Potencial das membranas de células-tronco mesenquimais na regeneração periodontal: uma revisão sistemática de estudos pré-clínicos em modelo animal / Potential of mesenchymal stem cell sheets on periodontal regeneration: a systematic review of pre-clinical animal studies

A periodontite é uma doença inflamatória crônica multifactorial caracterizada pela destruição progressiva do aparelho de suporte periodontal. Atualmente, as técnicas convencionais para regeneração desses tecidos periodontais perdidos tiveram sucesso limitado. A tecnologia de membranas de células usando células-tronco mesenquimais apareceu como uma estratégia promissora na medicina regenerativa periodontal. Embora estudos recentes tenham mostrado o papel das membranas de células-tronco mesenquimais (MSCSs) no aumento dos tecidos de suporte dentário e ósseo, não há uma revisão sistemática focada especificamente na avaliação da regeneração periodontal em modelos animais ortotópicos. Esta revisão tem como objetivo avaliar o potencial das MSCSs na regeneração periodontal em comparação ao controle, em modelos animais experimentais. Estudos pré-clínicos em defeitos periodontais de modelos animais foram considerados elegíveis. A busca eletrônica incluiu as bases de dados MEDLINE, Web of Science, EMBASE e LILACS. Além disso, uma busca manual avaliou as revistas científicas na área de periodontia/regeneração. A revisão sistemática foi conduzida de acordo com as diretrizes de Preferred Reporting Item for Systematic Reviews and Meta-Analyses statement guidelines. A ferramenta do Centro de Revisão Sistemática para Experimentação com Animais de Laboratório (SYRCLE) foi usada para avaliar o risco de viés. Dos 3989 estudos obtidos a partir da busca no banco de dados eletrônicos foram incluídos 17 artigos. Foram empregados MSCSs autólogos, alógenos e xenógenos para melhorar a regeneração periodontal. Estes incluíram MSCSs do folículo dentário (DF), MSCSs do ligamento periodontal (PDL), MSCSs da polpa dentária (DP), MSCSs da medula óssea (BM), MSCSs periosteais alveolares (AP) e MSCSs gengivais (G). Em relação ao protocolo de indução de células, a maioria dos estudos utilizou ácido ascórbico (52,94%), outros utilizaram placas de cultura com polímero termo responsivo (47,06%). Os efeitos adversos, em relação à utilização das MSCSs no sítio doador, não foram identificados na maioria dos estudos, mesmo com o uso adjunto de scaffolds, membranas ou ambos. Meta-análise não foi considerada devido a heterogeneidades metodológicas. PDL-MSCSs demonstrou ser superior para aumento da regeneração periodontal em comparação ao controle, mas em um microambiente inflamatório induzido, DF-MSCSs foram melhores. Os DF-MSCSs parecem estar relacionados à espessura do cemento e dimensão periodontal. Além disso, DP-MSCSs e BM-MSCSs mostraram resultados melhores em comparação com o controle. Em contraste, AP-MSCSs não foram associados a melhorias na regeneração periodontal. A avaliação do risco de viés com a ferramenta da SYRCLE revelou que 44,12% dos estudos apresentavam baixo risco de viés, 55,29% foram incertos e 0,59%, alto risco. A presente revisão sistemática mostrou que as MSCSs podem aumentar a regeneração periodontal em modelos animais de defeito periodontal, fornecendo uma estratégia promissora para aumentar a regeneração periodontal.

Descelularización y regeneración de tráquea porcina: un acercamiento a la ingeniería tisular / Decellularization and Regeneration of Porcine Trachea: an Approach to Tissue Engineering

Resumen Antecedentes: la ingeniería tisular permite obtener órganos como injertos a partir de tejidos descelularizados, regenerados con células autólogas. Objetivo: descelularizar y regenerar tráqueas porcinas. Material y métodos: se descelularizaron tráqueas porcinas colocándolas cada una en el epiplón de cuatro cerdos Yorkshire para su regeneración in vivo. Una tráquea desce-lularizada con tritón (DT), descelularizada con desoxicolato (DD), descelularizada con desoxicolato y reforzada con un polímero y células epiteliales (DDR), y una nativa crio-preservada (NC). Después de 8 días se obtuvieron la DD, NC y DDR; y al día 15, la DT. Se las evaluó mecánica e histológicamente, se realizó el análisis casuístico. Resultados: las tráqueas descelularizadas conservaron la integridad del cartílago, sin diferencias mecánicas, excepto la DDR con mayor rigidez. Las tráqueas regeneradas presentaron menor rigidez, excepto la DDR que además perdió el epitelio y la vascula-ridad. Las DT, DD mostraron epitelio no respiratorio, fibrosis y vasculogénesis con in-flamación. Conclusiones: las matrices conservaron sus características mecánicas. La regenera-ción in vivo ofrece ventajas como la esterilidad, interacción celular, nutrientes; es senci-llo, factible y económico, pero no hay control del crecimiento celular y vascularización, y los tejidos presentaron alteraciones mecánicas e histológicas. El polímero impidió la re-epitelialización y revascularización. Este estudio abre la posibilidad de mejorar las me-todologías de ingeniería tisular aplicadas al tejido traqueal.

Abstract Introduction: tissue engineering makes it possible to obtain organs as grafts from de-cellularized tissues, regenerated with autologous cells.Objective: decellularize and regenerate porcine tracheas.ARTÍCULO ORIGINAL | Respirar, 2023; 15(3): 188-199 | ISSN 2953-3414 | https://doi.org/10.55720/respirar.15.3.5RECIBIDO: 9 agosto 2023ACEP TADO: 31 agosto 2023 Elisa Barrera-Ramírezhttps://orcid.org/0000-0002-2778-0882Rubén Efraín Garrido-Cardonahttps://orcid.org/0000-0001-6083-5403Alejandro Martínez-Martínezhttps://orcid.org/0000-0003-3448-910XLuis Fernando Plenge-Tellecheahttps://orcid.org/0000-0002-1619-5004Edna Rico-Escobarhttps://orcid.org/0000-0002-0933-0220Esta revista está bajo una licencia de Creative Commons Reconocimiento 4.0 Internacional. Respirar 2023; 15 (3): 189ARTÍCULO ORIGINAL / E. Barrera-Ramírez, R.E. Garrido-Cardona, A. Martínez-Martínez, L.F. Plenge-Tellechea, E. Rico-EscobarDescelularización y regeneración de tráqueaISSN 2953-3414Materials and Methods: Porcine tracheas were decellularized by placing each one in the omentum of four Yorkshire pigs for regeneration in vivo. A trachea decellularized with triton (DT), decellularized with deoxycholate (DD), decellularized with deoxycho-late and reinforced with a polymer, and epithelial cells (DDR), and a cryopreserved na-tive (NC). After 8 days, the DD, NC and DDR were obtained; and on day 15, the DT. The evaluation was mechanically and histologically, performing the case analysis.Results: the decellularized tracheas preserved the integrity of the cartilage, with no me-chanical differences, except for the DDR with greater rigidity. The regenerated trache-as presented less rigidity, except the DDR, which also lost the epithelium and vascular-ity. The DT, DD showed non-respiratory epithelium, fibrosis and vasculogenesis with inflammation.Conclusions: the matrices retained their mechanical characteristics, in vivo regenera-tion offers advantages such as sterility, cell interaction, nutrients; it is simple, feasible and economical, but there is no control of cell growth and vascularization, and the tis-sues presented mechanical and histological alterations. The polymer prevented re-epi-thelialization and revascularization. This study opens the possibility of improving tissue engineering methodologies applied to tracheal tissue.

