Elastin-PLGA hybrid electrospun nanofiber scaffolds for salivary epithelial cell self-organization and polarization

Abstract

Development of electrospun nanofibers that mimic the structural, mechanical and biochemical properties of natural extracellular matrices (ECMs) is a promising approach for tissue regeneration. Electrospun fibers of synthetic polymers partially mimic the topography of the ECM, however, their high stiffness, poor hydrophilicity and lack of in vivo-like biochemical cues is not optimal for epithelial cell self-organization and function. In search of a biomimetic scaffold for salivary gland tissue regeneration, we investigated the potential of elastin, an ECM protein, to generate elastin hybrid nanofibers that have favorable physical and biochemical properties for regeneration of the salivary glands. Elastin was introduced to our previously developed poly-lactic-co-glycolic acid (PLGA) nanofiber scaffolds by two methods, blend electrospinning (EP-blend) and covalent conjugation (EP-covalent). Both methods for elastin incorporation into the nanofibers improved the wettability of the scaffolds while only blend electrospinning of elastin-PLGA nanofibers and not surface conjugation of elastin to PLGA fibers, conferred increased elasticity to the nanofibers measured by Young’s modulus. After two days, only the blend electrospun nanofiber scaffolds facilitated epithelial cell self-organization into cell clusters, assessed with nuclear area and nearest neighbor distance measurements, leading to the apicobasal polarization of salivary gland epithelial cells after six days, which is vital for cell function. This study suggests that elastin electrospun nanofiber scaffolds have potential application in regenerative therapies for salivary glands and other epithelial organs.

Fabrication and Plasma Modification of Nanofibrous Tissue Engineering Scaffolds

“…Besides the above-mentioned proteins, a few research papers have also been focusing on the grafting of elastin [287], gelatin [288,289], fibronectin [281] and soluble eggshell membrane protein [290] on nanofibrous scaffolds. Also, in these cases, better cellular interactions were observed on the protein-grafted scaffolds, consequently, the grafting of these less examined proteins will not be described in detail in this review paper.…”

Protein-Based Fiber Materials in Medicine: A Review

“…In biomaterials engineering, elastin is used to describe a variety of elastic proteins and peptides rather than one single molecule. It can be used in a variety of forms that include, most commonly, soluble elastin [ 18 , 38 , 39 ], recombinant tropoelastin [ 40 , 41 ], and synthetic elastin-like peptides that may also be hybrids with other proteins, such as silk [ 42 , 43 , 44 , 45 ]. The inclusion of elastin in nanofiber scaffolds has been shown to increase fiber elasticity and provide for better cell attachment [ 18 ].…”

“…It can be used in a variety of forms that include, most commonly, soluble elastin [ 18 , 38 , 39 ], recombinant tropoelastin [ 40 , 41 ], and synthetic elastin-like peptides that may also be hybrids with other proteins, such as silk [ 42 , 43 , 44 , 45 ]. The inclusion of elastin in nanofiber scaffolds has been shown to increase fiber elasticity and provide for better cell attachment [ 18 ]. Due to elastin’s elasticity and resilience, it has found special purpose in the development of vascular grafts, since fibrous scaffolds made from the protein have been shown to closely match the compliance of natural arteries [ 46 , 47 , 48 ].…”

“…Equally important in biomaterials engineering, however, is the need for materials to be both biocompatible and biodegradable. Therefore, to maximize these properties, natural polymer-based fibers made from proteins have begun to be developed [ 16 , 17 , 18 , 19 ].…”

Specific complexes derived from extracellular matrix facilitate generation of structural and drug‐responsive human salivary gland microtissues through maintenance stem cell homeostasis

“…Dry mouth is a common symptom and can develop from salivary glands diseases. Patients with reduced saliva production have symptoms of impaired oral health, difficulties in swallowing and digestion food and other complications, which significantly decreased their quality of life and general health status (Foraida, Kamaldinov, Nelson, Larsen, & Castracane, ; Frank, Herdly, & Philippe, ; Valdez, Atkinson, Ship, & Fox, ). However, due to the lack of ideal models to investigate disease mechanisms and screening efficient drugs, treatment of this disease is insufficiently efficacious (Konings, Coppes, & Vissink, ).…”