Tissue/organ-derived bioink formulations open up new avenues in 3D bioprinting research with the potential to create functional tissue or organs. Printing of tissue construct largely depends on material properties, as it needs to be fabricated in an aqueous environment while encapsulating living cells. The decellularized extracellular matrix bioinks proved to be a potential option for functional tissue development in vivo and as an alternative to chemically cross-linked bioinks. However, certain limitations such as printability and limited mechanical strength need to be addressed for enhancing their widespread applications. By drawing knowledge from the existing literature, emphasis has been given in this review to the development of decellularized extracellular matrix bioinks and their applications in printing functional tissue constructs.

The tumor microenvironment typically comprises cancer cells, tumor vasculature, stromal components like fibroblasts, and host immune cells that assemble to support tumorigenesis. However, preexisting classic cancer models like 2D cell culture methods, 3D cancer spheroids, and tumor organoids seem to lack essential tumor microenvironment components. 3D bioprinting offers enormous advantages for developing in vitro tumor models by allowing user-controlled deposition of multiple biomaterials, cells, and biomolecules in a predefined architecture. This review highlights the recent developments in 3D cancer modeling using different bioprinting techniques to recreate the TME. 3D bioprinters enable fabrication of high-resolution microstructures to reproduce TME intricacies. Furthermore, 3D bioprinted models can be applied as a preclinical model for versatile research applications in the tumor biology and pharmaceutical industries. These models provide an opportunity to develop high-throughput drug screening platforms and can further be developed to suit individual patient requirements hence giving a boost to the field of personalized anti-cancer therapeutics. We underlined the various ways the existing studies have tried to mimic the TME, mimic the hallmark events of cancer growth and metastasis within the 3D bioprinted models and showcase the 3D drug-tumor interaction and further utilization of such models to develop personalized medicine.

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There is an enormous demand for bone graft biomaterials to treat developmental and acquired bony defects arising from infections, trauma, tumor, and other conditions. Polycaprolactone (PCL) has been extensively utilized for bone tissue engineering but limited cellular interaction and tissue integration are the primary concerns. PCL-based composites with different biomaterials have been attempted to improve the mechanical and biological response. Interestingly, a few studies have tried to blend PCL with aqueous silk fibroin solution, but the structures prepared with the blend were mechanically weak due to phase mismatch. As a result, silk microparticle-based PCL composites have been prepared, but the microfibers-reinforced composites could be superior to them due to significant fiber-matrix interaction. This study aims at developing a unique composite by incorporating 100-150 μm long (aspect ratio; 8:1-5:1) silk-fibroin microfibers into the PCL matrix for superior biological and mechanical properties. Two silk variants were used, that is, Bombyx mori and a wild variant, Antheraea mylitta, reported to have cell recognizable Arginine-Glycine-Aspartic acid (RGD) sequences. A. mylitta silk fibroin microfibers were produced, and composites were made with PCL for the first time. The morphological, tensile, thermal, biodegradation, and biological properties of the composites were evaluated. Importantly, we tried to optimize the silk concentration within the composite to strike a balance among the cellular response, biodegradation, and mechanical strength of the composites. The results indicate that the PCL-silk fibroin microfiber composite could be an efficient biomaterial for bone tissue engineering.

The assessment of mechanical stiffness is an essential diagnostic tool for investigating the biomechanical properties of biological tissues. Surface wave elastography (SWE) is an emerging technique to quantify elastic properties of tissues in clinical diagnosis. High-speed optical imaging combined with SWE has enormous potential in quantifying the elastic properties of tissues at microscale resolutions. In this study, we implement surface wave elastography using high-speed optical interferometry to characterize the elastic properties of tissue-mimicking phantoms and ex-vivo native caprine liver tissue by imaging the surface wave induced by an electromechanical actuator. The sinusoidal mechanical excitations ranging from 120 Hz to 1.2 kHz on the surface of tissues are captured using a high-speed camera with a frame rate of 4 kHz at micrometer resolutions. The surface wavefront reconstruction is performed using a phase-shifting algorithm and linear regression is used to calculate the surface wave velocity. The mechanical stiffness estimated from the optical system is compared with the results of mechanical compression testing measurements. The results from this multimodal platform combining optical interferometry and vibrational spectroscopy using SWE are highly promising towards a non-invasive or minimally invasive imaging for in-vivo and ex-vivo mechanical characterization of tissues with future clinical applications.

Several hollow organs perform various crucial functions in the body and must be replaced, repaired, or augmented in many disease conditions. Fabrication of tissue analogues to these hollow organs is incredibly challenging. Still, recent advancements in biofabrication have allowed researchers to pursue the development of several hollow organs such as blood vessels, esophagus, trachea, urethra, and others. Materials like collagen, alginate, elastin, silk, fibrin, etc., have been predominantly used for organ development. However, the focus has been duly shifted toward decellularized extracellular matrix (dECM) to develop tissue-specific hydrogels because they provide relevant biochemical cues to promote cellular activity. Still, the dECMbased hydrogels are mechanically weak to fabricate self-supporting tubular structures. Here, an innovative approach using the stereolithography apparatus (SLA) 3D printed framework has been implemented to achieve a self-supporting tubular structure using caprine esophagus muscle dECM hydrogel. A significant improvement in the mechanical stability of the biofabricated tissue has been observed within 7 days of culture. Interestingly, the encapsulated L929 mouse fibroblasts transdifferentiated into myofibroblasts because of the cues provided by the muscle dECM. Overall, the potential of an SLA-based 3D printing strategy to fabricate frameworks, especially for fabricating tubular organs/tissues using mechanocompromised hydrogel, has been demonstrated here.

3D bioprinting brings new aspirations to the tissue engineering and regenerative medicine research community. However, despite its huge potential, its growth towards translation is severely impeded due to lack of suitable materials, technological barrier, and appropriate validation models. Recently, the use of decellularized extracellular matrices (dECM) from animal sources is gaining attention as printable bioink as it can provide a microenvironment close to the native tissue. Hence, it is worth exploring the use of xenogeneic dECM and its translation potential for human application. However, extensive studies on immunogenicity, safety-related issues, and animal welfare-related ethics are yet to be streamlined. In addition, the regulatory concerns need to be addressed with utmost priority in order to expedite the use of xenogeneic dECM bioink for 3D bioprinted implantable tissues for human welfare.

The hierarchical network of blood vessels comprises the larger vessels (veins and arteries), the smaller ones (venules and arterioles), and the thinnest capillaries. The proper functioning of most tissues in the body relies on vascularization, which is meant for the diffusion of gases, nutrients, and harmful waste. However, it is known that cell survival is compromised as the diffusion of oxygen is limited beyond 100–200 µm and damage can occur at any level of the complex system of the vascular network, as is the case in cardiovascular, musculoskeletal, and neurovascular diseases that recur and progress with age. These may prove fatal, hence the need for vascular tissue engineering (VTE) arises. VTE mainly focuses on the fabrication of vascular constructs using natural, synthetic material, or a combination of both using various techniques. The construct is expected to integrate and anastomose with the host vasculature. 4D bioprinting is an emerging field that allows the fabrication of hollow tubes employing different materials that respond to different stimuli. This review is a comprehensive summary of the major techniques employed in VTE and the recent technique of 4D bioprinting foreseen to revolutionize the field.