We report simple, water-based fabrication methods based on protein self-assembly to generate 3D silk fibroin bulk materials that can be easily hybridized with water-soluble molecules to obtain multiple solid formats with predesigned functions. Controlling self-assembly leads to robust, machinable formats that exhibit thermoplastic behavior consenting material reshaping at the nanoscale, microscale, and macroscale. We illustrate the versatility of the approach by realizing demonstrator devices where large silk monoliths can be generated, polished, and reshaped into functional mechanical components that can be nanopatterned, embed optical function, heated on demand in response to infrared light, or can visualize mechanical failure through colorimetric chemistries embedded in the assembled (bulk) protein matrix. Finally, we show an enzyme-loaded solid mechanical part, illustrating the ability to incorporate biological function within the bulk material with possible utility for sustained release in robust, programmably shapeable mechanical formats.iomimicry draws inspiration from multiple material functions (e.g., antibacterial and antifouling, light manipulation, heat dissipation, water sequestration, superhydrophobicity, adhesiveness, and enhanced mechanical properties) to develop universal fabrication strategies to design new structural materials with utility in a variety of fields ranging from the biomedical, to the technological and architectural. Naturally occurring materials are generated through a bottom-up "generative" process that involves a nontrivial interplay of mechanisms acting across scales from the atomic to the macroscopic. In this context, the assembly of structural biopolymers, the fundamental building blocks of natural materials, leads to hierarchically organized architectures that impart unique functionality to the end material formats.Among the several structural proteins that have been studied, silk fibroin was recently shown to be suited for the generation of a number of biopolymer-based advanced material formats leveraging control of form (through sol-gelsolid transitions) and function (through material modification). The ability to generate functional materials based on water-based silk assembly is predicated on the control of the sol-gel-solid transitions of silk fibroin materials in ambient conditions. In Fig. 1A, the formation of 3D silk fibroin constructs is depicted through its dimensional hierarchy, from the nano-to the macroscales. Silk is extracted from natural sources (i.e., Bombyx mori cocoons) with a previously developed protocol (1) that yields a water suspension of the fibroin protein, where the protein molecules are organized in nanoscopic micelles (or nanoparticles) (top row of Fig. 1A), with an average diameter that changes as a function of concentration and molecular weight (Fig. S1).Control over the dynamics of water evaporation regulates silk-fibroin assembly at the molecular level and the endmaterial format properties. This has been previously observed for natural silk ...

Morphine is the opioid most commonly used for neonatal pain management. In intravenous form, it is administered as continuous infusions and intermittent injections, mostly based on empirically

Avastin treatment in IH has lasting alterations in the balance between MMPs and their tissue inhibitors. These changes may lead to impaired alveologenesis and tissue damage consistent with bronchopulmonary dysplasia/chronic lung disease.

Given the complexity of oxygen-induced retinopathy (OIR), we tested the hypothesis that combination therapies and modes of administration would synergistically optimize efficacy for prevention of OIR. Newborn rats were exposed to neonatal intermittent hypoxia (IH) from the first day of life (P0) until P14 during which they received: (1) oral glutathione nanoparticles (nGSH) with topical ocular phosphate buffered saline (PBS); (2) nGSH with topical ocular Acuvail (ACV); (3) oral coenzyme Q10 (CoQ10) + ACV; (4) oral omega 3 polyunsaturated fatty acids (n-3 PUFAs) + ACV; (5) CoQ10 + n-3 PUFAs + PBS; or (6) CoQ10 + n-3 PUFAs + ACV. Treated groups raised in room air (RA) served as controls. At P14, pups were placed in RA with no treatment until P21. Retinal vascular pathology, ocular angiogenesis biomarkers, histopathology, and morphometry were determined. All combination treatments in IH resulted in the most beneficial retinal outcomes consistent with suppression of angiogenesis growth factors during reoxygenation/reperfusion and no significant adverse effects on somatic growth. nGSH + PBS also reversed IH-induced retinopathy, but had negative effects on growth. Simultaneously targeting oxidants, inflammation, and poor growth mitigates the damaging effects of neonatal IH on the developing retina. Therapeutic synergy with combination delivery methods enhance individual attributes and simultaneously target multiple pathways involved in complex diseases such as OIR.