Biophotonic Glass Scaffolds for Controlled Active Agent Release Under Light Stimulation

Abstract

Large bone defects typically require surgical treatment, and while regenerative medicine offers several options, each has its limitations. This has driven interest in synthetic biomaterials that can promote bone regeneration while overcoming these drawbacks. Ideal implants should support osteogenesis and angiogenesis. Bioactive glasses (BAGs) are attractive bone graft substitutes due to their osteoconductive and osteostimulative properties. Silicate-based BAGs (e.g., 45S5, S53P4) are commonly used in clinics but face limitations in 3D scaffold fabrication due to their high crystallization tendency. Borosilicate glass has been found to also promote osteogenesis and support angiogenesis to a greater extent than silicate bioactive glasses. Furthermore, borosilicate glasses have thermal properties enabling sintering without adverse crystallization. However, while boron release has been found to promote early stem cells differentiation, large boron release was also found to be, to some extent, toxic in static cell culture. Phosphate glasses, particularly metaphosphates, are bioresorbable alternatives with controllable ion release and excellent hot-forming domains suitable for 3D printing but have not yet been used clinically. To develop the biomaterials of the future, it is imperative to multifunctional materials. Drug delivery systems have been developed; however, the drug release is initiated as soon as the material is implanted and, generally, only relies on diffusion processes. The new generation of biomaterials should be able to release drug in spatial-temporal manner via an external stimulus. Light is a powerful external stimulus as it is highly controllable (time, intensity, localization). In this study, we developed multifunctional biophotonic scaffolds by incorporating upconverster (UC) crystals into the glass matrices, both bioactive and bioresorbable, to enable light- triggered nitric oxide (NO) release, from a NO-donor, as a model drug system. The scaffolds were fabricated using the porogen burn-off technique and 3D printing, and they exhibited suitable porosity, bioactivity, cell biocompatibility, and stable UC emission, even post immersion. When functionalized with a photocleavable NO donor, the system allowed precise, light-controlled NO release. These findings constitute proof of concept for the development of a biophotonic platform capable of on-demand, localized, drug release.