RESUMO
The rise in musculoskeletal disorders has prompted medical experts to devise novel effective alternatives to treat complicated orthopedic conditions. The ever-expanding field of regenerative medicine has allowed researchers to appreciate the therapeutic value of bone marrow-derived biological products, such as the bone marrow aspirate (BMA) clot, a potent orthobiologic which has often been dismissed and regarded as a technical complication. Numerous in vitro and in vivo studies have contributed to the expansion of medical knowledge, revealing optimistic results concerning the application of autologous bone marrow towards various impactful disorders. The bone marrow accommodates a diverse family of cell populations and a rich secretome; therefore, autologous BMA-derived products such as the "BMA Matrix", may represent a safe and viable approach, able to reduce the costs and some drawbacks linked to the expansion of bone marrow. BMA provides -it eliminates many hurdles associated with its preparation, especially in regards to regulatory compliance. The BMA Matrix represents a suitable alternative, indicated for the enhancement of tissue repair mechanisms by modulating inflammation and acting as a natural biological scaffold as well as a reservoir of cytokines and growth factors that support cell activity. Although promising, more clinical studies are warranted in order to further clarify the efficacy of this strategy.
Assuntos
Células da Medula Óssea/metabolismo , Medula Óssea/metabolismo , Matriz Extracelular , Medicina Regenerativa , Matriz Extracelular/metabolismo , Matriz Extracelular/transplante , HumanosRESUMO
Polymeric biomaterials composed of extracellular matrix components possess osteoconductive capacity that is essential for bone healing. The presence of collagen and the ability to undergo physicochemical modifications render these materials a suitable alternative in bone regenerative therapies. The objective of this study was to evaluate the osteogenic capacity of collagen-based matrices (native and anionic after alkaline hydrolysis) made from bovine intestinal serosa (MBIS). Twenty-five animals underwent surgery to create a cranial defect to be filled with native and anionic collagen matrixes, mmineralized and non mineralized. The animals were killed painlessly 6 weeks after surgery and samples of the wound area were submitted to routine histology and morphometric analysis. In the surgical area there was new bone formation projecting from the margins to the center of the defect. More marked bone neoformation occurred in the anionic matrices groups in such a way that permitted union of the opposite margins of the bone defect. The newly formed bone matrix exhibited good optical density of type I collagen fibers. Immunoexpression of osteocalcin by osteocytes was observed in the newly formed bone. Morphometric analysis showed a greater bone volume in the groups receiving the anionic matrices compared to the native membranes. Mineralization of the biomaterial did not increase its osteoregenerative capacity. In conclusion, the anionic matrix exhibits osteoregenerative capacity and is suitable for bone reconstruction therapies.
Assuntos
Regeneração Óssea/efeitos dos fármacos , Colágeno/farmacologia , Matriz Extracelular/transplante , Intestinos/química , Membrana Serosa/química , Fraturas Cranianas/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Regeneração Óssea/fisiologia , Calcificação Fisiológica/fisiologia , Bovinos , Colágeno/química , Colágeno/isolamento & purificação , Expressão Gênica , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Ratos , Ratos Wistar , Crânio/efeitos dos fármacos , Crânio/lesões , Crânio/patologia , Fraturas Cranianas/patologia , Cicatrização/efeitos dos fármacosRESUMO
BACKGROUND: Translational research to develop pharmaceutical and surgical treatments for pterygium requires a reliable and easy to produce animal model. Extracellular matrix and fibroblast are important components of pterygium. The aim of this study was to analyze the effect of the subconjunctival injection of fibroblast cells (NIH3T3 cell line) and exogenous extracellular matrix in rabbits in producing a pterygium-like lesion. METHODS: Six 3-month-old white New Zealand rabbits were injected with 20,000 NIH3T3 cells and 5 µL of Matrigel in the right conjunctiva, and with only 5 µL of Matrigel in the left conjunctiva. The eyes were photographed under a magnification of 16× using a 12-megapixel digital camera attached to the microscope on day 1, 3 and 7. Conjunctival vascularization was measured by analyzing images to measure red pixel saturation. Area of corneal and conjunctival fibrovascular tissue formation on the site of injection was assessed by analyzing the images on day 3 and 7 using area measurement software. Histopathologic characteristics were determined in the rabbit tissues and compared with a human primary pterygium. RESULTS: The two treatments promoted growth of conjunctival fibrovascular tissue at day 7. The red pixel saturation and area of fibrovascular tissue developed was significantly higher in right eyes (p < 0.05). Tissues from both treatments showed neovascularization in lesser extent to that observed in human pterygium. Acanthosis, stromal inflammation, and edema were found in tissues of both treatments. No elastosis was found in either treatment. CONCLUSIONS: Matrigel alone or in combination with NIH3T3 cells injected into the rabbits' conjunctiva can promote tissue growth with characteristics of human pterygium, including neovascularization, acanthosis, stromal inflammation, and edema. The combination of Matrigel with NIH3T3 cells seems to have an additive effect on the size and redness of the pterygium-like tissue developed.
