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1.
J Med Life ; 13(3): 418-425, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072218

RESUMO

The study aimed to investigate whether a 3D printed beta-tricalcium phosphate (ß-TCP) scaffold tethered with growth factors and fibrin glue implanted autologous bone marrow-derived mesenchymal stem cells would provide a 3D platform for bone regeneration resulting in new bone formation with plasticity. Twenty 3D printed ß-TCP scaffolds, ten scaffolds engrained with osteogenic mesenchymal stem cells with fibrin glue (group A), and ten scaffolds used as a control group with ß-TCP scaffold and fibrin glue inoculation only (group B) were included in the study. Cell infiltration, migration, and proliferation of human osteogenic stem cells on the scaffolds were executed under both static and dynamic culture conditions. Each scaffold was examined post culture after repeated changes in the nutrient medium at 2, 4 or 8 weeks and assessed for opacity and formation of any bone-like tissues macroscopic, radiographic, and microscopic evaluation. Significant changes in all the prerequisite parameters compiled with an evaluated difference of significance showing maxillofacial skeletal repair via tissue engineering by ß-TCP scaffold and MSCs remains will be the most promising alternative to autologous bone grafts and numerous modalities involving a variety of stem cells, growth factors from platelet-rich fibrin.


Assuntos
Fosfatos de Cálcio/farmacologia , Adesivo Tecidual de Fibrina/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Anormalidades Maxilofaciais/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Impressão Tridimensional , Engenharia Tecidual/métodos , Estudos de Casos e Controles , Sobrevivência Celular/efeitos dos fármacos , Humanos , Anormalidades Maxilofaciais/diagnóstico por imagem , Anormalidades Maxilofaciais/patologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Minerais/análise , Tecidos Suporte/química , Resultado do Tratamento
2.
Science ; 370(6514): 327-331, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33060357

RESUMO

In metazoan tissues, cells decide their fates by sensing positional information provided by specialized morphogen proteins. To explore what features are sufficient for positional encoding, we asked whether arbitrary molecules (e.g., green fluorescent protein or mCherry) could be converted into synthetic morphogens. Synthetic morphogens expressed from a localized source formed a gradient when trapped by surface-anchoring proteins, and they could be sensed by synthetic receptors. Despite their simplicity, these morphogen systems yielded patterns reminiscent of those observed in vivo. Gradients could be reshaped by altering anchor density or by providing a source of competing inhibitor. Gradient interpretation could be altered by adding feedback loops or morphogen cascades to receiver cell response circuits. Orthogonal cell-cell communication systems provide insight into morphogen evolution and a platform for engineering tissues.


Assuntos
Padronização Corporal , Proteínas de Fluorescência Verde/metabolismo , Engenharia Tecidual/métodos , Animais , Drosophila melanogaster/crescimento & desenvolvimento , Fibroblastos , Proteínas de Fluorescência Verde/genética , Engenharia de Proteínas , Receptores Notch/genética , Receptores Notch/metabolismo
3.
Science ; 370(6513)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33033191

RESUMO

Since the advent of the vascular anastomosis by Alexis Carrel in the early 20th century, the repair and replacement of blood vessels have been key to treating acute injuries, as well as chronic atherosclerotic disease. Arteries serve diverse mechanical and biological functions, such as conducting blood to tissues, interacting with the coagulation system, and modulating resistance to blood flow. Early approaches for arterial replacement used artificial materials, which were supplanted by polymer fabrics in recent decades. With recent advances in the engineering of connective tissues, including arteries, we are on the cusp of seeing engineered human arteries become mainstays of surgical therapy for vascular disease. Progress in our understanding of physiology, cell biology, and biomanufacturing over the past several decades has made these advances possible.


