The clinical translation of 3D-bioprinted tissues is significantly limited by the cytotoxicity of synthetic photoinitiators used in photopolymerizable bioinks. To address this critical challenge, we developed a novel, fully photoinitiator-free bioink platform based on methacrylated decellularized extracellular matrix (dECM-MA) and a biomacromolecular crosslinker zein (BMC-Z). The key innovation of this work is the exploitation of the innate UV reactivity of tyrosine residues naturally abundant in dECM, which function as an intrinsic photoinitiator system. BMC-Z plays a dual role, simultaneously providing immediate rheological stability through a hydrophobic physical network and enhancing the tyrosine-mediated radical generation for covalent photocrosslinking. A Full Factorial Design (FFD) was employed to efficiently optimize the complex interactions between dECM-MA, hyaluronic acid (HA), hydroxyapatite (HAp), and BMC-Z. The optimal formulation (40 mg/mL dECM-MA, 2 mg/mL HA, 3 mg/mL HAp, 160 μL BMC-Z) exhibited excellent viscoelastic properties (tan δ = 0.286) and significantly enhanced storage modulus (G'). Remarkably, this bioink supported outstanding biological performance, demonstrating 95% ± 3% cell viability over 14 days and a 4.8-fold increase in cell proliferation (4.16 × 105 → 2.0 × 106 cells/scaffold). This study introduces a paradigm-shifting, non-toxic, and high-performance bioink strategy that effectively eliminates the dependency on exogenous photoinitiators, paving the way for safer and more clinically relevant tissue engineering applications.
Coşkun et al. (Wed,) studied this question.