Fibra de carbono ativada: avaliação das interações biológicas in vitro / Activated carbon fiber: evaluation of biological interactions in vitro

Devido a constante necessidade de desenvolver materiais biocompatíveis com propriedades osteocondutores e osteoindutoras, a presente tese conta com o desenvolvimento de dois estudos in vitro com fibra de carbono obtida a partir de fibra PAN têxtil, incorporada com diferentes íons de metais, na osteogênese com vistas à compreensão das necessidades da engenharia tecidual no desenvolvimento desse biomaterial com adequadas propriedades biológicas. As células foram obtidas dos fêmures de 09 ratos machos adultos (Wistar) pesando 300g, com 90 dias.Estudo 1: A partir da preparação da fibras foram obtidos corpos de prova de 4 mm de diâmetro e 2 mm de altura, dos seguintes grupos: fibra de carbono não ativada (FCNA), fibra carbono ativada (FCA) e fibra carbono ativada com prata (FCAAg). Após plaqueamento (n=5) em meio suplementado (MTS) e meio suplementado osteogênico (MTSO) foram analisados: viabilidade celular, conteúdo de proteína total (PT), atividade de fosfatase alcalina (ALP), interaçãocelular e formação de nódulos de mineralização. Foi avaliada a formação de biofilme nos corpos de prova, utilizando cepas de S. aureus, P. aeruginosa e E. coli. Na viabilidade celular, houve diferença estatística entre grupo controle celular (C) e FCA-MTS, FCAAg-MTS e FCAAg-MTSO. Em PT, não houvediferença, na ALP houve diferença entre C-MTS e as fibras, C-MTSO se mostrou semelhante. Em nódulos, houve diferença entre C-MTS e C-MTSO e as fibras do MTSO. Houve redução de formação de biofilme do S. aureus na FCAAg.Estudo 2: Foram obtidos corpos de prova da mesma dimensão do estudo 1 (n=5) dos seguintes grupos: fibra carbono ativada com prata (FCAAg), fibra carbono ativada com ouro (FCAAu), fibra carbono ativada com cobre (FCACu), fibra carbono ativada com paládio (FCAPd) e fibra carbono ativada com platina (FCAPt). Foram quantificadas a proliferação celular, viabilidade celular, formação de nódulos de mineralização, conteúdo de PT e ALP. Todas as amostras mostraram-se semelhantes quanto a proliferação celular, com exceção do grupo FCAAg comparado ao grupo controle (C). Sobre viabilidade celular, C obteve maior viabilidade que os outros grupos, e FCA obteve maior taxa que os grupos FCAAg, FCACu, FCAPt, sendo semelhante aos grupos FCAAu e FCAPd. Já os grupos FCAAu e FCAPd apresentaram diferença aos grupos FCAAg e FCACu. Na análise de expressão de PT apenas houve diferença entre FCA e FCAAu, sendo FCAAu com menor expressão de produção de PT. Na avaliação da ALP os grupos FCAAg e FACu mostraram diferença estatística e inferior com os grupos C, FCAAu, FCAPd e FCAPt, além disso, o grupo FCA mostrou menor taxa que C.Conclusões: As fibras utilizadas de base para a incorporação dos íons demonstraram grande potencial para uso como scaffold para reparação óssea, isso porque em ambos os estudos, na forma ativada e não ativada, as fibras apresentaram viabilidade celular e quantificação de cálcio satisfatórias. Sendo a versão não ativada mais econômica no que diz respeito ao tempo e custo de preparação. Mais estudos devem ser empregados a fim de assegurar sua segurança clínica em relação à citotoxicidade da incorporação de íons de ouro e paládio.(AU)

Due to the constant need to develop biocompatible materials with osteoconductive and osteoinductive properties, this thesis involves the development of two in vitro studies with carbon fiber obtained from textile PAN fiber, incorporated with different metal ions, in osteogenesis with a view to understanding the needs of tissue engineering in the development of this biomaterial with adequate biological properties. The cells were obtained from the femurs of 9 adult male rats (Wistar) weighing 300g, aged 90 days. Study 1: From the fiber preparation, specimens measuring 4 mm in diameter and 2 mm in height were obtained from the following groups: non-activated carbon fiber (FCNA), activated carbon fiber (FCA) and silver-activated carbon fiber (FCAAg). After plating (n=5) in supplemented medium (MTS) and supplemented osteogenic medium (MTSO), cell viability, total protein content (PT), alkaline phosphatase (ALP) activity, cell interaction and formation of mineralization nodules were analyzed. . Biofilm formation was evaluated in the specimens, using strains of S. aureus, P. aeruginosa and E. coli. In cell viability, there was a statistical difference between the cell control group (C) and FCAMTS, FCAAg-MTS and FCAAg-MTSO. In PT, there was no difference, in ALP there was a difference between C-MTS and fibers, C-MTSO was similar. In nodules, there was a difference between C-MTS and C-MTSO and MTSO fibers. There was a reduction in S. aureus biofilm formation on FCAAg. Study 2: Specimens of the same size as in study 1 (n=5) were obtained from the following groups: carbon fiber activated with silver (FCAAg), carbon fiber activated with gold (FCAAu), carbon fiber activated with copper (FCACu), palladium-activated carbon fiber (FCAPd) and platinum-activated carbon fiber (FCAPt). Cell proliferation, cell viability, formation of mineralization nodules, PT and ALP content were quantified. All samples were similar in terms of cell proliferation, with the exception of the FCAAg group compared to the control group (C). Regarding cell viability, C obtained higher viability than the other groups, and FCA obtained a higher rate than the FCAAg, FCACu, FCAPt groups, being similar to the FCAAu and FCAPd groups. The FCAAu and FCAPd groups showed differences to the FCAAg and FCACu groups. In the analysis of PT expression, there was only a difference between FCA and FCAAu, with FCAAu having lower expression of PT production. In the ALP assessment, the FCAAg and FACu groups showed a lower statistical difference compared to the C, FCAAu, FCAPd and FCAPt groups, in addition, the FCA group showed a lower rate than C. Conclusions: The fibers used as the basis for the incorporation of ions demonstrated great potential for use as a scaffold for bone repair, because in both studies, in activated and non-activated form, the fibers showed satisfactory cell viability and calcium quantification. The non-activated version is moreeconomical in terms of preparation time and cost. More studies must be carried out to ensure its clinical safety in relation to the cytotoxicity of the incorporation of gold and palladium ions. (AU)