Assuntos
Artérias , Prótese Vascular , Engenharia Tecidual/métodos , Doenças Vasculares/cirurgia , Técnicas de Cultura de Células , Humanos
4.
Int J Nanomedicine ; 15: 6945-6960, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061361

RESUMO

Background: Natural clay nanomaterials are an emerging class of biomaterial with great potential for tissue engineering and regenerative medicine applications, most notably for osteogenesis. Materials and Methods: Herein, for the first time, novel tissue engineering scaffolds were prepared by 3D bioprinter using nontoxic and bioactive natural attapulgite (ATP) nanorods as starting materials, with polyvinyl alcohol as binder, and then sintered to obtain final scaffolds. The microscopic morphology and structure of ATP particles and scaffolds were observed by transmission electron microscope and scanning electron microscope. In vitro biocompatibility and osteogenesis with osteogenic precursor cell (hBMSCs) were assayed using MTT method, Live/Dead cell staining, alizarin red staining and RT-PCR. In vivo bone regeneration was evaluated with micro-CT and histology analysis in rat cranium defect model. Results: We successfully printed a novel porous nano-ATP scaffold designed with inner channels with a dimension of 500 µm and wall structures with a thickness of 330 µm. The porosity of current 3D-printed scaffolds ranges from 75% to 82% and the longitudinal compressive strength was up to 4.32±0.52 MPa. We found firstly that nano-ATP scaffolds with excellent biocompatibility for hBMSCscould upregulate the expression of osteogenesis-related genes bmp2 and runx2 and calcium deposits in vitro. Interestingly, micro-CT and histology analysis revealed abundant newly formed bone was observed along the defect margin, even above and within the 3D bioprinted porous ATP scaffolds in a rat cranial defect model. Furthermore, histology analysis demonstrated that bone was formed directly following a process similar to membranous ossification without any intermediate cartilage formation and that many newly formed blood vessels are within the pores of 3D-printed scaffolds at four and eight weeks. Conclusion: These results suggest that the 3D-printed porous nano-ATP scaffolds are promising candidates for bone tissue engineering by osteogenesis and angiogenesis.


Assuntos
Regeneração Óssea/fisiologia , Células-Tronco Mesenquimais/citologia , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Osso e Ossos/fisiologia , Cálcio/metabolismo , Chlorocebus aethiops , Condrogênese , Força Compressiva , Regulação da Expressão Gênica , Humanos , Compostos de Magnésio/química , Masculino , Teste de Materiais , Nanotubos/química , Osteogênese/fisiologia , Álcool de Polivinil/química , Porosidade , Impressão Tridimensional , Ratos Sprague-Dawley , Compostos de Silício/química , Células Vero , Microtomografia por Raio-X
5.
Int J Nanomedicine ; 15: 6097-6111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884266

RESUMO

The development of biomaterials, stem cells and bioactive factors has led to cartilage tissue engineering becoming a promising tactic to repair cartilage defects. Various polymer three-dimensional scaffolds that provide an extracellular matrix (ECM) mimicking environment play an important role in promoting cartilage regeneration. In addition, numerous growth factors have been found in the regenerative process. However, it has been elucidated that the uncontrolled delivery of these factors cannot fully exert regenerative potential and can also elicit undesired side effects. Considering the complexity of the ECM, neither scaffolds nor growth factors can independently obtain successful outcomes in cartilage tissue engineering. Therefore, collectively, an appropriate combination of growth factors and scaffolds have great potential to promote cartilage repair effectively; this approach has become an area of considerable interest in recent investigations. Of late, an increasing trend was observed in cartilage tissue engineering towards this combination to develop a controlled delivery system that provides adequate physical support for neo-cartilage formation and also enables spatiotemporally delivery of growth factors to precisely and fully exert their chondrogenic potential. This review will discuss the role of polymer scaffolds and various growth factors involved in cartilage tissue engineering. Several growth factor delivery strategies based on the polymer scaffolds will also be discussed, with examples from recent studies highlighting the importance of spatiotemporal strategies for the controlled delivery of single or multiple growth factors in cartilage tissue engineering applications.


