Abstract
Cutaneous wound repair regenerates skin integrity, but a chronic failure to heal results in compromised tissue function and increased morbidity. To address this, we have used an integrated approach, using nanobiotechnology to augment the rate of wound reepithelialization by combining self-assembling peptide (SAP) nanofiber scaffold and Epidermal Growth Factor (EGF). This SAP bioscaffold was tested in a bioengineered Human Skin Equivalent (HSE) tissue model that enabled wound reepithelialization to be monitored in a tissue that recapitulates molecular and cellular mechanisms of repair known to occur in human skin. We found that SAP underwent molecular self-assembly to form unique 3D structures that stably covered the surface of the wound, suggesting that this scaffold may serve as a viable wound dressing. We measured the rates of release of EGF from the SAP scaffold and determined that EGF was only released when the scaffold was in direct contact with the HSE. By measuring the length of the epithelial tongue during wound reepithelialization, we found that SAP scaffolds containing EGF accelerated the rate of wound coverage by 5 fold when compared to controls without scaffolds and by 3.5 fold when compared to the scaffold without EGF. In conclusion, our experiments demonstrated that biomaterials composed of a biofunctionalized peptidic scaffold have many properties that are well-suited for the treatment of cutaneous wounds including wound coverage, functionalization with bioactive molecules, localized growth factor release and activation of wound repair.
Highlights
Skin functions to provide a physical and chemical interface that protects the host against invasion by toxins and microorganisms and prevents dehydration that can result from loss of barrier function
To achieve this therapeutic goal, it would be optimal to deliver biologically-meaningful doses of Epidermal Growth Factor (EGF) in a wound dressing. Such a bioactive dressing should fulfill several criteria for its optimal function: 1) biocompatibility in the absence of cytotoxicity, 2) applied to the wound, able to conform to the wound surface, and removable after healing, 3) provides a moist environment and protects the wound against dehydration, 4) allows gas exchange between the wounded tissue and the external environment, 5) biofunctionalized to allow the slow release of bioactive agents. In consideration of these criteria, we have studied if a novel, selfassembling peptide (SAP) nanofiber scaffold combined with EGF, could serve as a bio-active wound dressing
We have advanced the use of self-assembling peptide (SAP) by demonstrating the biological activity of peptides incorporated into the scaffold and by using the altered amino acid sequences containing the RAD motif: RADA16-I, RADARADARADARADARADA that are similar to the ubiquitous integrin receptor-binding site RGD [18,19,20] that have previously shown to elevate cytocompatibility and biointegration [21]
Summary
Skin functions to provide a physical and chemical interface that protects the host against invasion by toxins and microorganisms and prevents dehydration that can result from loss of barrier function. The loss of skin integrity and function due to wound injury has led to efforts designed to better comprehend the molecular and cellular mechanisms that can optimize wound repair [1,2,3]. The complex nature of wound healing requires the migration and proliferation of keratinocytes that are temporally-regulated by numerous growth factors and their receptors that are upregulated in the wound environment [4,5,6]. The complexity of the wound environment has been recreated in human, bioengineered in vitro 3D tissues known as human skin equivalents (HSE), that have many morphologic and phenotypic properties of human skin. We used HSEs to study the effect of a new growth factor-releasing biomaterial on wound reepithelialization
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