Laminin-111 Peptides Conjugated to Fibrin Hydrogels Promote Formation of Lumen Containing Parotid Gland Cell Clusters

Abstract

Previous studies showed that mouse submandibular gland cells form three-dimensional structures when grown on Laminin-111 gels. The use of Laminin-111 for tissue bioengineering is complicated due to its lack of purity. By contrast, the use of synthetic peptides derived from Laminin-111 is beneficial due to their high purity and easy manipulation. Two Laminin-111 peptides have been identified for salivary cells: the A99 peptide corresponding to the α1 chain from Laminin-111 and the YIGSR peptide corresponding to the β1 chain from Laminin-111, which are important for cell adhesion and migration. We created three-dimensional salivary cell clusters using a modified fibrin hydrogel matrix containing immobilized Laminin-111 peptides. Results indicate that the YIGSR peptide improved morphology and lumen formation in rat parotid Par-C10 cells as compared to cells grown on unmodified fibrin hydrogel. Moreover, a combination of both peptides not only allowed the formation of functional three-dimensional salivary cell clusters but also increased attachment and number of cell clusters. In summary, we demonstrated that fibrin hydrogel decorated with Laminin-111 peptides supports attachment and differentiation of salivary gland cell clusters with mature lumens.

Fibrin functionalization with synthetic adhesive ligands interacting with α6β1 integrin receptor enhance neurite outgrowth of embryonic stem cell-derived neural stem/progenitors

“…Tethering of T1 or HYD1 at input peptide concentrations of 20 or 40 µM did not induce significant changes in the average pore diameter of Fb network or in Fb storage modulus. These results are in accordance with previous findings reporting minor disruption of Fb structure or alterations in Fb rheological properties due to peptide incorporation [49], [54]. Our results therefore indicate that the cell outgrowth enhancement observed in these gels was not associated to changes in Fb network structure or viscoelastic properties.…”

Encapsulation of primary salivary gland cells in enzymatically degradable poly(ethylene glycol) hydrogels promotes acinar cell characteristics

“…In this work, we did not investigate matrix proteins as a variable but included laminin in all hydrogels explored due to demonstrated efficacy for salivary gland tissue engineering approaches. Specifically, culture of salivary gland cells on fibrin hydrogel surfaces in the presence of laminin-111 protein and peptide derivatives was shown to promote lumen formation [27,52]. Further, a perlecan mimetic peptide used in hyaluronic acid hydrogels for the culture of primary salivary gland cells enhanced expression of polarized proteins and acinar cell markers [23–25].…”

Comparing human and mouse salivary glands: A practice guide for salivary researchers

“…These matrices may consist of decellularized tissue, Matrigel, polymers and hydrogels (Maria et al, 2011, McCall et al, 2013), all of which can be further optimized with peptides and growth factors (McCall et al, 2013, Nam et al, 2016). Regarding decellularization, rat SMG have been successfully decellularized for use as a scaffold to reseed primary cells (Gao et al, 2014); however, this technique has not yet been performed with human cells.…”