Michael Shin

Massachusetts General Hospital, Boston, Massachusetts, United States

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Publications (9)22.47 Total impact

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    ABSTRACT: Tissue engineering has been proposed as an approach to alleviate the shortage of donor tissue and organs by combining cells and a biodegradable scaffold as a temporary extracellular matrix. While numerous scaffold fabrication methods have been proposed, tissue formation is typically limited to the surface of the scaffolds in bone tissue engineering applications due to early calcification on the surface. To improve tissue formation, a novel scaffold with a hierarchical interconnected pore structure on two distinct length scales has been developed. Here we present the fabrication process and the application of the scaffold to bone tissue engineering. Porous poly(lactide-co-glycolide) (PLGA) scaffolds were made by combining solvent casting/particulate leaching with heat fusion. Porcine bone marrow-derived mesenchymal stem cells (MSCs) were differentiated into osteoblasts and cultured on these scaffolds in vitro for 2, 4, and 6 weeks. Subsequently, the constructs were assessed using histology and scanning electron microscopy. The bone marrow-derived osteoblasts attached well on these scaffolds. Cells were observed throughout the scaffolds. These initial results show promise for this scaffold to aid in the regeneration of bone.
    Journal of Biomedical Materials Research Part A 03/2008; 84(3):702-9. DOI:10.1002/jbm.a.31392 · 2.83 Impact Factor
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    Biomedical Microdevices 08/2006; 8(3):271-271. DOI:10.1007/s10544-006-9598-x · 2.77 Impact Factor
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    ABSTRACT: Cardiac tissue engineering has been proposed as a treatment to repair impaired hearts. Bioengineered cardiac grafts are created by combining autologous cell transplantation with a degradable scaffold as a temporary extracellular matrix. Here we present a system for engineered myocardium combining cultured cardiomyocytes and a novel biodegradable scaffold with a unique extracellular matrix-like topography. Cardiomyocytes were harvested from neonatal rats and cultured in vitro on biodegradable electrospun nanofibrous poly(epsilon-caprolactone) meshes. Between days 5 and 7, the meshes were overlaid to construct 3-dimensional cardiac grafts. On day 14 of in vitro culture, the engineered cardiac grafts were analyzed by means of histology, immunohistochemistry, and scanning electron microscopy. The cultured cardiomyocytes attached well to the meshes, and strong beating was observed throughout the experimental period. The average fiber diameter of the scaffold is about 250 nm, well below the size of an individual cardiomyocyte. Hence the number of cell-cell contacts is maximized. Constructs with up to 5 layers could be formed without any incidence of core ischemia. The individual layers adhered intimately. Morphologic and electrical communication between the layers was established, as verified by means of histology and immunohistochemistry. Synchronized beating was also observed. This report demonstrates the formation of thick cardiac grafts in vitro and the versatility of biodegradable electrospun meshes for cardiac tissue engineering. It is envisioned that cardiac grafts with clinically relevant dimensions can be created by using this approach and combining it with new technologies to induce vascularization.
    The Journal of thoracic and cardiovascular surgery 12/2005; 130(5):1358-63. DOI:10.1016/j.jtcvs.2005.05.048 · 3.41 Impact Factor
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    ABSTRACT: One key challenge in regenerating vital organs is the survival of transplanted cells. To meet their metabolic requirements, transport by diffusion is insufficient, and a convective pathway, i.e., a vasculature, is required. Our laboratory pioneered the concept of engineering a vasculature using microfabrication in silicon and Pyrex. Here we report the extension of this concept and the development of a methodology to create an endothelialized network with a vascular geometry in a biocompatible polymer, poly(dimethyl siloxane) (PDMS). High-resolution PDMS templates were produced by replica-molding from micromachined silicon wafers. Closed channels were formed by bonding the patterned PDMS templates to flat PDMS sheets using an oxygen plasma. Human microvascular endothelial cells (HMEC-1) were cultured for 2 weeks in PDMS networks under dynamic flow. The HMEC-1 cells proliferated well in these confined geometries (channel widths ranging from 35 mum to 5 mm) and became confluent after four days. The HMEC-1 cells lined the channels as a monolayer and expressed markers for CD31 and von Willebrand factor (vWF). These results demonstrate that endothelial cells can be cultured in confined geometries, which is an important step towards developing an in vitro vasculature for tissue-engineered organs.
    Biomedical Microdevices 01/2005; 6(4):269-78. DOI:10.1023/B:BMMD.0000048559.29932.27 · 2.77 Impact Factor