Assuntos
Colágeno/efeitos adversos , Modelos Animais de Doenças , Matriz Extracelular/transplante , Fibroblastos/transplante , Laminina/efeitos adversos , Proteoglicanas/efeitos adversos , Pterígio/etiologia , Animais , Colágeno/administração & dosagem , Combinação de Medicamentos , Laminina/administração & dosagem , Camundongos , Células NIH 3T3 , Proteoglicanas/administração & dosagem , Pterígio/patologia , CoelhosRESUMO
Regenerative medicine involves the study of cells, signaling cues and biomatrices to restore normal function of tissues and organs. To develop the matrices for use in tissue engineering there are three main groups of biomaterials: (i) naturally derived materials; (ii) synthetic polymers; and (iii) decellularized organ or tissue scaffolds. These biomaterials, in various forms such as hydrogels, nanofibers and 3D scaffolds, among others, have been employed for different tissue regeneration purposes, with several techniques involved in their production, including rapid prototyping, tissue decellularization and electrospinning. In this review, the main topics of hydrogels, 3D printing and electrospun scaffolds, other biomaterials and decellularization and recellularization will be discussed.
Assuntos
Materiais Biocompatíveis , Matriz Extracelular/fisiologia , Polímeros/química , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Alicerces Teciduais , Animais , Matriz Extracelular/transplante , Humanos , Hidrogéis , Impressão TridimensionalRESUMO
BACKGROUND: Translational research to develop pharmaceutical and surgical treatments for pterygium requires a reliable and easy to produce animal model. Extracellular matrix and fibroblast are important components of pterygium. The aim of this study was to analyze the effect of the subconjunctival injection of fibroblast cells (NIH3T3 cell line) and exogenous extracellular matrix in rabbits in producing a pterygium-like lesion. METHODS: Six 3-month-old white New Zealand rabbits were injected with 20,000 NIH3T3 cells and 5 µL of Matrigel in the right conjunctiva, and with only 5 µL of Matrigel in the left conjunctiva. The eyes were photographed under a magnification of 16× using a 12-megapixel digital camera attached to the microscope on day 1,3 and 7. Conjunctival vascularization was measured by analyzing images to measure red pixel saturation. Area of corneal and conjunctival fibrovascular tissue formation on the site of injection was assessed by analyzing the images on day 3 and 7 using area measurement software. Histopathologic characteristics were determined in the rabbit tissues and compared with a human primary pterygium. RESULTS: The two treatments promoted growth of conjunctival fibrovascular tissue at day 7. The red pixel saturation and area of fibrovascular tissue developed was significantly higher in right eyes (p < 0.05). Tissues from both treatments showed neovascularization in lesser extent to that observed in human pterygium. Acanthosis, stromal inflammation, and edema were found in tissues of both treatments. No elastosis was found in either treatment. CONCLUSIONS: Matrigel alone or in combination with NIH3T3 cells injected into the rabbits' conjunctiva can promote tissue growth with characteristics of human pterygium, including neovascularization, acanthosis, stromal inflammation, and edema. The combination of Matrigel with NIH3T3 cells seems to have an additive effect on the size and redness of the pterygium-like tissue developed.
