



@article {3268,
	title = {Influence of the stiffness of three-dimensional alginate/collagen-I interpenetrating networks on fibroblast biology},
	journal = {Biomaterials},
	volume = {35},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {8927 - 8936},
	abstract = {Wound dressing biomaterials are increasingly being designed to incorporate bioactive molecules to promote healing, but the impact of matrix mechanical properties on the biology of resident cells orchestrating skin repair and regeneration remains to be fully understood. This study investigated whether tuning the stiffness of a model wound dressing biomaterial could control the behavior of dermal fibroblasts. Fully interpenetrating networks (IPNs) of collagen-I and alginate were fabricated to enable gel stiffness to be tuned independently of gel architecture, polymer concentration or adhesion ligand density. Three-dimensional cultures of dermal fibroblasts encapsulated within matrices of different stiffness were shown to promote dramatically different cell morphologies, and enhanced stiffness resulted in upregulation of key-mediators of inflammation such as IL-10 and COX-2. These findings suggest that simply modulating the matrix mechanical properties of a given wound dressing biomaterial deposited at the wound site could regulate the progression of wound healing. {\textcopyright} 2014 Elsevier Ltd.},
	keywords = {ECM (extracellular matrix), Inflammation, Interpenetrating networks (IPNs), Mechanical properties, Wound dressing biomaterial, Wound healing},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905723265\&partnerID=40\&md5=dc192cf150d9176075beca26ae5ded3f},
	author = {Branco da Cunha, C. and Klumpers, D.D. and Li, W.A. and Koshy, S.T. and Weaver, J.C. and Chaudhuri, O. and Granja, P.L. and Mooney, D.J.}
}
@article {3280,
	title = {Injectable MMP-sensitive alginate hydrogels as hMSC delivery systems},
	journal = {Biomacromolecules},
	volume = {15},
	year = {2014},
	note = {Cited By (since 1996):3Export Date: 21 November 2014},
	month = {2014},
	pages = {380 - 390},
	abstract = {Hydrogels with the potential to provide minimally invasive cell delivery represent a powerful tool for tissue-regeneration therapies. In this context, entrapped cells should be able to escape the matrix becoming more available to actively participate in the healing process. Here, we analyzed the performance of proteolytically degradable alginate hydrogels as vehicles for human mesenchymal stem cells (hMSC) transplantation. Alginate was modified with the matrix metalloproteinase (MMP)-sensitive peptide Pro-Val-Gly-Leu-Iso-Gly (PVGLIG), which did not promote dendritic cell maturation in vitro, neither free nor conjugated to alginate chains, indicating low immunogenicity. hMSC were entrapped within MMP-sensitive and MMP-insensitive alginate hydrogels, both containing cell-adhesion RGD peptides. Softer (2 wt \% alginate) and stiffer (4 wt \% alginate) matrices were tested. When embedded in a Matrigel layer, hMSC-laden MMP-sensitive alginate hydrogels promoted more extensive outward cell migration and invasion into the tissue mimic. In vivo, after 4 weeks of subcutaneous implantation in a xenograft mouse model, hMSC-laden MMP-sensitive alginate hydrogels showed higher degradation and host tissue invasion than their MMP-insensitive equivalents. In both cases, softer matrices degraded faster than stiffer ones. The transplanted hMSC were able to produce their own collagenous extracellular matrix, and were located not only inside the hydrogels, but also outside, integrated in the host tissue. In summary, injectable MMP-sensitive alginate hydrogels can act as localized depots of cells and confer protection to transplanted cells while facilitating tissue regeneration. {\textcopyright} 2013 American Chemical Society.},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84892606344\&partnerID=40\&md5=835c11a6460fa62bc6da4a189fd06b25},
