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Principal Investigator: Basak Elif Uygun
Organization: MASSACHUSETTS GENERAL HOSPITAL
Fiscal Year: 2024
Award: $356,378
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
ABSTRACT
Deformities created by birth defects, trauma, inflammation, and medical conditions including cancer
constitute a significant global health burden accounting for 11% of worldwide disability-adjusted life years and
can be corrected by reconstructive surgery. Standard reconstructive techniques include autologous, pedicled
or vascularized tissue flaps to replace moderate to severe composite tissue defects. Limitation of these
methods include donor-site morbidity and difficulty in shaping the graft to restore complex three-dimensional
anatomy. In the case of fasciocutaneous flaps, both factors are limiting – and a significant portion of such
defects cannot be treated with current techniques. In the longer term, Vascularized composite allografts
(VCAs) have potential to revolutionize the treatment of complex soft tissue absence by providing an
anatomically exact tissue unit enabling like-for-like restoration, but is impractical as long as the recipient
requires toxic immunosuppression which limited the number of VCA transplants to about 150 over the last 2
decades.
Our long-term goal is to engineer vascular composite allografts using patient specific cells for repairing
composite tissue defects. The goal of this project is to develop a novel protocol for creating fasciocutaneous
flaps (FCF) that are vascularized and blood compatible, which would provide a straightforward path to treating
some currently unfixable defects clinically in the short-term, while laying the groundwork for building more
complex tissues in the long term. The rationale of the study is that while most past biomaterials research has
focused on producing the ideal scaffold from the ground up using synthetic materials, the native extracellular
matrix (ECM), de facto contains much of necessary architecture and environmental cues absent from synthetic
matrices, and hence presents a promising, more realistic alternative approach for producing engineered tissue
substitutes, which can vertically advance the field of tissue engineering.
Terms: <3-D><3-Dimensional><3D><Accounting><Allografting><Anatomic Abnormality><Anatomic Sites><Anatomic structures><Anatomical Abnormality><Anatomy><Animal Model><Animal Models and Related Studies><Architecture><Autologous><Binding><Biomaterials Research><Birth Defects><Blood><Blood Reticuloendothelial System><Blood Vessels><Blood capillaries><Body Tissues><CAT scan><CT X Ray><CT Xray><CT imaging><CT scan><Cancers><Cell Attachment><Cell Body><Cell Density><Cell fusion><Cell-Extracellular Matrix><Cell-Matrix Adhesions><Cell-Matrix Junction><Cells><Cellular Expansion><Cellular Growth><Chemicals><Clinic><Clinical><Clinical Trials><Cold-Insoluble Globulins><Complex><Computed Tomography><Congenital Abnormality><Congenital Anatomical Abnormality><Congenital Defects><Congenital Deformity><Congenital Malformation><Cues><DALY><Data><Defect><Deformity><Dermal><Development><ECM><Elastin><Endothelial Cells><Endothelium><Engineering><Engineering / Architecture><Environment><Extracellular Matrix><Extravasation><FN1><Face><Feedback><Fibroblasts><Fibronectin 1><Fibronectins><Generalized Growth><Goals><Growth><Growth Agents><Growth Factor><Growth Substances><Histologic><Histologically><Histology><Immune><Immunes><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Inflammation><LETS Proteins><Large External Transformation-Sensitive Protein><Leakage><Legal patent><Liquid substance><Malignant Neoplasms><Malignant Tumor><Medical><Methods><Modeling><Molecular><Molecular Interaction><Morbidity><Morbidity - disease rate><Opsonic Glycoprotein><Opsonic alpha(2)SB Glycoprotein><Patents><Patients><Peptides><Physiologic><Physiological><Population><Proliferating><Proteins Growth Factors><Protocol><Protocols documentation><Reconstructive Surgical Procedures><Research><Safety><Scanning><Shapes><Site><Skin><Spillage><Structure><System><Techniques><Testing><Tissue Engineering><Tissue Growth><Tissues><Tomodensitometry><Transplantation><Trauma><Trees><Vascularization><Whole Blood><Work><X-Ray CAT Scan><X-Ray Computed Tomography><X-Ray Computerized Tomography><Xray CAT scan><Xray Computed Tomography><Xray computerized tomography><alpha 2-Surface Binding Glycoprotein><bioengineered tissue><blood perfusion><capillary><catscan><cell growth><cell type><clinical relevance><clinical translation><clinically relevant><clinically translatable><computed axial tomography><computer tomography><computerized axial tomography><computerized tomography><design><designing><developmental><disability-adjusted life years><dosage><engineered tissue><engineered vascular tissue><engineered vascularized tissue><ex vivo perfusion><faces><facial><fluid><global health><immune suppression><immune suppressive activity><immune suppressive function><immunogenicity><immunosuppressive activity><immunosuppressive function><immunosuppressive response><in vivo><keratinocyte><liquid><malignancy><model of animal><neoplasm/cancer><non-contrast CT><noncontrast CT><noncontrast computed tomography><novel><ontogeny><peptide aminoacid sequence><peptide sequence><protein aminoacid sequence><public health relevance><reconstruction surgery><reconstructive surgery><recruit><repair><repaired><restoration><scaffold><scaffolding><soft tissue><synergism><three dimensional><thrombogenesis><thrombogenicity><translational study><transplant><vascular><vascular tissue engineering>