Periodic Reporting for period 3 - VesselNet (Engineering Composite Tissues for Facial Reconstruction)
Période du rapport: 2022-09-01 au 2024-02-29
Facial features are psychologically and practically associated with our identity. When an accident, disease or violent act alters a person's face, the damage can be beyond physical. Personalized facial reconstruction is in high demand. Tissue engineering of independent facial elements like bone, fat, skin and muscle tissues, has been demonstrated. However, to date, no thick tissue composed of multiple facial layers have been created. The engineering of large composite tissue is complicated by the challenges of effective vascularisation of transplants, which is required for tissue survival and integration. The transplant must have not only large blood vessels but the whole vascular hierarchy including capillary networks where the actual exchange of gases and nutrients takes place. Our concept is to create a functional hierarchical vascular network (VesselNet) within engineered tissue in vitro, enabling the generation of thick tissue transplants. During this project we develop 3D bioprinting techniques, which would allow us to fabricate customizable multilayered composite tissues with high complexity and accuracy. Our end-goal is to restore a full-thickness facial defect in a human scale preclinical model using our engineered transplant. The results of our project are expected to have a major impact on reconstructive surgery and shed light on yet unknown tissue organization mechanisms.
We engineered implantable hierarchical vascular networks using four different strategies. Starting with the classical scaffold-based tissue engineering approach, we gradually increased the complexity of the network and the ability to customize it by moving to 3D bioprinting approach. The in vivo experiments demonstrated that our engineered grafts can be directly connected to and integrated with the host vasculature.
These engineered vascular networks served as a basis for composite tissue. We successfully created a tissue flap composed of engineered vasculature and decellularized bone transplant. This composite flap promoted complex fracture recovery and showed superior quality compared to a non-vascularized bone transplant. Our novel method gives a possibility to replace soft tissue autografts with lab grown engineered tissue.
In the next steps, we focused on the 3D bioprinting of vascularized bone, fat and muscle tissue. We managed to 3D bioprint vascularized bony constructs as well as vascularized fat and dermis containing tissue. We also made progress in 3D bioprinting skeletal muscle.
These engineered vascular networks served as a basis for composite tissue. We successfully created a tissue flap composed of engineered vasculature and decellularized bone transplant. This composite flap promoted complex fracture recovery and showed superior quality compared to a non-vascularized bone transplant. Our novel method gives a possibility to replace soft tissue autografts with lab grown engineered tissue.
In the next steps, we focused on the 3D bioprinting of vascularized bone, fat and muscle tissue. We managed to 3D bioprint vascularized bony constructs as well as vascularized fat and dermis containing tissue. We also made progress in 3D bioprinting skeletal muscle.
The engineering of perfusable and implantable multiscale blood vessel network is a significant breakthrough in the tissue engineering field. This achievement is a of a notable value not only for facial reconstruction, but for the entire discipline.
While working on 3D bioprinting of vascularized tissues we invented a special support material for bioprinting, which enhanced structural stability of the bioprinted construct and increased cell survival. This invention has far-reaching implications beyond the state of the art. It may lead to emergence of universal and user-friendly 3D bioprinting technology for regenerative medicine and drug discovery.
In the second phase of our project, we will validate the functionality our 3D bioprinted vascularized tissues in vivo. Next, we plan to create a multilayered bioprinted tissue composed of vascularized bone, skeletal muscle, fat and dermis. We will investigate the cell crosstalk in the composite tissue and find optimal conditions for growing the multicomponent tissue in vitro. This complex tissue construct will be implanted in small and large animal models to investigate its functionality and therapeutic potential for facial reconstruction.
While working on 3D bioprinting of vascularized tissues we invented a special support material for bioprinting, which enhanced structural stability of the bioprinted construct and increased cell survival. This invention has far-reaching implications beyond the state of the art. It may lead to emergence of universal and user-friendly 3D bioprinting technology for regenerative medicine and drug discovery.
In the second phase of our project, we will validate the functionality our 3D bioprinted vascularized tissues in vivo. Next, we plan to create a multilayered bioprinted tissue composed of vascularized bone, skeletal muscle, fat and dermis. We will investigate the cell crosstalk in the composite tissue and find optimal conditions for growing the multicomponent tissue in vitro. This complex tissue construct will be implanted in small and large animal models to investigate its functionality and therapeutic potential for facial reconstruction.