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1.
Adv Sci (Weinh) ; 11(21): e2308381, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38447173

RESUMO

3D bioprinting techniques have enabled the fabrication of irregular large-sized tissue engineering scaffolds. However, complicated customized designs increase the medical burden. Meanwhile, the integrated printing process hinders the cellular uniform distribution and local angiogenesis. A novel approach is introduced to the construction of sizable tissue engineering grafts by employing hydrogel 3D printing for modular bioadhesion assembly, and a poly (ethylene glycol) diacrylate (PEGDA)-gelatin-dopamine (PGD) hydrogel, photosensitive and adhesive, enabling fine microcage module fabrication via DLP 3D printing is developed. The PGD hydrogel printed micocages are flexible, allowing various shapes and cell/tissue fillings for repairing diverse irregular tissue defects. In vivo experiments demonstrate robust vascularization and superior graft survival in nude mice. This assembly strategy based on scalable 3D printed hydrogel microcage module could simplify the construction of tissue with large volume and complex components, offering promise for diverse large tissue defect repairs.


Assuntos
Hidrogéis , Camundongos Nus , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais , Animais , Camundongos , Engenharia Tecidual/métodos , Hidrogéis/química , Alicerces Teciduais/química , Gelatina/química , Bioimpressão/métodos , Polietilenoglicóis/química , Neovascularização Fisiológica/fisiologia , Dopamina/metabolismo , Regeneração/fisiologia , Humanos
2.
J Nanobiotechnology ; 21(1): 264, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563652

RESUMO

ZIF-8 may experience ion-responsive degradation in ionic solutions, which will change its initial architecture and restrict its direct biological use. Herein, we report an abnormal phenomenon in which ZIF-8 induces large hydroxyapatite-like crystals when soaked directly in simulated body fluid. These crystals grew rapidly continuously for two weeks, with the volume increasing by over 10 folds. According to Zn2+ release and novel XRD diffraction peak presence, ZIF-8 particles can probably show gradual collapse and became congregate through re-nucleation and competitive coordination. The phenomenon could be found on ZIF-8/PCL composite surface and printed ZIF-8/PCL scaffold surface. ZIF-8 enhanced PCL roughness through changing the surface topography, while obviously improving the in-vivo and in-vitro osteoinductivity and biocompatibility. The pro-biomineralization property can make ZIF-8 also applicable in polylactic acid-based biomaterials. In summary, this study demonstrates that ZIF-8 may play the role of a bioactive additive enabling the surface modification of synthetic polymers, indicating that it can be applied in in-situ bone regeneration.


Assuntos
Durapatita , Alicerces Teciduais , Durapatita/química , Alicerces Teciduais/química , Materiais Biocompatíveis/química , Osteogênese , Poliésteres/química , Impressão Tridimensional , Engenharia Tecidual
3.
Adv Sci (Weinh) ; 10(25): e2300694, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37409801

RESUMO

All-liquid molding can be used to transform a liquid into free-form solid constructs, while maintaining internal fluidity. Traditional biological scaffolds, such as cured pre-gels, are normally processed in solid state, sacrificing flowability and permeability. However, it is essential to maintain the fluidity of the scaffold to truly mimic the complexity and heterogeneity of natural human tissues. Here, this work molds an aqueous biomaterial ink into liquid building blocks with rigid shapes while preserving internal fluidity. The molded ink blocks for bone-like vertebrae and cartilaginous-intervertebral-disc shapes, are magnetically manipulated to assemble into hierarchical structures as a scaffold for subsequent spinal column tissue growth. It is also possible to join separate ink blocks by interfacial coalescence, different from bridging solid blocks by interfacial fixation. Generally, aqueous biomaterial inks are molded into shapes with high fidelity by the interfacial jamming of alginate surfactants. The molded liquid blocks can be reconfigured using induced magnetic dipoles, that dictated the magnetic assembly behavior of liquid blocks. The implanted spinal column tissue exhibits a biocompatibility based on in vitro seeding and in vivo cultivating results, showing potential physiological function such as bending of the spinal column.