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    ABSTRACT: Maxillofacial reconstructive procedures often require bone graft harvesting, which results in donor site morbidity; the use of tissue-engineered bone would eliminate this problem. In this study, a novel scaffold design and new fabrication protocol were used to produce autologous tissue-engineered constructs (scaffolds seeded with cells) to reconstruct segmental mandibular defects in a minipig model. Porcine mesenchymal stem cells were isolated from the ilium. They were expanded in culture and seeded onto poly-dl-lactic-coglycolic acid scaffolds. The constructs were placed in a bioreactor and incubated for 10 days in medium and osteogenic supplements. Four full-thickness bony defects (2 x 2 cm) were created in the same pig's mandible. The constructs (n = 2) were placed into 2 of the defects as autologous grafts. One unseeded scaffold and 1 empty defect served as controls. At 6 weeks postimplantation, the pig was sacrificed, the mandible was harvested, and the grafted sites were evaluated by clinical, radiographic, and histologic methods. The construct-implanted defects appeared to be filled with hard tissue resembling bone, whereas controls were filled with fibrous tissue. Radiographically, the tissue-engineered constructs were uniformly radiodense with bone distributed throughout. The interface between native bone and constructs was indistinct. Complete bone ingrowth was not observed in control defects. Osteoblasts, osteocytes, bone trabeculae, and blood vessels were identified throughout the defects implanted with constructs. This "proof-of-principle" study indicates that porcine mandibular defects can be successfully reconstructed by in vitro cultured autologous porcine mesenchymal stem cells on a biodegradable polymer scaffold with penetration of bone and blood vessels.
    Journal of Oral and Maxillofacial Surgery 06/2004; 62(5):601-6. DOI:10.1016/j.joms.2003.11.010 · 1.28 Impact Factor
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    ABSTRACT: The objective of this study was to assess bone formation from mesenchymal stem cells (MSCs) on a novel nanofibrous scaffold in a rat model. A highly porous, degradable poly(epsilon-caprolactone) (PCL) scaffold with an extracellular matrix-like topography was produced by electrostatic fiber spinning. MSCs derived from the bone marrow of neonatal rats were cultured, expanded, and seeded on the scaffolds. The cell-polymer constructs were cultured with osteogenic supplements in a rotating bioreactor for 4 weeks, and subsequently implanted in the omenta of rats for 4 weeks. The constructs were explanted and characterized by histology, immunohistochemistry, and scanning electron microscopy. The constructs maintained the size and shape of the original scaffolds. Morphologically, the constructs were rigid and had a bone-like appearance. Cells and extracellular matrix (ECM) formation were observed throughout the constructs. In addition, mineralization and type I collagen were also detected. This study establishes the ability to develop bone grafts on electrospun nanofibrous scaffolds in a well-vascularized site using MSCs.
    Tissue Engineering 01/2004; 10(1-2):33-41. DOI:10.1089/107632704322791673 · 4.25 Impact Factor
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    ABSTRACT: The objective of this study is to assess the feasibility of creating a tissue engineered stomach using isolated stomach epithelium organoid unit from syngeneic adult donors and a biodegradable polymer scaffold in a rat model. Despite recent advances in reconstruction techniques, total gastrectomy is still accompanied by various complications. As an alternative treatment, a tissue engineered stomach that replaces the mechanical and metabolic functions of a normal stomach is proposed. Stomach epithelium organoid units were isolated from syngeneic adult rats and seeded onto biodegradable polymers. These constructs were implanted into the omenta of recipient adult rats. All constructs were harvested for histologic and immunohistochemical examination at designated time points. Cyst-like structures were formed that showed the development of vascularized tissue with a neomucosa. Immunohistochemical staining for alpha-actin smooth muscle, gastric mucin, and proton pump indicated the presence of a smooth muscle layer and gastric epithelium, as well as the existence of parietal cells of the stomach mucosa, respectively. Epithelium derived stomach organoid units seeded on biodegradable polymers were transplanted in donor rats and have been shown to vascularize, survive, and regenerate into complex tissue resembling a native stomach. These initial results are encouraging, and studies are currently underway to further assess this approach.
    ASAIO Journal 01/2004; 50(5):468-72. DOI:10.1097/01.MAT.0000138579.25835.F5 · 1.39 Impact Factor
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    ABSTRACT: Despite recent advances in reconstruction techniques, total gastrectomy is still accompanied by various complications. As an alternative treatment, we propose a tissue-engineered stomach that replaces the mechanical and metabolic functions of a normal stomach. The objective of this study was to demonstrate the function of a tissue-engineered stomach as a replacement of the native stomach. Tissue-engineered stomachs were formed in recipient rats from stomach epithelium organoid units isolated from neonatal donor rats. After 12 weeks, the animals underwent a second operation for replacement of the native stomachs. Tissue-engineered stomachs were successfully used as a substitute of the native stomach in a rat model. An upper gastrointestinal tract study revealed no evidence of bowel stenosis or obstruction at both anastomosis sites. Histologically, the tissue-engineered stomachs had well-developed vascularized tissue with a neomucosa continuously lining the lumen and stratified smooth muscle layers. Immunohistochemical staining for alpha-actin smooth muscle showed that the smooth muscle layers were arranged in a regular fashion. Scanning electron microscopy showed that the surface topography of the tissue-engineered stomachs resembled that of native stomachs. It has been demonstrated that a tissue-engineered stomach can replace a native stomach in a rat model. Replacement of the native stomach by a tissue-engineered stomach had beneficial effects on the formation of neomucosa and smooth muscle layers in the tissue-engineered stomach.
    Transplantation 08/2003; 76(1):61-5. DOI:10.1097/01.TP.0000068903.63554.1B · 3.78 Impact Factor
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