ReverTome

What it does

ReverTome is a surgical instrument that delivers cells in a bioink via a compact handheld bioprinter to treat severe burns. The modular design of the printhead allows sterile and consistent deposition of biological materials over large physiological surfaces.

Your inspiration

Nearly 500,000 burn injuries worldwide require medical attention each year, leading to 40,000 hospitalizations and 3,400 deaths (Gibran et al., 2013). Large area burn wounds are characterized as those greater than 20% of the body, and they have poor prognosis due to the elevated risk of shock. Current industry practice involves the use of a dermatome to isolate healthy skin to create meshed grafts, but this leads to the doubling of the injured area which may lead to additional infection. ReverTome reverses the process of isolating healthy skin and aims to deposit engineered skin tissues containing patient cells directly onto large area burns.

How it works

Two motors individually control the flow rate of the bioink and crosslinker filled syringes. The bioink then travels through the microfluidic cartridge and initiates gelation at the device exit after contact with the crosslinker. Rotational flexibility of the printhead allows homogenous printing on non-flat human surfaces, and a deformable wheel dissipates the pressure on the fragile wound bed while maximizing traction. We selected enzymatically and thermally gelled fibrin and collagen biomaterials for its relevance in burn wound healing. To prevent premature gelation, this design includes temperature control for the biomaterial-filled syringes and cartridge. A modular printhead design with quick assembly permits autoclaving of essential components to maintain sterility in the operating room. Other components in direct contact with either cells, biomaterials, or the wound, like the wheel, printer cartridges, and syringes, can be disposed after a single use.

Design process

We were initially challenged by our clinical collaborators to develop technology to allow direct deposition of cell friendly, but mechanically weak biomaterials onto the patient wound. The 1st generation of the handheld bioprinter (Hakimi et al., 2018) included motor driven syringes channeling biomaterials through the microfluidic cartridge, but after large animal studies we found that the printer was only reliable for small, flat, well-defined areas. The 2nd and 3rd generation design moved the wheel behind the microfluidic cartridge to promote large area bioprinting, and introduced a flexible printhead with two degrees of freedom to enable consistent deposition on the heterogenous surfaces of the human body. The 4th generation changed to a compliant wheel to minimize the pressure on the fragile wound bed and to ensure traction during the bioprinting process. In anticipation of clinical use, the printhead components were re-designed for quick disassembly for sterilization in between surgeries. The present-day design incorporates temperature control to expand the biomaterial choice to include thermally crosslinked proteins. We have also significantly improved the form factor of the handheld printer to include miniaturized control systems integrated inside an ergonomic handle.

How it is different

The competitive advantage of our design is the portability of the bioprinter, the flexibility of replacing sterile microfluidic cartridges, and the capacity to pattern soft materials with high fidelity on physiologically relevant surfaces in a clinical setting. Skin substitutes that are currently in the market include both natural and synthetic polymers like double layered dermal substitutes Integra and Nevelia, but they require expensive materials and a need for multiple surgeries. Alternative methods of cell delivery include direct spraying and implantable scaffolds, but they lack extracellular matrix organization and control over the composition of biomaterials across a complex human topography. Our indirect competitors are commercial bioprinters like RegenHu and EnvisionTEC. While similarly they support high resolution printing of many biomaterials, these machines are bulky, expensive, require high technical skill, and are mostly designed for research.

Future plans

We identify key value inflection points: publication in a peer-reviewed journal to validate the product in a laboratory and clinical setting; establishment of a manufacturing strategy for small-scale product development in spring 2019; dissemination of the product to national key opinion leaders, and then phase 1 and 2 human clinical trials in 2022. Our regulatory strategy involves partnering with manufacturers that are ISO certified for manufacturing of medical devices, utilizing commercially available biomaterials and cell lines for experiments and clinical trials, and manufacturing the bioprinter components using certified processes.

Awards