A cervical cancer tissue-derived decellularized extracellular matrix scaffold for cervical cancer tissue reconstruction in vitro / 南方医科大学学报

OBJECTIVE@#The prepare decellularized extracellular matrix (ECM) scaffold materials derived from human cervical carcinoma tissues for 3D culture of cervical carcinoma cells.@*METHODS@#Fresh human cervical carcinoma tissues were treated with sodium lauryl ether sulfate (SLES) solution to prepare decellularized ECM scaffolds. The scaffolds were examined for ECM microstructure and residual contents of key ECM components (collagen, glycosaminoglycan, and elastin) and genetic materials by pathological staining and biochemical content analysis. In vitro 3D culture models were established by injecting cultured cervical cancer cells into the prepared ECM scaffolds. The cells in the recellularized scaffolds were compared with those in a conventional 2D culture system for cell behaviors including migration, proliferation and epithelial-mesenchymal transition (EMT) wsing HE staining, immunohistochemical staining and molecular biological technology analysis. Resistance to 5-fluorouracil (5-Fu) of the cells in the two culture systems was tested by analyzing the cell apoptosis rates via flow cytometry.@*RESULTS@#SLES treatment effectively removed cells and genetic materials from human cervical carcinoma tissues but well preserved the microenvironment structure and biological activity of ECM. Compared with the 2D culture system, the 3D culture models significantly promoted proliferation, migration, EMT and 5-Fu resistance of human cervical cancer cells.@*CONCLUSION@#The decellularized ECM scaffolds prepared using human cervical carcinoma tissues provide the basis for construction of in vitro 3D culture models for human cervical cancer cells.

Progress in the application of patch materials in cardiovascular surgery / 中南大学学报(医学版)

The cardiovascular patch, served as artificial graft materials to replace heart or vascular tissue defect, is still playing a key role in cardiovascular surgeries. The defects of traditional cardiovascular patch materials may determine its unsatisfactory long-term effect or fatal complications after surgery. Recent studies on many new materials (such as tissue engineered materials, three-dimensional printed materials, etc) are being developed. Patch materials have been widely used in clinical procedures of cardiovascular surgeries such as angioplasty, cardiac atrioventricular wall or atrioventricular septum repair, and valve replacement. The clinical demand for better cardiovascular patch materials is still urgent. However, the cardiovascular patch materials need to adapt to normal coagulation mechanism and durability, promote short-term endothelialization after surgery, and inhibit long-term postoperative intimal hyperplasia, its research and development process is relatively complicated. Understanding the characteristics of various cardiovascular patch materials and their application in cardiovascular surgeries is important for the selection of new clinical surgical materials and the development of cardiovascular patch materials.

Applicatoin of chitosan-based hydrogel in oral tissue engineering / 中南大学学报(医学版)

Pulpitis, periodontitis, jaw bone defect, and temporomandibular joint damage are common oral and maxillofacial diseases in clinic, but traditional treatments are unable to restore the structure and function of the injured tissues. Due to their good biocompatibility, biodegradability, antioxidant effect, anti-inflammatory activity, and broad-spectrum antimicrobial property, chitosan-based hydrogels have shown broad applicable prospects in the field of oral tissue engineering. Quaternization, carboxymethylation, and sulfonation are common chemical modification strategies to improve the physicochemical properties and biological functions of chitosan-based hydrogels, while the construction of hydrogel composite systems via carrying porous microspheres or nanoparticles can achieve local sequential delivery of diverse drugs or bioactive factors, laying a solid foundation for the well-organized regeneration of defective tissues. Chemical cross-linking is commonly employed to fabricate irreversible permanent chitosan gels, and physical cross-linking enables the formation of reversible gel networks. Representing suitable scaffold biomaterials, several chitosan-based hydrogels transplanted with stem cells, growth factors or exosomes have been used in an attempt to regenerate oral soft and hard tissues. Currently, remarkable advances have been made in promoting the regeneration of pulp-dentin complex, cementum-periodontium-alveolar bone complex, jaw bone, and cartilage. However, the clinical translation of chitosan-based hydrogels still encounters multiple challenges. In future, more in vivo clinical exploration under the conditions of oral complex microenvironments should be performed, and the combined application of chitosan-based hydrogels and a variety of bioactive factors, biomaterials, and state-of-the-art biotechnologies can be pursued in order to realize multifaceted complete regeneration of oral tissue.

