Additively Manufactured Lattice-like Subperiosteal Implants for Rehabilitation of the Severely Atrophic Ridge.

Subperiosteal implants represent an alternative implant approach for cases with severe bone atrophy. Although some successful clinical cases have been reported, the biomechanical stability of subperiosteal implants remains unclear, and more data are needed to confirm the feasibility of this approach. Therefore, this study investigated the biomechanical characteristics of subperiosteal implants based on histological observation, clinical cases, and finite element analysis. Finite element analysis indicated that subperiosteal implants with a lattice-like structure could better disperse the stress to the underlying bone surface. A novel customized subperiosteal implant was then digitally designed and fabricated using an additive manufacturing technology. Six beagle dogs received such customized subperiosteal implants. Histological and microcomputed tomography examination showed new bone growth into and around the implant. Patient-specific subperiosteal implants were placed into the edentulous mandibular bone, with immediate loading. The implant was functional, without pain or infection, over a 12 month observation period. Images taken 12 months post-operatively showed new bone formation and osseointegration of the device. This indicated that 3D-printed lattice-like subperiosteal implants have sufficient stability for the rehabilitation of severely atrophic ridges.

Nanoparticle-Stabilized Emulsion Bioink for Digital Light Processing Based 3D Bioprinting of Porous Tissue Constructs.

A challenge for bioprinting tissue constructs is enabling the viability and functionality of encapsulated cells. Rationally designed bioink that can create appropriate biophysical cues shows great promise for overcoming such challenges. Here, a nanoparticle-stabilized emulsion bioink for direct fabrication of porous tissue constructs by digital light processing based 3D bioprinting technology is introduced. The emulsion bioink is integrated by the mixture of aqueous dextran microdroplets and gelatin methacryloyl solution and is further rendered stable by ß-lactoglobulin nanoparticles. After bioprinting, the printed tissue constructs create the macroporous structure via removal of dextran, thereby providing favorable biophysical cues to promote the viability, proliferation, and spreading of the encapsulated cells. Moreover, a trachea-shaped construct containing chondrocytes is bioprinted and implanted in vivo. The results demonstrate that the generated macroporous construct is of benefit to cartilage tissue rebuilding. This work offers an advanced bioink for the fabrication of living tissue constructs by activating the cell behaviors and functions in situ and can lead to the development of 3D bioprinting.

DLP-based bioprinting of void-forming hydrogels for enhanced stem-cell-mediated bone regeneration.

The integration of 3D bioprinting and stem cells is of great promise in facilitating the reconstruction of cranial defects. However, the effectiveness of the scaffolds has been hampered by the limited cell behavior and functions. Herein, a therapeutic cell-laden hydrogel for bone regeneration is therefore developed through the design of a void-forming hydrogel. This hydrogel is prepared by digital light processing (DLP)-based bioprinting of the bone marrow stem cells (BMSCs) mixed with gelatin methacrylate (GelMA)/dextran emulsion. The 3D-bioprinted hydrogel can not only promote the proliferation, migration, and spreading of the encapsulated BMSCs, but also stimulate the YAP signal pathway, thus leading to the enhanced osteogenic differentiation of BMSCs. In addition, the in vivo therapeutic assessments reveal that the void-forming hydrogel shows great potential for BMSCs delivery and can significantly promote bone regeneration. These findings suggest that the unique 3D-bioprinted void-forming hydrogels are promising candidates for applications in bone regeneration.

3D bioprinting of high-performance hydrogel with in-situ birth of stem cell spheroids.

Digital light processing (DLP)-based bioprinting technology holds immense promise for the advancement of hydrogel constructs in biomedical applications. However, creating high-performance hydrogel constructs with this method is still a challenge, as it requires balancing the physicochemical properties of the matrix while also retaining the cellular activity of the encapsulated cells. Herein, we propose a facile and practical strategy for the 3D bioprinting of high-performance hydrogel constructs through the in-situ birth of stem cell spheroids. The strategy is achieved by loading the cell/dextran microdroplets within gelatin methacryloyl (GelMA) emulsion, where dextran functions as a decoy to capture and aggregate the cells for bioprinting while GelMA enables the mechanical support without losing the structural complexity and fidelity. Post-bioprinting, the leaching of dextran results in a smooth curved surface that promotes in-situ birth of spheroids within hydrogel constructs. This process significant enhances differentiation potential of encapsulated stem cells. As a proof-of-concept, we encapsulate dental pulp stem cells (DPSCs) within hydrogel constructs, showcasing their regenerative capabilities in dentin and neovascular-like structures in vivo. The strategy in our study enables high-performance hydrogel tissue construct fabrication with DLP-based bioprinting, which is anticipated to pave a promising way for diverse biomedical applications.