Free microsurgical defect coverage using a hemodynamically stimulated and an axial vascularized stimulated soft tissue flap

Status:

completed 12/2016

Aims:

s. results

Activities/Methods:

see results

Results:

Autologous free flaps are the standard of care for reconstructions of complex soft tissue defects. However, they are limited by donor-site morbidities like functional muscle loss, nerve injury and scare formation. Moreover, in case of large burn injuries or extensive trauma, donor sites for free flaps are scarce in general. The replacement of free flaps by vascularized tissue engineered constructs is a promising approach to overcome this problem in the future. However, the requirements of early and homogenous perfusion are limiting large volume tissue transfer. A way to solve this dilemma is the in vivo creation of axially vascularized constructs. They can be harvested from healthy areas with minimal donor site morbidity, allowing defect-adapted custom manufacturing and an accessible vascular connection to recipient vessels because of a solid main vascular pedicle. In this study we used a rat model of axial vascularization in vivo. In this approach an autologous vein is grafted between the saphenous artery and vein at the medial thigh, resulting in an arteriovenous (AV) loop. After transferring the AV loop into a subcutaneous teflon chamber, the grafted vein exhibited angio-inductive properties, providing a functional microcirculatory system and secondary cell migration into the surrounding acellular matrix. We further established a standardized wound defect model with exposed scapular bone in rats and pointed out that AV loop based soft tissue free flaps are suitable for free microsurgical transfer and closure of these complex defects. Another aim of the present study was to determine the optimal matrix and the ideal prefabrication duration for a free connective tissue flap based on the AV loop. Comparison of two collagen-based matrices (MatriDerm® and Integra™ DRT) in our model revealed that MatriDerm® results in a higher vessel formation and cell migration than Integra™ DRT after two and four weeks of subcutaneous implantation. This has been associated with an increased maturation of MatriDerm®, which caused the peripheral areas of the constructs to well vascularize and colonize with cells after four weeks, in contrast to Integra™ DRT constructs, whose periphery remains avascular with poor cell migration after the same period of time. Furthermore, a correlation between a stiff, elastic matrix and increased in vivo vascularization, as well as increased cell migration, could be demonstrated. The appearance of quantitatively different dynamics of angiogenesis and maturation processes with the two collagen matrices implies the complexity of the functional interaction between angiogenesis and the extracellular matrix. The fabricated axially vascularized connective tissue flap was successfully transferred to a standardized defect with exposed bone on the rat’s bladebone for the first time. Thereby, in contrast to avascular treatments, sufficient coverage with a quick reconstruction of the wound was achieved after two weeks. The application of growth factors was not required for this process, which is highly beneficial as they are strongly discussed to be carcinogenic. Furthermore, it was possible to dispense with complex in vitro cell cultures, as the natural cell migration across the vessel surface has resulted in an adequate remodeling of the tissue. The particular suitability of MatriDerm® for generating a vascularized connective tissue flap due to its vascularization capabilities and cell recruitment kinetics was shown. The results reveal a simple and reliable approach for the fabrication of artificial, vascularized tissue flaps remote from the injury, tailored to the required size and shape. Thus, the extraction morbidity and limited availability of common autologous flaps could be avoided. Due to the aimed group of patients (burn injuries, polytrauma, critical wound defect, limb salvage etc.) the AV loop technique is of high therapeutic and economical relevance for the DGUV. Transferring the technique into a larger animal model is the next necessary step to enable a human application in the near future.

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