# Triazine‐Trione Thermosets with High Processability for Scaffold Applications in Bone Tissue Engineering

## TL;DR

New biocompatible materials called TATO thermosets support bone cell growth and can be processed at mild temperatures, making them promising for bone tissue engineering.

## Contribution

The development of novel photo-clickable triazine-trione thermosets with high processability and osteogenic potential for bone tissue engineering.

## Key findings

- TATO materials showed biocompatibility comparable to polycaprolactone (PCL) in cell behavior and CAM assays.
- Transcriptomic analysis revealed upregulated mitotic processes in cells on T-ene compared to T-yne and PCL.
- Osteogenic gene expression patterns differed on TATO materials compared to PCL, though differentiation assays showed no significant differences.

## Abstract

Despite advances in scaffold development, many current biomaterials suffer from limited processability or poor biological performance. To address this, we previously introduced two novel triazine‐trione (TATO)‐based thermosets, T‐ene and T‐yne, as candidates for tissue engineering applications. In the present study, we aim to comprehensively evaluate the initial cellular response of bone marrow mesenchymal stem/stromal cells (BMSC) on TATO materials and their osteogenic potential, with a particular focus on their suitability for bone tissue engineering applications. Both T‐ene and T‐yne demonstrated biocompatibility comparable to polycaprolactone (PCL), as assessed by in vitro cell behavior and the chorioallantoic membrane (CAM) assay. Transcriptomic profiling via RNA sequencing of BMSC cultured on the materials revealed upregulation of mitotic processes in cells on T‐ene compared to T‐yne and PCL. Expression profiling of 92 osteogenic genes after 14 days in osteogenic media showed distinct gene regulation patterns in BMSC on the TATO materials compared to PCL. However, osteogenic differentiation assays, such as Alkaline Phosphatase activity and Alizarin Red R staining, showed no significant differences among the groups. These results suggest that T‐ene and T‐yne are promising, formable, and biocompatible candidates for use in bone tissue engineering applications.

Novel photo‐clickable triazine‐trione thermosets can be shaped and cured under mild conditions, including room and physiological temperatures. These materials are biocompatible and support osteogenic differentiation of bone marrow–derived mesenchymal stem cells on their surface. Their processability and cell‐supportive properties highlight their potential as versatile scaffolding biomaterials for bone tissue engineering and regenerative medicine.