Assuntos
Cartilagem , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Polímeros/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/farmacologia , Cartilagem/citologia , Cartilagem/fisiologia , Condrogênese , Matriz Extracelular/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Células-Tronco
6.
PLoS One ; 15(9): e0239152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956427

RESUMO

Volumetric muscle loss (VML) is the loss of skeletal muscle that results in significant and persistent impairment of function. The unique characteristics of craniofacial muscle compared trunk and limb skeletal muscle, including differences in gene expression, satellite cell phenotype, and regenerative capacity, suggest that VML injuries may affect craniofacial muscle more severely. However, despite these notable differences, there are currently no animal models of craniofacial VML. In a previous sheep hindlimb VML study, we showed that our lab's tissue engineered skeletal muscle units (SMUs) were able to restore muscle force production to a level that was statistically indistinguishable from the uninjured contralateral muscle. Thus, the goals of this study were to: 1) develop a model of craniofacial VML in a large animal model and 2) to evaluate the efficacy of our SMUs in repairing a 30% VML in the ovine zygomaticus major muscle. Overall, there was no significant difference in functional recovery between the SMU-treated group and the unrepaired control. Despite the use of the same injury and repair model used in our previous study, results showed differences in pathophysiology between craniofacial and hindlimb VML. Specifically, the craniofacial model was affected by concomitant denervation and ischemia injuries that were not exhibited in the hindlimb model. While clinically realistic, the additional ischemia and denervation likely created an injury that was too severe for our SMUs to repair. This study highlights the importance of balancing the use of a clinically realistic model while also maintaining control over variables related to the severity of the injury. These variables include the volume of muscle removed, the location of the VML injury, and the geometry of the injury, as these affect both the muscle's ability to self-regenerate as well as the probability of success of the treatment.


Assuntos
Traumatismos Faciais/cirurgia , Músculos Faciais/cirurgia , Regeneração Tecidual Guiada/métodos , Doenças Musculares/cirurgia , Engenharia Tecidual/métodos , Animais , Modelos Animais de Doenças , Face/cirurgia , Traumatismos Faciais/complicações , Músculos Faciais/fisiopatologia , Feminino , Humanos , Masculino , Doenças Musculares/etiologia , Recuperação de Função Fisiológica , Regeneração/fisiologia , Ovinos , Tecidos Suporte
7.
PLoS One ; 15(9): e0238471, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32870933

RESUMO

Bone scaffolds are widely used as one of the main bone substitute materials. However, many bone scaffold microstructure topologies exist and it is still unclear which topology to use when designing scaffold for a specific application. The aim of the present study was to reveal the mechanism of the microstructure-driven performance of bone scaffold and thus to provide guideline on scaffold design. Finite element (FE) models of five TPMS (Diamond, Gyroid, Schwarz P, Fischer-Koch S and F-RD) and three traditional (Cube, FD-Cube and Octa) scaffolds were generated. The effective compressive and shear moduli of scaffolds were calculated from the mechanical analysis using the FE unit cell models with the periodic boundary condition. The scaffold permeability was calculated from the computational fluid dynamics (CFD) analysis using the 4×4×4 FE models. It is revealed that the surface-to-volume ratio of the Fischer-Koch S-based scaffold is the highest among the scaffolds investigated. The mechanical analysis revealed that the bending deformation dominated structures (e.g., the Diamond, the Gyroid, the Schwarz P) have higher effective shear moduli. The stretching deformation dominated structures (e.g., the Schwarz P, the Cube) have higher effective compressive moduli. For all the scaffolds, when the same amount of change in scaffold porosity is made, the corresponding change in the scaffold relative shear modulus is larger than that in the relative compressive modulus. The CFD analysis revealed that the structures with the simple and straight pores (e.g., Cube) have higher permeability than the structures with the complex pores (e.g., Fischer-Koch S). The main contribution of the present study is that the relationship between scaffold properties and the underlying microstructure is systematically investigated and thus some guidelines on the design of bone scaffolds are provided, for example, in the scenario where a high surface-to-volume ratio is required, it is suggested to use the Fischer-Koch S based scaffold.


