Engineering of Vascularized Transplantable Bone Tissues: Induction of Axial Vascularization in an Osteoconductive Matrix Using an Arteriovenous Loop

Abstract

This study demonstrates for the first time successful vascularization of solid porous matrices by means of an AV loop. Injection of osteogenic cells into axially prevascularized matrices may eventually create functional bioartificial bone tissues for reconstruction of large defects.

Taking a deep look: modern microscopy technologies to optimize the design and functionality of biocompatible scaffolds for tissue engineering in regenerative medicine

“…Besides basic bright-field illumination [36,60], enhanced contrast methods such as dark-field illumination, phase-contrast and differential interference contrast techniques have been applied [61][62][63][64]. White light microscopy is primarily used for routine analysis (monitoring cell number and morphology after seeding of scaffolds) and for imaging stained tissue slices (histology [65]; various stains such as H&E, Von Kossa, trichrome, alcian blue and others are available [39,50,[66][67][68][69][70][71]). A typical study that makes use of histology was carried out by Gerhardt et al [40], who investigated scaffolds after explanation to observe their degradation, cellular infiltration and vascularization (figure 2a).…”

De novo Generation of an Axially Vascularized Processed Bovine Cancellous-Bone Substitute in the Sheep Arteriovenous-Loop Model

“…Recognition of the potentials and characteristics of flap prelamination and prefabrication [16], demonstrating feasability of transferable tissue that is neovascularized by implantation of a vascular pedicle, has fathered new strategies in tissue engineering of vascularized tissue. The high potential of the AV loop as such a vascular carrier for an axial type of vascularization has been clearly demonstrated in the small-animal model and most recently even in a large-animal model [4,6,17,18,19]. Another successful approach to generate vascularized bone tissue in a large-animal (sheep) model has recently been presented by Cheng et al [20], who demonstrated that implantation of a poly(methyl methacrylate) chamber, filled with a morcellized-bone graft, onto the rib periosteum results in a vascularized prefabricated bone flap.…”

“…Our PBCB matrix has been assessed in a few preclinical studies in vitro and in vivo using a small-animal model [4,5,21]. Furthermore, successful application in a vertebral-fusion large-animal model was pursued [22].…”

“…in dorsal skinfold chambers [3], we then aimed for axially vascularized, thus transplantable, neobone generation. We therefore established the axial vascularization of PBCB matrices in an AV-loop rat model and achieved a significantly improved survival rate of implanted cells based on axial prevascularization of such a porous hard matrix [4,5]. These promising results led to the development of a new large-animal model in order to pave the way towards clinical application: the sheep AV-loop model [6].…”

Microsurgical Techniques Used to Construct the Vascularized and Neurotized Tissue Engineered Bone

“…There are many reports about the use of the carotid artery, jugular vein, and saphenous vascular bundle in biomaterials resulting in splendid osteogenesis and vascularization of the bone grafts [47–50]. Surgeons can embed a suitable axial blood vessel into the center of bone graft to get a vascularized bone tissue and then transfer the vascularized bone graft to the bone defect site using microsurgical vascular anastomosis.…”