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1.
Aesthetic Plast Surg ; 48(11): 2210-2219, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38499876

RESUMEN

BACKGROUND: The extracellular matrix isolated from adipose tissue, known as acellular adipose matrix (AAM), represents a novel biomaterial. AAM functions as a scaffold that not only supports stem cell proliferation and differentiation but also induces adipogenesis and angiogenesis. This study aims to investigate the volumetric effects and microenvironmental changes associated with injectable AAM in comparison to conventional fat grafting. METHODS: AAM was manufactured from fresh human abdominoplasty fat using a mechanically modified method and then transformed into an injectable form. Lipoaspirate was harvested employing the Coleman technique. A weight and volume study was conducted on athymic nude mice by injecting either injectable AAM or lipoaspirate into the scalp (n=6 per group). After eight weeks, graft retention was assessed through weight measurement and volumetric analysis using micro-computed tomography (micro-CT) scanning. Histological analysis was performed using immunofluorescence staining for perilipin and CD31. RESULTS: Injectable AAM exhibited similar weight and volume effects in murine models. Histological analysis revealed comparable inflammatory cell presence with minimal capsule formation when compared to conventional fat grafts. Adipogenesis occurred in both AAM-injected and conventional fat graft models, with no significant difference in the blood vessel area (%) between the two. CONCLUSIONS: In summary, injectable AAM demonstrates effectiveness comparable to conventional fat grafting concerning volume effects and tissue regeneration in soft tissue reconstruction. This promising allogeneic injectable holds the potential to serve as a safe and effective "Off-the-Shelf" alternative in both aesthetic and reconstructive clinical practices. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Abdominoplastia , Tejido Adiposo , Ratones Desnudos , Animales , Ratones , Tejido Adiposo/trasplante , Abdominoplastia/métodos , Humanos , Femenino , Procedimientos de Cirugía Plástica/métodos , Modelos Animales de Enfermedad , Microtomografía por Rayos X , Adipogénesis , Distribución Aleatoria , Supervivencia de Injerto , Modelos Animales , Matriz Extracelular/trasplante
2.
J Vasc Interv Radiol ; 32(1): 128-134, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33229185

RESUMEN

PURPOSE: To evaluate extracellular matrix enterocutaneous fistula plugs (ECMFPs) in treatment of enteric fistulae at a single institution. MATERIALS AND METHODS: The study included 18 patients who had an ECMFP placed between 2012 and 2018 with treatment follow-up through July 2020. Median patient age was 52.5 years (interquartile range, 11.5 y). There were 28 ECMFP procedures performed on 19 separate fistulae. Fistulae locations were gastrocutaneous (n = 4), enterocutaneous (n = 9), and colocutaneous (n = 6). Descriptive statistics were used to define closure rates, recurrence rates, and complications. RESULTS: Fistula closure was achieved in 1 of 4 gastrocutaneous (25%), 4 of 9 enterocutaneous (44%), and 3 of 6 colocutaneous (50%) locations. The median time from procedure to fistula tract closure was 29 days interquartile range 25 days. The median time from ECMFP placement to fistula recurrence was 28 days (interquartile range 27 days). Of the fistulae that eventually closed, 6 of 8 closed after the first attempt (75%), and 2 closed after the second attempt (25%). Of the procedures that resulted in complete closure, 7 of 8 were categorized as low flow, and 1 of 8 was categorized as high flow. Complications were seen in 4 patients (23%), with major complications in 3 patients (17%). CONCLUSIONS: Low-flow fistulae originating from the small bowel are most likely to have complete closure. High-flow and/or gastrocutaneous fistulae are less likely to benefit from this intervention. In patients who are not surgical candidates or who have failed surgical management, ECMFPs may provide a solution.


