



@article {3296,
	title = {Hydrogel depots for local co-delivery of osteoinductive peptides and mesenchymal stem cells},
	journal = {Journal of Controlled Release},
	volume = {189},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {158 - 168},
	abstract = {The outcome of cell-based therapies can benefit from carefully designed cell carriers. A multifunctional injectable vehicle for the co-delivery of human mesenchymal stem cells (hMSCs) and osteoinductive peptides is proposed, to specifically direct hMSCs osteogenic differentiation. The osteogenic growth peptide (OGP) inspired the design of two peptides, where the bioactive portion of OGP was flanked by a protease-sensitive linker, or its scrambled sequence, to provide faster and slower release rates, respectively. Peptides were fully characterized and chemically grafted to alginate. Both OGP analogs released bioactive fragments in vitro, at different kinetics, which stimulated hMSCs proliferation and osteogenesis. hMSCs-laden OGP-alginate hydrogels were tested at an ectopic site in a xenograft mouse model. After 4 weeks, OGP-alginate hydrogels were more degraded and colonized by vascularized connective tissue than the control (without OGP). hMSCs were able to proliferate, migrate outward the hydrogels, produce endogenous extracellular matrix and mineralize it. Moreover, OGP-groups stimulated hMSCs osteogenesis, as compared with the control. Overall, the ability of the proposed platform to direct the fate of transplanted hMSCs in loco was demonstrated, and OGP-releasing hydrogels emerged as a potentially useful system to promote bone regeneration. {\textcopyright} 2014 Elsevier B.V.},
	keywords = {Bone Regeneration, Co-delivery systems, Guided differentiation, Injectable alginate hydrogels, Mesenchymal Stem Cells, Osteoinductive peptides},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84904318888\&partnerID=40\&md5=5f671d3584c3b7fc785ffaf40c2f0b1d},
	author = {Maia, F.R. and Barbosa, M. and Gomes, D.B. and Vale, N. and Gomes, P. and Granja, P.L. and Barrias, C.C.}
}
@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.}
}
