Genetically engineered silk-elastinlike protein polymers for controlled drug delivery

Megeed, Zaki; Cappello, Joseph; Ghandehari, Hamidreza

doi:10.1016/s0169-409x(02)00063-7

Cited by 213 publications

(215 citation statements)

References 37 publications

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“…According to the literature, many SELRs have been purified by different methods that invariably comprise a chromatographic step 37 . However, chromatography is expensive, requires specialized equipment and is difficult to scale up, therefore alternative protocols are preferred.…”

Section: Mesllp-{[(vpgvg)2-(vpgeg)-(vpgvg)2]10[vgipg]60}2-v and (2) Mmentioning

confidence: 99%

Self-Organized ECM-Mimetic Model Based on an Amphiphilic Multiblock Silk-Elastin-Like Corecombinamer with a Concomitant Dual Physical Gelation Process

et al. 2014

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ABSTRACT. Although significant progress has been made in the area of injectable hydrogels for biomedical applications and model cell niches, further improvements are still needed, especially in terms of mechanical performance, stability and biomimicry of the native fibrillar architecture found in the extracellular matrix (ECM). This work focuses on the design and production of a silk-elastin-based injectable multiblock co-recombinamer that spontaneously forms a stable physical nanofibrillar hydrogel under physiological conditions. That differs from previously reported silk-elastin-like polymers on a major content and predominance of the elastin-like part, as well as a more complex structure and behavior of such part of the molecule, which is aimed to obtain well defined hydrogels.Rheological and DSC experiments showed that this system displays a coordinated and concomitant dual gelation mechanism. In a first stage, a rapid, thermally driven gelation of the co-recombinamer solution takes place once the system reaches body temperature due to the thermal responsiveness of the elastinlike (EL) parts and the amphiphilic multiblock design of the co-recombinamer. A bridged micellar 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 2 structure is the dominant microscopic feature of this stage, as demonstrated by AFM and TEM.Completion of the initial stage triggers the second, which comprises a stabilization, reinforcement, and microstructuring of the gel. FTIR analysis shows that these events involve the formation of β-sheets around the silk motifs. The emergence of such β-sheet structures leads to the spontaneous selforganization of the gel into the final fibrous structure. Despite the absence of biological cues, here we set the basis of the minimal structure that is able to display such a set of physical properties and undergo microscopic transformation from a solution to a fibrous hydrogel. The results point to the potential of this system as a basis for the development of injectable fibrillar biomaterial platforms towards a fully functional, biomimetic, artificial extracellular matrix and cell niches.

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Section: Mesllp-{[(vpgvg)2-(vpgeg)-(vpgvg)2]10[vgipg]60}2-v and (2) Mmentioning

confidence: 99%

Self-Organized ECM-Mimetic Model Based on an Amphiphilic Multiblock Silk-Elastin-Like Corecombinamer with a Concomitant Dual Physical Gelation Process

et al. 2014

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“…One route to increasing its solubility is the incorporation of peptide sequences from other proteins, such as elastin, that disrupt β-sheet formation [50]. Silk elastin-like polypeptides (SELPs) are chimeric proteins designed to retain the mechanical properties of silk, while incorporating the high solubility and environmental sensitivity of ELPs [139,161,168]. Some SELPs can be injected through hypodermic needles, and they then form insoluble hydrogels at the injection site without chemical assistance [162,[169][170][171].…”

Section: Silk-elp Hybridsmentioning

confidence: 99%

“…Multiple physical or chemical crosslinking sites can be genetically encoded so that the ELPs form networks, and reactive sites can be incorporated for controlled degradation. Specific ligands can also be added to impart functionality for cell adhesion and tissue growth [168,180,189,[195][196][197], and initial work by Urry et al demonstrated that ELPs cause minimal cytotoxicity and immune response when implanted [189,190].…”

