TY - JOUR AB - Diabetic wounds are characterized by drug-resistant bacterial infections, biofilm formation, impaired angiogenesis and perfusion, and oxidative damage to the microenvironment. Given their complex nature, diabetic wounds remain a major challenge in clinical practice. Reactive oxygen species (ROS), which have been shown to trigger hyperinflammation and excessive cellular apoptosis, play a pivotal role in the pathogenesis of diabetic wounds. ROS-scavenging nanosystems have recently emerged as smart and multifunctional nanomedicines with broad synergistic applicability. The documented anti-inflammatory and pro-angiogenic ability of ROS-scavenging treatments predestines these nanosystems as promising options for the treatment of diabetic wounds. Yet, in this context, the therapeutic applicability and efficacy of ROS-scavenging nanosystems remain to be elucidated. Herein, the role of ROS in diabetic wounds is deciphered, and the properties and strengths of nanosystems with ROS-scavenging capacity for the treatment of diabetic wounds are summarized. In addition, the current challenges of such nanosystems and their potential future directions are discussed through a clinical-translational lens. AU - Xiong, Y.* AU - Chu, X.* AU - Yu, T.* AU - Knoedler, S. AU - Schroeter, A.* AU - Lu, L.* AU - Zha, K.* AU - Lin, Z.* AU - Jiang, D. AU - Rinkevich, Y. AU - Panayi, A.C.* AU - Mi, B.* AU - Liu, G.* AU - Zhao, Y.* C1 - 67610 C2 - 53917 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - Reactive oxygen species-scavenging nanosystems in the treatment of diabetic wounds. JO - Adv. Healthc. Mater. VL - 12 IS - 25 PB - Wiley PY - 2023 SN - 2192-2640 ER - TY - JOUR AB - Near-infrared (NIR) light absorbing theranostic agents can integrate optoacoustic imaging and photothermal therapy for effective personalized precision medicine. However, most of these agents face the challenges of unstable optical properties, material-associated toxicity, and nonbiodegradability, all of which limit their biomedical application. Several croconaine-based organic agents able to overcome some of these limitations have been recently reported, but these suffer from complicated multistep synthesis protocols. Herein, the use of CR760, a croconaine dye with excellent optical properties, is reported for nanoparticle formulation and subsequent optoacoustic imaging and photothermal therapy. Importantly, CR760 can be conveniently prepared in a single step from commercially available materials. Furthermore, CR760 can be covalently attached, via a polyethylene glycol linker, to the αvβ3 integrin ligand c(RGDyC), resulting in self-assembled nanoparticles (NPs) with cancer-targeting capability. Such CR760RGD-NPs exhibit strong NIR absorption, high photostability, high optoacoustic generation efficiency, and active tumor-targeting, making them ideal candidates for optoacoustic imaging. Due to favorable electron transfer, CR760RGD-NPs display a 45.37% photothermal conversion efficiency thereby rendering them additionally useful for photothermal therapy. Targeted tumor elimination, biosafety, and biocompatibility are demonstrated in a 4T1 murine breast tumor model. This work points to the use of CR760RGD-NPs as a promising nanoagent for NIR-based cancer phototheranostics. AU - Liu, N. AU - O'Connor, P. AU - Gujrati, V. AU - Gorpas, D. AU - Glasl, S. AU - Blutke, A. AU - Walch, A.K. AU - Kleigrewe, K.* AU - Sattler, M. AU - Plettenburg, O. AU - Ntziachristos, V. C1 - 61632 C2 - 50360 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - Facile synthesis of a croconaine-based nanoformulation for optoacoustic imaging and photothermal therapy. JO - Adv. Healthc. Mater. VL - 10 IS - 9 PB - Wiley PY - 2021 SN - 2192-2640 ER - TY - JOUR AB - Cellular dynamics are modeled by the 3D architecture and mechanics of the extracellular matrix (ECM) and vice versa. These bidirectional cell-ECM interactions are the basis for all vital tissues, many of which have been investigated in 2D environments over the last decades. Experimental approaches to mimic in vivo cell niches in 3D with the highest biological conformity and resolution can enable new insights into these cell-ECM interactions including proliferation, differentiation, migration, and invasion assays. Here, two-photon stereolithography is adopted to print up to mm-sized high-precision 3D cell scaffolds at micrometer resolution with defined mechanical properties from protein-based resins, such as bovine serum albumin or gelatin methacryloyl. By modifying the manufacturing process including two-pass printing or post-print crosslinking, high precision scaffolds with varying Young's moduli ranging from 7-300 kPa are printed and quantified through atomic force microscopy. The impact of varying scaffold topographies on the dynamics of colonizing cells is observed using mouse myoblast cells and a 3D-lung microtissue replica colonized with primary human lung fibroblast. This approach will allow for a systematic investigation of single-cell and tissue dynamics in response to defined mechanical and bio-molecular cues and is ultimately scalable to full organs. AU - Erben, A.