Biocompatibility and immunogenicity of elastin‐like recombinamer biomaterials in mouse models

Abstract

Novel thermo‐sensitive elastin‐like recombinamers (ELRs) containing bioactive molecules were created for use as a biomimetic biomaterial for tissue regeneration. For effective use for in vivo applications, it is essential to ensure that they do not induce adverse inflammatory, immune, or allergic responses that inhibit tissue repair. Therefore, we sought to establish a pre‐clinical approach to evaluate biocompatibility in experimental mice using ELRs as a prototype biomaterial. First, we measured in vitro proliferation and cytokine production from BALB/c and C57BL/6 mouse splenocytes incubated with ELRs. Second, we used a rapid, high throughput in vivo approach in which inflammatory cells and cytokines were measured following an intraperitoneal implantation. Lastly, a subchronic in vivo approach was used in which ELRs or positive controls were subcutaneously implanted and the implantation sites were assessed for inflammation and gene expression. We found that ELRs induced mild inflammation and minimal fibrosis compared to the intense response to Vitoss. Additionally, implantation increased antigen‐specific antibody titers for both groups and gene expression profiling of the implantation sites revealed the upregulation of inflammation, fibrosis, and wound healing‐related genes in ELR and positive control‐implanted mice compared to sham controls. These data demonstrate that ELRs appear safe for use in tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 924–934, 2018.

Utilizing a Kidney-Targeting Peptide to Improve Renal Deposition of a Pro-Angiogenic Protein Biopolymer

“…Elastin-like polypeptides (ELP) are a class of protein biopolymers composed of repeating five-amino acid units (VPGxG, where x is any amino acid except proline) with unique physical properties [1] and many advantages as drug carriers [2]. ELPs are relatively biologically inert, having little to no cytotoxicity [3,4,5] and low immunogenicity [6,7]. Also, being proteins rather than chemically synthesized polymers, they degrade in vivo into non-toxic natural amino acids [8].…”

In vivo gene delivery mediated by non-viral vectors for cancer therapy

“…Enormous efforts are still underway for developing novel and effective gene delivery systems based on biocompatible nanomaterials to transfer the target genes to the tumor site [167,191,192]. For example, researchers have developed an elastin-like recombinant (ELR) and specific MUC1 aptamers for intracellular delivery of the MUC1 gene to breast tumors [193].…”

Targeting Tunable Physical Properties of Materials for Chronic Wound Care

“…Gonzalez de Torre et al (2018) described the "clickable" properties of ELRs and used electrospinning to prepare bioactive fibers from clickable ELRs with no crosslinking agent added. In another study, Changi et al (2018) developed thermo-sensitive ELRs which contained bioactive molecules and showed good biocompatibility and limited immunogenicity in BALB/c and C57BL/6 mouse models. Moreover, some functional sequences, such as growth factors, can be attached via chemical reactions to ELRs molecule or can be directly inserted into main sequences of ELRs through recombinant techniques (Flora et al, 2019).…”