Promoting Point-of-Care by Combining Bioengineered Constructs, Patient-Specific Design and 3D-Printing

Objectives: Treatment of large-scaled maxillofacial defects has progressed tremendously since virtual surgical planning, patient specific design of implants, additive manufacturing and 3D printing were introduced. These methods enabled clinicians to personalize the surgical treatment for every patient. These technologies enable the transformation of medical information such as CT or MRI data into a 3D printable and designable models, later utilized for accurate treatment. Still, clinicians in the surgical field are often faced with the challenge of utilizing non-biological materials and autologous tissue-harvest. Both, while considered as the standard of care in surgical settings, possess considerable drawbacks such as infections, foreign body reaction and tissue-site morbidity. Tissue engineering approaches may promote the point-of-care concept (POC) by combining patient specific methodology already employed in the clinic, with bio-fabrication and bio printing of tissue constructs.
Methods: First, bioengineered constructs are fabricated by loading appropriate stem cells onto porous, biocompatible, biodegradable soft tissue scaffolds. Bioengineered soft-tissue scaffolds are then combined with bone-regeneration constructs to yield composite neo-tissues. These in turn, undergo axial vascularization in a rat arteriovenous model. Both ex vivo and in vivo assessment of maturation and implantation are performed. Creation of Human-sized maxillofacial bone is followed, based on clinical imaging data, 3D printing and bio-fabrication, with the goal of creating a proof-of-concept up-scaled biohybrid tissue construct.
Results:
Pre-vascularization and osteogenic induction of tissue constructs are validated both in vitro and in vivo, and high-resolution micro-computed tomography is employed to assess bone deposition, remodeling and creation of micro-vessels within neo-tissues.
Conclusions: The presented methodology promotes biohybrid tissue fabrication. In addition, the underlying angiogenic connectivity between host and graft are evaluated as well as upscaling of human-sized constructs.