Graft-Host Interaction and Its Effect on Wound Repair Using Mouse Models.

Autologous skin grafting has been commonly used in clinics for decades to close large wounds, yet the cellular and molecular interactions between the wound bed and the graft that mediates the wound repair are not fully understood. The aim of this study was to better understand the molecular changes in the wound triggered by autologous and synthetic grafting. Defining the wound changes at the molecular level during grafting sets the basis to test other engineered skin grafts by design. In this study, a full-thickness skin graft (SKH-1 hairless) mouse model was established. An autologous full-thickness skin graft (FTSG) or an acellular fully synthetic Biodegradable Temporising Matrix (BTM) was grafted. The wound bed/grafts were analysed at histological, RNA, and protein levels during the inflammation (day 1), proliferation (day 5), and remodelling (day 21) phases of wound repair. The results showed that in this mouse model, similar to others, inflammatory marker levels, including Il-6, Cxcl-1, and Cxcl-5/6, were raised within a day post-wounding. Autologous grafting reduced the expression of these inflammatory markers. This was different from the wounds grafted with synthetic dermal grafts, in which Cxcl-1 and Cxcl-5/6 remained significantly high up to 21 days post-grafting. Autologous skin grafting reduced wound contraction compared to wounds that were left to spontaneously repair. Synthetic grafts contracted significantly more than FTSG by day 21. The observed wound contraction in synthetic grafts was most likely mediated at least partly by myofibroblasts. It is possible that high TGF-ß1 levels in days 1-21 were the driving force behind myofibroblast abundance in synthetic grafts, although no evidence of TGF-ß1-mediated Connective Tissue Growth Factor (CTGF) upregulation was observed.

High-Fidelity, Sub-5 nm Patterns from High-χ Block Copolymer Films with Vapor-Deposited Ultrathin, Cross-Linked Surface-Modification Layers.

Despite their capability, sub-10 nm periodic nano-patterns formed by strongly segregating block copolymer (BCP) thin films cannot be easily oriented perpendicular to the substrate due to the huge surface energy differences of the constituent blocks. To produce perpendicular nano-patterns, the interfacial energies of both the substrate and free interfaces should be controlled precisely to induce non-preferential wetting. Unfortunately, high-performance surface modification layers are challenging to design, and different kinds of surface modification methods must be devised respectively for each neutral layer and top coat. Furthermore, conventional approaches, largely based on spin-coating processes, are highly prone to defect formation and may readily cause dewetting at sub-10 nm thickness. To date, these obstacles have hampered the development of high-fidelity, sub-5 nm BCP patterns. Herein, an all-vapor phase deposition approach initiated chemical vapor deposition is demonstrated to form 9-nm-thick, uniform neutral bottom layer and top coat with exquisite control of composition and thickness. These layers are employed in BCP films to produce perpendicular cylinders with a diameter of ≈4 nm that propagate throughout a BCP thickness of up to ≈60 nm, corresponding to five natural domain spacings of the BCP. Such a robust approach will serve as an advancement for the reliable generation of sub-10 nm nano-patterns.

Combinatorially designed lipid-like nanoparticles for intracellular delivery of cytotoxic protein for cancer therapy.

An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein-based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid-like materials (termed "lipidoids"), coupled with a reversible chemical protein engineering approach. Using ribonuclease A (RNase A) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure-function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein-lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16-1) protein nanoparticle formulation inhibits cell proliferation in vitro and suppresses tumor growth in a murine breast cancer model.