Tissue engineering; drug delivery; gene therapy; biomaterials; islet; ovarian follicles; nerve regeneration

Tissue engineering is an emerging field that aims to provide functional tissue replacements for injury or disease that results in tissue loss or organ failure. The strategy combines cells, synthetic polymer scaffolds, and various bioactive factors to mimic the natural conditions that lead to tissue formation. My research group seeks to direct cellular responses and subsequent tissue formation through molecular manipulation of the cellular microenvironment. The design and fabrication of these environments may ultimately lead to novel therapeutic strategies within tissue engineering and beyond. Current translational applications focus on developing scaffolds for ovarian follicle maturation, islet transplantation, and nerve regeneration.

We develop three-dimensional scaffolds that present specific signals, or combinations of signals, and examine cellular responses. These scaffolds provide a three-dimensional structure that defines a space, and supports cell adhesion. Signals are presented in various forms, such as the delivery of genes and growth factors within the scaffold or attachment of molecules to the polymer surface. Of particular interest is the delivery of DNA encoding for therapeutic proteins, such as tissue inductive factors. Creating these biomimetic environments utilizes a variety of techniques, such as polymer processing, chemistry, cell and tissue culture, molecular biology, and animal models.

Strategies to enhance tissue formation are developed based on a fundamental understanding of cellular responses to specific signals. Polymer scaffolds may enhance natural tissue regeneration by delivering the appropriate signals or by serving as cell transplantation vehicles. Tissue formation and development is quantified both macroscopically (e.g., mechanical properties) and at the molecular level (e.g., gene expression). This approach of relating tissue development to molecular design of the scaffold may ultimately lead to the formation of engineered tissues that could provide alternatives to whole organ or tissue transplantation.

Jang, J.H., C.B Rives, and L.D. Shea, "Plasmid delivery in vivo from porous tissue-engineering scaffolds: Transgene expression and cellular transfection", Mol. Ther 12(3) 475-83, 2005.

Kreeger, P.K. N.N. Fernandes, T. K. Woodruff, and L.D. Shea, "Regulation of Murine Follicle Development by Follicle Stimulating Hormone in a Three-Dimensional In Vitro Culture System is Dependent on Follicle Stage and Dose" Biol. Reprod 73(5):942-50, 2005.

Bengali, Z., and L.D. Shea, "Gene Delivery by Immobilization to Cell-Adhesive Substrates", MRS Bulletin 2005.

Pannier, A.K. BC. Anderson, and L.D. Shea "Substrate-Mediated Delivery from Self-Assembled Monolayers: Effect of Surface Ionization, Hydrophilicity, and Patterning", Acta Biomat. 1(5), 511-522, 2005.

Whittlesey, K.J., and L.D. Shea, Neurotrophic factor expression by degradable scaffold-mediated lipofection" Biomaterials 27 (11): 2477-86 2006.

Kreeger, P.K., J.W. Deck, T.K. Woodruff, and L.D. Shea, "Extracellular Matrix Regulation of Follicle Development in an In Vitro Culture System", Biomat 27 (5): 714-23, 2006.

De Laporte, L., J. Cruz-Rea, L.D. Shea "Modular non-viral vectors for gene delivery", 27:947-954, 2006.

Jang, J.H., T. Houchin, Z. Bengali, and L.D. Shea. "Surface adsorption of DNA to tissue engineering scaffolds for efficient gene delivery" J Biomed Mater Res A. 77(1):50-8 2006.

Salvay, D., and L.D. Shea, "Inductive tissue engineering by protein and DNA releasing scaffolds", Mol Biosyst 2(1) 36-48 2006.

H. Blomeier, X. Zhang, C. Rives, E. Hughes, M Baker, M. Brissova, A.C. Powers, D.B. Kaufman, L.D. Shea, W.L. Lowe, Jr.," Polymer Scaffolds as Synthetic Microenvironments for Extrahepatic Islet Transplantation", Transplantation 82(4) 452-9 2006.

Jang, J.H., L.D. Shea, "Intramuscular delivery of DNA releasing microspheres: microsphere properties and transgene expression" J Control Release. 112(1):120-8. 2006.

Nieman CL, R Kazer, RE Brannigan, LS Zoloth, PL Chase-Lansdale, K, Kinahan, KJ Dilley, D. Roberts, LD Shea, TK Woodruff. "Cancer survivors and infertility: a review of a new problem and novel answers" J Support Oncol. Apr;4(4):171-8, 2006

Xu, M., P.K. Kreeger, L.D. Shea, and T.K. Woodruff, "Tissue Engineered Follicles Produce Live, Fertile Offspring", Tissue Eng 2006.

Bristol-Gould, S.K., P.K. Kreeger, C.G. Selkirk, S.M. Kilen, K.E. Mayo, L.D. Shea and T.K. Woodruff, "Fate of the initial follicle pool: Empirical and mathematical evidence supporting its sufficiency for adult fertility" Dev. Biol. 298(1) 149-154, 2006.

Bristol-Gould, S.K., P.K. Kreeger, C.G. Selkirk, S.M. Kilen, R.W. Cook, J.L. Kipp, L.D. Shea, K.E. Mayo and T.K. Woodruff "Postnatal regulation of germ cells by activin: The establishment of the initial follicle pool" Dev. Biol. 298 (1) 132-148, 2006.

Berkholtz, C.B., B.E. Lai, T.K,Woodruff, L.D. Shea, "Distribution of extracellular matrix proteins type I collagen, type IV collagen, fibronectin, and laminin in mouse folliculogenesis." Histochem Cell Biol. 126(5) 583-92, 2006.

Berkholtz, C.B., L.D. Shea, and T.K. Woodruff, "Extracellular matrix functions in follicle maturation", Semin Reprod Med. 24(4) 262-9, 2006.

Xu, M., E. West, L.D. Shea, and T.K. Woodruff "Identification of a Stage-Specific Permissive in vitro Culture Environment For Follicle Growth and Oocyte Development", Biol Reprod. 2006.

Houchin, T.L., K.J. Whittlesey, and L.D. Shea, "Spatially Patterned Gene Delivery for Directed Neurite Outgrowth", Mol. Ther. 15(4) 705-712, 2007.

Houchin, T.L., L. Swift, J.H. Jang, and L.D. Shea, "Patterned PLG substrates for localized DNA delivery and directed neurite extension", Biomat. 28(16): 2603-11 2007.

De Laporte, L., and L.D. Shea "Matrices and Scaffolds for DNA Delivery in Tissue Engineering", in press Adv. Drug Del. Reviews.

Pannier, A.K., E. Ariazi, A.D. Bellis, Z. Bengali, V.C. Jordan, and L.D. Shea "Bioluminescence Imaging for Assessment and Normalization in Transfected Cell Arrays", in press Biotech and Bioeng.

Bengali, Z. and L.D. Shea "Gene Expression and internalization following vector immobilization to proteins: dependence on protein identity and density" in press J Gene Med.

View all publications by publications by Lonnie D. Shea listed in the National Library of Medicine (PubMed).