Effect of pH on the chelation between strontium ions and decellularized small intestinal submucosal sponge scaffolds / 北京大学学报(医学版)

OBJECTIVE@#To investigate the preparation of decellularized small intestinal submucosa (dSIS) sponge scaffolds with chelated strontium (Sr) ions at different pH values, and to select the appropriate pH values for synthesizing Sr/dSIS scaffolds using the physicochemical properties and biocompatibility of the scaffolds as evaluation indexes.@*METHODS@#(1) Sr/dSIS scaffolds preparation and grouping: After mixing dSIS solution and strontium chloride solution in equal volumes, adjusting pH of the solution to 3, 5, 7, and 9 respectively, porous scaffolds were prepared by freeze-drying method after full reaction at 37℃, which were named Sr/dSIS-3, -5, -7, and -9 respectively, and the dSIS scaffolds were used as the control group. (2) Physicochemical property evaluation: The bulk morphology of the scaffolds was observed in each group, the microscopic morphology analyzed by scanning electron microscopy, and the porosity and pore size determined, the surface elements analyzed by energy spectroscopy, the structure of functional groups analyzed by infrared spectroscopy, the chelation rate determined by atomic spectrophotometry, the water absorption rate detected by using specific gravity method, and the compression strength evaluated by universal mechanical testing machine.(3) Biocompatibility evaluation: The cytotoxicity and proliferative effect to bone mesenchymal stem cells (BMSCs) of each group were evaluated by Calcein-AM/PI double staining method.@*RESULTS@#Scanning electron microscopy showed that the scaffolds of each group had an interconnected three-dimensional porous structure with no statistical difference in pore size and porosity. Energy spectrum analysis showed that strontium could be detected in Sr/dSIS-5, -7 and -9 groups, and strontium was uniformly distributed in the scaffolds. Functional group analysis further supported the formation of chelates in the Sr/dSIS-5, -7 and -9 groups. Chelation rate analysis showed that the Sr/dSIS-7 group had the highest strontium chelation rate, which was statistically different from the other groups (P < 0.05). The scaffolds in all the groups had good water absorption. The scaffolds in Sr/dSIS-5, -7 and -9 groups showed significantly improved mechanical properties compared with the control group (P < 0.05). The scaffolds in all the groups had good biocompatibility, and the Sr/dSIS-7 group showed the best proliferation of BMSCs.@*CONCLUSION@#When pH was 7, the Sr/dSIS scaffolds showed the highest strontium chelation rate and the best proliferation effect of BMSCs, which was the ideal pH value for the preparation of the Sr/dSIS scaffolds.

Research, development and application of collagen: a review / 生物工程学报

Collagen, which widely exists in skin, bone, muscle and other tissues, is a major structural protein in mammalian extracellular matrix. It participates in cell proliferation, differentiation, migration and signal transmission, plays an important role in tissue support and repair and exerts a protective effect. Collagen is widely used in tissue engineering, clinical medicine, food industry, packaging materials, cosmetics and medical beauty due to its good biological characteristics. This paper reviews the biological characteristics of collagen and its application in bioengineering research and development in recent years. Finally, we prospect the future application of collagen as a biomimetic material.

Cell-loaded hydrogel microspheres based on droplet microfluidics: a review / 生物工程学报

Droplet microfluidics technology offers refined control over the flows of multiple fluids in micro/nano-scale, enabling fabrication of micro/nano-droplets with precisely adjustable structures and compositions in a high-throughput manner. With the combination of proper hydrogel materials and preparation methods, single or multiple cells can be efficiently encapsulated into hydrogels to produce cell-loaded hydrogel microspheres. The cell-loaded hydrogel microspheres can provide a three-dimensional, relatively independent and controllable microenvironment for cell proliferation and differentiation, which is of great value for three-dimensional cell culture, tissue engineering and regenerative medicine, stem cell research, single cell study and many other biological science fields. In this review, the preparation methods of cell-loaded hydrogel microspheres based on droplet microfluidics and its applications in biomedical field are summarized and future prospects are proposed.

Research status and prospect of tissue engineering technology in treatment of atrophic rhinitis / 中国修复重建外科杂志

OBJECTIVE@#To review the research progress of the feasibility of a new treatment method for atrophic rhinitis (ATR) based on tissue engineering technology (seed cells, scaffold materials, and growth factors), and provide new ideas for the treatment of ATR.@*METHODS@#The literature related to ATR was extensively reviewed. Focusing on the three aspects of seed cells, scaffold materials, and growth factors, the recent research progress of ATR treatment was reviewed, and the future directions of tissue engineering technology to treat ATR were proposed.@*RESULTS@#The pathogenesis and etiology of ATR are still unclear, and the effectiveness of the current treatments are still unsatisfactory. The construction of a cell-scaffold complex with sustained and controlled release of exogenous cytokines is expected to reverse the pathological changes of ATR, promoting the regeneration of normal nasal mucosa and reconstructing the atrophic turbinate. In recent years, the research progress of exosomes, three-dimensional printing, and organoids will promote the development of tissue engineering technology for ATR.@*CONCLUSION@#Tissue engineering technology can provide a new treatment method for ATR.

Efeito biológico do laser de baixa intensidade em osteoblastos cultivados na superfície de arcabouços poliméricos tridimensionais / Biological effect of low-intensity laser on osteoblasts cultured on the surface of three-dimensional polymeric scaffolds

A primeira parte do trabalho avaliou, através de uma revisão sistemática de estudos in vitro, a aplicabilidade da fotobiomodulação como uma ferramenta auxiliar na engenharia de tecidos. De 8373 estudos inicialmente identificados a partir das estratégias de busca, dez artigos atingiram os critérios de inclusão para análise. Os dados obtidos na maioria dos estudos revisados indicaram que a laserterapia de baixa intensidade (LBI) pode aumentar a proliferação e diferenciação de células cultivadas na superfície dos biomateriais. Na segunda parte do trabalho foi avaliado o efeito da LBI na dose de 4 J/cm2 na proliferação de osteoblastos (OFCOL II) cultivados na superfície de arcabouços poliméricos tridimensionais (3D) de ácido polilático (PLA) e de PLA associado a quitosana (PLA/Q) produzidos pela técnica de fiação por sopro em solução. O ensaio do Alamar Blue demonstrou que as células OFCOL II cultivadas sobre os arcabouços 3D de PLA e irradiadas apresentaram uma maior atividade proliferativa quando comparadas aos grupos não irradiados no intervalo de 72 h. Além disso, as células OFCOL II cultivadas sobre arcabouços de PLA/Q também apresentaram uma maior atividade proliferativa em 24 h. A análise pela microscopia eletrônica de varredura (MEV) mostrou que os osteoblastos se encontravam ancorados em concavidades das fibras nos arcabouços examinados. Concluiu-se que o modelo proposto apresentou um potencial para estudos na área da engenharia tecidual óssea. Na terceira parte do trabalho foi avaliada a influência da LBI infravermelha (IV) e vermelha (V) em diferentes dosagens (1 J/cm², 4 J/cm² e 6 J/cm²) na proliferação e viabilidade das células OFCOL II. O ensaio do Alamar Blue mostrou diferenças significativas (p<0,05) na atividade mitocondrial do grupo IV utilizando a dose de 1 J/cm2 e 4 J/cm2, nos intervalos de 24 e 48 h. Já o ensaio do Live/Dead evidenciou que a LBI induziu aumento da viabilidade celular no grupo IV na dose de 4 J/cm2, quando comparada com os demais grupos. Em conjunto, os resultados sugerem que a LBI pode promover bioestimulação in vitro de osteoblastos, inclusive quando cultivados na superfície de arcabouços poliméricos 3D, representando assim uma ferramenta promissora nas técnicas de engenharia tecidual óssea (AU).

