An ultrasound-triggered injectable sodium alginate scaffold loaded with electrospun microspheres for on-demand drug delivery to accelerate bone defect regeneration

Abstract

Biological processes, such as bone defects healing are precisely controlled in both time and space. This spatiotemporal characteristic inspires novel therapeutic strategies. The sustained-release systems including hydrogels are commonly utilized in the treatment of bone defect; however, traditional hydrogels often release drugs at a consistent rate, lacking temporal precision. In this study, a hybrid hydrogel has been developed by using sodium alginate, sucrose acetate isobutyrate, and electrospray microspheres as the base materials, and designed with ultrasound response, and on-demand release properties. Sucrose acetate isobutyrate was added to the hybrid hydrogel to prevent burst release. The network structure of the hybrid hydrogel is formed by the interconnection of Ca²⁺ with the carboxyl groups of sodium alginate. Notably, when the hybrid hydrogel is exposed to ultrasound, the ionic bond can be broken to promote drug release; when ultrasound is turned off, the release returned to a low-release state. This hybrid hydrogel reveals not only injectability, degradability, and good mechanical properties but also shows multiple responses to ultrasound. And it has good biocompatibility and promotes osteogenesis efficiency in vivo. Thus, this hybrid hydrogel provides a promising therapeutic strategy for the treatment of bone defects.

Keywords: Bone regeneration; Electrospun microspheres; Hybrid hydrogel scaffold; On-demand drug release; Ultrasound-triggered.