Intra‐Operative Bioprinting of Hard, Soft, and Hard/Soft Composite Tissues for Craniomaxillofacial Reconstruction

Abstract

Reconstruction of complex craniomaxillofacial (CMF) defects is challenging dueto the highly organized layering of multiple tissue types. Such compartmentalization necessitates the precise and effective use of cells and other biologics to recapitulate the native tissue anatomy. In this study, intra-operative bioprinting (IOB) of different CMF tissues, including bone, skin, and composite (hard/soft) tissues, is demonstrated directly on rats in a surgical setting. A novel extrudable osteogenic hard tissue ink is introduced, which induced substantial bone regeneration, with ≈80% bone coverage area of calvarial defects in 6 weeks. Using droplet-based bioprinting, the soft tissue ink accelerated the reconstruction of full-thickness skin defects and facilitated up to 60% wound closure in 6 days. Most importantly, the use of a hybrid IOB approach is unveiled to reconstitute hard/soft composite tissues in a stratified arrangement with controlled spatial bioink deposition conforming the shape of a new composite defect model, which resulted in ≈80% skin wound closure in 10 days and 50% bone coverage area at Week 6. The presented approach will be absolutely unique in the clinical realm of CMF defects and will have a significant impact on translating bioprinting technologies into the clinic in the future.

In Situ 3D Bioprinting Living Photosynthetic Scaffolds for Autotrophic Wound Healing

“…Additionally, owing to the design flexibility and anatomical accuracy, 3D bioprinting technology has been widely employed for the fabrication of both living cell-laden and acellular biomimetic constructs in tissue engineering [ 29 – 34 ]. In particular, some attempts have been performed by in situ bioprinting of tissue constructs at defect sites, which enables accurate filling of irregular-shaped defects and concurrence of in vivo integration with native tissues [ 35 – 40 ]. Thus, it is conceivable that the in situ bioprinting of the photosynthetic microalgae into wound sites would provide a self-adaptive platform with an autotrophic oxygen supply for versatile wound healing.…”

Regenerative Engineering: Current Applications and Future Perspectives

“…Each offers its own set of advantageous and disadvantages, signifying that widespread clinical translation is not yet on the immediate horizon. However, research is progressing rapidly across a multitude of diverse applications, such as breast reconstruction ( 132 ), craniomaxillofacial injuries ( 133 ), and cardiovascular repair ( 134 ).…”

Strategies to Promote Vascularization in 3D Printed Tissue Scaffolds: Trends and Challenges

“…For instance, 2D MRI (magnetic resonance images) images of the craniomaxillofacial defects in rodents were converted into 3D models, which were then utilized for printing accurate structures. 18 Despite the rapid advancements in 3D printing in recent years, their clinical success is limited by the critical need to engineer means for the supply of oxygen and nutrients upon implantation. Diffusion alone can only supply cells in proximity of 100 to 200 μm from the nearest capillary in tissues.…”

“…There are specialized software to render clinical 2D images of the patient’s anatomy into 3D models, which can then be used as input files for printing. For instance, 2D MRI (magnetic resonance images) images of the craniomaxillofacial defects in rodents were converted into 3D models, which were then utilized for printing accurate structures …”