Assuntos
Animais , Camundongos , Coelhos , Proteoglicanas/efeitos adversos , Pterígio/etiologia , Colágeno/efeitos adversos , Laminina/efeitos adversos , Modelos Animais de Doenças , Matriz Extracelular/transplante , Fibroblastos/transplante , Proteoglicanas/administração & dosagem , Pterígio/patologia , Colágeno/administração & dosagem , Laminina/administração & dosagem , Células NIH 3T3 , Combinação de MedicamentosRESUMO
Objetivo: Describir, clasificar y discutir las indicaciones de los biomateriales de base biológica, moléculas bioactivas e ingeniería de tejidos que se están usando para el manejo de recesiones y aumento de encía en cirugía plástica periodontal. En esta revisión de la literatura, se utilizó una combinación de los términos de búsqueda específicos que consideraran los materiales en revisión, para el aumento de encía adherida, y el recubrimiento radicular. Materiales y Métodos: Se usaron las siguientes fuentes: Medline, Biblioteca Cochrane, y búsqueda manual de revistas específicas como el Journal of Periodontology, International Journal of Periodontics and Restorative Dentistry y Journal of Clinical Periodontology entre años 1985 y 2011. Se revisaron un total de 117 artículos y se seleccionaron 74 entre estudios clínicos controlados, estudios clínicos randomizados, reportes de casos y estudios en animales. Los artículos fueron revisados por los autores y aceptados por consenso para su discusión. Conclusiones: 1) Existe una serie de materiales que presentan gran potencial y podrían ser una alternativa viable a los injertos autógenos, pero se requiere más estudios a largo plazo. 2) Existe necesidad de estudios con la investigación de estos procedimientos en relación a resultados orientados a la estabilidad, seguridad y efectividad de los diferentes materiales existentes.
Objective: To describe, classify and discuss the clinical applications of biologically based biomaterials, bioactive molecules and tissue engineering being utilized in gingival recession therapy and gingival augmentation procedures in plastic periodontal surgery. In this literature review, a combination of specific search key words were used, including materials being reviewed, indicated for gingival augmentation and root coverage procedures. Materials and Methods: The following sources were consulted: Medline, Cochrane Library and manual search of specific scientific journals such as Journal of Periodontology, International Journal of Periodontics and Restorative Dentistry and Journal of Clinical Periodontology between the years 1985 and 2011. A total of 117 articles were reviewed with 74 being selected unanimously by the authors for discussion in the manuscript. These articles included controlled clinical studies, randomized clinical studies, case reports and animal studies. The selected articles were reviewed by the authors and accepted by consensus. Conclusions: 1) There is a cohort of materials that exhibit great potential which could be a viable alternative to autografts but are in need of further long term studies. 2) There is a need of research of these materials in relation to stability, safety and efficacy.
