Tissue Engineering by Intrinsic Vascularization in an <em>In Vivo</em> Tissue Engineering Chamber

Abstract

In reconstructive surgery, there is a clinical need for an alternative to the current methods of autologous reconstruction which are complex, costly and trade one defect for another. Tissue engineering holds the promise to address this increasing demand. However, most tissue engineering strategies fail to generate stable and functional tissue substitutes because of poor vascularization. This paper focuses on an in vivo tissue engineering chamber model of intrinsic vascularization where a perfused artery and a vein either as an arteriovenous loop or a flow-through pedicle configuration is directed inside a protected hollow chamber. In this chamber-based system angiogenic sprouting occurs from the arteriovenous vessels and this system attracts ischemic and inflammatory driven endogenous cell migration which gradually fills the chamber space with fibro-vascular tissue. Exogenous cell/matrix implantation at the time of chamber construction enhances cell survival and determines specificity of the engineered tissues which develop. Our studies have shown that this chamber model can successfully generate different tissues such as fat, cardiac muscle, liver and others. However, modifications and refinements are required to ensure target tissue formation is consistent and reproducible. This article describes a standardized protocol for the fabrication of two different vascularized tissue engineering chamber models in vivo.

Design and Fabrication of an Automatable, 3D Printed Perfusion Device for Tissue Infusion and Perfusion Engineering

“…This is particularly relevant for preventing kinks or twists in tissue pedicles, which can induce thrombosis during perfusion. 24 If a user's application does not require such motion, these components can be subtracted from the system with no adverse effect on the function of the electronics or software. Driving these servomotors, the valve servomotors, and the stepper motors governing the peristaltic pumps, is an Arduino microcontroller, which was selected because it is an open-source electronics platform based on an IDE that allows for control of a myriad of devices capable of interacting with the external environment and shares a large developer community that has written, tested, and published functional code.…”

A novel microsurgical rodent model for the transplantation of engineered cardiac muscle flap

“…An AVL tissue engineering chamber was constructed in the right groin of syngeneic adult Sprague Dawley rats ( n = 8, weight 250–350 //grams) intended as donors as previously described (Morritt et al, ; Zhan et al, ). In brief, the femoral artery and vein in the right groin were isolated, separated, and ligated distally.…”

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

“…According to Zhan et al [57] the critical factors for a successful AV loop surgery are "surgical technical, blood flow, thrombosis and spasm." A retrospective analysis of more than 600 AV loop surgeries showed a significant correlation of experience and practice of microsurgeons and the thrombosis rate and time of surgery [58].…”

“…For the reduction of vessel thrombosis, a range of different antiplatelet and/or anticoagulant drugs can be applied in the postoperative phase such as heparin, sodium-enoxaparin, or clopidogrel [18,24,59]. To reduce bending of the loop vessels and therefore the risk of thromboses, Zhan et al [57] suggest using the epigastric branches as tethers to hold the AV loop in position -or as an alternative, nylon stitches from the wall of the AV loop vessel to the surrounding tissue. Dong et al [36] tried to reduce thrombosis by reducing the number of anastomoses.…”

“…Another strategy to induce axial vascularization with a concurrent reduction of the risk of a vascular thrombosis is the so-called vascular bundle model [57]. It can be further divided into the "flow through" or "distal ligation" model [60].…”