Section: Genetically Engineered Polypeptidesmentioning

confidence: 99%

Peptide-based biopolymers in biomedicine and biotechnology

Chow

Nunalee

Lim

et al. 2008

Materials Science and Engineering: R: Reports

286

231

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Peptides are emerging as a new class of biomaterials due to their unique chemical, physical, and biological properties. The development of peptide-based biomaterials is driven by the convergence of protein engineering and macromolecular self-assembly. This review covers the basic principles, applications, and prospects of peptide-based biomaterials. We focus on both chemically synthesized and genetically encoded peptides, including poly-amino acids, elastin-like polypeptides, silk-like polymers and other biopolymers based on repetitive peptide motifs. Applications of these engineered biomolecules in protein purification, controlled drug delivery, tissue engineering, and biosurface engineering are discussed.

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“…As is the case with ELR-polymer solutions, SELP ones can be mixed with drugs, thus allowing homogenous entrapment of the compound once the gelling process occurs. Thus, the release profiles for different compounds, such as cytochrome c, theophylline, vitamin B12, the recombinant protein mitotoxin and several fluorescently labeled probes, have been explored and several parameters, such as the molecular weight of the drug, the concentration of the SELP and its specific composition, have been found to influence drug release [114,115]. The application of SELPs has not been limited exclusively to drug carriers as their use for the localized matrix-mediated delivery of viral vectors has also been explored.…”

Section: Drug Delivery From Elr-based Hydrogelsmentioning

confidence: 99%

“…Cryo-TEM image shows the morphological property of the assembly [124]. Adapted with permission from reference [115]. , , and , respectively, in PBS (pH 7.4) at (A) 25 °C and (B) 37 °C.…”

Section: Further Use Of Elrs In Drug Deliverymentioning

confidence: 99%

Recent Contributions of Elastin-Like Recombinamers to Biomedicine and Nanotechnology

Arias¹,

Santos²,

Fernández‐Colino³

et al. 2014

CTMC

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Abstract:The emergence of the new scientific field known as nanomedicine is being catalyzed by multiple improvements in nanoscience techniques and significant progress in materials science, especially as regards the testing of novel and sophisticated biomaterials. This conjuncture has furthered the development of promising instruments in terms of detection, bioanalysis, therapy, diagnostics and imaging. Some of the most innovative new biomaterials are protein-inspired biomimetic materials in which modern biotechnology and genetic-engineering techniques complement the huge amount of information afforded by natural protein evolution to create advanced and tailor-made multifunctional molecules. Amongst these protein-based biomaterials, Elastin-like Recombinamers (ELRs) have demonstrated their enormous potential in the fields of biomedicine and nanoscience in the last few years. This broad applicability derives from their unmatched properties, particularly their recombinant and tailor-made nature, the intrinsic characteristics derived from their elastin-based origin (mainly their mechanical properties and ability to self-assemble as a result of their stimuli-responsive behavior), their proven biocompatibility and biodegradability, as well as their versatility as regards incorporating advanced chemical or recombinant modifications into the original structure that open up an almost unlimited number of multifunctional possibilities in this developing field. This article provides an updated review of the recent challenges overcome by using these recombinant biomaterials in the fields of nano-and biomedicine, ranging from nanoscale applications in surface modifications and self-assembled nanostructures to drug delivery and regenerative medicine.

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Genetically engineered silk-elastinlike protein polymers for controlled drug delivery

Cited by 213 publications

References 37 publications

Self-Organized ECM-Mimetic Model Based on an Amphiphilic Multiblock Silk-Elastin-Like Corecombinamer with a Concomitant Dual Physical Gelation Process

Self-Organized ECM-Mimetic Model Based on an Amphiphilic Multiblock Silk-Elastin-Like Corecombinamer with a Concomitant Dual Physical Gelation Process

Peptide-based biopolymers in biomedicine and biotechnology

Recent Contributions of Elastin-Like Recombinamers to Biomedicine and Nanotechnology

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