Light‐Activated Decellularized Extracellular Matrix‐Based Bioinks for Volumetric Tissue Analogs at the Centimeter Scale

Abstract

Tissue engineering requires not only tissue‐specific functionality but also a realistic scale. Decellularized extracellular matrix (dECM) is presently applied to the extrusion‐based 3D printing technology. It has demonstrated excellent efficiency as bioscaffolds that allow engineering of living constructs with elaborate microarchitectures as well as the tissue‐specific biochemical milieu of target tissues and organs. However, dECM bioinks have poor printability and physical properties, resulting in limited shape fidelity and scalability. In this study, new light‐activated dECM bioinks with ruthenium/sodium persulfate (dERS) are introduced. The materials can be polymerized via a dityrosine‐based cross‐linking system with rapid reaction kinetics and improved mechanical properties. Complicated constructs with high aspect ratios can be fabricated similar to the geometry of the desired constructs with increased shape fidelity and excellent printing versatility using dERS. Furthermore, living tissue constructs can be safely fabricated with excellent tissue regenerative capacity identical to that of pure dECM. dERS may serve as a platform for a wider biofabrication window through building complex and centimeter‐scale living constructs as well as supporting tissue‐specific performances to encapsulated cells. This capability of dERS opens new avenues for upscaling the production of hydrogel‐based constructs without additional materials and processes, applicable in tissue engineering and regenerative medicine.

Tissue-Specific Decellularized Extracellular Matrix Bioinks for Musculoskeletal Tissue Regeneration and Modeling Using 3D Bioprinting Technology

“…While the processes for preserving biochemical components and solubilizing the dECM are focused on during decellularization, transient elastography and topography have been regarded as unavoidable processes [156]. To strengthen the weak physical properties of dECM bioinks, multiple approaches such as integrating with polymer scaffolds and incorporating into injectable dECM bioinks other synthetic and cross-linkable molecules such as polyethylene glycol diacrylate (PEGDA), vitamin B2, methacrylate, and Ru/SPS have been tried [81,85,157]. Furthermore, because the bioink has high mixability and modifiability through covalent bonds, hydrophobic and hydrophilic interactions, and electrostatic forces, cells, drugs, and growth factors can be introduced into dECM bioinks, which is also effective in recapitulating the heterogeneous microenvironment.…”

“…However, this process usually requires over 10 min to accomplish [79], and thus leads to the poor printability of dECM bioinks. To overcome this limitation, various strategies have been applied to improve the performance of tissue-specific bioinks, such as the incorporation of additives/crosslinkers and the chemical modification of dECM bioinks, which can help enable other rapid polymerizations (e.g., ionic and photo-gelation) [80,81].…”

Bioprinting Au Natural: The Biologics of Bioinks

“…Due to the high efficiency of ECM scaffolds at maintaining and promoting cellular adhesion/growth within their confines, additional work is underway on alternative stabilization techniques. Recent publications have shown that ECM can be stabilized by adding ruthenium and sodium persulfate, compounds that allow the bioink to be crosslinked using visible light following extrusion [ 86 ]. These gels were utilized in developing constructs up to 1 cm in size with high cell viability post-printing.…”

Recent Trends in Biofabrication Technologies for Studying Skeletal Muscle Tissue-Related Diseases

“…Notably, agrin—an ECM protein that enhances the clustering of acetylcholine receptors—was conserved in the mdECM ( Choi et al, 2016 ). In addition, dECM can be chemically processed or blended with other polymers before electrospinning or extrusion printing to fabricate a 3D scaffold integrated with tissue-specific biochemical cues and versatile structural cues ( Baiguera et al, 2014 ; Kim et al, 2020 ; Kim et al, 2021 ). Baiguera et al (2014) blended rat brain-derived dECM with gelatin prior to electrospinning and obtained a highly porous 3D scaffold that supported mesenchymal stem cell adhesion and growth.…”