Asunto(s)
Enfermedades del Colon/cirugía , Fístula Cutánea/cirugía , Matriz Extracelular/trasplante , Fístula Gástrica/cirugía , Fístula Intestinal/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades del Colon/diagnóstico por imagen , Fístula Cutánea/diagnóstico por imagen , Femenino , Fístula Gástrica/diagnóstico por imagen , Humanos , Fístula Intestinal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/cirugía , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento , Cicatrización de Heridas
3.
Methods ; 171: 108-118, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31051254

RESUMEN

Decellularization aims to remove cells from tissue ultrastructure while preserving the mechanical and biological properties, which makes the decellularized extracellular matrix (dECM) an appropriate scaffold for tissue engineering applications. Three-dimensional (3D) bioprinting technology as a reproducible and accurate method can print the combination of ECM and autologous cells layer by layer to fabricate patient based cell-laden structures representing the intrinsic cues of natural ECM. This review defines ECM, classifies decellularization agents and techniques, and explains different sources of ECM. Then, bioprinting techniques, bioink concept, applications of dECM bioinks, and finally the future perspectives of 3d bioprinting technology are discussed.


Asunto(s)
Matriz Extracelular/trasplante , Ingeniería de Tejidos/tendencias , Andamios del Tejido/química , Matriz Extracelular/química , Humanos , Impresión Tridimensional
4.
Methods ; 171: 62-67, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31302179

RESUMEN

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


Asunto(s)
Dermis Acelular/tendencias , Matriz Extracelular/trasplante , Procedimientos de Cirugía Plástica/tendencias , Ingeniería de Tejidos/tendencias , Animales , Criopreservación , Matriz Extracelular/química , Humanos , Piel/química , Piel/citología , Andamios del Tejido/química
5.
Methods ; 171: 86-96, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31128238

RESUMEN

The global shortage of donor corneas for transplantation has led to corneal bioengineering being investigated as a method to generate transplantable tissues. Decellularized corneas are among the most promising materials for engineering corneal tissue since they replicate the complex structure and composition of real corneas. Decellularization is a process that aims to remove cells from organs or tissues resulting in a cell-free scaffold consisting of the tissues extracellular matrix. Here different decellularization techniques are described, including physical, chemical and biological methods. Analytical techniques to confirm decellularization efficiency are also discussed. Different cell sources for the recellularization of the three layers of the cornea, recellularization methods used in the literature and techniques used to assess the outcome of the implantation of such scaffolds are examined. Studies involving the application of decellularized corneas in animal models and human clinical studies are discussed. Finally, challenges for this technology are explored involving scalability, automatization and regulatory affairs.


Asunto(s)
Córnea/crecimiento & desarrollo , Matriz Extracelular/trasplante , Ingeniería de Tejidos/tendencias , Andamios del Tejido/química , Animales , Bioingeniería/métodos , Córnea/patología , Matriz Extracelular/química , Humanos , Modelos Animales , Donantes de Tejidos
6.
Methods ; 171: 41-61, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31398392

RESUMEN

A variety of surgical and non-surgical approaches have been used to address the impacts of nervous system injuries, which can lead to either impairment or a complete loss of function for affected patients. The inherent ability of nervous tissues to repair and/or regenerate is dampened due to irreversible changes that occur within the tissue remodeling microenvironment following injury. Specifically, dysregulation of the extracellular matrix (i.e., scarring) has been suggested as one of the major factors that can directly impair normal cell function and could significantly alter the regenerative potential of these tissues. A number of tissue engineering and regenerative medicine-based approaches have been suggested to intervene in the process of remodeling which occurs following injury. Decellularization has become an increasingly popular technique used to obtain acellular scaffolds, and their derivatives (hydrogels, etc.), which retain tissue-specific components, including critical structural and functional proteins. These advantageous characteristics make this approach an intriguing option for creating materials capable of stimulating the sensitive repair mechanisms associated with nervous system injuries. Over the past decade, several diverse decellularization methods have been implemented specifically for nervous system applications in an attempt to carefully remove cellular content while preserving tissue morphology and composition. Each application-based decellularized ECM product requires carefully designed treatments that preserve the unique biochemical signatures associated within each tissue type to stimulate the repair of brain, spinal cord, and peripheral nerve tissues. Herein, we review the decellularization techniques that have been applied to create biomaterials with the potential to promote the repair and regeneration of tissues within the central and peripheral nervous system.


