کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1424855 986743 2012 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fibrin hydrogels for lentiviral gene delivery in vitro and in vivo
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Fibrin hydrogels for lentiviral gene delivery in vitro and in vivo
چکیده انگلیسی

Gene delivery from hydrogels represents a versatile approach for localized expression of tissue inductive factors that can promote cellular processes that lead to regeneration. Lentiviral gene therapy vectors were entrapped within fibrin hydrogels, either alone or complexed with hydroxylapatite (HA) nanoparticles. The inclusion of HA into the hydrogel led to the formation of small aggregates distributed throughout the hydrogel, with no obvious alteration of the pore structure outside the aggregates. The presence of HA slowed hydrogel degradation by collagenase and plasmin relative to fibrin alone, and also decreased the rate of cell migration. Lentivirus had similar release from the fibrin hydrogels formed with or without HA. The altered hydrogel properties suggest an interaction between the nanoparticle and fibrin, which may displace the virus from the particle leading to similar release profiles. Transgene expression by cells migrating into the hydrogel in vitro was reduced in the presence of HA, consistent with the role of cell migration on transgene expression. In vivo, lentivirus loaded fibrin hydrogels promoted localized transgene expression that increased through day 9 and decreased through day 14. For the fibrin only hydrogels, expression continued to decline after day 14. However, hydrogels with HA maintained this transgene expression level for an additional 2 weeks before declining. Immunostaining identified transgene primarily outside the fibrin-HA gel at day 9; however, at day 21, transgene expression was observed primarily within the fibrin-HA gel. The localized delivery of lentivirus provides an opportunity to enhance the bioactivity of fibrin hydrogels for a wide range of applications in regenerative medicine.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 157, Issue 1, 10 January 2012, Pages 80–85
نویسندگان
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