	author = {Fonseca, K.B. and Gomes, D.B. and Lee, K. and Santos, S.G. and Sousa, A. and Silva, E.A. and Mooney, D.J. and Granja, P.L. and Barrias, C.C.}
}
@article {2322,
	title = {Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement},
	journal = {Proceedings of the National Academy of Sciences of the United States of AmericaProc. Natl. Acad. Sci. U. S. A.},
	volume = {106},
	year = {2009},
	note = {Cited By (since 1996): 48Export Date: 21 November 2012Source: ScopusCODEN: PNASAdoi: 10.1073/pnas.0808932106PubMed ID: 19126683Language of Original Document: EnglishCorrespondence Address: Mooney, D. J.; School of Engineering and Applied Sciences, Harvard University, 40 Oxford Street, Cambridge, MA 02138, United States; email: mooneyd@seas.harvard.eduChemicals/CAS: arginylglycylaspartic acid, 99896-85-2; interleukin 8, 114308-91-7; vasculotropin, 127464-60-2; Hydrogels; Integrins; Interleukin-8; Vascular Endothelial Growth Factor AReferences: Debnath, J., Brugge, J.S., Modelling glandular epithelial cancers in 3-dimensional cultures (2005) Nat Rev Cancer, 5, pp. 675-688;Wang, F., Reciprocal interactions between β1-integrin and epidermal growth factor receptor in 3-dimensional basement membrane breast cultures: A different perspective in epithelial biology (1998) Proc Natl Acad Sci USA, 95, pp. 14821-14826; 
Fischbach, C., Engineering tumors with 3D scaffolds (2007) Nat Methods, 4, pp. 855-860; 
Paszek, M.J., Tensional homeostasis and the malignant phenotype (2005) Cancer Cell, 8, pp. 241-254; 
Hanahan, D., Weinberg, R.A., The hallmarks of cancer (2000) Cell, 100, pp. 57-70; 
De, S., VEGF-integrin interplay controls tumor growth and vascularization (2005) Proc Natl Acad Sci USA, 102, pp. 7589-7594; 
Lowrie, A.G., Salter, D.M., Ross, J.A., Latent effects of fibronectin, α5β1 integrin, αvβ5 integrin, and the cytoskeleton regulate pancreatic carcinoma cell IL-8 secretion (2004) Br J Cancer, 91, pp. 1327-1334; 
Cukierman, E., Pankov, R., Stevens, D.R., Yamada, K.M., Taking cell matrix adhesions to the third dimension (2001) Science, 294, pp. 1708-1712; 
Rowley, J.A., Madlambayan, G., Mooney, D.J., Alginate hydrogels as synthetic extracellular matrix materials (1999) Biomaterials, 20, pp. 45-53; 
Lingen, M.W., Angiogenesis in the development of head and neck cancer and its inhibition by chemopreventive agents (1999) Crit Rev Oral Biol Med, 10, pp. 153-164; 
Fischbach, C., Mooney, D., Polymeric systems for bioinspired delivery of angiogenic molecules (2006) Adv Polym Sci, 203, pp. 191-221; 
Ruoslahti, E., Pierschbacher, M.D., New perspectives in cell adhesion: RGD and integrins (1987) Science, 238, pp. 491-497; 
Kong, H.J., Boontheekul, T., Mooney, D.J., Quantifying the relation between adhesion ligand-receptor bond formation and cell phenotype (2006) Proc Natl Acad Sci USA, 103, pp. 18534-18539; 
Harris, A.L., Hypoxia: A key regulatory factor in tumour growth (2002) Nat Rev Cancer, 2, pp. 38-47; 
Xu, L., Hypoxia-induced elevation in interleukin-8 expression by human ovarian carcinoma cells (1999) Cancer Res, 59, pp. 5822-5829; 
Weaver, V.M., Reversion of the malignant phenotype of human breast cells in three-dimensional cultureandin vivo by integrin-blocking antibodies (1997) J Cell Biol, 137, pp. 231-245; 
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De Larco, J.E., A potential role for interleukin-8 in the metastatic phenotype of breast carcinoma cells (2001) Am J Pathol, 158, pp. 639-646; 
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Esposito, I., Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma (2004) J Clin Pathol, 57, pp. 630-636; 
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Goerges, A.L., Nugent, M.A., Regulation of vascular endothelial growth factor binding and activity by extracellular pH (2003) J Biol Chem, 278, pp. 19518-19525; 
