Peptide-modified Substrate for Modulating Gland Tissue Growth and Morphology In Vitro

Abstract

In vitro fabricated biological tissue would be a valuable tool to screen newly synthesized drugs or understand the tissue development process. Several studies have attempted to fabricate biological tissue in vitro. However, controlling the growth and morphology of the fabricated tissue remains a challenge. Therefore, new techniques are required to modulate tissue growth. RGD (arginine-glycine-aspartic acid), which is an integrin-binding domain of fibronectin, has been found to enhance cell adhesion and survival; it has been used to modify substrates for in vitro cell culture studies or used as tissue engineering scaffolds. In addition, this study shows novel functions of the RGD peptide, which enhances tissue growth and modulates tissue morphology in vitro. When an isolated submandibular gland (SMG) was cultured on an RGD-modified alginate hydrogel sheet, SMG growth including bud expansion and cleft formation was dramatically enhanced. Furthermore, we prepared small RGD-modified alginate beads and placed them on the growing SMG tissue. These RGD-modified beads successfully induced cleft formation at the bead position, guiding the desired SMG morphology. Thus, this RGD-modified material might be a promising tool to modulate tissue growth and morphology in vitro for biological tissue fabrication.

MCSF orchestrates branching morphogenesis in developing submandibular gland tissue

“…3A-C). Consistent with previous results, neutralization of FGF7 and FGF10 with their specific antibodies significantly suppressed SMG growth (Taketa et al, 2015), which was, however, partially restored by further MCSF supplementation (Fig. 3D,E).…”

Fibronectin‐induced ductal formation in salivary gland self‐organization model

“…Therefore, our findings would be helpful in developing a biophysical model to analyze the dynamics of multicellular interactions in 3D cell aggregates. 20 This result was noteworthy because RGD enhanced SMG growth along with both, bud formation and duct elongation. 34 Previous reports regarding salivary branching identified FN as a key regulator of cleft formation.…”

“…20 Therefore, we used it as a negative control to confirm the sole effect of exogenous FN supplementation. Previously, we showed that stiff alginate hydrogel sheet substrates (184 kPa) can attenuate SMG growth.…”

“…20 Briefly, sodium alginate solution 4 wt% (Wako Pure Chemical) was poured into a mold made of a porous alumina plate. 20 Briefly, sodium alginate solution 4 wt% (Wako Pure Chemical) was poured into a mold made of a porous alumina plate.…”

“…Previously, we showed that stiff alginate hydrogel sheet substrates (184 kPa) can attenuate SMG growth. 20 Therefore, we used it as a negative control to confirm the sole effect of exogenous FN supplementation. To do this, we cultured SMGs on stiff alginate hydrogel sheets (184 kPa), to compare the effect of fibronectin on this alternative substrate as a control ( Figure 6D).…”