The first part of the work evaluated, through a systematic review of in vitro studies, the applicability of photobiomodulation as an auxiliary tool in tissue engineering. Of 8373 studies initially identified from the search strategies, ten articles met the inclusion criteria for analysis. Data obtained from most of the reviewed studies indicated that low-intensity laser therapy (LLLT) could increase the proliferation and differentiation of cells cultured on the surface of biomaterials. The second part of the work evaluated the effect of LLLT at a dose of 4 J/cm² on the proliferation of osteoblasts (OFCOL II) cultivated on the surface of threedimensional (3D) polymer scaffolds of polylactic acid (PLA) and PLA associated with chitosan (PLA/Q) produced by the solution blow spinning technique. The Alamar Blue assay demonstrated that OFCOL II cells cultured on 3D PLA scaffolds and irradiated showed more significant proliferative activity when compared to non-irradiated groups within 72 h. Furthermore, OFCOL II cells cultured on PLA/Q scaffolds showed higher proliferative activity at 24 h. Analysis by scanning electron microscopy (SEM) showed that the osteoblasts were anchored in the concavities of the fibers of the examined scaffolds. It was concluded that the proposed model showed potential for studies in the field of bone tissue engineering. The third part of the work evaluated the influence of infrared (IR) and red (R) laser therapy at different dosages (1 J/cm², 4 J/cm², and 6 J/cm²) on the proliferation and viability of OFCOL II cells. The Alamar Blue assay showed significant differences (p<0.05) in the mitochondrial activity of group IR using the dose of 1 J/cm² and 4 J/cm² at 24 and 48 h. The Live/Dead assay showed that LLLT induced an increase in cell viability in the IR group at a dose of 4 J/cm² compared to the other groups. Taken together, the results suggest that LLLT can promote in vitro biostimulation of osteoblasts, even when cultivated on the surface of 3D polymeric scaffolds, thus representing a promising tool in bone tissue engineering techniques (AU).

Efeitos do laser de baixa intensidade em osteoblastos cultivados em arcabouços nanofibrosos de ácido polilático / Effects of low-intensity laser on osteoblasts cultured on polylactic acid nanofibrous scaffolds

A engenharia de tecidos ósseos é um ramo importante da medicina regenerativa e envolve o desenvolvimento de arcabouços com composição e arquitetura favoráveis à integração celular, além do estudo de fatores capazes de promover a adesão e proliferação celular, incluindo estímulos químicos e biofísicos. O objetivo do estudo foi avaliar a utilização do laser de baixa intensidade (LBI) como uma ferramenta para promover a bioestimulação in vitro de células osteoblásticas cultivadas em arcabouços nanofibrosos de ácido polilático (PLA). Os arcabouços foram produzidos pela técnica de eletrofiação e caracterizados quanto à molhabilidade, composição pela espectroscopia no infravermelho por transformada de Fourier (FTIR), morfologia da superfície por microscópica eletrônica de varredura (MEV), caracterização termogravimétrica (TGA), calorimetria diferencial exploratória (DSC) e cristalinidade por difração de raios-X (DRX). Os ensaios biológicos foram conduzidos com osteoblastos da linhagem OFCOL II cultivados na superfície dos arcabouços e submetidos ou não (grupo controle) a irradiação com laser diodo InGaAIP na potência de 30 mW, nas doses de 1, 4 e 6 J/cm² e nos comprimentos de onda de 660 nm (grupos V1, V4, V6, respectivo as doses) e 780 nm (grupos I1, I4 e I6, respectivo as doses). Os efeitos do LBI na proliferação dos osteoblastos foram avaliados através do método bioquímico Alamar Blue, nos intervalos de 24, 48 e 72h, enquanto a viabilidade e a morfologia celular foram analisadas no intervalo de 72h, através do ensaio Live/Dead e da microscopia eletrônica de varredura (MEV), respectivamente. Os dados do ensaio bioquímico de Alamar Blue mostraram uma maior proliferação celular nos grupos V6 em todos os intervalos analíticos em comparação ao grupo controle (p<0,05). Outras diferenças entre o grupo controle e irradiados foram encontradas apenas nos intervalos de 48h e 72h para V1, e para o grupo IV6 em 72h. O ensaio Live/Dead revelou um aumento na viabilidade celular nos grupos trados com LBI, sendo significativamente maior no grupo V1 quando comparado ao grupo controle. A análise por MEV mostrou adequada interação dos osteoblastos aos arcabouços, com o corpo celular se espalhando ao longo do eixo da nanofibra e a presença de contatos físicos mais evidentes, através da formação de ligação por meio de filopódios e lamelipódios, nos grupos V1, V6 e I6. Em conjunto, os dados do presente trabalho mostraram que o LBI promove a bioestimulação de osteoblastos cultivados sobre nanofibras de PLA, o que aponta para o seu uso potencial nas técnicas de engenharia tecidual óssea, sobretudo no que se refere ao uso do comprimento de onda de 660 nm, a qual apresentou grupos com mais resultados significativos (AU).

