Mandibular reconstruction using an axially vascularized tissue-engineered construct

Abstract

BackgroundCurrent reconstructive techniques for continuity defects of the mandible include the use of free flaps, bone grafts, and alloplastic materials. New methods of regenerative medicine designed to restore tissues depend mainly on the so-called extrinsic neovascularization, where the neovascular bed originates from the periphery of the construct. This method is not applicable for large defects in irradiated fields.MethodsWe are introducing a new animal model for mandibular reconstruction using intrinsic axial vascularization by the Arterio-Venous (AV) loop. In order to test this model, we made cadaveric, mechanical loading, and surgical pilot studies on adult male goats. The cadaveric study aimed at defining the best vascular axis to be used in creating the AV loop in the mandibular region. Mechanical loading studies (3 points bending test) were done to ensure that the mechanical properties of the mandible were significantly affected by the designed defect, and to put a base line for further mechanical testing after bone regeneration. A pilot surgical study was done to ensure smooth operative and post operative procedures.ResultsThe best vascular axis to reconstruct defects in the posterior half of the mandible is the facial artery (average length 32.5 ± 1.9 mm, caliber 2.5 mm), and facial vein (average length 33.3 ± 1.8 mm, caliber 2.6 mm). Defects in the anterior half require an additional venous graft. The defect was shown to be significantly affecting the mechanical properties of the mandible (P value 0.0204). The animal was able to feed on soft diet from the 3rd postoperative day and returned to normal diet within a week. The mandible did not break during the period of follow up (2 months).ConclusionsOur model introduces the concept of axial vascularization of mandibular constructs. This model can be used to assess bone regeneration for large bony defects in irradiated fields. This is the first study to introduce the concept of axial vascularization using the AV loop for angiogenesis in the mandibular region. Moreover, this is the first study aiming at axial vascularization of synthetic tissue engineering constructs at the site of the defect without any need for tissue transfer (in contrast to what was done previously in prefabricated flaps).

Engineering axially vascularized bone in the sheep arteriovenous-loop model

“…These concepts may be useful for reconstruction of complex defects, but the problem of donor site morbidity remains to be solved. Recently, a pilot study using an AV‐loop model in the goat was described to further assess bone regeneration in the mandibular region (Eweida et al ., ).…”

Bone Graft Prefabrication Following the In Vivo Bioreactor Principle

“…By scaling up the AVL model, clinically approved, mechanically stable bone grafts with a significant volume were prefabricated in sheep or goat models, implying the feasibility of clinical translation in future work (Beier et al, 2011, Beier et al, 2010, Boos et al, 2013). Using the AVL strategy, Eweida et al improved the commonly used ectopic prefabrication approach to the in situ prefabrication approach and tested its clinical translation possibility in goats (Eweida et al, 2011, Eweida et al, 2012, Eweida et al, 2014). The results showed that the AVL strategy induced better vascularization at the central regions and permitted more efficient bone regeneration.…”

αvβ3 and α5β1 integrin-specific ligands: From tumor angiogenesis inhibitors to vascularization promoters in regenerative medicine?

“…A natural solution to this problem is adding a vascular network to the construct before implantation, therefore accelerating its perfusion. Pre-vascularized engineered tissues can be quickly perfused with blood by inosculation with the host vasculature (Laschke et al, 2009) or by surgical anastomosis of feeding and draining blood vessels (Beier et al, 2009;Eweida et al, 2011). Such vascular networks must be highly branched in such a way that no cell is further than 200 μm from a vessel as this is broadly considered as the diffusion limit for oxygen and nutrients in tissues (Jain et al, 2005).…”