Assuntos
Materiais Biocompatíveis , Disco Intervertebral , Humanos , Materiais Biocompatíveis/química , Próteses e Implantes , Alginatos/química , Fenômenos Magnéticos
4.
Front Chem ; 11: 1094693, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860643

RESUMO

Although methods are used to treat wounds clinically, there are still many challenges in the treatment of chronic wounds due to excessive inflammatory response, difficulties in epithelialization, vascularization, and other factors. With the increasing research on adipose-derived stem cells (ADSCs) in recent years, accumulating evidence has shown that ADSCs scan promotes the healing of chronic wounds by regulating macrophage function and cellular immunity and promoting angiogenesis and epithelialization. The present study reviewed the difficulties in the treatment of chronic wounds, as well as the advantages and the mechanism of ADSCs in promoting the healing of chronic wounds, to provide a reference for the stem cell therapy of chronic wounds.

5.
Front Med (Lausanne) ; 10: 1130623, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36999072

RESUMO

Background: Prostaglandin analogs have been found to have more versatile uses: treatment of open-angle glaucoma, high intraocular pressure, vitiligo, and other treatments. And prostaglandin analogs have been found to have an important role in the hair growth cycle. However, prostaglandin analogs have not been sufficiently studied for hair (including hair, eyelashes, and eyebrows) regeneration. In this study, a systematic review and meta-analysis of topical prostaglandin analogs on hair loss was performed. Objective: The purpose of this meta-analysis is to determine the efficacy and safety of topical prostaglandin analogs for treating hair loss. Methods: We searched PubMed, Embase, and Cochrane Library databases comprehensively. Data were pooled using Review Manager 5.4.1, and subgroup analyses were performed if necessary. Results: There were six randomized controlled trials included in this meta-analysis. All studies compared prostaglandin analogs with placebo, and one trial consisted of two sets of data. The results showed that prostaglandin analogs could significantly improve the hair length and density (p < 0.001). As far as adverse events are concerned, there was no significant difference between the experimental group and the control group. Conclusion: In patients with hair loss, the topical prostaglandin analogs have better therapeutic efficacy and safety than placebo. However, the best dose and frequency of experimental treatment require further studies.

6.
Stem Cells Int ; 2022: 2799844, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117725

RESUMO

Background: Mesenchymal stromal cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) possess similar proregenerative effects when injected into defects immediately following trauma. However, MSC-EVs are superior to MSCs in terms of storage and rejection reflection, while immediate administration of MSC-EVs is related to several target cells for most donor cells die within few weeks. Besides, the inflammatory cascade is incited, providing an unfavorable environment for target cells. We hypothesized that delayed injection of MSC-EVs might have priority on tissue regeneration than instant injection. Method: Extracellular vesicles isolated from adipose-derived mesenchymal stromal cells (ADSC-EVs) were administered into human umbilical vein endothelial cells (HUVECs) in vitro at different doses. The migration of HUVECs was assessed using the scratch wound healing assay, whereas the length of tubes and number of vessel-like structures formed by HUVECs were determined using tube formation assay. Next, 24 BALB/c nude mice were randomly divided into three groups (n = 8). For the EV-delayed group, ADSC-EVs were injected into transplanted fat a week later than the EV-immediate group. The volume and weight of grafts were measured at 3 months after fat transplantation. Further, the number of CD31-possitive vessels and CD206-possitive cells in the fat grafts was quantified. Results: Compared with the EV-immediate group, the EV-delayed group had a higher fat tissue retention volume (0.11 ± 0.02 mL versus 0.08 ± 0.01 mL), more neovessels (31.00 ± 4.60 versus 24.20 ± 3.97), and fewer cysts. Furthermore, there were more Ki67-positive cells (25.40 ± 7.14 versus 16.20 ± 4.17) and CD206-positive M2 macrophages cells (23.60 ± 3.44 versus 14.00 ± 3.85) in the EV-delayed group than in the EV-immediate group. Conclusion: Delayed injection of ADSC-EVs promotes fat graft volume retention by stimulating angiogenesis. These findings suggest that delayed supplementation might be a more effective strategy for the application of MSC-EVs in tissue regeneration.

