Combinatorial Use of Therapeutic ELP‐Based Micelle Particles in Tissue Engineering

Abstract

Elastin-like peptides (ELPs) are a versatile platform for tissue engineering and drug delivery. Here, micelle forming ELP chains are genetically fused to three therapeutic molecules, keratinocyte growth factor (KGF), stromal cell-derived growth factor 1 (SDF1), and cathelicidin (LL37), to be used in wound healing. Chronic wounds represent a growing problem worldwide. A combinatorial therapy approach targeting different aspects of wound healing would be beneficial, providing a controlled and sustained release of active molecules, while simultaneously protecting these therapeutics from the surrounding harsh wound environment. The results of this study demonstrate that the conjugation of the growth factors KGF and SDF1 and the antimicrobial peptide LL37 to ELPs does not affect the micelle structure and that all three therapeutic moieties retain their bioactivity in vitro. Importantly, when the combination of these micelle ELP nanoparticles are applied to wounds in diabetic mice, over 90 % wound closure is observed, which is significantly higher than when the therapeutics are applied in their naked forms. The application of the nanoparticles designed here is the first report of targeting different aspect of wound healing synergistically.

Molecular Complementarity of Proteomimetic Materials for Target‐Specific Recognition and Recognition‐Mediated Complex Functions

“…This temperature-responsive property of ELP has recently been combined with wound healing-related proteins or peptides for the effective delivery of therapeutic molecules (Figure 5a). [299] For Figure 5. Use of various stimuli to control protein-like functions.…”

“…This temperature‐responsive property of ELP has recently been combined with wound healing‐related proteins or peptides for the effective delivery of therapeutic molecules (Figure 5a). [ 299 ] For this purpose, the ELP was designed with 60 repeats of hydrophilic as well as hydrophobic pentamers, respectively to induce micelle formation at a temperature above 34 °C, and further modified with three different proteins: keratinocyte growth factor for epidermal regeneration, stromal cell‐derived factor 1 for dermal regeneration, and the human antimicrobial peptide, LL37, for antimicrobial activity. These protein‐modified ELPs, exhibiting spherical micelle formation above 34 °C, were beneficial for in vivo administration and protection of the labelled proteins during delivery.…”

The construction of elastin-like polypeptides and their applications in drug delivery system and tissue repair

“…In cancer therapy, drug delivery focuses primarily on delivering an adequate amount of medication to the disease location, thereby minimizing drug dispersion in healthy tissue [97,98]. In order to do this, two basic tactics that both aim to change the drug's pharmacokinetic characteristics have been widely used.…”

Extracellular Matrix-Mimetic Intrinsic Versatile Coating Derived from Marine Adhesive Protein Promotes Diabetic Wound Healing through Regulating the Microenvironment

“…On the other hand, ECM components, including collagen, laminin, and growth factors, are able to specifically recognize immune cell surface receptors to mediate cell adhesion, which plays a critical role in regulating macrophage polarization. , Moreover, to better manage bacterial infections, the commonly used strategy is loading antibiotics, silver nanoparticles, and extracted drugs into dressings . But undeniably, the antibiotic resistance of pathogenic bacteria, potential toxicity, and low bioavailability have attracted more attention. ,, Alternatively, antibacterial peptides (AMPs) have been widely used in diabetic wounds due to their broad-spectrum antibacterial properties. , LL37, as the only member of the human cathelicidin family of AMPs, has been proven to promote wound healing by exerting antibacterial activity, promoting angiogenesis, and regulating inflammation. − Therefore, it is critical to exquisitely engineer ECM-mimetic functional dressings that are easy to fabricate and possess intrinsic activities, including antibacterial and immunoregulatory activities for diabetic wound healing.…”