Assuntos
Transplante Ósseo/métodos , Osso e Ossos/patologia , Tecidos Suporte/química , Substitutos Ósseos/farmacologia , Força Compressiva , Análise de Elementos Finitos , Hidrodinâmica , Teste de Materiais , Permeabilidade , Porosidade , Pressão , Estresse Mecânico , Engenharia Tecidual/métodos
8.
Plast Reconstr Surg ; 146(4): 409e-413e, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32969997

RESUMO

Breast reconstruction remains an important field in plastic surgery, with most procedures using implants and/or autologous tissue. Few series report on experience with fat grafting as the primary form of breast reconstruction. The present article describes a new method of breast reconstruction using a three-dimensional absorbable mesh construct-or Lotus scaffold-and autologous fat grafting. A retrospective review was performed for all patients who underwent breast reconstruction using the Lotus scaffold and autologous fat grafting. Postoperative mammograms and magnetic resonance imaging scans were analyzed. Tissue specimens collected at subsequent procedures were harvested and stained with hematoxylin and eosin for histologic evaluation. Lastly, compression testing of the scaffold was performed using a tensiometer and digital tracking technology. Twenty-two patients underwent reconstruction of 28 breasts using the Lotus scaffold and autologous fat grafting between February of 2015 and February of 2018. Average follow-up was 19 months. All patients were satisfied with final breast shape and size. Mean patient age was 60.5 years and the average body mass index was 28 kg/m. Patients required on average two fat grafting sessions to achieve a successful result (range, zero to four). Postoperative mammography and magnetic resonance imaging showed robust adipose tissue in the breast with a slowly resorbing mesh and no oil cysts or calcifications. Histologic evaluation showed the presence of fat tissue around the scaffold and no evidence of capsule formation. Compression testing revealed the Lotus scaffold to be compliant with a high-resilience profile. The Lotus scaffold with autologous fat grafting is a viable method for breast reconstruction, giving the patient an autologous reconstruction with less morbidity compared to free tissue transfer. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, IV.


Assuntos
Implantes Absorvíveis , Tecido Adiposo/transplante , Mamoplastia/métodos , Telas Cirúrgicas , Engenharia Tecidual/métodos , Tecidos Suporte , Idoso , Feminino , Humanos , Mamoplastia/instrumentação , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo
9.
Int J Nanomedicine ; 15: 5027-5042, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764934

RESUMO

Background: Bactericidal capacity, durable inhibition of biofilm formation, and a three-dimensional (3D) porous structure are the emphases of infected bone defect (IBD) treatment via local scaffold implantation strategy. Purpose: In this study, silver nanoparticle (AgNP)-loaded nano-hydroxyapatite (nHA)@ reduced graphene oxide (RGO) 3D scaffolds (AHRG scaffolds) were designed to alleviate bone infection, inhibit biofilm formation, and promote bone repair through the synergistic effects of AgNPs, RGO, and nHA. Materials and Methods: AHRGs were prepared using a one-step preparation method, to create a 3D porous scaffold to facilitate a uniform distribution of AgNPs and nHA. Methicillin-resistant Staphylococcus aureus (MRSA) was used as a model-resistant bacterium, and the effects of different silver loadings on the antimicrobial activity and cytocompatibility of materials were evaluated. Finally, a rabbit IBD model was used to evaluate the therapeutic effect of the AHRG scaffold in vivo. Results: The results showed successful synthesis of the AHRG scaffold. The ideal 3D porous structure was verified using scanning electron microscopy and transmission electron microscopy, and X-ray photoelectron spectroscopy and selected area electron diffraction measurements revealed uniform distributions of AgNP and nHA. In vitro antibacterial and cytocompatibility indicated that the 4% AHRG scaffolds possessed the most favorable balance of bactericidal properties and cytocompatibility. In vivo evaluation of the IBD model showed promising treatment efficacy of AHRG scaffolds. Conclusion: The as-fabricated AHRG scaffolds effectively eliminated infection and inhibited biofilm formation. IBD repair was facilitated by the bactericidal properties and 3D porous structure of the AHRG scaffold, suggesting its potential in the treatment of IBDs.


