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However, the therapeutic use of growth factors is limited by their susceptibility to degradation, and the need to maintain prolonged local release of growth factor at levels sufficient to stimulate hMSC. The aim of this study was to investigate whether a device containing heparan sulfate (HS), which is a co\u2010factor in growth factor\u2010mediated cell proliferation and differentiation, could potentiate and prolong the delivery of fibroblast growth factor\u20102 (FGF\u20102) and thus enhance hMSC stimulation. To this aim, we synthesized cationic polyelectrolyte polymers covalently and non\u2010covalently anchored to HS and evaluated their effect on hMSC proliferation. Polymers non\u2010covalently bound to HS resulted in the release of an HS\/FGF\u20102 complex rather than FGF\u20102 alone. The release of this complex significantly restored hMSC proliferation, which was abolished in serum\u2010free medium and only partially restored by the release of FGF\u20102 alone as occurred with polymer covalently bound to HS. We also demonstrate that exposure to HS\/FGF\u20102 during early growth but not during post\u2010confluence is essential for hMSC differentiation down the fibroblast lineage, which suggests that both factors are required to establish the correct stem cell commitment that is necessary to support subsequent differentiation. In conclusion, the delivery platform described here is a step towards the development of a new class of biomaterial that enables the prolonged, non\u2010covalent binding and controlled delivery of growth factors and cofactors without altering their potency. J. Cell. Biochem. 110: ??\u2013??, 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.22602","type":"journal-article","created":{"date-parts":[[2010,4,14]],"date-time":"2010-04-14T14:29:39Z","timestamp":1271255379000},"page":"903-909","source":"Crossref","is-referenced-by-count":16,"title":["Controlled delivery of the heparan sulfate\/FGF\u20102 complex by a polyelectrolyte scaffold promotes maximal hMSC proliferation and differentiation"],"prefix":"10.1002","volume":"110","author":[{"given":"Anna","family":"Calarco","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orsolina","family":"Petillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Bosetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Torpedine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Cannas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"Perrone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umberto","family":"Galderisi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariarosa A.B.","family":"Melone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranco","family":"Peluso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,4,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0656fje"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1994.1037"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.729"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35102181"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912700122010230"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(01)02016-0"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/000164700317381234"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025034925152"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.30261"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.4.1099"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10397"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0142-9612(94)90164-3"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4628(19991017)74:3<655::AID-APP19>3.0.CO;2-N"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2008.0157"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0142-9612(91)90107-L"},{"key":"e_1_2_6_17_1","first-page":"1443","article-title":"Differential binding of fibroblast growth factor\u20102 and \u20107 to basement membrane heparan sulfate: Comparison of normal and abnormal human tissues","volume":"150","author":"Friedl A","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2005.11.41"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-3659(99)00268-0"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20813"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.05.031"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)00988-8"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-001-0131-3"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.03.008"},{"key":"e_1_2_6_25_1","unstructured":"LiuLS ThompsonAY PoserJW SpiroRC.1998.Hyaluronate derivatives\u2010based materials for growth factor delivery and tissue regeneration. 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