Acellular Human Placenta Small-Diameter Vessels as a Favorable Source of Super-Microsurgical Vascular Replacements: A Proof of Concept

Author:

Falkner Florian1,Mayer Simon Andreas1ORCID,Thomas Benjamin1ORCID,Zimmermann Sarah Onon2,Walter Sonja1ORCID,Heimel Patrick34ORCID,Thiele Wilko5ORCID,Sleeman Jonathan Paul56ORCID,Bigdeli Amir Khosrow1ORCID,Kiss Herbert7,Podesser Bruno Karl27ORCID,Kneser Ulrich1ORCID,Bergmeister Helga289,Schneider Karl Heinrich289ORCID

Affiliation:

1. Department of Hand, Plastic and Reconstructive Surgery, BG Trauma Center Ludwigshafen, University of Heidelberg, 69117 Heidelberg, Germany

2. Center for Biomedical Research and Translational Surgery, Medical University of Vienna, 1090 Vienna, Austria

3. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, 1200 Vienna, Austria

4. Core Facility Hard Tissue and Biomaterial Research, Karl Donath Laboratory, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria

5. Department of Microvascular Biology and Pathobiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany

6. Institute for Biological and Chemical Systems, Karlsruhe Institute of Technology, Campus North, 76131 Karlsruhe, Germany

7. Department of Obstetrics and Gynecology, Division of Obstetrics and Feto-Maternal Medicine, Medical University of Vienna, 1090 Vienna, Austria

8. Ludwig Boltzmann Institute for Cardiovascular Research, 1090 Vienna, Austria

9. Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria

Abstract

In this study, we aimed to evaluate the human placenta as a source of blood vessels that can be harvested for vascular graft fabrication in the submillimeter range. Our approach included graft modification to prevent thrombotic events. Submillimeter arterial grafts harvested from the human placenta were decellularized and chemically crosslinked to heparin. Graft performance was evaluated using a microsurgical arteriovenous loop (AVL) model in Lewis rats. Specimens were evaluated through hematoxylin-eosin and CD31 staining of histological sections to analyze host cell immigration and vascular remodeling. Graft patency was determined 3 weeks after implantation using a vascular patency test, histology, and micro-computed tomography. A total of 14 human placenta submillimeter vessel grafts were successfully decellularized and implanted into AVLs in rats. An appropriate inner diameter to graft length ratio of 0.81 ± 0.16 mm to 7.72 ± 3.20 mm was achieved in all animals. Grafts were left in situ for a mean of 24 ± 4 days. Decellularized human placental grafts had an overall patency rate of 71% and elicited no apparent immunological responses. Histological staining revealed host cell immigration into the graft and re-endothelialization of the vessel luminal surface. This study demonstrates that decellularized vascular grafts from the human placenta have the potential to serve as super-microsurgical vascular replacements.

Funder

Austrian Science Fund

Publisher

MDPI AG

Subject

Bioengineering

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