7.
Acta Biomater ; 148: 90-105, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35671873

RESUMO

Breast tissue engineering is a promising alternative intervention for breast reconstruction. Due to their low immunogenicity and well-preserved adipogenic microenvironment, decellularized adipose tissue (DAT) can potentially regenerate adipose tissue in vivo. However, the volume of adipose tissue regenerated from DAT can hardly satisfy the demand for breast reconstruction. Tissue engineering chamber (TEC) is an effective technique for generation of large adipose tissue volumes. However, TEC applications necessitate reoperation to remove non-degradable plastic chambers and harvest autologous tissue flaps, which prolongs the operation time and causes potential damage to donor sites. We improved the TEC strategy by combining bioresorbable polycaprolactone (PCL) chambers and decellularized adipose tissues (DAT). A miniaturized porous PCL chamber was fabricated based on scaling differences between human and rabbit chests, and basic fibroblast growth factor (bFGF)-loaded DAT successfully prepared. In rabbit models, a highly vascularized adipose tissue that nearly filled up the PCL chamber (5 mL) was generated de novo from 0.5 mL bFGF-loaded DAT. The newly formed tissue had significantly high expressions of adipogenic genes, compared to the endogenous adipose tissue. The concept described here can be exploited for breast tissue engineering. STATEMENT OF SIGNIFICANCE: Decellularized adipose tissue (DAT), which provides infiltrated cells adipogenic microenvironment, can potentially regenerate adipose tissue in vivo. Nevertheless, the volume of regenerated adipose tissue is insufficient to repair large sized tissue defect. Tissue engineering chamber (TEC) could provide a protective space for in situ regeneration of large volume tissue. Herein, a new strategy by combining biodegradable polycaprolactone chambers and basic fibroblast growth factor-loaded decellularized adipose tissue is proposed. In rabbit model, newly formed adipose tissue regenerated from DAT successfully filled the dome shaped chamber with ten folds higher volume than DAT, which is proportionally similar to women breast. This work highlighted the importance of adipogenic microenvironment and protective space for adipose tissue regeneration.


Assuntos
Tecido Adiposo , Fator 2 de Crescimento de Fibroblastos , Adipogenia , Tecido Adiposo/metabolismo , Animais , Matriz Extracelular/metabolismo , Feminino , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Coelhos , Engenharia Tecidual/métodos , Alicerces Teciduais
8.
Int J Nanomedicine ; 16: 3803-3818, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34113101

RESUMO

BACKGROUND: Effective repair of full-thickness abdominal wall defects requires a patch with sufficient mechanical strength and anti-adhesion characteristics to avoid the formation of hernias and intra-abdominal complications such as intestinal obstruction and fistula. However, patches made from polymers or bio-derived materials may not meet these requirements and lack the bionic characteristics of the abdominal wall. MATERIALS AND METHODS: In this study, we report a consecutive electrospun method for preparing a double-layer structured nanofiber membrane (GO-PCL/CS-PCL) using polycaprolactone (PCL), graphene oxide (GO) and chitosan (CS). To expand the bio-functions (angiogenesis/reducing reactive oxygen species) of the patch (GO-PCL/NAC-CS-PCL), N-acetylcysteine (NAC) was loaded for the repair of full-thickness abdominal wall defects (2×1.5cm) in rat model. RESULTS: The double-layered patch (GO-PCL/NAC-CS-PCL) showed excellent mechanical strength and biocompatibility. After 2 months, rats treated with the patch exhibited the desired repair effect with no hernia formation, less adhesion (adhesion score: 1.50±0.50, P<0.001) and more collagen deposition (percentage of collagen deposition: 34.94%±3.31%, P<0.001). CONCLUSION: The double-layered nanomembranes presented in this study have good anti-hernia and anti-adhesion effects, as well as improve the microenvironment in vivo. It, therefore, holds good prospects for the repair of abdominal wall defects and provides a promising key as a postoperative anti-adhesion agent.


