Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials

Abstract

Materials engineered to elicit targeted cellular responses in regenerative medicine must display bioligands with precise spatial and temporal control. Although materials with temporally regulated presentation of bioadhesive ligands using external triggers, such as light and electric fields, have been recently realized for cells in culture, the impact of in vivo temporal ligand presentation on cell-material responses is unknown. Here, we present a general strategy to temporally and spatially control the in vivo presentation of bioligands using cell adhesive peptides with a protecting group that can be easily removed via transdermal light exposure to render the peptide fully active. We demonstrate that non-invasive, transdermal time-regulated activation of cell-adhesive RGD peptide on implanted biomaterials regulates in vivo cell adhesion, inflammation, fibrous encapsulation, and vascularization of the material. This work shows that triggered in vivo presentation of bioligands can be harnessed to direct tissue reparative responses associated with implanted biomaterials.

Rapid Reversible Photoswitching of Integrin‐Mediated Adhesion at the Single‐Cell Level

“…[5][6][7] Studies using this approach revealed that the time point of cell exposure to adhesion ligands and their density signifi cantly infl uences cell differentiation [ 8 ] and guides vascularization in vivo. [ 9 ] This shows that cells keep track of their adhesion history and that dynamic changes in adhesion signals are imperative in controlling cell functions.…”

Dynamic and Responsive Growth Factor Delivery from Electrospun and Hydrogel Tissue Engineering Materials

“…Poly(ethylene glycol) di-acrylate hydrogels functionalized with the bioactive RGD peptide sequence have been designed with a photolabile capping blocking the RGD peptide until released by a transdermal UV trigger. [72] This transdermal UV trigger system used lower energy 350-365 nm light, which was able to achieve transdermal activation without detectable harm to murine skin in vivo. [72] However, penetration depth is still a concern [72] and, as is common with photostimulated systems, is not suited for deep tissue applications.…”

Progress in material design for biomedical applications

“…Light penetration can be attenuated at many depths and wavelengths; however, there are numerous examples where light has been used to either form materials (73) their properties when implanted (74). Ultrasound is another trigger that can be introduced to disrupt polymer structure and release therapeutics (75,76).…”