Asunto(s)
Matriz Extracelular/trasplante , Sistema Nervioso/crecimiento & desarrollo , Medicina Regenerativa/tendencias , Ingeniería de Tejidos , Animales , Matriz Extracelular/química , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Sistema Nervioso/efectos de los fármacos , Andamios del Tejido/química
7.
Methods ; 171: 20-27, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31546012

RESUMEN

Although several decellularized extracellular matrix (ECM) sheets or patches have been commercialized for use in the clinic, only one injectable decellularized ECM hydrogel, a decellularized myocardial matrix, has reached clinical trials. Consequently, very little information is available for established manufacturing standards or assessments of these materials. Here we present detailed methodology for investigating three parameters related to manufacturing optimization for a porcine derived skeletal muscle ECM hydrogel - animal-to-animal variability, bioburden reduction, and harvesting conditions. Results from characterization assays, including residual dsDNA content and sulfated glycosaminoglycan content, did not yield noteworthy differences amongst individual animals or following the addition of a bioburden reducing agent. However, the tissue collected under different harvesting conditions contained varying amounts of fat, and the protein compositions of the decellularized products differed, which could ultimately impact subsequent efficacy in vitro or in vivo. As decellularized ECM hydrogels continue to be evaluated for various applications, the differences between laboratory-scale and manufacturing-scale material batches should be thoroughly considered to avoid costly and timely optimization during scale-up.


Asunto(s)
Dermis Acelular , Matriz Extracelular/química , Hidrogeles/química , Andamios del Tejido/química , Animales , ADN/química , ADN/efectos de los fármacos , Matriz Extracelular/trasplante , Humanos , Hidrogeles/farmacología , Hidrogeles/normas , Músculo Esquelético/química , Músculo Esquelético/trasplante , Miocardio/química , Porcinos , Ingeniería de Tejidos/normas
8.
Methods ; 171: 77-85, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31278981

RESUMEN

The cell-based tissue engineering strategies have gained attention in restoring normal tissue function after skeletal muscle injuries; however, these approaches require a donor tissue biopsy and extensive cell expansion process prior to implantation. In order to avoid this limitation, we developed a novel cell-free muscle-specific scaffolding system that consisted of a skeletal muscle-derived decellularized extracellular matrix (dECM) and a myogenic factor, insulin growth factor-1 (IGF-1). Rheological, morphological, and biological properties of this muscle-specific scaffold (IGF-1/dECM) as well as collagen and dECM scaffolds were examined. The cell viability in all scaffolds had over 90% at 1, 3, and 7 days in culture. The cell proliferation in the IGF-1/dECM was significantly increased when compared with other groups. More importantly, the IGF-1/dECM strongly supported the myogenic differentiation in the scaffold as confirmed by myosin heavy chain (MHC) immunofluorescence. We also investigated the feasibility in a rabbit tibialis anterior (TA) muscle defect model. The IGF-1/dECM had a significantly greater number of myofibers when compared to both collagen and dECM groups at 1 and 2 months after implantation. We demonstrated that this novel muscle-specific scaffolding system could effectively promote the muscle tissue regeneration in situ.


Asunto(s)
Matriz Extracelular/química , Músculo Esquelético/crecimiento & desarrollo , Ingeniería de Tejidos , Andamios del Tejido/química , Animales , Diferenciación Celular/genética , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Colágeno/química , Colágeno/farmacología , Matriz Extracelular/trasplante , Células Madre Mesenquimatosas/citología , Desarrollo de Músculos/efectos de los fármacos , Músculo Esquelético/trasplante , Conejos
9.
Methods ; 171: 68-76, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31299290

RESUMEN

Chronic non-healing wounds are detrimental for the quality of life of the affected individuals and represent a major burden for the health care systems. Adipose-derived stem cells (ASCs) are being investigated for the development of novel treatments of chronic wounds, as they have shown several positive effects on wound healing. While these effects appear to be mediated by the release of soluble factors, it is has also become apparent that the extracellular matrix (ECM) deposited by ASCs is essential in several phases of the wound healing process. In this work, we describe an approach to produce ECM scaffolds derived from ASCs in culture. Upon growth of ASCs into an overconfluent cell layer, a detergent-based cell extraction approach is applied to remove the cellular components. The extraction is followed by an enzymatic treatment to remove the residual DNA. The resultant cell-derived scaffolds are depleted of cellular components, display low DNA remnant, and retain the native fibrillar organization of the ECM. Analysis of the molecular composition of the ECM scaffolds revealed that they are composed of collagens type I and III, and fibronectin. The decellularized scaffolds represent a substrate that supports adhesion and proliferation of primary human fibroblasts and dermal microvascular endothelial cells, indicating their potential as platforms for wound healing studies.


