Multilayered hydrogel scaffold construct with native tissue matched elastic modulus: A regenerative microenvironment for urethral scar-free healing.

The unsuitable deformation stimulus, harsh urine environment, and lack of a regenerative microenvironment (RME) prevent scaffold-based urethral repair and ultimately lead to irreversible urethral scarring. The researchers clarify the optimal elastic modulus of the urethral scaffolds for urethral repair and design a multilayered PVA hydrogel scaffold for urethral scar-free healing. The inner layer of the scaffold has self-healing properties, which ensures that the wound effectively resists harsh urine erosion, even when subjected to sutures. In addition, the scaffold's outer layer has an extracellular matrix-like structure that synergizes with adipose-derived stem cells to create a favorable RME. In vivo experiments confirm successful urethral scar-free healing using the PVA multilayered hydrogel scaffold. Further mechanistic study shows that the PVA multilayer hydrogel effectively resists the urine-induced inflammatory response and accelerates the transition of urethral wound healing to the proliferative phase by regulating macrophage polarization, thus providing favorable conditions for urethral scar-free healing. This study provides mechanical criteria for the fabrication of urethral tissue-engineered scaffolds, as well as important insights into their design.

Light-based 3D bioprinting technology applied to repair and regeneration of different tissues: A rational proposal for biomedical applications.

3D bioprinting technology, a subset of 3D printing technology, is currently witnessing widespread utilization in tissue repair and regeneration endeavors. In particular, light-based 3D bioprinting technology has garnered significant interest and favor. Central to its successful implementation lies the judicious selection of photosensitive polymers. Moreover, by fine-tuning parameters such as light irradiation time, choice of photoinitiators and crosslinkers, and their concentrations, the properties of the scaffolds can be tailored to suit the specific requirements of the targeted tissue repair sites. In this comprehensive review, we provide an overview of commonly utilized bio-inks suitable for light-based 3D bioprinting, delving into the distinctive characteristics of each material. Furthermore, we delineate strategies for bio-ink selection tailored to diverse repair locations, alongside methods for optimizing printing parameters. Ultimately, we present a coherent synthesis aimed at enhancing the practical application of light-based 3D bioprinting technology in tissue engineering, while also addressing current challenges and future prospects.

Injectable Decellularized Extracellular Matrix-Based Bio-Ink with Excellent Biocompatibility for Scarless Urethra Repair.

In recent years, decellularized extracellular matrices (dECM) derived from organs have attracted much attention from researchers due to their excellent biocompatibility, capacity to promote cell proliferation and migration, as well as pro-vascularization. However, their inferior mechanical properties, slow cross-linking, weak strengths, and poor supporting properties remain their inevitable challenges. In our study, we fabricated a novel dECM hydrogel with better crosslinking strength and speed, stronger support properties, and better mechanical properties. The hydrogel, which we named gelatin-based dECM powder hydrogel (gelatin-dECM hydrogel), was prepared by mixing dECM microparticles in gelatin solution and adding certain amount of 1-Ethyl-3-(3-dimethyl-aminopropyl-1-carbodiimide) (EDC) and N-hydroxysuccinimide (NHS). We evaluated the utility of this hydrogel by assessing the degradation rate, mechanical properties, and biocompatibility. The results showed that the gelatin-dECM hydrogel has high mechanical properties and biocompatibility and also has the ability to promote cell proliferation and migration. After injection of this hydrogel around the surgical sites of urethras in rabbits, the incorporation of dECM powder was demonstrated to promote angiogenesis as well as scarless repair by histological sections after surgery. The application of this novel hydrogel provides a new perspective for the treatment of post-traumatic urethral stricture.

Four-dimensional hydrogel dressing adaptable to the urethral microenvironment for scarless urethral reconstruction.

