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Luminescent Biofunctional Collagen Mimetic Nanofibers.

ABSTRACT: Collagen has long been one of the top targets for biomimetic design due to its superior structural and functional properties. Significant progress has been achieved to construct self-assembling peptides to mimic the fibrous nanostructure of native collagen, while it is still very demanding to fabricate peptide assemblies that can recapitulate both structural and biofunctional features of collagen. Herein, collagen-like peptides have been synthesized to contain negatively charged amino acids as the binding groups of lanthanide ions and the integrin-binding motif GFOGER. The simultaneous inclusion of negatively charged amino acids in the middle as well as at both terminals drives the peptides to self-assemble to form well-ordered nanofibers with distinct periodic banding patterns specifically mediated by lanthanide ions. The aggregation tendency and the morphology of the final assembled materials for the peptides are modulated in a pH-cooperative manner, which well mimics the pH-dependent fibrillogenesis of Type I collagen. The utilization of lanthanide ions in the system not only offers a convenient external stimulus but also functionalizes assembled materials with excellent luminescent features. Most notably, the lanthanide-triggered peptide assembled nanomaterials possess good cell adhesion properties, which resemble the biological function of collagen. This peptide-Ln3+ system provides a facile and potent strategy to generate nanofibers that mimic both the structural and functional properties of natural collagen. These novel pH-responsive, luminescent, and biofunctional collagen mimetic nanofibers open fascinating opportunities in the development of improved functional biomaterials in tissue engineering, drug delivery, and medical diagnostics.

SUBMITTER: Sun X

PROVIDER: S-EPMC6787889 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Project description:Gene therapies have great potential in regenerative medicine; however, clinical translation has been inhibited by low stability and limited transfection efficiencies. Herein, we incorporate collagen-mimetic peptide (CMP)-linked polyplexes in collagen scaffolds to increase DNA stability by up to 400% and enable tailorable in vivo transgene expression at 100-fold higher levels and 10-fold longer time periods. These improvements were directly linked to a sustained interaction between collagen and polyplexes that persisted during cellular remodeling, polyplex uptake, and intracellular trafficking. Specifically, incorporation of CMPs into polyethylenimine (PEI) polyplexes preserved serum-exposed polyplex-collagen activity over a period of 14days, with 4 orders-of-magnitude more intact DNA present in CMP-modified polyplex-collagen relative to unmodified polyplex-collagen after a 10day incubation under cell culture conditions. CMP-modification also altered endocytic uptake, as indicated by gene silencing studies showing a nearly 50% decrease in transgene expression in response to caveolin-1 silencing in modified samples versus only 30% in unmodified samples. Furthermore, cellular internalization studies demonstrated that polyplex-collagen association persisted within cells in CMP polyplexes, but not in unmodified polyplexes, suggesting that CMP linkage to collagen regulates intracellular transport. Moreover, experiments in an in vivo repair model showed that CMP modification enabled tailoring of transgene expression from 4 to 25days over a range of concentrations. Overall, these findings demonstrate that CMP decoration provides substantial improvements in gene retention, altered release kinetics, improved serum-stability, and improved gene activity in vivo. This versatile technique has great potential for multiple applications in regenerative medicine. STATEMENT OF SIGNIFICANCE:In this work, we demonstrate a novel approach for stably integrating DNA into collagen scaffolds to exploit the natural process of collagen remodelling for high efficiency non-viral gene delivery. The incorporation of CMPs into DNA polyplexes, coupled with the innate affinity between CMPs and collagen, not only permitted improved control over polyplex retention and release, but also provided a series of substantial and highly unique benefits via the stable and persistent linkage between CMP-polyplexes and collagen fragments. Specifically, CMP-modification of polyplexes was demonstrated to (i) control release for nearly a month, (ii) improve vector stability under physiological-like conditions, and (iii) provide ligands able to efficiently transfer genes via endocytic collagen pathways. These unique properties overcome key barriers inhibiting non-viral gene therapy.

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Luminescent Biofunctional Collagen Mimetic Nanofibers.

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