Assuntos
Parede Abdominal/anormalidades , Quitosana/química , Grafite/química , Hérnia/tratamento farmacológico , Nanofibras/administração & dosagem , Poliésteres/administração & dosagem , Aderências Teciduais/tratamento farmacológico , Animais , Colágeno/química , Hérnia/etiologia , Hérnia/patologia , Masculino , Nanofibras/química , Poliésteres/química , Ratos , Ratos Sprague-Dawley , Aderências Teciduais/etiologia , Aderências Teciduais/patologia
9.
Bioact Mater ; 5(4): 859-870, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32637749

RESUMO

Graphene Oxide (GO)-related hydrogels have been extensively studied in hard tissue repair, because GO can not only enhance the mechanical properties of polymers but also promote osteogenic differentiation of mesenchymal stem cells. However, simple GO-related hydrogels are not ideal for the repair of osteoporotic bone defects as the overactive osteoclasts in osteoporosis. Alendronate (Aln) is known to inhibit osteoclasts and may bind to GO through covalent connection. Therefore, delivering Aln in GO-related hydrogels may be effective to repair osteoporotic bone defects. Here, we developed a control-released system which is constructed by collagen (Col)-GO sponges loaded with Aln (Col-GO-Aln) for osteoporotic bone defect repair. In vitro, Col-GO-Aln sponges prolonged the release period of Aln, and the sponge containing 0.05% (w/v) GO released Aln faster than sponge with 0.2% GO. Furthermore, tartrate-resistant acid phosphatase (TRAP) and F-actin staining demonstrated that Col-GO-Aln sponges effectively inhibited osteoclastogenesis of monocyte-macrophages. In vivo, micro-CT scan showed that the volume of newborn bone in defect site by 0.05% GO sponge was nearly three times larger than that of other groups. Moreover, the CT and histological examinations of rat femur proved that Col-GO-Aln sponges decreased the number of osteoclasts and suppressed the systemic bone loss in osteoporotic rats. These findings reveal that the application of GO as carriers of anti-osteoporosis drugs is a viable treatment for osteoporosis. The results also underscore the potential of GO-related hydrogels with Aln-releasing capacity for bone regeneration in osteoporosis.

10.
J Plast Reconstr Aesthet Surg ; 73(7): 1318-1325, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32430265

RESUMO

BACKGROUND: Application of distant skin flaps in facial defect reconstruction has limitations such as leaving a patch like appearance and being restricted by the length of the vascular pedicles. Leveraging the abundance of blood supply from superficial muscular aponeurotic system (SMAS), a local skin flap pedicled by SMAS can be used to avoid the aforementioned problems. Herein, we report the clinical application as well as the anatomical study of SMAS-pedicled skin flaps. METHODS: This study enrolled patients who underwent facial defect reconstruction surgery between 2013 and 2018 using SMAS-pedicled skin flaps. The flaps were designed according to the size and location of the defect. A follow-up was performed to evaluate the treatment outcomes and incidence of adverse events. In addition, six cadaveric heads were used to perform an anatomical study on the distribution and blood supply of SMAS. RESULTS: Twenty-three cases underwent the defect reconstruction surgery in the frontal regions (three cases), temporal region (four cases), periocular region (four cases), nasal region (seven cases), and other regions (five cases). All the flaps survived well. During the follow-up period up to 12 months, the flaps showed a satisfactory appearance, blood supply, and elasticity. The distribution and blood supply of SMAS at different anatomical regions have been successfully observed. Abundant vascular networks could be found in the SMAS layer. CONCLUSION: Based on the broad distribution of SMAS and the abundant blood supply, an SMAS-pedicled skin flap could be flexibly designed and versatilely used to reconstruct post-traumatic or post-excisional facial defects.


Assuntos
Aponeurose/anatomia & histologia , Face/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aponeurose/irrigação sanguínea , Aponeurose/transplante , Cadáver , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
J Biomed Mater Res A ; 108(12): 2460-2472, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32419333

RESUMO

Researches of biomaterials for osteoporotic bone defects focus on the improvement of its anti-osteoporosis ability, due to osteoporosis is a kind of systemic and long-range bone metabolism disorder. Nevertheless, how to steadily deliver anti-osteoporosis drugs in osteoporotic bone defects is rarely studied. Reported evidences have shown that alendronate (Aln) is known to not only restrain osteoclasts from mediating bone resorption but also stimulate osteoblasts to regenerate bone tissue. Here, we developed an engineered implantable scaffold that could sustainably release Aln for osteoporotic bone defects. Briefly, Aln was added into 2% collagen (Col) solution to form a 5 mg/ml mixture. Then the mixture was filled into pre-designed round models (diameter: 5 mm, height: 2 mm) and crosslinked to obtain engineered Col-Aln scaffolds. The release kinetics showed that Aln was released at an average rate of 2.99 µg/d in the initial 8 days and could sustainably release for 1 month. To detect the repair effects of the Col-Aln scaffolds for osteoporotic defects, the Col and Col-Aln scaffolds were implanted into 5 mm cranial defects in ovariectomized rats. After 3 months, the cranial defects implanted with Col-Aln scaffolds achieved more bone regeneration in defect area (11.74 ± 3.82%) than Col scaffold (5.12 ± 1.15%) (p < .05). Moreover, ovariectomized rats in Col-Aln scaffold group possessed more trabecular bone in femur metaphysis than Col scaffold group as analyzed by Micro-CT. This study demonstrated the engineered Col-Aln scaffold has the potential to repair osteoporotic bone defects and resist bone loss in osteoporosis.


