Microgels have emerged as a versatile platform in tissue engineering and regenerative medicine, offering unique physicochemical properties, modularity, and the ability to mimic native extracellular matrix microenvironments. Derived from natural or synthetic hydrogels, microgels exhibit biocompatibility, controllability, and injectability, which make them suitable for diverse tissue engineering applications. This review systematically explores the fabrication methods of microgels and highlights their role in cell encapsulation, therapeutic delivery, and structural tissue development. Advanced strategies in microgel manufacturing, such as injectable hydrogels, assembled microgel platforms, and in-gel assemblies, have enabled the creation of highly customizable and functional tissue constructs. Additionally, three-dimensional bioprinting of microgels provides a high-throughput strategy to generate patient-specific scaffolds with precise spatial organization and enhanced cellular viability. It is expected that more efficient and cost-effective strategies for mass production and customization of microgel systems to specific cell types or patient needs are essential for future studies. The innovations, including stimuli-responsive and four-dimensional microgels, will expand their potential by enabling dynamic in situ tunable microenvironments. These advancements will enable optimal design, scalability, and integration into therapeutic applications, thereby accelerating the clinical translation of microgel-based therapies and driving the development of multifunctional tissue products.

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230–430 μm as primary pores, 40–70 μm as secondary inner microchannels, and 200–400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.

Successful recovery from vascular diseases has relied on the repair of damaged blood vessels (BVs), and most of the current approaches involve the implantation of autologous BVs, which critically suffers from the shortage of donors. Researchers have attempted to develop artificial vessels as an alternative solution. However, the manufacturing of small-diameter (< 6 mm) BVs is still considered one of the biggest challenges due to its difficulty in the precise fabrication and the replication of a biomimetic architecture. In this study, we successfully developed 3D printed flexible small-diameter BVs that consist of smooth muscle and endothelium. In the developed artificial BV, a rubber-like elastomer was printed as the outermost layer to demonstrate enhanced mechanical properties, and human induced pluripotent stem cell (iPSC)-derived vascular smooth muscle cells (iSMCs) and endothelial cells (iECs) embedded fibrinogen solutions were coaxially extruded with thrombin solution to form cell-laden fibrin gel inner layers. Our results showed that the 3D BVs possessed proper mechanical properties, and the cells in the fibrin layers substantially proliferated over time to form a stable BV construct. Our study demonstrated that the 3D printed flexible small-diameter BV using iPSCs could be a promising platform for the treatment of vascular diseases.