Assuntos
Antibacterianos/farmacologia , Doenças Ósseas Infecciosas/terapia , Grafite/química , Nanopartículas Metálicas/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos , Osso e Ossos/efeitos dos fármacos , Modelos Animais de Doenças , Durapatita/química , Feminino , Masculino , Teste de Materiais , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Porosidade , Coelhos , Ratos , Prata/química , Prata/farmacologia , Infecções Estafilocócicas/terapia
10.
Bone Joint J ; 102-B(8): 1095-1106, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32731821

RESUMO

AIMS: Achilles tendon injuries are a frequent problem in orthopaedic surgery due to their limited healing capacity and the controversy surrounding surgical treatment. In recent years, tissue engineering research has focused on the development of biomaterials to improve this healing process. The aim of this study was to analyze the effect of tendon augmentation with a nanostructured fibrin-agarose hydrogel (NFAH) or genipin cross-linked nanostructured fibrin-agarose hydrogel (GP-NFAH), on the healing process of the Achilles tendon in rats. METHODS: NFAH, GP-NFAH, and MatriDerm (control) scaffolds were generated (five in each group). A biomechanical and cell-biomaterial-interaction characterization of these biomaterials was then performed: Live/Dead Cell Viability Assay, water-soluble tetrazolium salt-1 (WST-1) assay, and DNA-released after 48 hours. Additionally, a complete section of the left Achilles tendon was made in 24 Wistar rats. Animals were separated into four treatment groups (six in each group): direct repair (Control), tendon repair with MatriDerm, or NFAH, or GP-NFAH. Animals were euthanized for further histological analyses after four or eight weeks post-surgery. The Achilles tendons were harvested and a histopathological analysis was performed. RESULTS: Tensile test revealed that NFAH and GP-NFAH had significantly higher overall biomechanical properties compared with MatriDerm. Moreover, biological studies confirmed a high cell viability in all biomaterials, especially in NFAH. In addition, in vivo evaluation of repaired tendons using biomaterials (NFAH, GP-NFAH, and MatriDerm) resulted in better organization of the collagen fibres and cell alignment without clinical complications than direct repair, with a better histological score in GP-NFAH. CONCLUSION: In this animal model we demonstrated that NFAH and GP-NFAH had the potential to improve tendon healing following a surgical repair. However, future studies are needed to determine the clinical usefulness of these engineered strategies. Cite this article: Bone Joint J 2020;102-B(8):1095-1106.


Assuntos
Tendão do Calcâneo/cirurgia , Microambiente Celular/efeitos dos fármacos , Colágeno/uso terapêutico , Elastina/uso terapêutico , Regeneração/efeitos dos fármacos , Traumatismos dos Tendões/cirurgia , Tendão do Calcâneo/lesões , Animais , Materiais Biocompatíveis/farmacologia , Modelos Animais de Doenças , Fibrina/farmacologia , Hidrogéis/farmacologia , Masculino , Nanoestruturas , Distribuição Aleatória , Ratos , Ratos Wistar , Tendões/fisiologia , Engenharia Tecidual/métodos , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia
12.
Nat Biomed Eng ; 4(9): 916-932, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32601395

RESUMO

Sacrificial templates for patterning perfusable vascular networks in engineered tissues have been constrained in architectural complexity, owing to the limitations of extrusion-based 3D printing techniques. Here, we show that cell-laden hydrogels can be patterned with algorithmically generated dendritic vessel networks and other complex hierarchical networks by using sacrificial templates made from laser-sintered carbohydrate powders. We quantified and modulated gradients of cell proliferation and cell metabolism emerging in response to fluid convection through these networks and to diffusion of oxygen and metabolites out of them. We also show scalable strategies for the fabrication, perfusion culture and volumetric analysis of large tissue-like constructs with complex and heterogeneous internal vascular architectures. Perfusable dendritic networks in cell-laden hydrogels may help sustain thick and densely cellularized engineered tissues, and assist interrogations of the interplay between mass transport and tissue function.