Assuntos
Alendronato , Colágeno , Osteoblastos , Osteoporose , Alendronato/química , Alendronato/farmacocinética , Alendronato/farmacologia , Animais , Colágeno/química , Colágeno/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Feminino , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/patologia , Ovariectomia , Ratos , Ratos Sprague-Dawley
12.
Theranostics ; 10(6): 2759-2772, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194833

RESUMO

The survival of transplanted cells and tissues in bone regeneration requires a microenvironment with a vibrant vascular network. A tissue engineering chamber can provide this in vivo. However, the commonly used silicone chamber is biologically inert and can cause rejection reactions and fibrous capsule. Studies have revealed that collagen is highly biocompatible and graphene oxide (GO) could regulate osteogenic activity in vivo. Besides, GO can be cross-linked with natural biodegradable polymers to construct scaffolds. Methods: A vascularized GO-collagen chamber model was built by placing vessels traversing through the embedded tissue-engineered grafts (osteogenic-induced bone mesenchymal stem cells -gelatin) in the rat groin area. Osteogenic activity and inflammatory reactions were assessed using different methods including micro-CT scanning, Alizarin red staining, and immunohistochemical staining. Results: After one month, in vivo results showed that bone mineralization and inflammatory responses were significantly pronounced in the silicone model or no chamber (control) groups. Vascular perfusion analysis confirmed that the GO-collagen chamber improved the angiogenic processes. Cells labeled with EdU revealed that the GO-collagen chamber promoted the survival and osteogenic differentiation of bone mesenchymal stem cells. Conclusion: Overall, the novel biocompatible GO-collagen chamber exhibited osteoinductive and anti-fibrosis effects which improved bone regeneration in vivo. It can, therefore, be applied to other fields of regenerative medicine.


Assuntos
Materiais Biocompatíveis , Regeneração Óssea/efeitos dos fármacos , Colágeno , Grafite , Engenharia Tecidual , Alicerces Teciduais , Animais , Anti-Inflamatórios/uso terapêutico , Materiais Biocompatíveis/uso terapêutico , Calcificação Fisiológica/efeitos dos fármacos , Células Cultivadas , Colágeno/uso terapêutico , Feminino , Grafite/uso terapêutico , Células-Tronco Mesenquimais , Ratos , Ratos Sprague-Dawley
13.
Int J Nanomedicine ; 15: 1349-1361, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184590

RESUMO

BACKGROUND: Impaired wound healing might be associated with many issues, especially overactive of reactive oxygen species (ROS), deficiency of blood vessels and immature of epidermis. N-acetylcysteine (NAC), as an antioxidant, could solve these problems by inhibiting overreactive of ROS, promoting revascularization and accelerating re-epithelialization. How to deliver NAC in situ with a controllable releasing speed still remain a challenge. MATERIALS AND METHODS: In this study, we combined collagen (Col) with N-acetylcysteine to perform the characteristics of sustained release and chemically crosslinked Col/NAC composite with polyamide (PA) nanofibers to enhance the mechanical property of collagen and fabricated this multi-layered scaffold (PA-Col/NAC scaffold). The physical properties of the scaffolds such as surface characteristics, water absorption and tensile modulus were tested. Meanwhile, the ability to promote wound healing in vitro and in vivo were investigated. RESULTS: These scaffolds were porous and performed great water absorption. The PA-Col/NAC scaffold could sustainably release NAC for at least 14 days. After cell implantation, PA-Col/NAC scaffold showed better cell proliferation and cell migration than the other groups. In vivo, PA-Col/NAC scaffolds could promote wound healing best among all the groups. CONCLUSION: The multi-layered scaffolds could obviously accelerate the process of wound healing and exert better and prolonged effects.


