Journal
ACS APPLIED BIO MATERIALS
Volume 3, Issue 11, Pages 7540-7549Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.0c00755
Keywords
collagen; transdermal delivery; glycosidic hydrolase; biomaterials; skin regeneration
Funding
- Council of Scientific and Industrial Research (CSIR), New Delhi
- DST
- Indian Council of Medical Research [5/3/8/4/2019-ITR]
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The present study reports a method for transporting high molecular weight collagen for skin regeneration. An independent engineered enzymatic vehicle that has the ability for efficient transdermal delivery of regenerative biomaterial was developed for tissue regeneration. Collagen has been well recognized as a skin regeneration molecule due to its interaction with the extracellular matrix to stimulate skin cell growth, proliferation, and differentiation. However, the transdermal delivery of collagen poses a significant challenge due to its high molecular weight as well as a lack of efficient approaches. Here, to improve the transdermal delivery efficiency, alpha-1,4-glycosidic hydrolase was engineered with genetically encoded 3,4-dihydroxy-L-phenylalanine, which enhanced its biological activity as revealed by microscale thermophoresis. The remodeled catalytic pocket resulted in enhanced substrate binding activity of the enzyme with a predominant glycosaminoglycan (chondroitin sulfate) present in the extracellular matrix of the skin. The engineered enzyme rapidly opened up the skin extracellular matrix fiber (15 min) to ferry collagen across the wall, without disturbing the cellular bundle architecture. Confocal microscopy indicated that macromolecules had diffused three times deeper into the engineered enzyme-treated skin than the native enzyme-treated skin. Gene expression, histopathology, and hematology analysis also supported the penetration of macromolecules. Cytotoxicity (mammalian cell culture) and in vivo (Caenorhabditis elegans and Rattus noryegicus) studies revealed that the congener enzyme could potentially be used as a penetration enhancer, which is of paramount importance for the multimillion cosmetic industries. Hence, it offers promise as a pharmaceutical enzyme for transdermal delivery bioenhancement and dermatological applications.
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