Abstract
In tissue engineering and regenerative medicine, the formation of vascular beds is an effective method to supply oxygen and nutrients to implanted cells or tissues to improve their survival and promote normal cellular functions. Various types of angiogenic materials have been developed by incorporating growth factors, such as vascular endothelial growth factor, in biocompatible materials. However, these exogenous growth factors suffer from instability and inactivation under physiological conditions. In this study, we designed a novel angiogenic electrospun fiber sheet (C16-FS) composed of Alaska pollock-derived gelatin (ApGltn) modified with hexadecyl (C16) groups to induce localized and sustained angiogenesis without growth factors. C16-FS was thermally crosslinked to enhance its stability. We demonstrated that C16-FS swells in phosphate-buffered saline for over 24 h and resists degradation. Laser doppler perfusion imaging showed that C16-FS induced increased blood perfusion when implanted subcutaneously in rats compared with unmodified ApGltn-fiber sheets (Org-FS) and the sham control. Furthermore, angiogenesis was sustained for up to 7 days following implantation. Immunohistochemical studies revealed elevated nuclear factor-κB and CD31 levels around the C16-FS implantation site compared with the Org-FS implantation site and the control incision site. These results demonstrate that C16-FS is a promising angiogenic material to promote the formation of vascular beds for cell and tissue transplantation without the need for growth factors.
Highlights
Tissue engineering and regenerative medicine is a promising approach to repair or replace damaged tissues and organs
We previously reported that saturated fatty acids (SFAs)-modi ed Alaska-pollock-derived gelatin (ApGltn), self-assembles into a hydrogel when hydrated with phosphate-buffered saline (PBS) and stimulated vascular endothelial growth factor (VEGF) secretion and angiogenesis in vitro and in vivo.[29]
nuclear factor-kB (NF-kB) promotes genes associated with in ammatory cytokines and growth factors, such as VEGF, and we have previously shown that SFAmodi ed gelatin stimulates NF-kB via TLR4-mediated pathways.[27]
Summary
Tissue engineering and regenerative medicine is a promising approach to repair or replace damaged tissues and organs. We used a hexadecyl group (C16) as an immune activator[25] to synthesize C16-modi ed ApGltn (C16ApGltn), used electrospinning to fabricated C16-ApGltnbased ber sheets (C16-FSs) thermally crosslinked to increase the crosslinking density and enhance their stability. Hexadecanal and 2-picoline borane were dissolved in ethanol and added to the ApGltn solution in 1.5-fold molar excesses relative to the remaining amino groups in the ApGltn. Before the modi cation ApGltn with hexadecyl groups, the amino group concentration in the gelatin was quanti ed by the TNBS method, as previously reported.[39,40,41] Brie y, 100 ml of 0.1 w/v% ApGltn dissolved in 1 : 1 DMSO/H2O was dispensed into each well of a 48-well plate. The FSs were weighed at each time point to determine the degradation pro les
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