Assuntos
Acetilcisteína/farmacologia , Colágeno/química , Sequestradores de Radicais Livres/farmacologia , Nylons/química , Reepitelização/efeitos dos fármacos , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Preparações de Ação Retardada , Masculino , Nanofibras/química , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
14.
Wound Repair Regen ; 28(1): 126-144, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31509318

RESUMO

Human skin wound repair may result in various outcomes with most of them leading to scar formation. Commonly seen in many cutaneous wound healing cases, hypertrophic scars are considered as phenotypes of abnormal wound repair. To prevent the formation of hypertrophic scars, efforts have been made to understand the mechanism of scarring following wound closure. Numerous in vivo and in vitro models have been created to facilitate investigations into cutaneous scarring and the development of antiscarring treatments. To select the best model for a specific study, background knowledge of the current models of hypertrophic scars is necessary. In this review, we describe in vivo and in vitro models for studying hypertrophic scars, as well as the distinct characteristics of these models. The choice of models for a specific study should be based on the characteristics of the model and the goal of the study. In general, in vivo animal models are often used in phenotypical scar formation analysis, development of antiscarring treatment, and functional analyses of individual genes. In contrast, in vitro models are chosen to pathway identification during scar formation as well as in high-throughput analysis in drug development. Besides helping investigators choose the best scarring model for their research, the goal of this review is to provide knowledge for improving the existing models and development of new models. These will contribute to the progress of scarring studies.


Assuntos
Cicatriz Hipertrófica/patologia , Modelos Animais de Doenças , Técnicas In Vitro , Pele/patologia , Animais , Técnicas de Cultura de Células , Cicatriz Hipertrófica/metabolismo , Cricetinae , Cobaias , Humanos , Camundongos , Modelos Teóricos , Coelhos , Ratos , Pele/metabolismo , Suínos
15.
Plast Reconstr Surg ; 144(4): 869-880, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31568294

RESUMO

BACKGROUND: The efficacy of autologous fat transplantation is reduced by fat absorption and fibrosis that are closely related to unsatisfactory vascularization. Extracellular vesicles are key components of the cell secretome, which can mirror the functional and molecular characteristics of their parental cells. Growing evidence has revealed that adipose-derived mesenchymal stem cells have the ability to enhance vascularization, which is partly ascribed to extracellular vesicles. The authors evaluated whether adipose-derived mesenchymal stem cell-derived extracellular vesicles improved vascularization of fat grafts and increased their retention rate. METHODS: To test the angiogenesis ability of adipose-derived mesenchymal stem cell-derived extracellular vesicles, they were isolated from the supernatant of cultured human adipose-derived mesenchymal stem cells and incubated with human umbilical vein endothelial cells in vitro. Then, the vesicles were co-transplanted with fat into nude mice subcutaneously. Three months after transplantation, the retention rate and inflammatory reaction of the grafts were analyzed by histologic assay. RESULTS: The experimental group could significantly promote migration and tube formation at the concentration of 20 µg/ml. At 3 months after transplantation, the volume of the experimental group (0.12 ± 0.03 mm) was larger compared with the blank group (0.05 ± 0.01 mm). Histology and immunohistology results demonstrated significantly fewer cysts and vacuoles, less fibrosis, and more neovessels in the extracelluar vesicle group. CONCLUSIONS: The authors co-transplanted adipose-derived mesenchymal stem cell-derived extracellular vesicles with fat into a nude mouse model and found that the vesicles improved volume retention by enhancing vascularization and regulating the inflammatory response.


