TGF-␤ has been shown to play a critical role in anti-inflammation; however, the signaling mechanisms of TGF-␤ in anti-inflammatory response remains largely unclear. This study reported that mice that overexpress latent TGF-␤1 on skin are protected against renal inflammation in a model of obstructive kidney disease and investigated the signaling mechanism of TGF-␤1 in inhibition of renal inflammation in vivo and in vitro. Seven days after urinary obstruction, wild-type mice developed severe renal inflammation, including massive T cell and macrophage infiltration and marked upregulation of IL-1␤, TNF-␣, and intercellular adhesion molecule-1 (all P < 0.001). Surprising, renal inflammation was prevented in transgenic mice. This was associated with an increase in latent TGF-␤1 in circulation (a 10-fold increase) and renal tissues (a 2.5-fold increase). Further studies showed that inhibition of renal inflammation in TGF-␤1 transgenic mice was also associated with a marked upregulation of renal Smad7 and IB␣ and a suppression of NF-B activation in the diseased kidney (all P < 0.01). These in vivo findings suggested the importance of TGF-␤-NF-B cross-talk signaling pathway in regulating renal inflammation. This was tested in vitro in a doxycycline-regulated Smad7-expressing renal tubular cell line. Overexpression of Smad7 was able to upregulate IB␣ directly in a time-and dose-dependent manner, thereby inhibiting NF-B activation and NF-B-driven inflammatory response. In conclusion, latent TGF-␤ may have protective roles in renal inflammation. Smad7-mediated inhibition of NF-B activation via the induction of IkB␣ may be the central mechanism by which latent TGF-␤ prevents renal inflammation.

Cellulose nanofibrils (CNFs) in the form of hydrogels stand out as a platform biomaterial in bioink formulation for 3D printing because of their low cytotoxicity and structural similarity to extracellular matrices. In the present study, 3D scaffolds were successfully printed with low-concentration inks formulated by 1 w/v % 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized CNF with less than 1 w/v % gelatin methacrylate (GelMA). Quartz crystal microbalance with dissipation monitoring (QCM-D) measurements showed strong interaction between the two biopolymers. The UV cross-linking ability of GelMA (≤1 w/v %) was enhanced in the presence of TEMPO-oxidized CNFs. Multiple factors including strong physical interaction between CNF and GelMA, in situ cross-linking of CNF by Ca 2+ , and UV cross-linking of GelMA enabled successful 3D printing of low-concentration inks of CNF/GelMA into scaffolds possessing good structural stability. The mechanical strength of the scaffolds was tuned in the range of 2.5 to 5 kPa. The cell culture with 3T3 fibroblasts revealed noncytotoxic and biocompatible features for the formulated inks and printed scaffolds. More importantly, the incorporated GelMA in the CNF hydrogel promoted the proliferation of fibroblasts. The developed low-concentration CNF/GelMA formulations with a facile yet effective approach to fabricate scaffolds showed great potential in 3D printing for wound healing application.

Wood-derived biopolymers have attracted great attention over the past few decades due to their abundant and versatile properties. The well-separated three main components, i.e., cellulose, hemicelluloses, and lignin, are considered significant candidates for replacing and improving on oil-based chemicals and materials. The production of nanocellulose from wood pulp opens an opportunity for novel material development and applications in nanotechnology. Currently, increased research efforts are focused on developing 3D printing techniques for wood-derived biopolymers for use in emerging application areas, including as biomaterials for various biomedical applications and as novel composite materials for electronics and energy devices. This Review highlights recent work on emerging applications of wood-derived biopolymers and their advanced composites with a specific focus on customized pharmaceutical products and advanced functional biomedical devices prepared via three-dimensional printing. Specifically, various biofabrication strategies in which woody biopolymers are used to fabricate customized drug delivery devices, cartilage implants, tissue engineering scaffolds and items for other biomedical applications are discussed.

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Despite the critical role that TGF-␤ plays in renal fibrosis, transgenic mice that overexpress human latent TGF-␤1 in the skin exhibit normal renal histology and function even though circulating levels of latent TGF-␤1 are an order of magnitude higher than wild-type animals. In fact, latent TGF-␤1 seems to protect against renal inflammation in a model of ureteral obstruction. It is unknown, however, whether latent TGF-␤1 also has this effect in immunologically mediated forms of renal disease such as anti-GBM crescentic glomerulonephritis. We induced anti-GBM disease in wild-type and transgenic mice overexpressing latent TGF-␤1 in keratinocytes. After 14 days, wild-type mice developed progressive crescentic glomerulonephritis with severe renal inflammation and fibrosis. In transgenic mice, proteinuria was reduced by 50%, renal function was preserved, and the formation of glomerular crescents was suppressed by 70%. In addition, transgenic animals had reduced renal inflammation, evidenced by a 70% decrease in the accumulation of T cells and macrophages, and reduced expression of renal IL-1␤, TNF␣, and MCP-1 by 70 to 80%. Progressive renal fibrosis was also prevented in the transgenic mice, and these protective effects were associated with elevated levels of latent, but not active, TGF-␤1 in plasma and renal tissue. Renal Smad7 was up-regulated and both NF-B and TGF-␤/Smad2/3 activation were suppressed. In conclusion, mice overexpressing latent TGF-␤1 in the skin were protected against anti-GBM crescentic glomerulonephritis, possibly via Smad 7-mediated inhibition of NF-B-dependent renal inflammation and TGF-␤/Smad2/3-dependent fibrosis.

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Hydrogel scaffolds with tunable mechanical strength were prepared by 3D-printing of 1 wt% one-component-only wood derived nanocellulose, and may support fibroblast cells’ proliferation.