Kuschert, G.S., Identification of a glycosaminoglycan binding surface on human interleukin-8 (1998) Biochemistry, 37, pp. 11193-11201; 
Kerbel, R., Folkman, J., Clinical translation of angiogenesis inhibitors (2002) Nat Rev Cancer, 2, pp. 727-739; 
Fischbach, C., Mooney, D.J., Polymers for pro- and antiangiogenic therapy (2007) Biomaterials, 28, pp. 2069-2076; 
Alsberg, E., Engineering growing tissues (2002) Proc Natl Acad Sci USA, 99, pp. 12025-12030; 
Simmons, C.A., Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells (2004) Bone, 35, pp. 562-569; 
Comisar, W.A., Kazmers, N.H., Mooney, D.J., Linderman, J.J., Engineering RGD nanopatterned hydrogels to control preosteoblast behavior: A combined computational and experimental approach (2007) Biomaterials, 28, pp. 4409-4417; 
Alsberg, E., Regulating bone formation via controlled scaffold degradation (2003) J Dent Res, 82, pp. 903-908; 
Richardson, T.P., Peters, M.C., Ennett, A.B., Mooney, D.J., Polymeric system for dual growth factor delivery (2001) Nat Biotechnol, 19, pp. 1029-1034
},
	month = {2009///},
	pages = {399 - 404},
	abstract = {Three-dimensional culture alters cancer cell signaling; however, the underlying mechanisms and importance of these changes on tumor vascularization remain unclear. A hydrogel system was used to examine the role of the transition from 2D to 3D culture, with and without integrin engagement, on cancer cell angiogenic capability. Three-dimensional culture recreated tumor microenvironmental cues and led to enhanced interleukin 8 (IL-8) secretion that depended on integrin engagement with adhesion peptides coupled to the polymer. In contrast, vascular endothelial growth factor (VEGF) secretion was unaffected by 3D culture with or without substrate adhesion. IL-8 diffused greater distances and was present in higher concentrations in the systemic circulation, relative to VEGF. Implantation of a polymeric IL-8 delivery system into GFP bone marrow-transplanted mice revealed that localized IL-8 up-regulation was critical to both the local and systemic control of tumor vascularization in vivo. In summary, 3D integrin engagement within tumor microenvironments regulates cancer cell angiogenic signaling, and controlled local and systemic blockade of both IL-8 and VEGF signaling may improve antiangiogenic therapies. {\textcopyright} 2009 by The National Academy of Sciences of the USA.},
	keywords = {animal experiment, animal model, Animals, arginylglycylaspartic acid, article, bone marrow transplantation, cancer cell, cancer cell culture, Cell Culture Techniques, concentration (parameters), controlled study, cytokine release, Diffusion, Drug delivery, ECM, Humans, hydrogel, Hydrogels, IL-8, implantation, in vivo study, integrin, Integrins, interleukin 8, Interleukin-8, Mice, microenvironment, Models, Biological, mouse, Mus, Neoplasms, Neovascularization, Pathologic, nonhuman, polymer, priority journal, signal transduction, systemic circulation, Tumor vascularization, upregulation, Vascular Endothelial Growth Factor A, vasculotropin},
	isbn = {00278424 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-58849121351\&partnerID=40\&md5=acc07042d6f5801f7b704a3f355917cf},
	author = {Fischbach, C. and Hyun, J.K. and Hsiong, S.X. and Evangelista, M.B. and Yuen, W. and Mooney, D.J.}
}
@article {2376,
	title = {Upregulation of bone cell differentiation through immobilization within a synthetic extracellular matrix},
	journal = {BiomaterialsBiomaterials},
	volume = {28},
	year = {2007},
