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1.
J Biomed Mater Res B Appl Biomater ; 110(7): 1637-1650, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35113492

RESUMO

The reconstruction of chronic skin wounds remains a public health challenge in dermatology. Precisely controlling and monitoring the wound-healing process should result in enhanced outcomes for the patient. Cell-based therapies have shown great potential in medicine due to their immunomodulatory and healing properties. Herein, we produced activated macrophages by treating circulating monocytes with mesenchymal stem cell (MSC) supernatant. We also demonstrated the critical role of activated macrophages transplantation using amniotic membranes in accelerating wound healing in an animal wound model. The activated macrophages not only exhibited immunomodulatory cytokines like transforming growth factorß (TGFß) and interleukin 10 (and IL10) secretion but also showed attachment and proliferation ability on the amniotic membrane scaffold. Moreover, MSCs supernatant-treated cells also displayed significant ARG1, CD206, and IL 10 genes expression. Inspired by the in vitro results, we examined the in vivo therapeutic efficacy of the activated macrophage transplantation using an acellular amniotic membrane carrier in a full-thickness cutaneous wound model. The wound healing rate was significant in the group treated with macrophages generated via mesenchymal cell therapy seeded human amniotic membrane. There was less scarring in the wound sites after placing cell-scaffold constructs in the wound sites in the animal models. Overall, macrophages stimulated with mesenchymal cells' supernatant exhibited improved healing processes in incisional wounds by decreasing the inflammatory phase, increasing angiogenesis, and reducing scar tissue development.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Âmnio , Animais , Humanos , Macrófagos , Células-Tronco Mesenquimais/metabolismo , Modelos Animais , Pele , Cicatrização
2.
Artif Organs ; 46(3): 375-386, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35023156

RESUMO

The placenta, as a large discarded tissue and rich in extracellular matrix (ECM), is an excellent candidate for biological scaffolds in reconstructive medicine. Considering the importance of ECM structure in cell fate, the aim of this study was to achieve human placenta decellularization protocol that preserve the structure of scaffolds. Thus, human placenta was decellularized by four protocols and decellularization efficacy was compared by hematoxylin and eosin (H&E), 4',6-diamidino-2-phenylindole (DAPI) staining, and DNA measurement. Decellularized placenta structure preservation was assessed by Masson's trichrome staining, scanning electron microscopy (SEM), and immunofluorescence (IF) for collagen I, IV, and fibronectin. Finally, liquid displacement measured scaffolds' porosity. After culturing menstrual blood-derived stem cells (MenSCs) on placenta scaffolds, cell adhesion was investigated by SEM imaging, and cell viability and proliferation were assessed by MTT assay. According to H&E and DAPI staining, only protocols 1 and 3 could completely remove cells from the scaffolds. DNA measurements confirmed a significant reduction in the genetic material of decellularized scaffolds compared to native placenta. According to Masson's trichrome, IF, and SEM imaging, scaffold structure is better preserved in P3 than P1 protocol. Liquid displacement showed higher porosity of P3 scaffold than P1. SEM imaging confirmed cells adhesion to the decellularized placenta, and the attached cells showed good viability and maintained their proliferative capacity, indicating the suitability of the scaffolds for cell growth. Results introduced an optimized protocol for placenta decellularization that preserves the scaffold structure and supports cell adhesion and proliferation.


Assuntos
Separação Celular/métodos , Placenta/citologia , Engenharia Tecidual/métodos , DNA/análise , Feminino , Humanos , Placenta/ultraestrutura , Gravidez , Tecidos Suporte
3.
Mater Sci Eng C Mater Biol Appl ; 122: 111938, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33641926

