Collecting human skin samples for medical research, including developing microneedle-based medical devices, is challenging and time-consuming. Researchers rely on human skin substitutes and skin preservation techniques, such as freezing, to overcome the lack of skin availability. Porcine skin is considered the best substitute to human skin, but their mechanical resemblance has not been fully validated. We provide a direct mechanical comparison between human and porcine skin samples using a conventional mechano-analytical technique (microindentation) and a medical application (microneedle insertion), at 35% and 100% relative humidity. Human and porcine skin samples were tested immediately after surgical excision from subjects, and after one freeze-thaw cycle at −80 °C to assess the impact of freezing on their mechanical properties. The mechanical properties of fresh human and porcine skin (especially of the stratum corneum) were found to be different for bulk measurements using microindentation; and both types of skin were mechanically affected by freezing. Localized in-plane mechanical properties of skin during microneedle insertion appeared to be more comparable between human and porcine skin samples than their bulk out-of-plane mechanical properties. The results from this study serve as a reference for future mechanical tests conducted with frozen human skin and/or porcine skin as a human skin substitute.
Dynamic combinatorial chemistry (DCC) explores the thermodynamic equilibrium of reversible reactions. Its application in the discovery of protein binders is largely limited by difficulties in the analysis of complex reaction mixtures. DNA-encoded chemical library (DECL) technology allows the selection of binders from a mixture of up to billions of different compounds; however, experimental results often show low a signal-to-noise ratio and poor correlation between enrichment factor and binding affinity. Herein we describe the design and application of DNA-encoded dynamic combinatorial chemical libraries (EDCCLs). Our experiments have shown that the EDCCL approach can be used not only to convert monovalent binders into high-affinity bivalent binders, but also to cause remarkably enhanced enrichment of potent bivalent binders by driving their in situ synthesis. We also demonstrate the application of EDCCLs in DNA-templated chemical reactions.
Microneedles are small needle-like structures that are almost invisible to the naked eye. They have an immense potential to serve as a valuable tool in many medical applications, such as painless vaccination. Microneedles work by breaking through the stratum corneum, the outermost barrier layer of the skin, and providing a direct path for drug delivery into the skin. A lot of research has been presented over the past two decades on the applications of microneedles, yet the fundamental mechanism of how they interact, pressure, and penetrate the skin in its native state is worth examining further. As such, a major diffi culty with understanding the mechanism of microneedle-skin interaction is the lack of an artifi cial mechanical human skin model to use as a standardized substrate. In this research news, the development of an artifi cial mechanical skin model based on a thorough mechanical study of fresh human and porcine skin samples is presented. The artifi cial mechanical skin model can be used to study the mechanical interactions between microneedles and skin, but not diffusion of molecules across skin. This model can assist in improving the performance of microneedles by enhancing the reproducibility of microneedle depth insertions for optimal drug delivery and biosensing.
Dynamic combinatorial chemistry (DCC) explores the thermodynamic equilibrium of reversible reactions.I ts application in the discovery of protein binders is largely limited by difficulties in the analysis of complex reaction mixtures. DNA-encoded chemical library (DECL) technology allows the selection of binders from am ixture of up to billions of different compounds;h owever,e xperimental results often show low asignal-to-noise ratio and poor correlation between enrichment factor and binding affinity.Herein we describe the design and application of DNA-encoded dynamic combinatorial chemical libraries (EDCCLs). Our experiments have shown that the EDCCL approachc an be used not only to convert monovalent binders into high-affinity bivalent binders, but also to cause remarkably enhanced enrichment of potent bivalent binders by driving their in situ synthesis.W ea lso demonstrate the application of EDCCLs in DNA-templated chemical reactions.
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