Repair of osteochondral defects is still a challenge, especially the regeneration of hyaline cartilage. Parathyroid hormone (PTH) can inhibit the hypertrophy of chondrocytes to maintain the phenotype of hyaline...

Organoids developed from pluripotent stem cells or adult stem cells are three-dimensional cell cultures possessing certain key characteristics of their organ counterparts, and they can mimic certain biological developmental processes of organs in vitro. Therefore, they have promising applications in drug screening, disease modeling, and regenerative repair of tissues and organs. However, the construction of organoids currently faces numerous challenges, such as breakthroughs in scale size, vascularization, better reproducibility, and precise architecture in time and space. Recently, the application of bioprinting has accelerated the process of organoid construction. In this review, we present current bioprinting techniques and the application of bioinks and summarize examples of successful organoid bioprinting. In the future, a multidisciplinary combination of developmental biology, disease pathology, cell biology, and materials science will aid in overcoming the obstacles pertaining to the bioprinting of organoids. The combination of bioprinting and organoids with a focus on structure and function can facilitate further development of real organs.

Precise fabrication of microscale vasculatures (MSVs) has long been an unresolved challenge in tissue engineering. Currently, light-assisted printing is the most common approach. However, this approach is often associated with an intricate fabrication process, high cost, and a requirement for specific photoresponsive materials. Here, thermoresponsive hydrogels are employed to induce volume shrinkage at 37 °C, which allows for MSV engineering without complex protocols. The thermoresponsive hydrogel consists of thermosensitive poly(N-isopropylacrylamide) and biocompatible gelatin methacrylate (GelMA). In cell culture, the thermoresponsive hydrogel exhibits an apparent volume shrinkage and effectively triggers the creation of MSVs with smaller size. The results show that a higher concentration of GelMA blocks the shrinkage, and the thermoresponsive hydrogel demonstrates different behaviors in water and air at 37 °C. The MSVs can be effectively fabricated using the sacrificial alginate fibers, and the minimum MSV diameter achieved is 50 µm. Human umbilical vein endothelial cells form endothelial monolayers in the MSVs. Osteosarcoma cells maintain high viability in the thermoresponsive hydrogel, and the in vivo experiment shows that the MSVs provide a site for the perfusion of host vessels. This technique may help in the development of a facile method for fabricating MSVs and demonstrates strong potential for clinical application in tissue regeneration.

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Functional articular repair is known to be hampered by tissue degradation, which occurs in the defective local inflammatory environment that is also characterized by disrupted angiogenesis. The advanced fabrication of scaffolds with designed chemical and physical cues, which provide a biomimetic environment for tissue regeneration, holds considerable promise to circumvent the problem and thus allows functional articular repair. Herein, we developed scaffolds with controllable shapes with hydroxybutyl chitosan (HBC) and oxidized chondroitin sulfate (OCS) hydrogels, whose chemical composition was similar to that of the cartilage extracellular matrix (ECM). By optimizing the concentration of OCS, the functional cross-linker, we achieved a hydrogel promoting proliferation, adhesion, and ECM formation of chondrocytes and inhibiting tube formation of endothelial cells. Using a hydration procedure and bioactivation of mesenchymal stem cells (MSCs), we obtained mesoporous silicate-doped calcium phosphate cement (MS/CPC) scaffolds with a bioactive surface similar to that of bones, with improved osteogenesis and vascularization properties. Personalized cartilage–subchondral repair scaffolds with stable combination were successfully fabricated based on the self-cross-linking properties of the Schiff-based HBC/OCS hydrogel and the macroporous structure of MS/CPC scaffolds with the aid of a 3D printing technique. This study proposes a strategy to design individualized tissue repair biomimetic gradient scaffolds. Further assessments of their osteochondral defect repair properties in vivo should be performed.

Defects in the formation of microvascular networks, which provide oxygen and nutrients to cells, are the main reason for the engraftment failure of clinically applicable engineered tissues. Inflammatory responses and immunomodulation can promote the vascularization of the engineered tissues. We developed a capillary construct composed of a gelatin methacrylate-based cell-laden hydrogel framework complexed with interleukin-4 (IL-4)-loaded alginate-chitosan (AC) microspheres and endothelial progenitor cells (EPCs) and RAW264.7 macrophages as model cells. The AC microspheres maintained and guided the EPCs through electrostatic adhesion, facilitating the formation of microvascular networks. The IL-4-loaded microspheres promoted the polarization of the macrophages into the M2 type, leading to a reduction in pro-inflammatory factors and enhancement of the vascularization. Hematoxylin and eosin staining and immunohistochemical analysis revealed that, without IL-4 or AC microspheres, the scaffold was less effective in angiogenesis. We provide an alternative and promising approach for constructing vascularized tissues.

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