To create tissue replacements with qualities similar to human tissues, and for ease of tissue loss repair, novel 3D printing fabrication methods have recently been introduced and popularized in the field of tissue engineering and regenerative medicine as an alternative to the scaffold fabrication methods. 3D printing may provide the fabricate process to better mimic the internal microstructure and external appearance. Printable bioink should be developed for stable 3D structure stratification. Advanced bioinks for 3D printing are rationally designed materials intended to improve the functionality of printed tissue scaffolds. The search for an appropriate bioink capable of providing a suitable microenvironment to support cellular activities is ongoing. The extracellular matrix (ECM) provides instructive cues for cell attachment, proliferation, differentiation, and ultimately tissue regeneration. The use of ECM-based biomaterials in regenerative medicine is therefore, rapidly expanding. In this respect, the decellularized ECM biomaterials have gained popularity as an excellent source of bioink, given its capability to inherit the intrinsic cues from a native ECM. In this chapter, we describe the current status of ECM-based biomaterials, the emerging trends in ECM bioink development, and bioink requirements that could enable proper selection of the bioink to fabricate an engineered tissue/organ. In particular, rheological properties of bioprinting materials are significant for printing resolution and shape fidelity. We propose a general method of measuring non-Newtonian rheological properties based on rotational rheometers in oscillatory mode. In addition, the mathematical modeling incorporating the power law model is discussed. These approaches can be easily used to optimize printing parameters and verify the bioink printability because a variety of dECM-based bioinks possess shear-thinning properties.

This comprehensive review delves into the world of hyaluronic acid (HA) hydrogels, exploring their creation, characteristics, research methodologies, and uses. HA hydrogels stand out among natural polysaccharides due to their distinct features. Their exceptional biocompatibility makes them a top choice for diverse biomedical purposes, with a great ability to coexist harmoniously with living cells and tissues. Furthermore, their biodegradability permits their gradual breakdown by bodily enzymes, enabling the creation of temporary frameworks for tissue engineering endeavors. Additionally, since HA is a vital component of the extracellular matrix (ECM) in numerous tissues, HA hydrogels can replicate the ECM’s structure and functions. This mimicry is pivotal in tissue engineering applications by providing an ideal setting for cellular growth and maturation. Various cross-linking techniques like chemical, physical, enzymatic, and hybrid methods impact the mechanical strength, swelling capacity, and degradation speed of the hydrogels. Assessment tools such as rheological analysis, electron microscopy, spectroscopy, swelling tests, and degradation studies are employed to examine their attributes. HA-based hydrogels feature prominently in tissue engineering, drug distribution, wound recovery, ophthalmology, and cartilage mending. Crafting HA hydrogels enables the production of biomaterials with sought-after qualities, offering avenues for advancements in the realm of biomedicine.

In this work, we developed novel stimuli-responsive injectable hydrogels composed of a highly biocompatible cartilage acellularized matrix (CAM) and a water-soluble cross-linker containing a diselenide bridge by using ultrafast norbornene (Nb)-tetrazine (Tz) click chemistry. The cross-linking reaction between the Nb groups of the CAM and Tz groups of the cross-linker evolved nitrogen gas and resulted in injectable hydrogels with highly porous structures. The synthesized hydrogels demonstrated high drug loading efficiencies (up to 93%), good swelling ratios, and useful mechanical properties. The doxorubicin (DOX)-loaded hydrogels released minimal amounts of DOX in the simulated physiological medium; however, sustained release of DOX was detected under reducing conditions, revealing more than 90% DOX release after 96 h. Interestingly, the indocyanine green (ICG)-incorporated hydrogels produced reactive oxygen species upon exposure to NIR light and exhibited burst release (>50% DOX release) of DOX during the first 4 h, followed by a sustained release phase. In vitro cytocompatibility tests showed that the synthesized CAM-Nb and hydrogels are essentially nontoxic to HFF-1 fibroblast cells and human colorectal adenocarcinoma cells (HT-29), indicating their excellent bioorthogonality and biocompatibility. Furthermore, DOX-loaded and DOX + ICG-loaded hydrogels inhibited the metabolic activities of HT-29 cells after GSH or NIR exposure and induced antitumor effects similar to those of free DOX. Therefore, these biocompatible and reduction-responsive injectable hydrogels, which exhibited on-demand drug release after NIR exposure, could be promising candidates for minimally invasive local delivery of cancer therapeutics.