Assuntos
Humanos , Materiais Biocompatíveis , Gengiva/cirurgia , Procedimentos Cirúrgicos Bucais/métodos , Retração Gengival/cirurgia , Colágeno/uso terapêutico , Derme/transplante , Gengivoplastia/métodos , Matriz Extracelular/transplante , Periodonto/cirurgia , Pele Artificial , Retalhos Cirúrgicos , Tecido Conjuntivo/transplante , Transplante de Tecidos/métodosRESUMO
PURPOSE: To investigate histological features and biocompatibility of a latex biomembrane for bladder augmentation using a rabbit model. MATERIAL AND METHODS: After a partial cystectomy, a patch of a non-vulcanized latex biomembrane (2x4 cm) was sewn to the bladder with 5/0 monofilament polydioxanone sulfate in a watertight manner. Groups of 5 animals were sacrificed at 15, 45 and 90 days after surgery and the bladder was removed. The 5-mum preparations obtained from grafted area and normal bladder were stained with hematoxylin-eosin. Immunohistochemical staining was performed with a primary antibody against alpha-actin to assess muscle regeneration. RESULTS: No death, urinary leakage or graft extrusion occurred in any group. All bladders showed a spherical shape. Macroscopically, after 90 days, the latex biomembrane was not identifiable and the patch was indistinguishable from normal bladder. A bladder stone was found in one animal (6.6%). On the 90th day, histology revealed continuity of transitional epithelium of host bladder tissue on the patch area. At this time, the muscle layers were well organized in a similar fashion to native bladder muscle layers. The inflammatory process was higher on grafted areas when compared to controls: 15 days--p < 0.0001, 45 days--p < 0.001, and 90 days--p < 0.01. The anti alpha-actin immunoexpression peaked at 45 days, when the graft was observed covered by muscle cells. CONCLUSION: The latex biomembrane is biocompatible and can be used in models for bladder augmentation in rabbits. It promotes epithelium and muscle regeneration without urinary leakage.
Assuntos
Materiais Biocompatíveis , Matriz Extracelular/transplante , Látex , Músculo Liso/fisiologia , Regeneração , Bexiga Urinária , Animais , Modelos Animais de Doenças , Reação Hospedeiro-Enxerto/fisiologia , Mucosa Intestinal/transplante , Masculino , Membranas Artificiais , Músculo Liso/citologia , Coelhos , Bexiga Urinária/fisiologia , Bexiga Urinária/cirurgiaRESUMO
PURPOSE: To investigate histological features and biocompatibility of a latex biomembrane for bladder augmentation using a rabbit model. MATERIAL AND METHODS: After a partial cystectomy, a patch of a non-vulcanized latex biomembrane (2x4 cm) was sewn to the bladder with 5/0 monofilament polydioxanone sulfate in a watertight manner. Groups of 5 animals were sacrificed at 15, 45 and 90 days after surgery and the bladder was removed. The 5-µm preparations obtained from grafted area and normal bladder were stained with hematoxylin-eosin. Immunohistochemical staining was performed with a primary antibody against alpha-actin to assess muscle regeneration. RESULTS: No death, urinary leakage or graft extrusion occurred in any group. All bladders showed a spherical shape. Macroscopically, after 90 days, the latex biomembrane was not identifiable and the patch was indistinguishable from normal bladder. A bladder stone was found in one animal (6.6 percent). On the 90th day, histology revealed continuity of transitional epithelium of host bladder tissue on the patch area. At this time, the muscle layers were well organized in a similar fashion to native bladder muscle layers. The inflammatory process was higher on grafted areas when compared to controls: 15 days - p < 0.0001, 45 days - p < 0.001, and 90 days - p < 0.01. The anti alpha-actin immunoexpression peaked at 45 days, when the graft was observed covered by muscle cells. CONCLUSION: The latex biomembrane is biocompatible and can be used in models for bladder augmentation in rabbits. It promotes epithelium and muscle regeneration without urinary leakage.