Assuntos
Vasos Sanguíneos/citologia , Carboidratos/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Vasos Sanguíneos/fisiologia , Proliferação de Células , Desenho de Equipamento , Hepatócitos/citologia , Humanos , Hidrogéis/química , Consumo de Oxigênio , Perfusão , Impressão Tridimensional , Engenharia Tecidual/instrumentação
13.
Life Sci ; 257: 118038, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622947

RESUMO

PURPOSE: The importance of regeneration in large bone defects forces the orthopedic surgeons to search for a proper methodology. The present experiment evaluated the capability of polylactic acid/polycaprolactone/hydroxyapatite (PLA/PCL/HA) scaffold loaded with and without mesenchymal stem cells (MSCs) on bone regeneration. METHODS: Fourier transform infrared spectrometry, X-ray diffraction, scanning electron microscopy, and rheology methodologies were used to characterize the scaffold. Forty Wistar rats were randomly divided into the four groups including the untreated defects as the control group and three other groups in which the bone defects were treated with autologous bones (autograft group), the PLA/PCL/HA scaffolds (PLA/PCL/HA group), and the MSCs-seeded scaffolds (MSCs-seeded PLA/PCL/HA group). RESULTS: Based on the qRT-PCR results, significantly higher expression levels of osteocalcin, osteopontin, and CD31 were seen in the cell-seeded scaffold group compared to the control group (P < 0.05). The CT scanning and radiographic images depicted significantly more newly formed bonny tissue in the MSCs-loaded scaffold and autograft groups than the untreated group (P < 0.001). The immunohistochemistry, biomechanical, histopathologic, and histomorphometric evaluations demonstrated significantly improved regeneration in the autograft and MSCs-loaded scaffold groups compared to the non-treated group (P < 0.05). There were significant differences between the scaffold and untreated groups in all in vivo evaluations (P < 0.05). CONCLUSION: The MSCs enhanced bone healing potential of the PLA/PCL/HA scaffold and the MSCs-seeded scaffold was comparable to the autograft as the golden treatment regimen (P > 0.05).


Assuntos
Regeneração Óssea/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Engenharia Tecidual/métodos , Animais , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Durapatita/química , Masculino , Células-Tronco Mesenquimais/fisiologia , Poliésteres/química , Rádio (Anatomia)/metabolismo , Ratos , Ratos Wistar , Tecidos Suporte/química
14.
Int J Nanomedicine ; 15: 4205-4224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606673

RESUMO

Cardiovascular diseases are the number one cause of heart failure and death in the world, and the transplantation of the heart is an effective and viable choice for treatment despite presenting many disadvantages (most notably, transplant heart availability). To overcome this problem, cardiac tissue engineering is considered a promising approach by using implantable artificial blood vessels, injectable gels, and cardiac patches (to name a few) made from biodegradable polymers. Biodegradable polymers are classified into two main categories: natural and synthetic polymers. Natural biodegradable polymers have some distinct advantages such as biodegradability, abundant availability, and renewability but have some significant drawbacks such as rapid degradation, insufficient electrical conductivity, immunological reaction, and poor mechanical properties for cardiac tissue engineering. Synthetic biodegradable polymers have some advantages such as strong mechanical properties, controlled structure, great processing flexibility, and usually no immunological concerns; however, they have some drawbacks such as a lack of cell attachment and possible low biocompatibility. Some applications have combined the best of both and exciting new natural/synthetic composites have been utilized. Recently, the use of nanostructured polymers and polymer nanocomposites has revolutionized the field of cardiac tissue engineering due to their enhanced mechanical, electrical, and surface properties promoting tissue growth. In this review, recent research on the use of biodegradable natural/synthetic nanocomposite polymers in cardiac tissue engineering is presented with forward looking thoughts provided for what is needed for the field to mature.