RESUMO

The concept of providing tissue engineering scaffolds with natural physical properties and minimal immunogenicity has not been systematically approached for the lungs yet. Here, the rat acellular lung tissue (ALT) was cross-linked to provide either EDC/NHS cross-linked tissue (EDC/NHS-CLT) or tannic acid cross-linked tissue (TA-CLT). Young's modulus revealed that EDC/NHS-CLT had mechanical properties similar to the native lung and culture of lung mesenchymal cells showed a higher potential of cell proliferation on EDC/NHS-CLT versus TA-CLT and ALT. The in vitro immunogenicity tests showed a strong induction of T-cell proliferation by TA-CLT and an attenuated macrophage induction by TA-CLT. Processed rat lungs were implanted xenogenically into the mouse peritoneal cavity and the host-implant interactions showed that tannic acid is not released from TA-CLT in a physiologically effective dose. The profile of peritoneal fluid proinflammatory (TNFα, IL-1ß, IL-12p70 and IL-17) and anti-inflammatory (IL-10 and TGFß1) cytokines, and CD3+ T-lymphocytes and CD11b+ macrophages revealed that apart from induction of high levels of IL-17 during the first week and IL-10 during the second to third weeks after implantation by TA-CLT, other indicators of immune reactions to cross-linked tissues were not significantly different from ALT. Also, a high fibrotic reaction to TA-CLT was observed on the weeks 2-3, but alveolar structures were preserved in EDC/NHS-CLT. Our findings show that by controlled EDC/NHS cross-linking, an acellular lung scaffold could be provided with mechanical properties similar to native lung, which promotes mesenchymal lung cells proliferation and does not stimulate recipient's immune system more than a non-cross-linked tissue.


Assuntos
Células-Tronco Mesenquimais , Engenharia Tecidual , Animais , Reagentes de Ligações Cruzadas , Pulmão , Camundongos , Ratos , Tecidos Suporte
4.
Carbohydr Polym ; 255: 117336, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33436179

RESUMO

In this study, the effects of various parameters of the water-in-oil emulsification/internal gelation method on the properties of calcium-alginate microparticles were evaluated and optimized. Results showed that the spherical-shaped microparticles with the highest circularity and high production yield can be produced by alginate solution with a concentration of 2 wt.%, calcium carbonate/alginate ratio of 10/1 (w/w), water/oil volume ratio of 1/20, emulsifier concentration of 5 % (v/v), and emulsification speed of 1000 rpm. Two model drugs including simvastatin lactone and simvastatin ß-hydroxyacid were loaded into the microspheres with promising encapsulation efficiencies of 73 % and 69 %, respectively. The microspheres showed a pH-responsive swelling behavior with a percentage of 10.60 %, 352.65 %, 690.03 %, and 1211.46 % at the pH values of 2.0, 4.5, 7.4, and 8.5, respectively. The microspheres showed an increasing trend of release rate in direct proportion to pH. These findings would be useful for therapeutic applications which need pH-responsive drug carriers.

5.
Bioimpacts ; 11(1): 45-52, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33469507

RESUMO

Introduction: Porous 3D scaffolds synthesized using biocompatible and biodegradable materials could provide suitable microenvironment and mechanical support for optimal cell growth and function. The effect of the scaffold porosity on the mechanical properties, as well as the TiO2 nanoparticles addition on the bioactivity, antimicrobial, photocatalytic, and cytotoxicity properties of scaffolds were investigated. Methods: In the present study, porous scaffolds consisting poly (lactide-co-glycolide) (PLGA) containing TiO2 nanoparticles were fabricated via air-liquid foaming technique, which is a novel method and has more advantages due to not using additives for nucleation compared to former ways. Results: Adjustment of the foaming process parameters was demonstrated to allow for textural control of the resulting scaffolds and their pore size tuning in the range of 200-600 µm. Mechanical properties of the scaffolds, in particular, their compressive strength, revealed an inverse relationship with the pore size, and varied in the range of 0.97-0.75 MPa. The scaffold with the pore size 270 µm, compressive strength 0.97 MPa, and porosity level 90%, was chosen as the optimum case for the bone tissue engineering (BTE) application. Furthermore, 99% antibacterial effect of the PLGA/10 wt.% TiO2 nanocomposite scaffolds against the strain was achieved using Escherichia coli. Besides, no negative effect of the new method was observed on the bioactivity behavior and apatite forming ability of scaffolds in the simulated body fluid (SBF). This nanocomposite also displayed a good cytocompatibility when assayed with MG 63 cells. Lastly, the nanocomposite scaffolds revealed the capability to degrade methylene blue (MB) dye by nearly 90% under the UV irradiation for 3 hours. Conclusion: Based on the results, nanocomposite new scaffolds are proposed as a promising candidate for the BTE applications as a replacement for the previous ones.