Assuntos
Tecido Adiposo/transplante , Vesículas Extracelulares , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica , Animais , Células Cultivadas , Humanos , Camundongos
16.
Biofabrication ; 12(1): 015023, 2019 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-31665714

RESUMO

Breast tissue engineering is a promising alternative to standard treatments for breast defects. Although there is a consensus that the mechanical property of the scaffold should best match the reconstructed tissue, the simulation of the soft and elastic tactility of native breast tissues using conventional materials and architecture design requires further study. Previous research has shown that the crystal microstructure-like design can drastically alter the mechanical properties of the constructed scaffolds. In this study, we designed and additive manufactured four kinds of breast scaffolds using polyurethane and termed their architectures as N5S4, N9S8, N7S6 and N4S6. The basic unit cell of each scaffold was similar to a lattice structure from the isometric crystal system. The scaffolds possessed identical porosity but different mechanical properties in which the compressive modulus of the softest scaffolds (N5S4) were similar to that of native breast tissue. When applied in the construction of tissue-engineered breast combining with delayed fat injection technique in nude rat models, the soft scaffolds(N5S4) performed better compared to its stiff counterpart (N4S6), as higher adipose survival, vascularization and milder fibrosis could be observed in N5S4 scaffolds . Lastly, using finite element analysis, we further investigated the influence of the unit cell architectures on the mechanical properties of the scaffolds and simulated the deformation as well as stress distribution patterns of the implanted scaffolds in detail. Thus, a crystal lattice-like architecture design was introduced to tune the mechanical properties of the scaffolds and match the requirements for tissue engineering applications.


Assuntos
Mama/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Bioimpressão , Mama/citologia , Feminino , Porosidade , Impressão Tridimensional , Ratos , Ratos Nus , Engenharia Tecidual/instrumentação
17.
Mater Sci Eng C Mater Biol Appl ; 105: 110137, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546424

RESUMO

The developing bone graft substitutes have become a promising strategy for repairing large bone loss. Aerogels that made from natural polymers were widely investigated for synthetic bone graft due to their high porosity and great biocompatibility. However, the mechanical properties of natural polymer aerogel are extremely poor for large bone repair. Graphene oxide (GO) is one of the nanomaterials with great mechanical properties as well as biocompatibility, making it a promising component when constructing hybrid aerogels for bone regeneration. In the present study, we have developed a highly porous aerogel consist of GO and type I collagen (COL) using sol-gel process (concentrations of GO: 0%, 0.05%, 0.1%, and 0.2% w/v). Results indicated that GO-COL aerogels were highly porous and hydrophilic. Furthermore, the compressive modulus of GO-COL aerogels was enhanced with the GO concentration increased. For in vitro experiment, 0.1% GO-COL aerogel exhibited better biomineralization rate and cell compatibility than other groups of aerogels. For in vivo study, a better bone repair effect was observed in 0.1% GO-COL aerogels than COL aerogel in rat cranial defect models. This study indicated that 0.1% GO-COL aerogel exhibited good biocompatibility and osteogenic ability in vivo, which make it a promising biocompatible scaffold for bone regeneration and tissue engineering.


Assuntos
Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Colágeno/farmacologia , Géis/química , Grafite/farmacologia , Animais , Fenômenos Biomecânicos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Masculino , Ratos Sprague-Dawley , Ratos Wistar , Tela Subcutânea/efeitos dos fármacos , Microtomografia por Raio-X
18.
Theranostics ; 9(16): 4663-4677, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367248

RESUMO

Background: Microtissues constructed with hydrogels promote cell expansion and specific differentiation by mimicking the microarchitecture of native tissues. However, the suboptimal mechanical property and osteogenic activity of microtissues fabricated by natural polymers need further improvement for bone reconstruction application. Core-shell designed structures are composed of an inner core part and an outer part shell, combining the characteristics of different materials, which improve the mechanical property of microtissues. Methods: A micro-stencil array chip was used to fabricate an open porous core-shell micro-scaffold consisting of gelatin as shell and demineralized bone matrix particles modified with bone morphogenetic protein-2 (BMP-2) as core. Single gelatin micro-scaffold was fabricated as a control. Rat bone marrow mesenchymal stem cells (BMSCs) were seeded on the micro-scaffolds, after which they were dynamic cultured and osteo-induced in mini-capsule bioreactors to fabricate microtissues. The physical characteristics, biocompatibility, osteo-inducing and controlled release ability of the core-shell microtissue were evaluated in vitro respectively. Then microtissues were tested in vivo via ectopic implantation and orthotopic bone implantation in rat model. Results: The Young's modulus of core-shell micro-scaffold was nearly triple that of gelatin micro-scaffold, which means the core-shell micro-scaffolds have better mechanical property. BMSCs rapidly proliferated and retained the highest viability on core-shell microtissues. The improved osteogenic potential of core-shell microtissues was evidenced by the increased calcification based on von kossa staining and osteo-relative gene expression. At 3months after transplantation, core-shell microtissue group formed the highest number of mineralized tissues in rat ectopic subcutaneous model, and displayed the largest amount of new bony tissue deposition in rat orthotopic cranial defect. Conclusion: The novel core-shell microtissue construction strategy developed may become a promising cell delivery platform for bone regeneration.