Bone tissue engineering is a relevant branch of regenerative medicine and involves the development of scaffolds with composition and architecture favorable to cell integration, in addition to studying factors capable of promoting cell adhesion and proliferation, including chemical and biophysical stimuli. The study aimed to evaluate the use of low-level laser irradiation (LLLI) to promote in vitro biostimulation of osteoblastic cells cultured on polylactic acid (PLA) nanofibrous scaffolds. The scaffolds were produced by the electrospinning technique and characterized in terms of wettability, composition by Fourier transform infrared spectroscopy (FTIR), surface morphology by scanning electron microscopy (SEM), thermogravimetric characterization (TGA), differential scanning calorimetry (DSC) and crystallinity by Xray diffraction (XRD). The biological assays were conducted with osteoblasts of the OFCOL II lineage cultured on the surface of the scaffolds and submitted or not (control group) to irradiation with InGaAIP diode laser, power of 30 mW, with doses of 1, 4 and 6 J/cm² and wavelengths of 660 nm (groups V1, V4, V6, respectively doses) and 780 nm (groups I1, I4 and I6, respectively doses). The effects of LLLT from the perspective of osteoblasts were evaluated using the biochemical method Alamar Blue assay, at intervals of 24, 48 and 72h, while cell viability and morphology were observed at 72h, using the Live/Dead assay and electron microscopy. scan (SEM), respectively. The Alamar Blue assay data showed more significant cell proliferation in groups in the V6 groups at all analytical intervals compared to the control group (p<0.05). Other differences between the control and irradiated groups were found only at intervals of 48h and 72h for V1, and for group IV6 at 72h. The Live/Dead assay revealed an increase in cell viability in the groups treated with LLLT, being significantly higher in the V1 group when compared to the control group. SEM analysis showed adequate interaction between osteoblasts and scaffolds, with the cell body spreading along the nanofiber axis and the presence of more evident physical contacts, through the formation of bonds through filopodia and lamellipodia, in groups V1, V6 and I6. Together, the data from the present study observed that LLLT promotes the biostimulation of osteoblasts cultured on PLA nanofibers, which pointed to its potential use in bone tissue engineering techniques, especially with regard to the use of the wavelength of 660 nm, which presented groups with more significant results (AU).

Automated Assessment of Cell Infiltration and Removal in Decellularized Scaffolds - Experimental Study in Rabbits / Avaliação automatizada da infiltração e remoção celular em scaffolds descelularizados - Estudo experimental em coelhos

Abstract Objective Semiquantitative and automated measurement of nuclear material removal and cell infiltration in decellularized tendon scaffolds (DTSs). Method 16 pure New Zealand rabbits were used, and the gastrocnemius muscle tendon was collected bilaterally from half of these animals (16 tendons collected); 4 were kept as control and 12 were submitted to the decellularization protocol (DTS). Eight of the DTSs were used as an in vivo implant in the experimental rotator cuff tear (RCT) model, and the rest, as well as the controls, were used in the semiquantitative and automated evaluation of nuclear material removal. The eight additional rabbits were used to make the experimental model of RCT and subsequent evaluation of cellular infiltration after 2 or 8 weeks, within the DTS. Results The semiquantitative and automated analysis used demonstrated a removal of 79% of nuclear material (p< 0.001 and power > 99%) and a decrease of 88% (p < 0.001 and power >99%) in the area occupied by nuclear material after the decellularization protocol. On cell infiltration in DTS, an increase of 256% (p < 0.001 and power >99%) in the number of cells within the DTS was observed in the comparison between 2 and 8 weeks postoperatively. Conclusion The proposed semiquantitative and automated measurement method was able to objectively measure the removal of nuclear material and cell infiltration in DTS.

Resumo Objetivo Mensuração semiquantitativa e automatizada da remoção de material nuclear e da infiltração celular em scaffolds tendinosos descelularizados (STDs). Método Foram utilizados 16 coelhos Nova Zelândia puros, sendo o tendão do músculo gastrocnêmio coletado bilateralmente de metade destes animais (16 tendões coletados); 4 foram mantidos como controle e 12 foram submetidos ao protocolo de descelularização (STD). Dos STDs, 8 foram utilizados como implante in vivo no modelo experimental de lesão do manguito rotador (LMR) e os restantes, assim como os controles, foram utilizados na avaliação semiquantitativa e automatizada da remoção de material nuclear. Os oito coelhos adicionais foram utilizados na confecção do modelo experimental de LMR e posterior avaliação da infiltração celular após 2 ou 8 semanas, dentro do STD. Resultados A análise semiquantitativa e automatizada utilizada demonstrou uma remoção de 79% do material nuclear (p< 0,001 e poder > 99%) e uma diminuição de 88% (p< 0,001 e poder > 99%) na área ocupada por material nuclear após o protocolo de descelularização. Sobre a infiltração celular no STD, foi observado um aumento de 256% (p< 0,001 e poder > 99%) no número de células dentro do STD na comparação entre 2 e 8 semanas de pós-operatório. Conclusão O método de mensuração semiquantitativo e automatizado proposto foi capaz de mensurar objetivamente a remoção de material nuclear e a infiltração celular no STD.

Regeneración en recesiones periodontales. Valor de la fibrina rica en plaquetas en la terapéutica mucogingival / Regeneration in periodontal recessions. Value of platelet-rich fibrin in mucogingival therapy

RESUMEN Introducción: Los mecanismos reparativos logrados con los procedimientos de cobertura radicular presentan una gran complejidad por el crecimiento adelantado del tejido epitelial y conectivo gingival durante la cicatrización, por lo que en la actualidad se promueven nuevas técnicas plásticas que permiten no solo el aislamiento de estos, sino el aporte de elementos biológicos que pueden tributar a una regeneración de varios de los tejidos perdidos por la enfermedad distrófica. Objetivo: Describir los procesos de regeneración de los tejidos perdidos por la enfermedad distrófica, durante la cicatrización de las diferentes técnicas plásticas periodontales. Método: Se realizó una revisión bibliográfica de la literatura disponible, a través de la búsqueda automatizada en las bases de datos: SciELO, Pubmed, Scopus y Elsevier, que abarcaron los años desde el 2012 hasta el 2021. Se evaluaron 98 artículos, y el estudio se circunscribió a los 35 que se enfocaban de manera integral en la temática. Conclusiones: El proceso de cicatrización de los injertos de tejidos blandos se logra a expensas de la migración del epitelio gingival sobre la porción coronaria de la recesión periodontal y una inserción fibrosa en la región apical del injerto. Con la regeneración tisular guiada se logra mantener al epitelio en una posición coronal a la recesión periodontal y una conexión fibrosa en la mayor extensión de la raíz expuesta. La membrana de fibrina rica en plaquetas actúa como barrera que modula la regeneración del sitio y aporta factores de crecimiento y otros elementos celulares que inducen el proceso regenerativo.