6.
Carbohydr Polym ; 254: 117465, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357924

RESUMO

Designing multifunctional surfaces is key to develop advanced materials for orthopedic applications. In this study, we design a double-layer coating, assembled onto the completely regular titania nanotubes (cRTNT) array. Benefiting from the biological and topological characteristics of chitosan nanofibers (CH) and reduced graphene oxide (RGO) through a unique assembly, the designed material features promoted osteoblast cell viability, prolonged antibiotic release profile, as well as inhibited bacterial biofilm formation. The synergistic effect of RGO and CH on the biological performance of the surface is investigatSed. The unique morphology of the nanofibers leads to the partial coverage of RGO-modified nanotubes, providing an opportunity to access the sublayer properties. Another merit of this coating lies in its morphological similarity to the extracellular matrix (ECM) to boost cellular performance. According to the results of this study, this platform holds promising advantages over the bare and bulk biopolymer-modified TNTs.


Assuntos
Quitosana/síntese química , Materiais Revestidos Biocompatíveis/química , Grafite/química , Nanocompostos/química , Osteoblastos/efeitos dos fármacos , Titânio/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Portadores de Fármacos , Liberação Controlada de Fármacos , Humanos , Cinética , Nanocompostos/ultraestrutura , Nanotubos/química , Nanotubos/ultraestrutura , Osteoblastos/citologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Vancomicina/farmacologia
7.
J Tissue Eng Regen Med ; 15(1): 78-87, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33175464

RESUMO

Diaphragmatic wall defects caused by congenital disorders or disease remain a major challenge for physicians worldwide. Polymeric patches have been extensively explored within research laboratories and the clinic for soft tissue and diaphragm reconstruction. However, patch usage may be associated with allergic reaction, infection, granulation, and recurrence of the hernia. In this study, we designed and fabricated a porous scaffold using a combination of 3D printing and freeze-drying techniques. A 3D printed polycaprolactone (PCL) mesh was used to reinforcegelatin scaffolds, representing an advantage over previously reported examples since it provides mechanical strength and flexibility. In vitro studies showed that adherent cells were anchorage-dependent and grew as a monolayer attached to the scaffolds. Microscopic observations indicated better cell attachments for the scaffolds with higher gelatin content as compared with the PCL control samples. Tensile testing demonstrated the mechanical strength of samples was significantly greater than adult diaphragm tissue. The biocompatibility of the specimens was investigated in vivo using a subcutaneous implantation method in Bagg albino adult mice for 20 days, with the results indicating superior cellular behavior and attachment on scaffolds containing gelatin in comparison to pure PCL scaffolds, suggesting that the porous PCL/gelatin scaffolds have potential as biodegradable and flexible constructs for diaphragm reconstruction.


Assuntos
Diafragma , Gelatina , Poliésteres , Impressão Tridimensional , Procedimentos Cirúrgicos Reconstrutivos , Tecidos Suporte/química , Células 3T3 , Animais , Diafragma/metabolismo , Diafragma/cirurgia , Liofilização , Gelatina/química , Gelatina/farmacologia , Camundongos , Poliésteres/química , Poliésteres/farmacologia , Porosidade
8.
RSC Adv ; 11(26): 15795-15807, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35481217

