The development of peptide-based interfacial biomaterials for generating biological functionality on the surface of bioinert materials

Abstract

Biomaterials used in implants have traditionally been selected based on their mechanical properties, chemical stability, and biocompatibility. However, the durability and clinical efficacy of implantable biomedical devices remains limited in part due to the absence of appropriate biological interactions at the implant interface and the lack of integration into adjacent tissues. Herein, we describe a robust peptide-based coating technology capable of modifying the surface of existing biomaterials and medical devices through the non-covalent binding of modular biofunctional peptides. These peptides contain at least one material binding sequence and at least one biologically active sequence and thus are termed, “Interfacial Biomaterials” (IFBMs). IFBMs can simultaneously bind the biomaterial surface while endowing it with desired biological functionalities at the interface between the material and biological realms. We demonstrate the capabilities of model IFBMs to convert native polystyrene, a bioinert surface, into a bioactive surface that can support a range of cell activities. We further distinguish between simple cell attachment with insufficient integrin interactions, which in some cases can adversely impact downstream biology, versus biologically appropriate adhesion, cell spreading, and cell survival mediated by IFBMs. Moreover, we show that we can use the coating technology to create spatially resolved patterns of fluorophores and cells on substrates and that these patterns retain their borders in culture.

Peptide Interfacial Biomaterials Improve Endothelial Cell Adhesion and Spreading on Synthetic Polyglycolic Acid Materials

“…In this fashion, these peptides create an interface that allows for appropriate biological interactions with inert materials. Our previous research focused on using bifunctional resulting peptides to regulate the interactions that occurred at the biological-material interface including: promotion of surface cellularization, 34 suppression of apoptosis, 36 prevention of fouling, 23,24 and, more recently, release of a therapeutic from a surface. 35 In this report, we have approached the problem of poor biological activity of PGA fibers by developing a modular IFBM peptide that is capable of binding to PGA and modifying its surface to provide biological cues that direct endothelial cell adhesion, spreading, cytoskeletal reorganization, and focal adhesion plaque formation.…”

“…23,24,[34][35][36]54 These bifunctional, two-domain peptide coatings must recognize and bind both the inert surface through non-covalent physisorption, while also providing a mechanism to interact with the surrounding biology. In this fashion, these peptides create an interface that allows for appropriate biological interactions with inert materials.…”

Biological response on a titanium implant-grade surface functionalized with modular peptides

“…It was found that the presence of polar (Ser, Asn) and basic (Arg) amino acids were prominent in the selected peptides. The role of amino acid composition vs. amino acid positioning in the sequence and the role of peptide net charge vs. local charge distribution have been studied by different research groups, including the present authors, to investigate the binding mechanism of peptides to the desired surfaces [32,37,42,56,57,68,69]. A number of related probing studies in the literature focused on the interactions of peptides with metal, metal-oxide and mineral surfaces based on amino acid type and position relations [37,68,69].…”

“…Their potential use was increasingly demonstrated in various scientific disciplines including surface functionalization [28–32], biomineralization [33,34], tissue engineering [31] and regenerative medicine [35,36]. Application of surface-binding peptides to hard tissue regeneration and restorative medicine is particularly intriguing and, consequently, there has been a great deal of interest in identifying and characterizing peptides that bind to various materials, such as TiO 2 [37], Au [38,39], SiO 2 [40,41], HAP [33,42,43] and select polymers [44].…”

Examination of cell–host–biomaterial interactions via high-throughput technologies: A re-appraisal

“…These characteristics also determine whether proteins are adsorbed in a biologically active conformation [25]. In most cases, successfully adsorbed proteins will allow for cell adhesion to the biomaterial through interactions with the protein layer, while unsuccessfully adsorbed proteins or proteins exhibiting an anti-adhesive effect will not permit cell adhesion and the material can be considered 'bioinert' [26]. Cell phenotype, including cell spreading, proliferation and morphology, are also affected by even discrete modifications of biomaterials, resulting in altered molecular responses.…”