Dominika Zielinska

Nature has perfected the reversible control over the activity of molecules and biomolecules in the human body. Pho- tocages aim to mimic this control in space and time using light as a trigger, and the field has witnessed many excellent contributions that extend their use to the tissue-penetrating region. Yet little attention has been paid to developing simple caging strategies which are crucial to translating photocages into a widely accepted tool beyond chemical space. Here, we report a robust and user-friendly protocol that enables the installation of complex amine, thiol and phenol pay- loads in a single step under mild conditions and using bench-stable in- termediates. The protocol displays excellent compatibility with a range of payloads, manifested by caging hormones, neurotransmitters, a tripeptide and many highly complex FDA-approved drugs, including antibiotics and anti-cancer agents. As a proof of concept, we applied this strategy to cage the clinically approved CDK4/6 inhibitor palbo- ciclib and evaluated its near-infrared (NIR) light-dependent activation in modulating the tumor-suppressing retinoblastoma protein. We an- ticipate that this user-friendly synthetic approach to accessing NIR- absorbing photocages will accelerate research across various scientific disciplines.

Microtia is a congenital disorder that manifests as a malformation of the external ear leading to psychosocial problems in affected children. Here, we present a tissue-engineered treatment approach based on a bioprinted autologous auricular cartilage construct (EarCartilage) combined with a bioengineered human pigmented and prevascularized dermo-epidermal skin substitute (EarSkin) tested in immunocompromised rats. We confirmed that human-engineered blood capillaries of EarSkin connected to the recipient’s vasculature within 1 week, enabling rapid blood perfusion and epidermal maturation. Bioengineered EarSkin displayed a stratified epidermis containing mature keratinocytes and melanocytes. The latter resided within the basal layer of the epidermis and efficiently restored the skin color. Further, in vivo tests demonstrated favorable mechanical stability of EarCartilage along with enhanced extracellular matrix deposition. In conclusion, EarCartilage combined with EarSkin represents a novel approach for the treatment of microtia with the potential to circumvent existing limitations and improve the aesthetic outcome of microtia reconstruction.

Microtia is a congenital condition of abnormal development of the outer ear. Tissue engineering of the ear is an alternative treatment option for microtia patients. However, for this approach, the identification of high regenerative cartilage progenitor cells is of vital importance. Raman analysis provides a novel, non-invasive, label-free diagnostic tool to detect distinctive biochemical features of single cells or tissues. Using micro-Raman spectroscopy, we were able to distinguish and characterize the particular molecular fingerprints of differentiated chondrocytes and perichondrocytes and their respective progenitors isolated from healthy individuals and microtia patients. We found that microtia chondrocytes exhibited lower lipid concentrations in comparison to healthy cells, thus indicating the importance of fat storage. Moreover, we suggest that collagen is a useful biomarker for distinguishing between populations obtained from the cartilage and perichondrium because of the higher spectral contributions of collagen in the chondrocytes compared to perichondrocytes from healthy individuals and microtia patients. Our results represent a contribution to the identification of cell markers that may allow the selection of specific cell populations for cartilage tissue engineering. Moreover, the observed differences between microtia and healthy cells are essential for gaining better knowledge of the cause of microtia. It can be useful for designing novel treatment options based on further investigations of the discovered biochemical substrate alterations.

Primary thymic carcinomas are very rare tumors. Their incidence is estimated around 1 to 3 cases per 10 million inhabitants. In this group, lymphoepithelioma-like carcinoma occurs (LELC) in 5–32% and the prognosis of advanced cases is poor. A 17-year-old man was admitted to the hospital...