Simple Complexity: Incorporating Bioinspired Delivery Machinery within Self-Assembled Peptide Biogels

Abstract

Bioinspired self-assembly is a bottom-up strategy enabling biologically sophisticated nanostructured biogels that can mimic natural tissue. Self-assembling peptides (SAPs), carefully designed, form signal-rich supramolecular nanostructures that intertwine to form a hydrogel material that can be used for a range of cell and tissue engineering scaffolds. Using the tools of nature, they are a versatile framework for the supply and presentation of important biological factors. Recent developments have shown promise for many applications such as therapeutic gene, drug and cell delivery and yet are stable enough for large-scale tissue engineering. This is due to their excellent programmability—features can be incorporated for innate biocompatibility, biodegradability, synthetic feasibility, biological functionality and responsiveness to external stimuli. SAPs can be used independently or combined with other (macro)molecules to recapitulate surprisingly complex biological functions in a simple framework. It is easy to accomplish localized delivery, since they can be injected and can deliver targeted and sustained effects. In this review, we discuss the categories of SAPs, applications for gene and drug delivery, and their inherent design challenges. We highlight selected applications from the literature and make suggestions to advance the field with SAPs as a simple, yet smart delivery platform for emerging BioMedTech applications.

Injectable self-assembled GDF5-containing dipeptide hydrogels for enhanced tendon repair

“…The authors found that the composite hydrogel exhibited injectable characteristics and excellent hemostatic functions. Tanmay et al [ 27 ] synthesized a composite hydrogel using amino acids/peptides. The hydrogel also showed excellent injectability during the experiment, was used as a delivery vehicle for anticancer drugs, and was not affected by the external environment.…”

“…Compared with traditional biomaterials, self-assembled polypeptide hydrogels exhibit unique characteristics. First, the hydrogel can be used as a drug delivery system to deliver drugs precisely to the repair site in a sustained, metered manner [ [25] , [26] , [27] ]. Second, it can support and promote cell proliferation, differentiation, and tissue regeneration, providing favorable conditions for successful tissue engineering [ 22 , 28 , 29 ].…”

A Selective, Hydrogel‐Based Prodrug Delivery System Efficiently Activates a Suicide Gene to Remove Undifferentiated Human Stem Cells Within Neural Grafts

“…Biomaterials have been used extensively as drug delivery systems to improve the treatment of a plethora of disorders (see review), [ 12 ] including the delivery of drugs targeted at activating suicide genes. Most noteworthy has been the development [ 38 ] and subsequent clinical trial [ 39 ] of the intraocular polyvinyl alcohol (PVA) and ethylene vinyl acetate (EVA) suture‐implanted device (Vitrasert®) that sustained GCV over several months, delaying the progression of cytomegalovirus retinitis.…”

“…Additional to this will be the need for regulatory approval for the use of a genetically modified cell product, however the HSV-TK suicide gene has previously been used in several clinical trials of haematopoietic stem cell transplantation in leukemia within the EU and USA -see review. [37] Biomaterials have been used extensively as drug delivery systems to improve the treatment of a plethora of disorders (see review), [12] including the delivery of drugs targeted at activating suicide genes. Most noteworthy has been the development [38] and subsequent clinical trial [39] of the intraocular polyvinyl alcohol (PVA) and ethylene vinyl acetate (EVA) suture-implanted device (Vitrasert®) that sustained GCV over several months, delaying the progression of cytomegalovirus retinitis.…”

“…Previous studies have shown nanofibrous structure formation in SAP hydrogels, with subsequent modifications to enable biological signaling by the addition of a second component or the decoration of the core sequence – see review. [ 12 ] These systems however, lack an inherent delivery mechanism beyond steric hinderance of drug conjugates. Here, in a key technological advance, we utilized the peptide sequence isoleucine‐lysine‐valine‐alanine‐valine (IKVAV) of the α 1 subunit of laminin – the brain's major extracellular matrix (ECM) protein essential for cell adhesion and neuronal differentiation [ 23 ] – not only as decoration or for biochemical function, but also as the structure‐forming unit.…”