Assuntos
Animais , Masculino , Coelhos , Materiais Biocompatíveis , Matriz Extracelular/transplante , Látex , Músculo Liso/fisiologia , Regeneração , Bexiga Urinária , Modelos Animais de Doenças , Reação Hospedeiro-Enxerto/fisiologia , Mucosa Intestinal/transplante , Membranas Artificiais , Músculo Liso/citologia , Bexiga Urinária/fisiologia , Bexiga Urinária/cirurgiaRESUMO
PURPOSE: Bilateral anorchia, either congenital or acquired, often requires testicular prostheses placement and testosterone supplementation. Several types of testosterone compounds and various modes of hormone delivery are currently used clinically, however, their pharmacokinetic properties are not ideal. In this study, we explored the possibility of creating hormone releasing testicular prostheses that could continuously supply and maintain physiologic levels of testosterone in vivo over time. METHODS: Chondrocytes, harvested from bovine articular cartilage, were seeded on testicular shaped polymer scaffolds at a concentration of 100 x 10(6) ml(-1). The scaffolds were maintained in a bioreactor for 4 weeks to form cartilage tissue. Subsequently, testosterone enanthate (100 microg) was injected into the central hollow space of each testicular prosthesis, and maintained for 40 weeks in culture. A sample of the medium was collected every 2 days for testosterone assays. Another group of ex vivo engineered testicular prostheses was implanted into the scrotal space of castrated athymic mice (n = 10). Intratesticular injection of testosterone enanthate was made into each prosthesis at a concentration of 100 microg. Control groups consisted of animals with castration only (n = 8) and sham operations (n = 5). Testosterone levels were measured prior and 2 weeks after castration, 1 day after testosterone administration, and weekly up to 14 weeks. The engineered testicular prostheses were retrieved at sacrifice for histomorphological and immunocytochemical analyses. RESULTS: Milky white cartilage testicular protheses were formed by 4 weeks. The ex vivo prostheses showed an initial burst effect of testosterone followed by a broad plateau for 16 weeks (>500 ng/dl) and a decreased level of testosterone until 40 weeks. The testosterone levels were physiologic throughout 40 weeks and the entire testosterone released was calculated as 60% of the injected volume. The circulating testosterone levels in the protheses implanted animals demonstrated a maximum peak on day 1 and a continued physiologic range during the entire study period. Histologically, the retrieved testicular implants showed mature chondrocytes with a hollow center in each prosthesis. CONCLUSION: This study demonstrates that engineered cartilage testis can be created in bioreactors, can be implanted in vivo, and can release testosterone for a prolonged period. Furthermore, the levels of testosterone release can be maintained within the physiologic range. Periodic reinjection may potentially provide permanent physiologic hormonal replacement. This novel technology may be beneficial for patients who require testicular prostheses and chronic hormone supplementation.
Assuntos
Próteses e Implantes , Testículo/metabolismo , Testículo/cirurgia , Testosterona/metabolismo , Engenharia Tecidual/métodos , Animais , Reatores Biológicos , Cartilagem Articular/citologia , Bovinos , Condrócitos/citologia , Colágeno/metabolismo , Matriz Extracelular/transplante , Masculino , Camundongos , Camundongos Nus , Orquiectomia , Implantação de Prótese , Escroto/cirurgiaRESUMO
PURPOSE: There is an increasingly large body of literature concerning tissue-engineering products that may be used in urology. Some of these are quite complex (such as multilayer patient-specific cell-seeded implants) yet the most simple and successful products to date are also the most uncomplicated: resorbable acellular extra-cellular matrices (ECMs) harvested from animals. ECMs have been used in a variety of difficult urologic reconstruction problems, and this review is intended to summarize this complex literature for the practicing urologist. METHODS: Medline search of related terms such as "SIS, small intestinal submucosa, ECM, extracellular matrix, acellular matrix and urologic reconstruction". Manuscripts missed in the initial search were taken from the bibliographies of the primary references. RESULTS: Full review of potential clinical uses of resorbable extra-cellular matrices in urologic reconstruction. CONCLUSIONS: Currently, the "state of the art" in tissue engineering solutions for urologic reconstruction means resorbable acellular xenograft matrices. They show promise when used as a pubovaginal sling or extra bolstering layers in ureteral or urethral repairs, although recent problems with inflammation following 8-ply pubovaginal sling use and failures after 1- and 4-ply SIS repair of Peyronie's disease underscore the need for research before wide adoption. Preliminary data is mixed concerning the potential for ECM urethral patch graft, and more data is needed before extended uses such as bladder augmentation and ureteral replacement are contemplated. The distant future of ECMs in urology likely will include cell-seeded grafts with the eventual hope of producing "off the shelf" replacement materials. Until that day arrives, ECMs only fulfill some of the requirements for the reconstructive urologist.