Assuntos
Materiais Biocompatíveis/química , Coração/fisiologia , Nanocompostos/química , Nanomedicina , Polímeros/química , Engenharia Tecidual/métodos , Animais , Humanos , Nanocompostos/ultraestrutura
15.
Nat Commun ; 11(1): 3416, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32651372

RESUMO

The recent demonstration that primary cells from the liver can be expanded in vitro as organoids holds enormous promise for regenerative medicine and disease modelling. The use of three-dimensional (3D) cultures based on ill-defined and potentially immunogenic matrices, however, hampers the translation of liver organoid technology into real-life applications. We here use chemically defined hydrogels for the efficient derivation of both mouse and human hepatic organoids. Organoid growth is found to be highly stiffness-sensitive, a mechanism independent of acto-myosin contractility and requiring instead activation of the Src family of kinases (SFKs) and yes-associated protein 1 (YAP). Aberrant matrix stiffness, on the other hand, results in compromised proliferative capacity. Finally, we demonstrate the establishment of biopsy-derived human liver organoids without the use of animal components at any step of the process. Our approach thus opens up exciting perspectives for the establishment of protocols for liver organoid-based regenerative medicine.


Assuntos
Fígado/citologia , Organoides/citologia , Humanos , Hidrogéis , Fígado/metabolismo , Organoides/metabolismo , Engenharia Tecidual/métodos , Fatores de Transcrição/metabolismo , Quinases da Família src/metabolismo
16.
Adv Exp Med Biol ; 1250: 3-13, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32601934

RESUMO

Collagen is an important component that makes 25-35% of our body proteins. Over the past decades, tissue engineers have been designing collagen-based biocompatible materials and studying their applications in different fields. Collagen obtained from cattle and pigs has been mainly used until now, but collagen derived from fish and other livestock has attracted more attention since the outbreak of mad cow disease, and they are also used as a raw material for cosmetics and foods. Due to the zoonotic infection using collagen derived from pigs and cattle, their application in developing biomaterials is limited; hence, the development of new animal-derived collagen is required. In addition, there is a religion (Islam, Hinduism, and Judaism) limited to export raw materials and products derived from cattle and pig. Hence, high-value collagen that is universally accessible in the world market is required. Therefore, in this review, we have dealt with the use of duck's feet-derived collagen (DC) as an emerging alternative to solve this problem and also presenting few original investigated bone regeneration results performed using DC.


Assuntos
Regeneração Óssea , Colágeno , Patos , Engenharia Tecidual , Animais , Materiais Biocompatíveis , Regeneração Óssea/fisiologia , Colágeno/química , Colágeno/metabolismo , Engenharia Tecidual/métodos , Tecidos Suporte
17.
Adv Exp Med Biol ; 1250: 15-31, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32601935

RESUMO

Decellularized extracellular matrices (dECMs) from mammalian tissues and organs are particularly interesting as scaffolds for tissue engineering and regeneration when considering their ability to retain chemical compositions and three-dimensional (3D) microstructures that are similar to native ECMs. This review discusses the advantages and disadvantages of different decellularization methods that use various agents, such as ionic and nonionic detergents and biological enzymes. The applications of dECMs as scaffolds or hydrogels for tissue engineering of specific tissues including heart valves, blood vessels, and skin, as well as their performance in vitro and in vivo, are also discussed. In addition, whole organ regeneration (i.e., the heart, kidney, liver) using dECM scaffolds has been explored, which are able to recapitulate partial functions of native organs.


Assuntos
Matriz Extracelular , Regeneração Tecidual Guiada/métodos , Engenharia Tecidual , Animais , Detergentes , Hidrogéis , Engenharia Tecidual/métodos
18.
Adv Exp Med Biol ; 1250: 63-78, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32601938

