Abstract
Recently developed biofabrication technologies are enabling the production of three-dimensional engineered tissues containing vascular networks which can deliver oxygen and nutrients across large tissue volumes. Tissues at this scale show promise for eventual regenerative medicine applications; however, the implantation and integration of these constructs in vivo remains poorly studied. Here, we introduce a surgical model for implantation and direct in-line vascular connection of 3D printed hydrogels in a porcine arteriovenous shunt configuration. Utilizing perfusable poly(ethylene glycol) diacrylate (PEGDA) hydrogels fabricated through projection stereolithography, we first optimized the implantation procedure in deceased piglets. Subsequently, we utilized the arteriovenous shunt model to evaluate blood flow through implanted PEGDA hydrogels in non-survivable studies. Connections between the host femoral artery and vein were robust and the patterned vascular channels withstood arterial pressure, permitting blood flow for 6 h. Our study demonstrates rapid prototyping of a biocompatible and perfusable hydrogel that can be implanted in vivo as a porcine arteriovenous shunt, suggesting a viable surgical approach for in-line implantation of bioprinted tissues, along with design considerations for future in vivo studies. We further envision that this surgical model may be broadly applicable for assessing whether biomaterials optimized for 3D printing and cell function can also withstand vascular cannulation and arterial blood pressure. This provides a crucial step toward generated transplantable engineered organs, demonstrating successful implantation of engineered tissues within host vasculature.
Highlights
In the current era of solid organ transplantation, several barriers exist for patients with endorgan disease before they can get a life-saving transplant
We hypothesized that the greater pressure differential between the artery and the vein would aid in increasing blood flow rate and thereby help prevent clotting [29, 30]
We found that the hydrogels allowed for blood flow using the model’s blood pressure to sustain flow
Summary
In the current era of solid organ transplantation, several barriers exist for patients with endorgan disease before they can get a life-saving transplant. Blood 3D Vascular Construct Porcine viable, transplantable organs sorely outweighs the supply which leads to the use of marginal or extended-criteria organs, unsurprisingly leading to more complications. Those who are sicker with greater wait time are those who receive organ transplants, thereby increasing the risk for more complications. Immunosuppression regimens, a requirement for transplantation, expose the recipient to greater risks of infection, malignancy and overall greater morbidity to stave off rejection. These pitfalls of transplantation assume that patients make it to the transplant list in the first place; often, those without social and economic support will not be eligible. Disruptive new ideas will be necessary to treat patients in the future and to overcome the current and significant barriers one faces in the modern era of solid organ transplantation
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