Tunable Delivery of siRNA from a Biodegradable Scaffold to Promote Angiogenesis In Vivo

Abstract

A system has been engineered for temporally controlled delivery of siRNA from biodegradable tissue regenerative scaffolds. Therapeutic application of this approach to silence prolyl hydroxylase domain 2 promoted expression of pro-angiogenic genes controlled by HIF1α and enhanced scaffold vascularization in vivo. This technology provides a new standard for efficient and controllable gene silencing to modulate host response within regenerative biomaterials.

Light-Triggered RNA Release and Induction of Hmsc Osteogenesis Via Photodegradable, Dual-Crosslinked Hydrogels

“…Lyophilized RNA/PEI complexes prepared in the presence of lyo-protectants such as sucrose [1] or trehalose [27] have been reported to help retain the bioactivity of RNA materials. Retention of siRNA bioactivity using this strategy was confirmed in this report (Supplementary Figure 2).…”

“…The RNA release rates were adjusted by tailoring the degradation rate of the hydrogel networks [1,6,21,27,[39][40][41] and the affinity between RNA molecules and functional groups incorporated in the hydrogels [39][40][41][42]. In contrast, the approach reported here provides a flexible strategy to accelerate siRNA release from photolabile hydrogel networks 'on-demand' at designated time points via exposure to a UV light source.…”

“…Delivering small interfering RNA (siRNA) or microRNA (miRNA) [17,18] to inhibit gene expression post-transcriptionally is a promising biomedical technology that has been investigated for many applications including cancer therapeutics [19][20][21][22][23], wound healing [24][25][26], and tissue regeneration [6][7][8][9][10][27][28][29][30][31][32]. For example, RNAs have been used in tissue regeneration to induce the differentiation of human MSCs (hMSCs) [6][7][8][9][10], canine MSCs [30] and rat MSCs [31] into osteoblasts [6][7][8][9]30,31], chondrocytes [10] or adipocytes [7,8].…”

“…To tackle these challenges, synthetic and natural materials have been examined to increase their delivery efficacy [34,[49][50][51][52]. For example, nanocomplexes of anionic siRNA and miRNA with cationic macromers, such as polyethylenimines (PEIs) [46], chitosan [34,49], poly(β-amino ester) [21], and others [27,50,51] have been shown to increase their stability and cellular internalization. However, locally delivering these nanocarriers to specific regions in the body is hampered by their rapid dispersion in vivo as a result of their small size [6,[32][33][34][35][36][37][38]47,[52][53][54].…”

Depth-resolved analytical model and correction algorithm for photothermal optical coherence tomography

“…Finally, optical techniques are limited to low imaging depths but allow for both large field-of-views with low resolution (e.g. whole body bioluminescence imaging [8]) and small field-of-views with very high resolution (e.g. fluorescence microscopy [9]).…”