Asunto(s)
Células Madre Mesenquimatosas/citología , Ingeniería de Tejidos , Andamios del Tejido/química , Cicatrización de Heridas/efectos de los fármacos , Adipocitos/citología , Tejido Adiposo/citología , Tejido Adiposo/trasplante , Animales , Células Endoteliales/citología , Células Endoteliales/trasplante , Matriz Extracelular/química , Matriz Extracelular/trasplante , Fibroblastos/efectos de los fármacos , Fibronectinas/química , Humanos , Células Madre Mesenquimatosas/química , Calidad de Vida
10.
Methods ; 171: 28-40, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31394166

RESUMEN

Decellularised tissues and organs have been successfully used in a variety of tissue engineering/regenerative medicine applications. Because of the complexity of each tissue (size, porosity, extracellular matrix (ECM) composition etc.), there is no standardised protocol and the decellularisation methods vary widely, thus leading to heterogeneous outcomes. Physical, chemical, and enzymatic methods have been developed and optimised for each specific application and this review describes the most common strategies utilised to achieve decellularisation of soft and hard tissues. While removal of the DNA is the primary goal of decellularisation, it is generally achieved at the expense of ECM preservation due to the harsh chemical or enzymatic processing conditions. As denaturation of the native ECM has been associated with undesired host responses, decellularisation conditions aimed at effectively achieving simultaneous DNA removal and minimal ECM damage will be highlighted. Additionally, the utilisation of decellularised matrices in regenerative medicine is explored, as are the most recent strategies implemented to circumvent challenges in this field. In summary, this review focusses on the latest advancements and future perspectives in the utilisation of natural ECM for the decoration of synthetic porous scaffolds.


Asunto(s)
Regeneración Ósea/genética , Matriz Extracelular/química , Ingeniería de Tejidos , Andamios del Tejido/química , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , ADN/efectos de los fármacos , Matriz Extracelular/trasplante , Humanos , Ligamentos/efectos de los fármacos , Ligamentos/crecimiento & desarrollo , Medicina Regenerativa/normas , Tendones/efectos de los fármacos , Tendones/crecimiento & desarrollo , Andamios del Tejido/normas
11.
Arthroscopy ; 37(5): 1512-1521, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33539978

RESUMEN

PURPOSE: To determine the short-term outcomes following microfracture augmented with cartilage allograft extracellular matrix for the treatment of symptomatic focal cartilage defects of the adult knee. METHODS: Forty-eight patients enrolled by 8 surgeons from 8 separate institutions were included in this study. Patients underwent microfracture augmented by cartilage allograft extracellular matrix (BioCartilage; Arthrex, Naples, FL) and were followed at designated time points (3, 6, 12, and 24 months) to assess patient-reported outcomes (PROs), clinically significant outcomes (CSOs), and failure and complication rates. Magnetic resonance imaging (MRI) was offered at 2 years postoperatively regardless of symptomatology, and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score was documented. RESULTS: PRO compliance was 81.3% at 6 months, 72.9% at 12 months, and 47.9% at 2 years. All joint-specific and function-related PROs significantly improved compared to baseline at 3, 6, 12, 18, and 24 months of follow-up (P < .01), apart from Marx activity scale, which demonstrated a significant decline in postoperative scores at 2 years (P = .034). The percentage of patients achieving CSOs (as defined for microfracture) at 2 years was 90% for minimal clinically important difference and 85% for patient acceptable symptomatic state. Patient factors including age, sex, body mass index, symptoms duration, smoking, presence of a meniscal tear, lesion size, and location were not associated with CSO achievement at 2 years. One patient (2.1%) failed treatment 9.5 months postoperatively due to graft delamination and required a reoperation consisting of arthroscopic debridement. One complication (2.1%) consisting of complaints of clicking, grinding, and crepitus 15 months following the index procedure was reported. Two-year postoperative MRI demonstrated a mean 40.5 ± 22.9 MOCART 2.0 score. CONCLUSIONS: In this preliminary study, we found cartilage allograft extracellular matrix to be associated with improvement in functional outcomes, high rates of CSO achievement, and low failure and complication rates at 2-year follow-up. LEVEL OF EVIDENCE: Level III, prospective multicenter cohort study.