RESUMO

Engineered polymeric hydrogels have been extensively utilized in tissue engineering and regenerative medicine because of their biocompatibility, tunable properties, and structural similarity in their native extracellular microenvironment. The native extracellular matrix (ECM) has been implicated as a crucial factor in the regulation of cellular behaviors and their fate. The emerging trend in the design of hydrogels involves the development of advanced materials to precisely recapitulate the native ECM or to stimulate the surrounding tissues via physical, chemical, or biological stimuli. The ECM presents various parameters such as ECM components, soluble factors, cell-to-cell and cell-to-matrix interactions, physical forces, and physicochemical environments. Among these environmental factors, oxygen is considered as an essential signaling molecule. In particular, abnormal oxygen tension such as a lack of oxygen (defined as hypoxia) and an excess supply of oxygen (defined as hyperoxia) plays a pivotal role during early vascular development, tissue regeneration and repair, and tumor progression and metastasis. In this chapter, we discuss how engineered polymeric hydrogels serve as either an artificial extracellular microenvironment to create engineered tissues or as an acellular matrix to stimulate the native tissues for a wide range of biomedical applications including tissue engineering and regenerative medicine, wound healing, and engineered disease models. Specifically, we focus on emerging technologies to create advanced polymeric hydrogel materials that accurately mimic or stimulate the native ECM.


Assuntos
Hidrogéis , Oxigênio , Medicina Regenerativa , Engenharia Tecidual , Matriz Extracelular/química , Hidrogéis/química , Oxigênio/metabolismo , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos
19.
Adv Exp Med Biol ; 1250: 79-93, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32601939

RESUMO

Treatment for the osteochondral defects (ODs) is more challenging nowadays that needs to be addressed by developing alternative bone tissue engineering materials. Gellan gum (GG) is a widely used natural polysaccharide in the field of tissue engineering (TE) and regenerative medicine due to its versatile properties. There are many reports about the successful application of GG in cartilage tissue engineering and guiding bone formation. Functional coatings and porous composite materials have been introduced in next-generation materials for treating OD, whereas osteoconductive materials, such as demineralized bone particle (DBP) or bone derivatives, are used. However, modification of porosity, biocompatibility, cell proliferation, and mechanical properties is needed. DBP can activate human mesenchymal stem cells to differentiate into osteoblast cells. In this chapter, the potential application of GG with DBP in different combinations was reviewed, and the best suitable combinations were selected and further studied in small animal models for the soft and hard tissue engineering applications; also its application in the osteochondral integration fields were briefly discussed.


Assuntos
Regeneração Óssea , Polissacarídeos Bacterianos , Engenharia Tecidual , Animais , Galinhas , Humanos , Hidrogéis , Polissacarídeos Bacterianos/química , Engenharia Tecidual/métodos
20.
Adv Exp Med Biol ; 1250: 97-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32601940

RESUMO

The clinical need for effective bone regeneration remains in huge demands. Although autologous and allogeneic bone grafts are generally considered "gold standard" treatments for bone defects, these approaches may result in various complications. Furthermore, safety considerations of gene- and cell-based therapies require further clarification and approval from regulatory authorities. Therefore, developing new therapeutic biomaterials that can empower endogenous regenerative properties to accelerate bone repair and regeneration is of great significance. Extracellular vesicles (EVs) comprise a heterogeneous population of naturally derived nanoparticles that play a critical role in mediating cell-cell communication. The vast amount of biological processes that EVs are involved in, such as immune modulation, senescence, and angiogenesis, and the versatility of manner in which they can influence the behavior of recipient cells make EVs an interesting source for both diagnostic and therapeutic applications. Advancement of knowledge in the fields of immunology and cell biology has sparked the exploration of the potential of EVs in the field of regenerative medicine. EVs travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating the recruitment, proliferation, and differentiation of recipient cells. Numerous studies have demonstrated the pivotal role of EVs in tissue regeneration both in vitro and in vivo. In this chapter, we will outline current knowledge surrounding EVs, summarize their functional roles in bone regenerative medicine, and elaborate on potential application and challenges of EV-integrated biomaterials in bone tissue engineering.


Assuntos
Materiais Biocompatíveis , Regeneração Óssea , Vesículas Extracelulares , Medicina Regenerativa , Engenharia Tecidual , Materiais Biocompatíveis/química , Materiais Biocompatíveis/normas , Humanos , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos
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