	note = {Cited By (since 1996): 39Export Date: 21 November 2012Source: ScopusCODEN: BIMADdoi: 10.1016/j.biomaterials.2007.04.028PubMed ID: 17532040Language of Original Document: EnglishCorrespondence Address: Evangelista, M.B.; INEB-Instituto de Engenharia Biom{\'e}dica, Laborat{\'o}rio de Biomateriais, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; email: mbe@ineb.up.ptChemicals/CAS: alginic acid, 28961-37-7, 29894-36-8, 9005-32-7, 9005-38-3; alkaline phosphatase, 9001-78-9; arginylglycylaspartic acid, 99896-85-2; DNA, 9007-49-2; osteocalcin, 136461-80-8; Alginates; alginic acid, 9005-32-7; Alkaline Phosphatase, EC 3.1.3.1; arginyl-glycyl-aspartic acid, 99896-85-2; Glucuronic Acid, 576-37-4; Hexuronic Acids; Oligopeptides; Osteocalcin, 104982-03-8References: de Vos, P., de Haan, B., Wolters, G.H.J., VanSchilfgaarde, R., Factors influencing the adequacy of microencapsulation of rat pancreatic islets (1996) Transplantation, 62 (7), pp. 888-893;Brissova, M., Lacik, I., Powers, A.C., Anilkumar, A.V., Wang, T., Control and measurement of permeability for design of microcapsule cell delivery system (1998) J Biomed Mater Res, 39 (1), pp. 61-70; 
Strand, B.L., Gaserod, O., Kulseng, B., Espevik, T., Skjak-Braek, G., Alginate-polylysine-alginate microcapsules: effect of size reduction on capsule properties (2002) J Microencapsul, 19 (5), pp. 615-630; 
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},
	month = {2007///},
	pages = {3644 - 3655},
	abstract = {There is a need for new therapeutic strategies to treat bone defects caused by trauma, disease or tissue loss. Injectable systems for cell transplantation have the advantage of allowing the use of minimally invasive surgical procedures, and thus for less discomfort to patients. In the present study, it is hypothesized that Arg-Gly-Asp (RGD)-coupled in a binary (low and high molecular weight) injectable alginate composition is able to influence bone cell differentiation in a three-dimensional (3D) structure. Viability, metabolic activity, cytoskeleton organization, ultrastructure and differentiation (alkaline phosphatase (ALP), von Kossa, alizarin red stainings and osteocalcin quantification) of immobilized cells were assessed. Cells within RGD-modified alginate microspheres were able to establish more interactions with the synthetic extracellular matrix as visualized by confocal laser scanning microscope and transmission electron microscopy imaging, and presented a much higher level of differentiation (more intense ALP and mineralization stainings and higher levels of osteocalcin secretion) when compared to cells immobilized within unmodified alginate microspheres. These findings demonstrate that peptides covalently coupled to alginate were efficient in influencing cell behavior within this 3D system, and may provide adequate preparation of osteoblasts for cell transplantation. {\textcopyright} 2007 Elsevier Ltd. All rights reserved.},
	keywords = {3T3 Cells, Alginate, Alginates, alginic acid, alkaline phosphatase, animal cell, Animals, arginylglycylaspartic acid, article, Bone, bone cell, Bone Regeneration, calvaria, cell adhesion, cell differentiation, Cell encapsulation, Cell immobilization, cell metabolism, cell proliferation, cell survival, cell ultrastructure, cell viability, confocal laser microscopy, controlled study, cytology, cytoskeleton, DNA, DNA content, ECM (extracellular matrix), enzyme activity, extracellular matrix, Glucuronic Acid, Hexuronic Acids, hydrogel, immobilized cell, metabolism, Mice, Microscopy, Confocal, Microscopy, Electron, Transmission, microsphere, Microspheres, nonhuman, Oligopeptides, osteoblast, Osteoblasts, osteocalcin, Patient treatment, priority journal, rat, RGD peptide, structure analysis, three dimensional imaging, Tissue engineering, transmission electron microscopy, Transplantation (surgical)},
	isbn = {01429612 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-34249870130\&partnerID=40\&md5=4476a4b1ee80320328c1bf37054037bb},
	author = {Evangelista, M.B. and Hsiong, S.X. and Fernandes, R. and Sampaio, P. and Kong, H.-J. and Barrias, C.C. and Salema, R. and Barbosa, M.A. and Mooney, D.J. and Granja, P.L.}
}