ABSTRACT Introduction: the reparative mechanisms achieved with root coverage procedures present a great complexity due to the advanced growth of the gingival epithelial and connective tissue during healing, for which new plastic techniques are currently promoted, allowing us not only the isolation of these, but the contribution of biological elements that can contribute to a regeneration of several of the tissues lost by dystrophic disease. Objective: to describe the regeneration processes of the tissues lost by the dystrophic disease, during the healing of the different periodontal plastic techniques. Methods: a bibliographic review of the available literature was carried out through the automated search in SciELO, Pubmed, Scopus and Elsevier databases from 2012 to 2021. A number of 98 articles was evaluated, and the study was limited to the 35 that focused comprehensively on the subject. Conclusions: the healing process of soft tissue grafts is achieved at the expense of the migration of the gingival epithelium over the coronary portion of the periodontal recession and a fibrous insertion in the apical region of the graft. It is possible to maintain the epithelium in a coronal position to the periodontal recession and a fibrous connection in the greatest extension of the exposed root with guided tissue regeneration. The platelet-rich fibrin membrane acts as a barrier that modulates the regeneration of the site and provides growth factors and other cellular elements that induce the regenerative process.

Células madre en odontología: nuevas perspectivas / Stem cells in dentistry: new perspectives

En el campo de la odontología, prevalecen actualmente alternativas terapéuticas con una filosofía conservadora. Sin embargo, con el advenimiento de los tratamientos con células madre (CM), se amplían las posibilidades terapéuticas, que buscan la combinación y el equilibrio entre la intervención tradicional y las posibilidades de reposición de estructuras anatómicas dañadas, a través de la regeneración de tejidos utilizando células madre o sus derivados (AU)

In the dentistry field, therapeutic alternatives with a conservative philosophy currently prevail. However, with the advent of stem cell (SC) treatments, therapeutic possibilities are expanding, seeking a combination and balance between traditional intervention and the pos- sibility of replacing damaged anatomical structures through tissue regeneration, using stem cells or their derivatives (AU)

Perspectivas atuais da Engenharia de Tecidos da articulação temporomandibular / Perspectivas Actuales de la Ingeniería de Tejidos para la Articulación Temporomandibular / Current Perspectives of Tissue Engineering for the Temporomandibular Joint

Introdução: As limitações das terapias atuais para doenças degenerativas da articulação temporomandibular (ATM) levaram ao aumento do interesse em estratégias regenerativas. A engenharia de tecidos (ET), combinando células-tronco, arcabouços e fatores de crescimento, pode fornecer uma substituição biológica funcional e permanente das estruturas da ATM, além de prevenir o avanço de doenças degenerativas. Objetivo: Este artigo descreve as perspectivas atuais da ET das estruturas da ATM em modelos animais. Metodologia: As abordagens da ET foram categorizadas de acordo com as estruturas primárias da ATM: 1) o disco articular, 2) o côndilo mandibular e 3) a fossa glenóide e eminência articular. Resultados: As áreas com a maior quantidade de estudos são o côndilo mandibular e disco articular, em estudos que abordam o uso de arcabouços tridimensionais, de origem sintética e/ou natural, podendo ou não estar associados a células tronco (diferenciadas ou não) e a fatores de crescimento. Conclusão: A ET da ATM ainda é uma área relativamente nova, em desenvolvimento e em constante avanço. Os avanços tecnológicos desenvolvidos nessa área têm o potencial de auxiliar no desenvolvimento de terapias mais eficientes e menos invasivos... (AU)

Introducción: Las limitaciones de las terapias actuales para las enfermedades degenerativas de la articulación temporomandibular (ATM) han llevado a un mayor interés en las estrategias regenerativas. La ingeniería de tejidos, que combina células, andamios y factores de crecimiento, puede proporcionar un reemplazo biológico funcional y permanente de las estructuras de la ATM, además de prevenir el avance de enfermedades degenerativas. Objetivo: Este artículo describe las perspectivas actuales de la ingeniería de tecidos de las estructuras de la ATM en modelos animales. Metodología: Los enfoques de ingeniería de tejidos se clasificaron según las estructuras primarias de la ATM: 1) el disco articular, 2) el cóndilo mandibular y 3) la fosa glenoidea y la eminencia articular. Resultados: Las áreas con mayor número de estudios son el cóndilo mandibular y el disco articular, en estudios que abordan el uso de estructuras tridimensionales, de origen sintético y/o natural, que pueden o no estar asociadas a células (diferenciadas o no) y con factores de crecimiento. Conclusión: La ingeniería de tejidos de la ATM es todavía un área relativamente nueva, en desarrollo y em constante avance. Los avances tecnológicos desarrollados en esta área tienen el potencial de ayudar en el desarrollo de terapias más eficientes y menos invasivas... (AU)

Introduction: The limitations of current therapies for degenerative diseases of the temporomandibular joint (TMJ) have led to increased interest in regenerative strategies. Tissue engineering (TE), combining stem cells, scaffolds, and growth factors, can provide a functional and permanent biological replacement of TMJ structures, in addition to preventing the advancement of degenerative diseases. Aim: This article describes current TE perspectives of TMJ structures in animal models. Methods: TE approaches were categorized according to the primary TMJ structures: 1) the articular disc, 2) the mandibular condyle, and 3) the glenoid fossa and articular eminence. Results: The areas with the greatest number of studies are the mandibular condyle and articular disc, in studies that address the use of three-dimensional scaffolds, of synthetic and/or natural origin, which may or may not be associated with stem cells (differentiated or not) and with growth factors. Conclusion: TE of the TMJ is still a relatively new, developing, and constantly advancing area. The technological advances developed in this area have the potential to assist in the development of more efficient and less invasive therapies... (AU)

3D spheroid cell cultures and their role in bone regeneration: a systematic review / Cultivos de esferoides 3D y su papel en la regeneración ósea: una revisión sistemática

Abstract Recently, the 3D spheroid cell culture application has been extensively used in the treatment of bone defects. A wide variety of methodologies have been used, which has made the comparison of results complex. Therefore, this systematic review has two aims: (i) to perform an analysis focused on the role of 3D spheroid cell culture in bone regeneration strategies; and (ii) address the main challenges in clinical application. A search of the following keywords "3D cell culture", "spheroid", and "bone regeneration" was carried out in the PubMed, Scopus, and ScienceDirect databases and limited to the years 2010-2020. Studies were included if their primary objective was the behavior of cell aggregates to formed spheroids structures by different 3D cell culture techniques focused on the regeneration of bone tissue. To address the risk of bias for in vitro studies, the United States national toxicology program tool was applied, and descriptive statistics of the data were performed, with the SPSS V.22 program. A total of 16 studies were included, which met the established criteria corresponding to in vitro and in vitro/in vivo studies; most of these studies used stem cells for the 3D cell spheroids. The most often methods used for the 3D formation were low adherence surface and rotational methods, moreover, mesenchymal stem cells were the cell line most frequently used because of their regenerative potential in the field of bone tissue engineering. Although the advances in research on the potential use of 3D spheroids in bone regeneration have made great strides, the constant innovation in cell spheroid formation methodologies means that clinical application remains in the future as strategy for 3D tissue bioprinting.