Asunto(s)
Aloinjertos/trasplante , Cartílago Articular/cirugía , Matriz Extracelular/trasplante , Fracturas por Estrés/patología , Articulación de la Rodilla/patología , Articulación de la Rodilla/cirugía , Adulto , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Fracturas por Estrés/diagnóstico por imagen , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Medición de Resultados Informados por el Paciente , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Resultado del Tratamiento
12.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-33803231

RESUMEN

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.


Asunto(s)
Células de la Médula Ósea/metabolismo , Médula Ósea/metabolismo , Matriz Extracelular , Medicina Regenerativa , Matriz Extracelular/metabolismo , Matriz Extracelular/trasplante , Humanos
13.
Artif Organs ; 44(4): E161-E171, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31609006

RESUMEN

Chronic and acute tendon injuries are frequent afflictions, for which treatment is often long and unsatisfactory. When facing extended injuries, matrices and scaffolds with sufficient biomechanical properties are required for surgical repair and could additionally serve as supports for cellular therapies to improve healing. In this study, protocols of either commonly used detergents only (SDS 1%, Triton 1%, TBP 1%, and Tween-20 1%) or a combination of freeze/thaw (F/T) cycles with decellularization agents (NaCl 1M, ddH2 O) were evaluated for the decellularization of horse equine superficial digital flexor tendon (SDFT) for hand flexor or extensor tendon reconstruction. Decellularization efficiency was assessed microscopically by histological staining (HE, DAPI) and DNA quantification. Macroscopical structure and biomechanical integrity of the tendon matrices were further assessed by gross observation, histological staining (SR), and mechanical testing (ultimate strain and stress, Young's modulus, energy to failure) for select protocols. Decellularization with hypertonic NaCl 1M in association with F/T cycles produced the most robust tendon matrices, which were nontoxic after 10 days for subsequent recellularization with human fetal progenitor tendon cells (hFPTs). This standardized protocol uses a less aggressive decellularization agent than current practice, which allows subsequent reseeding with allogenic cells, therefore making them very suitable and bioengineered tendon matrices for human tendon reconstruction in the clinic.


Asunto(s)
Matriz Extracelular/trasplante , Tendones , Andamios del Tejido , Animales , Fenómenos Biomecánicos , Células Madre Fetales/trasplante , Congelación , Caballos , Humanos , Ensayo de Materiales , Cloruro de Sodio , Traumatismos de los Tendones/cirugía
14.
Artif Organs ; 44(4): E136-E149, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31660625

RESUMEN

Cartilage extracellular matrix contains antiadhesive and antiangiogenic molecules such as chondromodulin-1, thrombospondin-1, and endostatin. We have aimed to develop a cross-linked cartilage acellular matrix (CAM) barrier for peritendinous adhesion prevention. CAM film was fabricated using decellularized porcine cartilage tissue powder and chemical cross-linking. Biochemical analysis of the film showed retention of collagen and glycosaminoglycans after the fabrication process. Physical characterization of the film showed denser collagen microstructure, increased water contact angle, and higher tensile strength after cross-linking. The degradation time in vivo was 14 d after cross-linking. The film extract and film surface showed similar cell proliferation, while inhibiting cell migration and cell adhesion compared to standard media and culture plate, respectively. Application of the film after repair resulted in similar tendon healing and significantly less peritendinous adhesions in a rabbit Achilles tendon injury model compared to repair only group, demonstrated by histology, ultrasonography, and biomechanical testing. In conclusion, the current study developed a CAM film having biological properties of antiadhesion, together with biomechanical properties and degradation profile suitable for prevention of peritendinous adhesions.