RESUMO

Biophysical characteristics of engineered scaffolds such as topography and electroconductivity have shown potentially beneficial effects on stem cell morphology, proliferation, and differentiation toward neural cells. In this study, we fabricated a conductive hydrogel made from chitosan (CS) and polyaniline (PANI) with induced PC12 cell surface topography using a cell imprinting technique to provide both topographical properties and conductivity in a platform. The engineered hydrogel's potential for neural priming of rat adipose-derived stem cells (rADSCs) was determined in vitro. The biomechanical analysis revealed that the electrical conductivity, stiffness, and hydrophobicity of flat (F) and cell-imprinted (CI) substrates increased with increased PANI content in the CS/PANI scaffold. The conductive substrates exhibited a lower degradation rate compared to non-conductive substrates. According to data obtained from F-actin staining and AFM micrographs, both CI(CS) and CI(CS-PANI) substrates induced the morphology of rADSCs from their irregular shape (on flat substrates) into the elongated and bipolar shape of the neuronal-like PC12 cells. Immunostaining analysis revealed that both CI(CS) and CI (CS-PANI) significantly upregulated the expression of GFAP and MAP2, two neural precursor-specific genes, in rADSCs compared with flat substrates. Although the results reveal that both cell-imprinted topography and electrical conductivity affect the neural lineage differentiation, some data demonstrate that the topography effects of the cell-imprinted surface have a more critical role than electrical conductivity on neural priming of ADSCs. The current study provides new insight into the engineering of scaffolds for nerve tissue engineering.

10.
Stem Cell Res Ther ; 11(1): 436, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036643

RESUMO

BACKGROUND: Mesenchymal stem cells are a promising cell source for chondrogenic differentiation and have been widely used in several preclinical and clinical studies. However, they are prone to an unwanted differentiation process towards hypertrophy that limits their therapeutic efficacy. Matrix metallopeptidase 13 (MMP-13) is a well-known factor regulated during this undesirable event. MMP-13 is a collagen degrading enzyme, which is also highly expressed in the hypertrophic zone of the growth plate and in OA cartilage. Accordingly, we investigated the effect of MMP-13 inhibition on MSC hypertrophy. METHODS: In this study, 5-bromoindole-2-carboxylic acid (BICA) was used as an inhibitory agent for MMP-13 expression. After identifying its optimal concentration, BICA was mixed into a hydrogel and the release rate was studied. To prepare the ideal hydrogel, chondroitin sulfate (CS) and platelet lysate (PL) were mixed with sodium alginate (Alg) at concentrations selected based on synergistic mechanical and rheometric properties. Then, four hydrogels were prepared by combining alginate (1.5%w/v) and/or CS (1%w/v) and/or PL (20%v/v). The chondrogenic potential and progression to hypertrophy of human bone marrow-derived mesenchymal stem cell (hBM-MSC)-loaded hydrogels were investigated under free swelling and mechanical loading conditions, in the presence and absence of BICA. RESULTS: Viability of hBM-MSCs seeded in the four hydrogels was similar. qRT-PCR revealed that BICA could successfully inhibit MMP-13 expression, which led to an inhibition of Coll X and induction of Coll-II, in both free swelling and loading conditions. The GAG deposition was higher in the group combining BICA and mechanical stimulation. CONCLUSIONS: It is concluded that BICA inhibition of MMP-13 reduces MSC hypertrophy during chondrogenesis.


Assuntos
Diferenciação Celular , Condrogênese , Hidrogéis , Inibidores de Metaloproteinases de Matriz , Alginatos , Células Cultivadas , Condrócitos , Sulfatos de Condroitina/farmacologia , Humanos , Hipertrofia , Metaloproteinase 13 da Matriz/genética , Células-Tronco Mesenquimais
11.
BioDrugs ; 34(5): 567-586, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32754790

RESUMO

Desirable features of exosomes have made them a suitable manipulative platform for biomedical applications, including targeted drug delivery, gene therapy, cancer diagnosis and therapy, development of vaccines, and tissue regeneration. Although natural exosomes have various potentials, their clinical application is associated with some inherent limitations. Recently, these limitations inspired various attempts to engineer exosomes and develop designer exosomes. Mostly, designer exosomes are being developed to overcome the natural limitations of exosomes for targeted delivery of drugs and functional molecules to wounds, neurons, and the cardiovascular system for healing of damage. In this review, we summarize the possible improvements of natural exosomes by means of two main approaches: parental cell-based or pre-isolation exosome engineering and direct or post-isolation exosome engineering. Parental cell-based engineering methods use genetic engineering for loading of therapeutic molecules into the lumen or displaying them on the surface of exosomes. On the other hand, the post-isolation exosome engineering approach uses several chemical and mechanical methods including click chemistry, cloaking, bio-conjugation, sonication, extrusion, and electroporation. This review focuses on the latest research, mostly aimed at the development of designer exosomes using parental cell-based engineering and their application in cancer treatment and regenerative medicine.


