repair of various tissues, making it an excellent biomaterial for use in regenerative medicine based on tissue engineering.

Role and mechanism of hierarchical microchanneled bone scaffolds in promoting osteogenesis and angiogenesis / 中国组织工程研究

BACKGROUND: How to recruit endogenous seed cells to promote osteogenesis, provide appropriate bone regeneration microenvironment for cells and ensure the vascularization process of new bone are the difficulties of bone tissue engineering research. OBJECTIVE: To review the osteogenesis and vasculogenesis from the aspects of hierarchical microchanneled bone scaffold. METHODS: The first author searched relevant literature on the promoting effect of hierarchical microchanneled bone scaffold on osteogenesis and angiogenesis from China National Knowledge Infrastructure, Wanfang, PubMed and Web of Science databases from 1950 to 2020. The key words were “hierarchical microchanneled scaffolds, osteogenesis, and angiogenesis” in Chinese and English. Finally, a total of 52 articles meeting the inclusion criteria were selected. RESULTS AND CONCLUSION: Hierarchical microchanneled bone scaffold has a good role in promoting osteogenesis and vascularization, and has a good application prospect in bone tissue engineering. At present, hierarchical microchanneled bone scaffold is mature in the theory of bone tissue engineering. In vitro experiments have confirmed that the hierarchical microchanneled bone scaffold can promote the adhesion and differentiation of mesenchymal stem cells into osteoblasts, but the osteogenic effect in vivo is still poor, and it is still possible to further improve the osteogenic effect. In the future, we should focus on the construction of hierarchical microchanneled bone scaffold complexes, such as chemokines or cytokines, which can further improve the osteogenic efficiency in vivo.

Mesenchymal stem cells in the treatment of spinal cord injury: Cell therapy and combination of new drugs and biomaterials / 中国组织工程研究

BACKGROUND: The treatment of spinal cord injury is mainly to improve the inflammation microenvironment of the injury site, as well as the regeneration and repair of neural function. Mesenchymal stem cells have the characteristics of easy proliferation in vitro, multi-directional differentiation, and suppression of secondary inflammation and immunomodulation, which makes the transplantation of mesenchymal stem cells for various refractory tissue injury diseases including spinal cord injury become a potential cell therapy. OBJECTIVE: To summarize the preclinical and clinical research of mesenchymal stem cells in the treatment of spinal cord injury in recent years, and put forward the problems and development directions of mesenchymal stem cells in experimental research. METHODS: We searched the articles published in Wanfang databases, CNKI and PubMed databases from 2000 to 2020. The key words were “mesenchymal stem cells, spinal cord injury, cell transplantation, immunomodulation, combination therapy, biomaterials” in Chinese and English, respectively. RESULTS AND CONCLUSION: (1) Mesenchymal stem cells from different sources play the role of anti-inflammatory, inducing axon and neuron regeneration in animal models and clinical experiments, and effectively improve the neural function of the damaged area. (2) The exosomes derived from mesenchymal stem cells show the effects of immunomodulation and angiogenesis in the disease model of spinal cord injury. (3) In order to maximize the potential of mesenchymal stem cells, exploring cell pretreatment, combined with new drugs or biological materials is the research direction of mesenchymal stem cells in the treatment of spinal cord injury.

Mesenchymal stem cells and skin injury repair / 生物医学工程学杂志

Mesenchymal stem cells (MSCs) are pluripotent stem cells with high self-proliferation and multidirectional differentiation potential. They also have other functions including immune regulation, paracrine and so on, playing an important role in repairing injured tissues. In recent years, a lot of research has been done on how MSCs promote skin injury repair, and a lot of progress has been made. Compared with direct injection of MSCs in the wound area, some special treatments or transplantation methods could enhance the ability of MSCs to repair skin injury. This paper mainly discusses the role of MSCs in skin injury repair and technical ways to improve its repairing capacity, and discusses the existing problems in this field and prospects for future research directions.

Aplicabilidade da ozonioterapia na odontologia: uma revisão de literatura / Applicability of ozone therapy in dentistry: a literature review

A Ozonioterapia, método que utiliza a mistura gasosa de ozônio e oxigênio, é uma das Práticas Integrativas aprovadas pelo Ministério da Saúde. Atualmente é utilizada na Odontologia devido, principalmente, às suas características estruturais que permitem vastas aplicações. Essa Prática tem como principal objetivo os fins terapêuticos, por meio de propostas cada vez mais efetivas, que corroboram para técnicas e métodos capazes de propiciar tratamentos complementares a fim de curar e prevenir patologias inerentes à cavidade oral, contribuindo para a potencialização de resultados das técnicas já existentes. Em virtude da busca por técnicas complementares, a Ozonioterapia ganhou destaque e tem se mostrado efetiva e segura em diversas práticas odontológicas. O presente trabalho tem por objetivo, por meio de uma revisão de literatura, ressaltar as aplicabilidades do Ozônio (O3) na área odontológica, explicitando meios de utilização e suas respectivas ações, bem como, as contraindicações frente às ocorrências que acometem a cavidade oral.

Ozone therapy, a method that uses a gaseous mixture of ozone and oxygen, is one of the Integrative Practices approved by the Brazilian Ministry of Health. It is currently used in dentistry mainly due to its structural characteristics that allow a wide range of applications. This Practice focuses on therapeutic purposes through increasingly effective proposals that corroborate techniques and methods capable of providing complementary treatments in order to cure and prevent pathologies inherent to the oral cavity, contributing to the potentiation of results from existing techniques. Due to the search for complementary techniques, ozone therapy has gained prominence and has proven to be both effective and safe in several dental practices. This work aims at highlighting the applicability of Ozone (O3) in the dental area through a literature review, explaining means of use and their respective actions, as well as the contraindications to occurrences that affect the oral cavity.