Resumen Recientemente, la aplicación del cultivo 3D de esferoides se ha utilizado ampliamente en el tratamiento de defectos óseos. La variedad de metodologías para lograr los cultivos 3D de esferoides ha hecho compleja la comparación de resultados. Por tanto, esta revisión sistemática tiene dos objetivos: (i) realizar un análisis centrado en el papel de los cultivos 3D de esferoides en las estrategias de regeneración ósea; y (ii) abordar los principales desafíos en la aplicación clínica. Se realizó una búsqueda de las siguientes palabras clave "cultivo celular 3D", "esferoide" y "regeneración ósea" en las bases de datos PubMed, Scopus y ScienceDirect y se limitó a los años 2010-2020. Se incluyeron los estudios si su principal objetivo era el comportamiento de agregados celulares para generar las estructuras esferoidales desarrollados por diferentes técnicas de cultivo celular 3D enfocadas a la regeneración del tejido óseo. Para abordar el riesgo de sesgo de los estudios in vitro, se aplicó la herramienta del programa nacional de toxicología de Estados Unidos y se realizaron estadísticas descriptivas de los datos, con el programa SPSS V.22. Se incluyeron un total de 16 estudios, que cumplieron con los criterios establecidos correspondientes a estudios in vitro e in vitro/in vivo; la mayoría de estos estudios utilizaron células troncales para generar los esferoides celulares 3D. Los métodos más utilizados para la formación de los esferoides 3D fueron la superficie de baja adherencia y los métodos de rotación, asimismo, la línea celular de células troncales mesenquimales fueron las más utilizadas debido a su gran potencial regenerativo en el campo de la ingeniería de tejidos óseos. Aunque los avances en la investigación sobre el uso potencial de los cultivos celulares de esferoides 3D en la regeneración ósea han logrado grandes avances, la constante innovación en las metodologías de la generación de esferoides 3D deja claro que la aplicación clínica de estos permanecerá en el futuro como estrategia en la bioimpresión tisular.

Perspectivas atuais da engenharia de tecidos da articulação temporomandibular / Perspectivas Actuales de la Ingeniería de Tejidos para la Articulación Temporomandibular / Current Perspectives of Tissue Engineering for the Temporomandibular Joint

Introdução: As limitações das terapias atuais para doenças degenerativas da articulação temporomandibular (ATM) levaram ao aumento do interesse em estratégias regenerativas. A engenharia de tecidos (ET), combinando células-tronco, arcabouços e fatores de crescimento, pode fornecer uma substituição biológica funcional e permanente das estruturas da ATM, além de prevenir o avanço de doenças degenerativas. Objetivo: Este artigo descreve as perspectivas atuais da ET das estruturas da ATM em modelos animais. Metodologia: As abordagens da ET foram categorizadas de acordo com as estruturas primárias da ATM: 1) o disco articular, 2) o côndilo mandibular e 3) a fossa glenóide e eminência articular. Resultados: As áreas com a maior quantidade de estudos são o côndilo mandibular e disco articular, em estudos que abordam o uso de arcabouços tridimensionais, de origem sintética e/ou natural, podendo ou não estar associados a células tronco (diferenciadas ou não) e a fatores de crescimento. Conclusão: A ET da ATM ainda é uma área relativamente nova, em desenvolvimento e em constante avanço. Os avanços tecnológicos desenvolvidos nessa área têm o potencial de auxiliar no desenvolvimento de terapias mais eficientes e menos invasivos... (AU)

Introducción: Las limitaciones de las terapias actuales para las enfermedades degenerativas de la articulación temporomandibular (ATM) han llevado a un mayor interés en las estrategias regenerativas. La ingeniería de tejidos, que combina células, andamios y factores de crecimiento, puede proporcionar un reemplazo biológico funcional y permanente de las estructuras de la ATM, además de prevenir el avance de enfermedades degenerativas. Objetivo: Este artículo describe las perspectivas actuales de la ingeniería de tecidos de las estructuras de la ATM en modelos animales. Metodología: Los enfoques de ingeniería de tejidos se clasificaron según las estructuras primarias de la ATM: 1) el disco articular, 2) el cóndilo mandibular y 3) la fosa glenoidea y la eminencia articular. Resultados: Las áreas con mayor número de estudios son el cóndilo mandibular y el disco articular, en estudios que abordan el uso de estructuras tridimensionales, de origen sintético y/o natural, que pueden o no estar asociadas a células (diferenciadas o no) y con factores de crecimiento. Conclusión: La ingeniería de tejidos de la ATM es todavía un área relativamente nueva, en desarrollo y en constante avance. Los avances tecnológicos desarrollados en esta área tienen el potencial de ayudar en el desarrollo de terapias más eficientes y menos invasivas... (AU)

Introduction: The limitations of current therapies for degenerative diseases of the temporomandibular joint (TMJ) have led to increased interest in regenerative strategies. Tissue engineering (TE), combining stem cells, scaffolds, and growth factors, can provide a functional and permanent biological replacement of TMJ structures, in addition to preventing the advancement of degenerative diseases. Aim: This article describes current TE perspectives of TMJ structures in animal models. Methods: TE approaches were categorized according to the primary TMJ structures: 1) the articular disc, 2) the mandibular condyle, and 3) the glenoid fossa and articular eminence. Results: The areas with the greatest number of studies are the mandibular condyle and articular disc, in studies that address the use of three-dimensional scaffolds, of synthetic and/ or natural origin, which may or may not be associated with stem cells (differentiated or not) and with growth factors. Conclusion: TE of the TMJ is still a relatively new, developing, and constantly advancing area. The technological advances developed in this area have the potential to assist in the development of more efficient and less invasive therapies... (AU)

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.

Immunomodulatory effects and mechanisms of distraction osteogenesis / 国际口腔科学杂志·英文版

Distraction osteogenesis (DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.