Assuntos
Exossomos , Biotecnologia , Sistemas de Liberação de Medicamentos , Medicina Regenerativa
12.
Crit Rev Biotechnol ; 40(8): 1098-1112, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32772758

RESUMO

Exosomes are the most researched extracellular vesicles. In many biological, physiological, and pathological studies, they have been identified as suitable candidates for treatment and diagnosis of diseases by acting as the carriers of both drugs and genes. Considerable success has been achieved regarding the use of exosomes for tissue regeneration, cancer diagnosis, and targeted drug/gene delivery to specific tissues. While major progress has been made in exosome extraction and purification, extraction of large quantities of exosomes is still a major challenge. This issue limits the scope of both exosome-based research and therapeutic development. In this review, we have aimed to summarize experimental studies focused at increasing the number of exosomes. Biotechnological studies aimed at identifying the pathways of exosome biogenesis to manipulate some genes in order to increase the production of exosomes. Generally, two major strategies are employed to increase the production of exosomes. First, oogenesis pathways are genetically manipulated to overexpress activator genes of exosome biogenesis and downregulate the genes involved in exosome recycling pathways. Second, manipulation of the cell culture medium, treatment with specific drugs, and limiting certain conditions can force the cell to produce more exosomes. In this study, we have reviewed and categorized these strategies. It is hoped that the information presented in this review will provide a better understanding for expanding biotechnological approaches in exosome-based therapeutic development.


Assuntos
Biotecnologia , Exossomos/metabolismo , Exossomos/genética , Engenharia Genética , Engenharia Metabólica , Redes e Vias Metabólicas , Proteômica
13.
J Biomed Mater Res A ; 108(6): 1390-1407, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32108983

RESUMO

Poly (lactate-co-glycolate) (PLGA) is a typical biocompatible and biodegradable synthetic polymer. The addition of TiO2 nanoparticles has shown to improve compressive modulus of PLGA scaffolds and reduced fast degradation. A novel method has been applied to fabricate PLGA/TiO2 scaffolds without using any inorganic solvent, with aim of improving the biocompatibility, macroscale morphology, and well inter-connected pores efficacy: Air-Liquid Foaming. Field Emission Scanning Electron Microscopy (FESEM) revealed an increase in interconnected porosity of up to 98%. As well the compressive testing showed enhancement in modulus. Bioactivity and in vitro degradation were studied with immersion of scaffolds in Simulated Body Fluid (SBF) and incubation in Phosphate Buffered Saline (PBS), respectively. Formation of apatite layer corroborated the bioactivity after soaking in SBF. Degradation rate of scaffolds was increased with excessive addition of TiO2 contents withal. The in vitro cultured human-like MG63 ostoblast cells showed attachment, proliferation, and nontoxcitiy in contact, using MTT assay [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide]. According to the results, the novel method utilized in this study generated porous viable tissue without using any inorganic solvent or porogen can be a promising candidate in further treatment of orthopedic patients effectively.