Assuntos
Osso e Ossos/química , Animais , Fenômenos Biomecânicos , Biomimética , Proteína Morfogenética Óssea 2/metabolismo , Osso e Ossos/metabolismo , Gelatina/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Porosidade , Ratos , Ratos Sprague-Dawley , Engenharia Tecidual
19.
Sci Rep ; 9(1): 6035, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988335

RESUMO

Tissue engineering is a promising technology used as an alternative to organ/tissue transplantation which is often limited by donor shortage. The construction of large-sized engineered tissue requires a fast and sufficient vascularization process. Previous studies have shown that hypoxia-inducible factor (HIF) -1α may promote the vascularization process implying that stabilized HIF-1α can be applied in the engineering of large-sized tissue. However, the toxicity and off-target effect of previously reported HIF-1α stabilizers limit their clinical application. FG-4592, a small molecule specific HIF stabilizer, was previously investigated as an anti-anemia drug in a phase-III clinical trial. Here we found that FG-4592 promoted tube formation in an in vitro model of angiogenesis by stabilizing HIF-1α and activating vascular endothelial growth factor (VEGF). When FG-4592 immobilized fibrin gel scaffold was implanted into a subcutaneous tissue engineering chamber, the vascularization process was significantly enhanced through the similar mechanisms which was verified in vitro. We conclude that FG-4592 may serve as a pro-angiogenic molecule for the construction of large-sized engineered tissue where intensive angiogenesis is required.


Assuntos
Indutores da Angiogênese/farmacologia , Glicina/análogos & derivados , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoquinolinas/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Indutores da Angiogênese/administração & dosagem , Animais , Fibrina/química , Glicina/administração & dosagem , Glicina/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Isoquinolinas/administração & dosagem , Masculino , Ratos Sprague-Dawley , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
J Biomed Mater Res A ; 107(7): 1414-1424, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30737888

RESUMO

PCL (poly-caprolactone) nanofibers have good biocompatibility and high porosity, which are usually utilized for application in wound dressings. However, wound healing could be hindered by the overproduction of reactive oxygen species (ROS) and different factors. Pure nanofibers cannot satisfy these requirements of wound healing. N-acetylcysteine (NAC), as an antioxidant, meets the requirements for wound healing by resisting the overproduction of ROS and by promoting angiogenesis and maturation of the epidermis. In this study, we prepared a sandwich structured PCL-Col/NAC scaffold using the molding method, which consisted of PCL nanofibers at the core and NAC-loaded collagen on both sides. The hydroscopicity and tensile modulus of PCL-Col/NAC scaffolds showed best performance of these properties among groups. Meanwhile, the drug release profiles of PCL-Col/NAC scaffolds were investigated using the HPLC method and the results suggested a sustained drug release of NAC for PCL-Col/NAC scaffolds. In addition, PCL-Col/NAC scaffolds presented better properties than the control groups in cell migration and proliferation. The in vivo wound healing therapy effect was studied using an oval (2 × 1 cm) full-thickness skin defect wound model for SD rats. After 21 days, gross view and histological analysis showed a favorable beneficial therapeutic effect as well as better epidermal maturation compared with the control groups. CD31 immunohistology results revealed relatively more new vessels in the PCL-Col/NAC group than the control groups. This study developed novel PCL-Col/NAC scaffolds with an excellent hydroscopicity, tensile modulus and the ability to promote epidermal maturation and angiogenesis, demonstrating its promising potential in wound healing treatment. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.


Assuntos
Acetilcisteína/farmacologia , Colágeno/química , Poliésteres/química , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/farmacologia , Movimento Celular/efeitos dos fármacos , Preparações de Ação Retardada , Modelos Animais de Doenças , Camundongos , Células NIH 3T3 , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Implantação de Prótese , Ratos Sprague-Dawley , Resistência à Tração , Fatores de Tempo
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