Asunto(s)
Matriz Extracelular/trasplante , Traumatismos de los Tendones/cirugía , Adherencias Tisulares/prevención & control , Animales , Reactivos de Enlaces Cruzados , Matriz Extracelular/ultraestructura , Glutaral , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Ratones , Conejos , Porcinos , Andamios del Tejido
15.
Artif Organs ; 44(12): e532-e551, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32671848

RESUMEN

The development of pancreatic extracellular matrices enriched with insulin-secreting ß-cells is a promising tissue engineering approach to treat type 1 diabetes. However, its long-term therapeutic efficacy is restricted by the defensive mechanism of host immune response and the lack of developed vascularization as appropriate after transplantation. Platelet-rich plasma (PRP), as an autologous platelet concentrate, contains a large number of active factors that are essential for the cell viability, vascularization, and immune regulation. In this study, we have incorporated pancreatic extracellular matrix (PEM) with PRP to develop a three-dimensional (3D) injectable PEM-PRP hydrogel to coculture and transplant rat insulinoma cells (INS-1) and human umbilical vein endothelial cells (HUVECs). Results from this study demonstrated that PEM-PRP hydrogel mimicked the biochemical compositions of native extracellular matrices, and possessed the enhanced elastic modulus and resistance to enzymatic degradation that enabled biomaterials to maintain its volume and slowly degrade. Additionally, PEM-PRP hydrogel could release growth factors in a sustained manner. In vitro, PEM-PRP hydrogel significantly promoted the viability, insulin-secreting function, and insulin gene expression of gel encapsulated INS-1 cells. Moreover, HUVECs encapsulated in PEM-PRP hydrogel were found to constitute many lumen-like structures and exhibited high expression of proangiogenic genes. In vivo transplantation of PEM-PRP hydrogel encapsulated with INS-1 cells and HUVECs improved the viability of INS-1 cells, promoted vascularization, inhibited the host inflammatory response, and reversed hyperglycemia of diabetic rats. Our study suggests that the PEM-PRP hydrogel offers excellent biocompatibility and proangiogenic property, and may serve as an effective biomaterial platform to maintain the long-term survival and function of insulin-secreting ß cells.


Asunto(s)
Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/terapia , Matriz Extracelular/trasplante , Hidrogeles/administración & dosificación , Plasma Rico en Plaquetas , Ingeniería de Tejidos/métodos , Animales , Materiales Biocompatibles , Técnicas de Cultivo de Célula/métodos , Línea Celular Tumoral , Supervivencia Celular , Técnicas de Cocultivo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/patología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Insulina/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Ensayo de Materiales , Páncreas/citología , Páncreas/metabolismo , Páncreas/patología , Ratas , Estreptozocina/administración & dosificación , Estreptozocina/toxicidad
16.
Pediatr Cardiol ; 41(7): 1458-1465, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32607741

RESUMEN

Mitral valve replacement (MVR) in children under 2 years is associated with significant morbidity and mortality. Decellularized porcine intestinal submucosa is a commercially available formulation of an extracellular matrix (ECM) with an indication for cardiac tissue repair. The present study reports our experience using ECM cylinder valves in patients for MVR. A retrospective review of patients under 2 years who underwent ECM custom-made cylinder mitral valve (ECM-MV) replacement was performed. Clinical, demographic, operative and post-operative follow-up data, including serial echocardiographic data are presented. Eight patients (age 5.6 ± 1.6 months; weight: 6.0 ± 1.1 kg) were identified who underwent ECM-MVR. There was one in-hospital death and no major neurological events. Six patients underwent replacement of their cylinder valve with either a Melody valve inside the ECM-MVR (n = 3), a mechanical valve (n = 2), or a decellularized bovine pericardial cylinder valve (n = 1). The mean time to replacement surgery was 8.4 ± 2.6 months after ECM-MV. The indications for replacement of ECM-MV included mitral stenosis/regurgitation (n = 4) or dehiscence (n = 2). One remaining patient is 24 months from ECM-MV, with trivial regurgitation and no stenosis. Mitral valve creation using ECM is an option for MVR in pediatrics, avoiding anticoagulation, and provides a suitable construct for later placement of a Melody valve, extending surgical and non-surgical options. However, the durability of the native ECM-MV in the mitral position is concerning considering the high re-intervention rate in a relatively short time period. Further studies are needed to determine the longer-term outcomes of this valve in this complex patient population.