Assuntos
Materiais Biocompatíveis/química , Nanocompostos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Tecidos Suporte/química , Titânio/química , Implantes Absorvíveis , Linhagem Celular , Humanos , Nanocompostos/ultraestrutura , Osteoblastos/citologia , Porosidade , Engenharia Tecidual
14.
Biomed Mater ; 15(3): 035014, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-31896091

RESUMO

Tendon tissue engineering based on stem cell differentiation has attracted a great deal of attention in recent years. Previous studies have examined the effect of cell-imprinted polydimethylsiloxane (PDMS) substrate on induction differentiation in stem cells. In this study, we used tenocyte morphology as a positive mold to create a tenocyte-imprinted substrate on PDMS. The morphology and topography of this tenocyte replica on PDMS was evaluated with scanning electron microscopy (SEM) and atomic force microscopy. The tenogenic differentiation induction capacity of the tenocyte replica in adipose tissue-derived mesenchymal stem cells (ADSCs) was then investigated and compared with other groups, including tissue replica (which was produced similarly to the tenocyte replica and was evaluated by SEM), decellularized tendon, and bone morphogenic protein (BMP)-12, as other potential inducers. This comparison gives us an estimate of the ability of tenocyte-imprinted PDMS (called cell replica in the present study) to induce differentiation compared to other inducers. For this reason, ADSCs were divided into five groups, including control, cell replica, tissue replica, decellularized tendon and BMP-12. ADSCs were seeded on each group separately and investigated by the real-time reverse transcription polymerase chain reaction (RT-PCR) technique after seven and 14 days. Our results showed that in spite of the higher effect of the growth factor on tenogenic differentiation, the cell replica can also induce tenocyte marker expression (scleraxis and tenomodulin) in ADSCs. Moreover, the tenogenic differentiation induction capacity of the cell replica was greater than tissue replica. Immunocytochemistry analysis revealed that ADSCs seeding on the cell replica for 14 days led to scleraxis and tenomodulin expression at the protein level. In addition, immunohistochemistry indicated that contrary to the promising results in vitro, there was little difference between ADSCs cultured on tenocyte-imprinted PDMS and untreated ADSCs. The results of such studies could lead to the production of inexpensive cell culture plates or biomaterials that can induce differentiation in stem cells without growth factors or other supplements.


Assuntos
Tecido Adiposo/metabolismo , Células-Tronco Mesenquimais/citologia , Tenócitos/citologia , Engenharia Tecidual/métodos , Adulto , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Materiais Biocompatíveis , Proteínas Morfogenéticas Ósseas/química , Diferenciação Celular , Dimetilpolisiloxanos/química , Fatores de Diferenciação de Crescimento/química , Humanos , Imuno-Histoquímica , Masculino , Proteínas de Membrana/química , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Impressão Molecular , Ratos , Tendões/citologia
15.
Sci Rep ; 10(1): 997, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969618

RESUMO

Lacto-n-neotatraose (LNnT) oligosaccharide shows properties such as anti-inflammatory, type 2 immune response induction, induced angiogenesis, and anti-bacterial effects. Here, we hypothesized that the application of LnNT in the skin full-thickness wound can accelerate the healing process through its anti-inflammatory effect as well as induction of type 2 immune responses. In this study, we evaluated the cell viability of fibroblasts in the presence of LNnT. The full-thickness wound model was created by punch biopsy. The mice were treated intradermaly with LNnT at the concentrations of 100 and 200 µg or PBS as a control group. The wounds samples were compared based on the macroscopic and histological evaluations. The amount of collagen deposition and expression of genes involved in type 2 immunity were measured by the hydroxyproline assay and real time PCR method, respectively. Our results showed that LNnT had no negative effect on the cell viability of fibroblasts. LNnT increased the wound closure rate on day 7 post-wounding. H&E stain analysis revealed that mice treated with 200 µg LNnT exhibited better healing score, follicle formation, and lower epidermal thickness index. The mice treated with LNnT exhibited a lower collagen deposition on day 21 and higher collagen content on days 7 and 14 post-treatment. The LNnT groups also exhibited a lower number of neutrophils and a higher number of basal cells and fibroblasts. The expression rate of IL-10, IL-4, and IL-13 was higher in the LNnT groups. These results showed the high potential of LNnT for use in treatment of full-thickness wounds.


