Rodent Model for Orthotopic Implantation of Engineered Liver Devices.

This study presents a novel surgical model developed to provide hematological support for implanted cellularized devices augmenting or replacing liver tissue function. Advances in bioengineering provide tools and materials to create living tissue replacements designed to restore that lost to disease, trauma, or congenital deformity. Such substitutes are often assembled and matured in vitro and need an immediate blood supply upon implantation, necessitating the development of supporting protocols. Animal translational models are required for continued development of engineered structures before clinical implementation, with rodent models often playing an essential early role. Our long-term goal has been generation of living tissue to provide liver function, utilizing advances in additive manufacturing technology to create 3D structures with intrinsic micron to millimeter scale channels modeled on natural vasculature. The surgical protocol developed enables testing various design iterations in vivo by anastomosis to the host rat vasculature. Lobation of rodent liver facilitates partial hepatectomy and repurposing the remaining vasculature to support implanted engineered tissue. Removal of the left lateral lobe exposes the underlying hepatic vasculature and can create space for a device. A shunt is created from the left portal vein to the left hepatic vein by cannulating each with separate silicone tubing. The device is then integrated into the shunt by connecting its inflow and outflow ports to the tubing and reestablishing blood flow. Sustained anticoagulation is maintained with an implanted osmotic pump. In our studies, animals were freely mobile after implantation; devices remained patent while maintaining blood flow through their millifluidic channels. This vascular anastomosis model has been greatly refined during the process of performing over 200 implantation procedures. We anticipate that the model described herein will find utility in developing preclinical translational protocols for evaluation of engineered liver tissue. Impact statement Tissue and organ transplantation are often the best clinically effective treatments for a variety of human ailments. However, the availability of suitable donor organs remains a critical problem. Advances in biotechnology hold potential in alleviating shortages, yet further work is required to surgically integrate large engineered tissues to host vasculature. Improved animal models such as the one described are valuable tools to support continued development and evaluation of novel therapies.

Tissue engineering: from the bedside to the bench and back to the bedside.

The field of Tissue Engineering and Regenerative Medicine has evolved rapidly over the past thirty years. This review will summarize its history, current status and direction through the lens of clinical need, its progress through science in the laboratory and application back into patients. We can take pride in the fact that much effort and progress began with the surgical problems of children and that many surgeons in the pediatric surgical specialties have become pioneers and investigators in this new field of science, engineering, and medicine. Although the field has yet to fulfill its great promise, there have been several examples where a therapy has progressed from the first idea to human application within a short span of time and, in many cases, it has been applied in the surgical care of children.

Return of motor function after repair of a 3-cm gap in a rabbit peroneal nerve: a comparison of autograft, collagen conduit, and conduit filled with collagen-GAG matrix.

BACKGROUND: The purpose of this study was to evaluate the motor nerve recovery in a rabbit model after repair of a 3-cm gap in the peroneal nerve with a conduit filled with a collagen-GAG (glycosaminoglycan) matrix and compare the results with those after reconstruction with an autograft or an empty collagen conduit. METHODS: Forty-two male New Zealand rabbits were divided into three experimental groups. In each group, a unilateral 3-cm peroneal nerve defect was repaired with a nerve autograft, an empty collagen conduit, or a conduit filled with a collagen-GAG matrix. At six months, nerve regeneration was evaluated on the basis of the compound muscle action potentials, maximum isometric tetanic force, and wet muscle weight of the tibialis anterior muscle as well as nerve histomorphometry. RESULTS: The autograft group had significantly better motor recovery than the conduit groups. The empty collagen conduits and conduits filled with the collagen-GAG matrix led to results that were similar to each other. CONCLUSIONS: On the basis of this rabbit model, autologous nerve grafting remains the gold standard in the reconstruction of 3-cm segmental motor nerve defects. CLINICAL RELEVANCE: Segmental motor nerve defects should be reconstructed with autograft nerves. The use of a collagen conduit filled with a collagen-GAG matrix for motor nerve reconstruction should be limited until additional animal studies are performed.