3D assembly of bidirectional bioelectronic scaffolds towards accelerated tissue repair
Abstract
Injury and associated tissue loss results in loss of function and long (often incomplete) recovery, amounting to significant burden on the healthcare system, loss of productivity, and loss of readiness for the naval warfighter. Bioelectronic integration and intervention in personalized injury treatment is a promising approach towards improved outcomes and faster healing, however significant technology gaps exist to seamlessly communicate with healing tissue. The rise of multimodal (i.e. electrical, biochemical) and bi-directional (sensing and stimulating) bioelectronic devices, has opened new opportunities in real time tissue diagnostics as well as in the responsive actuation of processes implicated in tissue growth or repair. Traditional bioelectronics are thin film devices most commonly fabricated in two dimensions and limited in their facile integration into bulk, 3D tissue, a characteristic required for localized, real time monitoring of tissue healing. Thus, there is need for a generalizable approach to assemble biomaterial scaffolds with functional, optoelectronically active constructs that can interrogate and affect 3D tissues in a prescribed, spatiotemporally defined manner. Recent advances in polymer-based electroactive materials and fabricated devices present an opportunity for soft, flexible bioelectronics that provide an advantageous interface with cells and tissue. The challenge remains, however, to integrate bioelectronic sensors with multifunctional, 3D patterned elements, to enable a hybrid construct that can both serve as a bioactive scaffold for tissue repair and also sense healing progress and provide responsive bioelectronic intervention. In this ONR Young Investigators Program project, I propose to combine the design freedom of functional 3D printed scaffolds, with the unparalleled sensing ability provided by thin film bioelectronics by developing and validating the capability to co-assemble bioelectronic sensor probes throughout the bulk of 3D-printed components. This assembled hybrid construct will enable bulk tissue stimulation, patterning of structural and/or bioactive components (i.e. conduits or supports), and tissue-integrated thin film electronic sensors. While my approach is generalizable to multiple tissue types and applications, I will pursue validation using in vitro models relevant to both bone regeneration and peripheral nerve repair. I propose to accomplish this through the following objectives: (1) Develop 3D printed conducting polymer scaffolds to affect biological processes in vitro, (2) Develop processes to manufacture multi-functional hybrid scaffolds capable of both sensing and stimulating healing tissue and (3) Demonstrate bioelectronic sensing and modulation in an ex vivo organotypic model for peripheral nerve repair.This project will develop the foundation for on-demand active tissue repair constructs. It will demonstrate the simultaneous ability to sense signals associated with regenerative processes (i.e. neurite growth and associated signal propagation, as is relevant for nerve gap repair), and to stimulate/enhance their healing potential. The success of this proposal will deliver innovative tools for active (potentially closed-loop) personalized injury treatment, as well as for broad implementation in 3D tissue culture settings. My approach, filling a needed manufacturing gap between 3D printing and (sub)-microscale electronics fabrication, has the potential to enhance capabilities for personalized advanced medical care at sea or in other remote locations, and to do so with minimal delay afteense capabilities. APPROVED FOR PUBLIC RELEASE.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 31, 2020
- Source ID
- N000142012777
Entities
People
- Jonathan Rivnay
Organizations
- Northwestern University
- Office of Naval Research
- United States Navy