Optogenetics and photonic technologies are changing the future of medicine. To implement light-based therapies in the clinic, patient-friendly devices that can deliver light inside the body while offering tunable properties and compatibility with soft tissues are needed. Here extrusion printing of degradable, hydrogel-based optical waveguides with optical losses as low as 0.1 dB cm −1 at visible wavelengths is described. Core-only and core-cladding fibers are printed at room temperature from polyethylene glycol (PEG)-based and PEG/Pluronic precursors, and cured by in situ photopolymerization. The obtained waveguides are flexible, with mechanical properties tunable within a tissue-compatible range. Degradation times are also tunable by adjusting the molar mass of the diacrylate gel precursors, which are synthesized by linking PEG diacrylate (PEGDA) with varying proportions of DL-dithiothreitol (DTT). The printed waveguides are used to activate photochemical and optogenetic processes in close-to-physiological environments. Light-triggered migration of cells in a photoresponsive 3D hydrogel and drug release from an optogenetically-engineered living material by delivering light across >5 cm of muscle tissue are demonstrated. These results quantify the in vitro performance, and reflect the potential of the printed degradable fibers for in vivo and clinical applications.

Hydrogels for wound management and tissue gluing applications have to adhere to tissues for a given time scale and then disappear, either by removal from the skin or by slow degradation for applications inside the body. Advanced wound management materials also envision the encapsulation of therapeutic drugs or cells to support the natural healing process. The design of hydrogels that can fulfill all of these properties with minimal chemical complexity, a stringent condition to favor transfer into a real medical device, is challenging. Herein, we present a hydrogel design with a moderate structural complexity that fulfills a number of relevant properties for wound dressing: it can form in situ and encapsulate cells, it can adhere to tissues, and it can be degraded on demand by light exposure under cytocompatible conditions. The hydrogels are based on starPEG macromers terminated with catechol groups as cross-linking units and contain intercalated photocleavable nitrobenzyl triazole groups. Hydrogels are formed under mild conditions (N-(2-hydroxyethyl)­piperazine-N′-ethanesulfonic acid (HEPES) buffer with 9–18 mM sodium periodate as the oxidant) and are compatible with encapsulated cells. Upon light irradiation, the cleavage of the nitrobenzyl group mediates depolymerization, which enables the on-demand release of cells and debonding from tissues. The molecular design and obtained properties reported here are interesting for the development of advanced wound dressings and cell therapies and expand the range of functionality of current alternatives.

Geminin, a DNA replication licensing inhibitor, ensures faithful DNA replication in vertebrates. Several studies have shown that geminin depletion in vitro results in rereplication and DNA damage, whereas increased expression of geminin has been observed in human cancers. However, conditional inactivation of geminin during embryogenesis has not revealed any detectable DNA replication defects. In order to examine its role in vivo, we conditionally inactivated geminin in the murine colon and lung, and assessed chemically induced carcinogenesis. We show here that mice lacking geminin develop a significantly higher number of tumors and bear a larger tumor burden than sham-treated controls in urethane-induced lung and azoxymethane/dextran sodium sulfate-induced colon carcinogenesis. Survival is also significantly reduced in mice lacking geminin during lung carcinogenesis. A significant increase in the total number and grade of lesions (hyperplasias, adenomas, and carcinomas) was also confirmed by hematoxylin and eosin staining. Moreover, increased genomic aberrations, identified by increased ATR and γH2AX expression, was detected with immunohistochemistry analysis. In addition, we analyzed geminin expression in human colon cancer, and found increased expression, as well as a positive correlation with ATM/ATR levels and a non-monotonic association with γH2AX. Taken together, our data demonstrate that geminin acts as a tumor suppressor by safeguarding genome stability, whereas its overexpression is also associated with genomic instability. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.