The harsh urethral microenvironment (UME) after trauma severely hinders the current hydrogel-based urethral repair. In fact, four-dimensional (4D) consideration to mimic time-dependent physiological processes is essential for scarless urethral reconstruction, which requires balancing extracellular matrix (ECM) deposition and remodeling at different healing stages. In this study, we develop a UME-adaptable 4D hydrogel dressing to sequentially provide an early-vascularized microenvironment and later-antifibrogenic microenvironment for scarless urethral reconstruction. With the combination of dynamic boronic ester crosslinking and covalent photopolymerization, the resultant gelatin methacryloyl phenylboronic acid/cis-diol-crosslinked (GMPD) hydrogels exhibit mussel-mimetic viscoelasticity, satisfactory adhesion, and acid-reinforced stability, which can adapt to harsh UME. In addition, a temporally on-demand regulatory (TOR) technical platform is introduced into GMPD hydrogels to create a time-dependent 4D microenvironment. As a result, physiological urethral recovery is successfully mimicked by means of an early-vascularized microenvironment to promote wound healing by activating the vascular endothelial growth factor (VEGF) signaling pathway, as well as a later-antifibrogenic microenvironment to prevent hypertrophic scar formation by timing transforming growth factor-ß (TGFß) signaling pathway inhibition. Both in vitro molecular mechanisms of the physiological healing process and in vivo scarless urethral reconstruction in a rabbit model are effectively verified, providing a promising alternative for urethral injury treatment.

Cell-Based Therapy for Urethral Regeneration: A Narrative Review and Future Perspectives.

Urethral stricture is a common urological disease that seriously affects quality of life. Urethroplasty with grafts is the primary treatment, but the autografts used in clinical practice have unavoidable disadvantages, which have contributed to the development of urethral tissue engineering. Using various types of seed cells in combination with biomaterials to construct a tissue-engineered urethra provides a new treatment method to repair long-segment urethral strictures. To date, various cell types have been explored and applied in the field of urethral regeneration. However, no optimal strategy for the source, selection, and application conditions of the cells is available. This review systematically summarizes the use of various cell types in urethral regeneration and their characteristics in recent years and discusses possible future directions of cell-based therapies.

Hydrogels for 3D bioprinting in tissue engineering and regenerative medicine: Current progress and challenges.

Three-dimensional (3D) bioprinting is a promising and innovative biomanufacturing technology, which can achieve precise position controlling of cells and extracellular matrix components, and further create complex and functional multi-cellular tissues or organs in a 3D environment. Bioink in the form of the cell-loaded hydrogel is most commonly used in bioprinting, and it is vital to the process of bioprinting. The bionic scaffold should possess suitable mechanical strength, biocompatibility, cell proliferation, survival, and other biological characteristics. The disadvantages of natural polymer hydrogel materials include poor mechanical properties as well as low printing performance and shape fidelity. Over the past years, a series of synthetic, modified, and nanocomposite hydrogels have been developed, which can interact through physical interactions, chemical covalent bond crosslinking, and bioconjugation reactions to change the characteristics to satisfy the requirements. In this review, a comprehensive summary is provided on recent research regarding the unique properties of hydrogel bioinks for bioprinting, with optimized methods and technologies highlighted, which have both high-value research significance and potential clinical applications. A critical analysis of the strengths and weaknesses of each hydrogel-based biomaterial ink is presented at the beginning or end of each section, alongside the latest improvement strategies employed by current researchers to address their respective shortcomings. Furthermore, we propose potential repair sites for each hydrogel-based ink based on their distinctive repair features, while reflecting on current research limitations. Finally, we synthesize and analyze expert opinions on the future of these hydrogel-based bioinks in the broader context of tissue engineering and regenerative medicine, offering valuable insights for future investigations.

Review on Additives in Hydrogels for 3D Bioprinting of Regenerative Medicine: From Mechanism to Methodology.

The regeneration of biological tissues in medicine is challenging, and 3D bioprinting offers an innovative way to create functional multicellular tissues. One common way in bioprinting is bioink, which is one type of the cell-loaded hydrogel. For clinical application, however, the bioprinting still suffers from satisfactory performance, e.g., in vascularization, effective antibacterial, immunomodulation, and regulation of collagen deposition. Many studies incorporated different bioactive materials into the 3D-printed scaffolds to optimize the bioprinting. Here, we reviewed a variety of additives added to the 3D bioprinting hydrogel. The underlying mechanisms and methodology for biological regeneration are important and will provide a useful basis for future research.