* AU - Hörning, M.* AU - Hartmann, B.* AU - Becke, T.* AU - Eisler, S.A.* AU - Southan, A.* AU - Cranz, S. AU - Hayden, O.* AU - Kneidinger, N. AU - Königshoff, M. AU - Lindner, M. AU - Tovar, G.E.M.* AU - Burgstaller, G. AU - Clausen-Schaumann, H.* AU - Sudhop, S.* AU - Heymann, M.* C1 - 60281 C2 - 49307 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - Precision 3D-printed cell scaffolds mimicking native tissue composition and mechanics. JO - Adv. Healthc. Mater. VL - 9 IS - 24 PB - Wiley PY - 2020 SN - 2192-2640 ER - TY - JOUR AB - Transplantation of pancreatic islets is a promising strategy to alleviate the unstable blood-glucose control that some patients with diabetes type 1 exhibit and has seen many advances over the years. Protection of transplanted islets from the immune system can be accomplished by encapsulation within a hydrogel, the most investigated of which is alginate. In this study, islet encapsulation is combined with 3D extrusion bioprinting, an additive manufacturing method which enables the fabrication of 3D structures with a precise geometry to produce macroporous hydrogel constructs with embedded islets. Using a plottable hydrogel blend consisting of clinically approved ultrapure alginate and methylcellulose (Alg/MC) enables encapsulating pancreatic islets in macroporous 3D hydrogel constructs of defined geometry while retaining their viability, morphology, and functionality. Diffusion of glucose and insulin in the Alg/MC hydrogel is comparable to diffusion in plain alginate; the embedded islets continuously produce insulin and glucagon throughout the observation and still react to glucose stimulation albeit to a lesser degree than control islets. AU - Duin, S.* AU - Schütz, K.* AU - Ahlfeld, T.* AU - Lehmann, S. AU - Lode, A.* AU - Ludwig, B. AU - Gelinsky, M.* C1 - 55612 C2 - 46441 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - 3D bioprinting of functional islets of Langerhans in an alginate/methylcellulose hydrogel blend. JO - Adv. Healthc. Mater. VL - 8 IS - 7 PB - Wiley PY - 2019 SN - 2192-2640 ER - TY - JOUR AB - Metal-organic frameworks (MOFs) are promising platforms for the synthesis of nanoparticles for diverse medical applications. Their fundamental design principles allow for significant control of the framework architecture and pore chemistry, enabling directed functionalization for nanomedical applications. However, before applying novel nanomaterials to patients, it is imperative to understand their potential health risks. In this study, the nanosafety of different MOF nanoparticles is analyzed comprehensively for diverse medical applications. The authors first evaluate the effects of MOFs on human endothelial and mouse lung cells, which constitute a first line of defense upon systemic blood-mediated and local lung-specific applications of nanoparticles. Second, we validated these MOFs for multifunctional surface coatings of dental implants using human gingiva fibroblasts. Moreover, biocompatibility of MOFs is assessed for surface coating of nerve guidance tubes using human Schwann cells and rat dorsal root ganglion cultures. The main finding of this study is that the nanosafety and principal suitability of our MOF nanoparticles as novel agents for drug delivery and implant coatings strongly varies with the effector cell type. We conclude that it is therefore necessary to carefully evaluate the nanosafety of MOF nanomaterials with respect to their particular medical application and their interacting primary cell types, respectively. AU - Wuttke, S.* AU - Zimpel, A.* AU - Bein, T.* AU - Braig, S.* AU - Stoiber, K.* AU - Vollmar, A.* AU - Müller, D.* AU - Haastert-Talini, K.* AU - Schaeske, J.* AU - Stiesch, M.* AU - Zahn, G.* AU - Mohmeyer, A.* AU - Behrens, P.* AU - Eickelberg, O. AU - Bölükbas, D.A. AU - Meiners, S. C1 - 50092 C2 - 42018 CY - Hoboken TI - Validating metal-organic framework nanoparticles for their nanosafety in diverse biomedical applications. JO - Adv. Healthc. Mater. VL - 6 IS - 2 PB - Wiley-blackwell PY - 2016 SN - 2192-2640 ER -