Combining Biologically Active β-Lactams Integrin Agonists with Poly(l-lactic acid) Nanofibers: Enhancement of Human Mesenchymal Stem Cell Adhesion

Abstract

Regulating stem cell adhesion and growth onto functionalized biomaterial scaffolds is an important issue in the field of tissue engineering and regenerative medicine. In this study, new electrospun scaffolds of poly( l -lactic acid) (PLLA), as bioresorbable polymer, and β-lactam compounds agonists of selected integrins, as functional components with cell adhesive properties, are designed. The new β-lactam-PLLA scaffolds contribute significantly in guiding protein translation involved in human bone marrow mesenchymal stem cells (hBM-MSC) adhesion and integrin gene expression. Scanning electron microscopy, confocal laser scanning microscopy, and Western Blot analyses reveal that GM18-PLLA shows the best results, promoting cell adhesion by significantly driving changes in focal adhesion proteins distribution (β 1 integrin and vinculin) and activation (pFAK), with a notable increase of GM18-targets subunits integrin gene expression, α 4 and β 1 . These novel functionalized submicrometric fibrous scaffolds demonstrate, for the first time, the powerful combination of selective β-lactams agonists of integrins with biomimetic scaffolds, suggesting a designed rule that could be suitably applied to tissue repair and regeneration.

An Integrative Dual-Layer Poly-L-Lactic Acid Fibrous Membrane Prevents Peritendinous Adhesions

“…The beneficial characteristics of poly(L-lactic acid) (PLLA), including viscosity, biodegradability, biocompatibility, and biosafety, have facilitate the application of PLLA in the biomedical field (Kumar et al, 2015;Ge et al, 2018). The PLLA membrane can be an ideal barrier for effective tissue separation with satisfactory biocompatibility (Li et al, 2017;Sensini et al, 2017;Martelli et al, 2020). Moreover, the porous design of this scaffold confers the product with high porosity, large surface area to volume ratio, and small pore size, which helps improve intrinsic regeneration by permitting free exchange of nutrients into the injured area (Landau et al, 2017;Morelli et al, 2019).…”

Precision-engineered niche for directed differentiation of MSCs to lineage-restricted mineralized tissues

“…Several post-fabrication approaches have been utilized to improve these mechanical properties. 35 Radiofrequency glow discharge treatment (RFGDT) has been used to disinfect and improve the hydrophilicity of biomaterials. Pre-treatments of biomaterials with RFGDT have been noted to increase osteoblast cell functions and gene expression.…”

Integrin-Targeting Peptides for the Design of Functional Cell-Responsive Biomaterials

“…β-lactams were also reported to be integrin ligands, especially for integrin αvβ5, α5β1, or α4β1 [ 50 , 51 , 52 ]. To improve human mesenchymal stem cell adhesion and promote the application in tissue engineering and regeneration medicine, β-lactam-based agonist ligands (see also section “Addressing Integrins with Agonist Ligands”) were incorporated into poly(L-lactic acid) (PLLA) to form functionalized scaffolds by electrospin technology [ 138 ].…”