Assuntos
Fibroblastos/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Oligossacarídeos/farmacologia , Pele/efeitos dos fármacos , Cicatrização/genética , Animais , Fibroblastos/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Camundongos , Pele/metabolismo , Cicatrização/efeitos dos fármacos
16.
Med Hypotheses ; 134: 109389, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31627122

RESUMO

The healing process of non-healing and full-thickness wounds is currently facing some serious challenges. In such ulcers, losing a large part of skin causes a chronic infection due to the entrance of various pathogens in the wound bed. Moreover, poor vascularization, uncontrolled inflammation, and delayed re-epithelialization increase the healing time in patients suffering from such wounds. In this light, tissue engineering provides a wide range of strategies using a variety of biomaterials, biofactors and stem cells to decrease the healing time and restore the function of the damaged site. A suitable wound healing agent should possess some critical parameters such as inducing re-epithelialization, anti-inflammatory and anti-bacterial properties, and angiogenic capability. The Lacto-n-Neotetraose (LNnT) with chemical formula C26H45NO21 is an oligosaccharide present in human milk and soluble antigens extracted from Schistosoma mansoni eggs. It is reported that LNnT induces type 2 immune response (Th2 immunity). Th2 immunity promotes re-epithelialization, angiogenesis and wound contraction by recruiting the cells which produce Th2-related cytokines. Moreover, LNnT shows some special characteristics such as angiogenic capability, anti-inflammatory, and anti-bacterial effects which can address the mentioned challenges in the treatment of non-healing and full-thickness wounds. Here, we hypothesize that utilizing LNnT is an appropriate biofactor which would improve the healing process in full-thickness and non-healing wounds.


Assuntos
Neovascularização Fisiológica/efeitos dos fármacos , Oligossacarídeos/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/imunologia , Pé Diabético/tratamento farmacológico , Pé Diabético/microbiologia , Avaliação Pré-Clínica de Medicamentos , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/lesões , Humanos , Linfocinas/fisiologia , Camundongos , Leite Humano/química , Modelos Biológicos , Oligossacarídeos/isolamento & purificação , Células Th2/imunologia , Cicatrização/imunologia , Cicatrização/fisiologia
17.
Methods ; 171: 62-67, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31302179

RESUMO

A matrix derived from natural tissue functions as a highly biocompatible and versatile scaffold for tissue engineering applications. It can act as a supportive construct that provides a niche for colonization by host cells. In this work, we describe a cost-effective, reliable and reproducible protocol for decellularization and preservation of human skin as a potential soft tissue replacement. The decellularized human skin is achieved using purely chemical agents without any enzymatic steps. The suitability of the proposed method for the preservation of the extracellular matrix (ECM) structure and its main components and integrity were evaluated using histological and immunohistochemical analysis. Cryopreservation and final sterility were conducted using programmable freeze-drying and gamma irradiation. The architecture, basement membrane and 3D structure of ECM can be successfully preserved after decellularization. Our protocol was found to be appropriate to maintain key proteins such as collagen type I, III, IV and laminin in the structure of final scaffold. This protocol offers a novel platform for the preparation of a dermal substitute for potential clinical applications. STATEMENT OF SIGNIFICANCE: Clinical application of naturally-based scaffolds for verity of health problems obliges development of a reproducible and effective technology that does not change structural and compositional material properties during scaffold preparation and preservation. Lack of an effective protocol for the production of biological products using decellularization method is still remaining. This effort is directing to solve this challenge in order to accomplish the off-the -shelf availability of decellularized dermal scaffold in market for clinical application.


Assuntos
Derme Acelular/tendências , Matriz Extracelular/transplante , Procedimentos Cirúrgicos Reconstrutivos/tendências , Engenharia Tecidual/tendências , Animais , Criopreservação , Matriz Extracelular/química , Humanos , Pele/química , Pele/citologia , Tecidos Suporte/química
18.
Adv Drug Deliv Rev ; 153: 28-53, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678360