Asunto(s)
Implantación de Prótesis de Válvulas Cardíacas/métodos , Insuficiencia de la Válvula Mitral/cirugía , Estenosis de la Válvula Mitral/cirugía , Ecocardiografía , Matriz Extracelular/trasplante , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
17.
J Shoulder Elbow Surg ; 29(12): e478-e490, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32713662

RESUMEN

INTRODUCTION: Extracellular matrix (ECM) gels have shown efficacy for the treatment of damaged tissues, most notably cardiac muscle. We hypothesized that the ECM gel prepared from skeletal muscle could be used as a treatment strategy for fatty shoulder cuff muscle degeneration. METHODS: We conducted experiments to (1) evaluate host biocompatibility to ECM gel injection using a rat model and (2) examine the effect of ECM gel injection on muscle recovery after delayed repair of a released supraspinatus (SSP) tendon using a rabbit model. RESULTS: The host biocompatibility to the ECM gel was characterized by a transient rise (first 2 weeks only) in several genes associated with macrophage infiltration, matrix deposition, and inflammatory cytokine production. By 8 weeks all genes had returned to baseline levels and no evidence of fibrosis or chronic inflammation was observed from histology. When gel injection was combined with SSP tendon repair, we observed a significant reduction (7%) in SSP muscle atrophy (24 + 3% reduction from uninjured) when compared with treatment with tendon repair only (31 + 7% reduction). Although fatty degeneration was elevated in both treatment groups, fat content trended lower (2%) in response to combined tendon repair and intramuscular ECM injection (4.1 + 2.1%) when compared with tendon repair only (6.1 + 2.9%). Transcriptome analysis revealed adipogenesis and osteoarthritis pathway activation in the repair only group. These key pathways were abrogated in response to treatment using combined repair plus gel. DISCUSSION: The findings suggest that ECM injection had a modest but positive effect on muscle mass, fatty degeneration, and key cellular signaling pathways.


Asunto(s)
Matriz Extracelular , Atrofia Muscular/terapia , Lesiones del Manguito de los Rotadores/terapia , Tejido Adiposo/patología , Animales , Modelos Animales de Enfermedad , Matriz Extracelular/trasplante , Geles/administración & dosificación , Inyecciones Intramusculares , Masculino , Ensayo de Materiales , Músculo Esquelético/patología , Atrofia Muscular/diagnóstico , Atrofia Muscular/patología , Atrofia Muscular/cirugía , Conejos , Ratas , Ratas Sprague-Dawley , Manguito de los Rotadores/patología , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/diagnóstico , Lesiones del Manguito de los Rotadores/patología , Lesiones del Manguito de los Rotadores/cirugía , Tenodesis
18.
Artif Organs ; 43(3): 278-287, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30374978

RESUMEN

This study introduces an implantable scaffold-free cartilage tissue construct (SF) that is composed of chondrocytes and their self-produced extracellular matrix (ECM). Chondrocytes were grown in vitro for up to 5 weeks and subjected to various assays at different time points (1, 7, 21, and 35 days). For in vivo implantation, full-thickness defects (n = 5) were manually created on the trochlear groove of the both knees of rabbits (16-week old) and 3 week-cultured SF construct was implanted as an allograft for a month. The left knee defects were implanted with 1, 7, and 21 days in vitro cultured scaffold-free engineered cartilages. (group 2, 3, and 4, respectively). The maturity of the engineered cartilages was evaluated by histological, chemical and mechanical assays. The repair of damaged cartilages was also evaluated by gross images and histological observations at 4, 8, and 12 weeks postsurgery. Although defect of groups 1, 2, and 3 were repaired with fibrocartilage tissues, group 4 (21 days) showed hyaline cartilage in the histological observation. In particular, mature matrix and columnar organization of chondrocytes and highly expressed type II collagen were observed only in 21 days in vitro cultured SF cartilage (group 4) at 12 weeks. As a conclusion, cartilage repair with maturation was recapitulated when implanted the 21 day in vitro cultured scaffold-free engineered cartilage. When implanting tissue-engineered cartilage, the maturity of the cartilage tissue along with the cultivation period can affect the cartilage repair.