RESUMO

Several synthetic and natural materials are used in soft tissue engineering and regenerative medicine with varying degrees of success. Among them, silkworm silk protein fibroin, a naturally occurring protein-based biomaterial, exhibits many promising characteristics such as biocompatibility, controllable biodegradability, tunable mechanical properties, aqueous preparation, minimal inflammation in host tissue, low cost and ease of use. Silk fibroin is often used alone or in combination with other materials in various formats and is also a promising delivery system for bioactive compounds as part of such repair scenarios. These properties make silk fibroin an excellent biomaterial for skin tissue engineering and repair applications. This review focuses on the promising characteristics and recent advances in the use of silk fibroin for skin wound healing and/or soft-tissue repair applications. The benefits and limitations of silk fibroin as a scaffolding biomaterial in this context are also discussed. STATEMENT OF SIGNIFICANCE: Silk protein fibroin is a natural biomaterial with important biological and mechanical properties for soft tissue engineering applications. Silk fibroin is obtained from silkworms and can be purified using alkali or enzyme based degumming (removal of glue protein sericin) procedures. Fibroin is used alone or in combination with other materials in different scaffold forms, such as nanofibrous mats, hydrogels, sponges or films tailored for specific applications. The investigations carried out using silk fibroin or its blends in skin tissue engineering have increased dramatically in recent years due to the advantages of this unique biomaterial. This review focuses on the promising characteristics of silk fibroin for skin wound healing and/or soft-tissue repair applications.


Assuntos
Fibroínas/farmacologia , Fibroínas/uso terapêutico , Pele/fisiopatologia , Engenharia Tecidual/métodos , Ferimentos e Lesões/terapia , Implantes Absorvíveis , Materiais Biocompatíveis , Fenômenos Biomecânicos , Processos de Crescimento Celular/fisiologia , Ensaios Clínicos como Assunto , Fibroínas/química , Humanos , Tecidos Suporte , Cicatrização/fisiologia
19.
ACS Biomater Sci Eng ; 6(11): 6285-6298, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33449643

RESUMO

The human amniotic membrane (HAM) has been viewed as a potential regenerative material for a wide variety of injured tissues because of its collagen-rich content. High degradability of HAM limits its wide practical application in bone tissue engineering. In this study, the natural matrix of the decellularized amniotic membrane was developed by the double diffusion method. The results confirmed a reduction of the amniotic membrane's degradability because of the deposition of calcium and phosphate ions during the double diffusion process. Real-time PCR results showed a high expression of osteogenesis-related genes from adipose-derived mesenchymal stem cells (ADMSCs) cultured on the surface of the developed mineralized amniotic membrane (MAM). Further in vivo experiments were conducted using an MAM preseeded with ADMSCs and a critical-size rat calvarial defect model. Histopathological results confirmed that the MAM + cell sample has excellent potential in bone regeneration.


Assuntos
Âmnio , Engenharia Tecidual , Animais , Biomimética , Regeneração Óssea , Diferenciação Celular , Humanos , Ratos
20.
Biochimie ; 165: 76-89, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302163

RESUMO

At least, more than half of our understanding of extracellular vesicles owes to the studies conducted over the past few years. When it became clear that the exosomes have various potentials in medicine, extensive research has focused on these potentials in a variety of areas including cancer, drug delivery and regenerative medicine. The growing understanding of molecular structure and functions of exosomes causes the vision to become brighter in the exosomes complexity, and our attitude toward these vesicles has undergone changes accordingly. Proteomic and transcriptomic studies on exosomes have highlighted their molecular diversity. In this review, we explicitly examine the exosomes composition, molecular structure and their therapeutic potentials in some diseases. Due to the very heterogeneous nature of exosomes, the process of their use as a therapeutic agent in the clinic has been challenged. We are still at the beginning of recognizing the molecular composition of exosomes and mechanisms that affect their physiology and biology. The growing trend of engineering of exosomes has shown a promising future to further utilize them in a different field. Molecular profiling of exosomes and their content for their related potentials in regenerative medicine should be done exactly for further defining a minimum content for specific therapeutic potentials.


Assuntos
Exossomos/química , Exossomos/fisiologia , Células-Tronco Mesenquimais/metabolismo , Animais , Antineoplásicos/administração & dosagem , Células Cultivadas , Sistemas de Liberação de Medicamentos , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Proteômica , Ratos , Medicina Regenerativa
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