Asunto(s)
Enfermedades de los Cartílagos/cirugía , Cartílago Articular/cirugía , Cultivo Primario de Células/métodos , Ingeniería de Tejidos/métodos , Animales , Enfermedades de los Cartílagos/patología , Cartílago Articular/citología , Cartílago Articular/lesiones , Cartílago Articular/patología , Condrocitos/trasplante , Modelos Animales de Enfermedad , Matriz Extracelular/trasplante , Humanos , Masculino , Conejos , Resultado del Tratamiento
19.
Thorac Cardiovasc Surg ; 67(1): 44-49, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29078233

RESUMEN

BACKGROUND: Comparing the structural changes, and local host reactions to CorMatrix (CorMatrix Cardiovascular Inc., Roswell, Georgia, United States) and different biomaterials implanted subcutaneously in growing pig model. METHODS: Four pigs harboring implanted patches of CorMatrix, Vascutek porcine pericardium (Vascutek; Scotland, United Kingdom), SJM bovine pericardium (St. Jude Medical, Inc., Minnesota, United States), and Gore-Tex (W. L. Gore & Associates GmbH, Flagstaff, Arizona, United States) were studied for 1, 3, 6, and 12 months. The explants were examined histologically. RESULTS: CorMatrix showed gradual and consistent patch resorption and subsiding inflammatory and fibrosis process. Full scaffold degradation and replacement by mild fibrosis and subcutaneous tissue were seen by 1 year. Xenopericardial patches remained intact, and the initially severe inflammatory and fibrotic reactions reduced gradually to moderate fibrosis and chronic inflammation. Gore-Tex showed foreign body reaction. CONCLUSIONS: Patches were biotolerated by pigs. Xenopericardial patches elicited encapsulating fibrosis and no remodeling. CorMatrix resorbs completely and degrades consistently without leaving residues. Lack of encapsulating fibrosis toward CorMatrix allows tissue ingrowth and matrix remodeling.


Asunto(s)
Materiales Biocompatibles/toxicidad , Procedimientos Quirúrgicos Cardíacos/instrumentación , Matriz Extracelular/trasplante , Reacción a Cuerpo Extraño/etiología , Membranas Artificiales , Pericardio/trasplante , Politetrafluoroetileno/toxicidad , Tejido Subcutáneo/cirugía , Factores de Edad , Aloinjertos , Animales , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Bovinos , Reacción a Cuerpo Extraño/metabolismo , Reacción a Cuerpo Extraño/patología , Xenoinjertos , Tejido Subcutáneo/metabolismo , Tejido Subcutáneo/patología , Porcinos , Porcinos Enanos , Factores de Tiempo
20.
Ophthalmic Plast Reconstr Surg ; 35(5): e122-e124, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31503171

RESUMEN

The aim of exenteration reconstruction is to stabilize the postsurgical wound bed to promote expeditious healing particularly in patients who are undergoing adjuvant radiation and/or chemotherapy. Porcine urinary bladder matrix has previously been used successfully as a wound-healing scaffold in treatment of burns and in acute, chronic, and surgical wounds, but the use of these products has not previously been reported in the exenterated orbit. The authors present a case of the novel use of porcine urinary bladder matrix in a pediatric patient who underwent exenteration for recurrent embryonal rhabdomyosarcoma, subsequent split-thickness skin grafting, and adjuvant radiation.


Asunto(s)
Evisceración Orbitaria , Neoplasias Orbitales/cirugía , Rabdomiosarcoma/cirugía , Vejiga Urinaria , Animales , Niño , Matriz Extracelular/trasplante , Humanos , Masculino , Porcinos
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