Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization.

During the last decades, a range of excellent and promising strategies in Bone Tissue Engineering have been developed. However, the remaining major problem is the lack of vascularization. In this study, extrinsic and intrinsic vascularization strategies were combined for acceleration of vascularization. For optimal biomechanical stability of the defect site and simplifying future transition into clinical application, a primary stable and approved nanostructured bone substitute in clinically relevant size was used. An arteriovenous (AV) loop was microsurgically created in sheep and implanted, together with the bone substitute, in either perforated titanium chambers (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated Teflon® chambers (intrinsic) for 18 weeks. Over time, magnetic resonance imaging and micro-computed tomography (CT) analyses illustrate the dense vascularization arising from the AV loop. The bone substitute was completely interspersed with newly formed tissue after...

[1]  E. Tsiridis,et al.  Transformation of a prefabricated hydroxyapatite/osteogenic protein-1 implant into a vascularised pedicled bone flap in the human chest. , 2006, International journal of oral and maxillofacial surgery.

[2]  Ulrich Kneser,et al.  Engineering axially vascularized bone in the sheep arteriovenous‐loop model , 2013, Journal of tissue engineering and regenerative medicine.

[3]  L. Applegate,et al.  Bone regeneration and stem cells , 2011, Journal of cellular and molecular medicine.

[4]  Kiyofumi Takabatake,et al.  Basic fibroblast growth factor supports expansion of mouse compact bone-derived mesenchymal stem cells (MSCs) and regeneration of bone from MSC in vivo , 2011, Journal of Molecular Histology.

[5]  A. Arkudas,et al.  Dose-finding study of fibrin gel-immobilized vascular endothelial growth factor 165 and basic fibroblast growth factor in the arteriovenous loop rat model. , 2009, Tissue engineering. Part A.

[6]  Björn Möller,et al.  Tissue engineering of a vascularized bone graft of critical size with an osteogenic and angiogenic factor-based in vivo bioreactor. , 2014, Tissue engineering. Part A.

[7]  H. Schaller,et al.  De-novo Generierung von vaskularisiertem Gewebe mittels unterschiedlicher Gefässstielkonfigurationen in perforierten und geschlossenen Wachstumskammern , 2010, Wiener Medizinische Wochenschrift.

[8]  H. Sorg,et al.  Early matrix change of a nanostructured bone grafting substitute in the rat. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[9]  A. Boos,et al.  New aspects on efficient anticoagulation and antiplatelet strategies in sheep , 2013, BMC Veterinary Research.

[10]  Ulrich Kneser,et al.  Successful human long-term application of in situ bone tissue engineering , 2014, Journal of cellular and molecular medicine.

[11]  D. Mooney,et al.  Polymeric system for dual growth factor delivery , 2001, Nature Biotechnology.

[12]  Xiaohong Li,et al.  Comparative studies on ectopic bone formation in porous hydroxyapatite scaffolds with complementary pore structures. , 2013, Acta biomaterialia.

[13]  Ali Khademhosseini,et al.  Vascularized bone tissue engineering: approaches for potential improvement. , 2012, Tissue engineering. Part B, Reviews.

[14]  G. Rogers,et al.  Autogenous bone graft: basic science and clinical implications. , 2012, The Journal of craniofacial surgery.

[15]  H. Eufinger,et al.  Growth and transplantation of a custom vascularised bone graft in a man , 2004, The Lancet.

[16]  N. Gellrich,et al.  Prefabrication of vascularized bioartificial bone grafts in vivo for segmental mandibular reconstruction: experimental pilot study in sheep and first clinical application. , 2010, International journal of oral and maxillofacial surgery.

[17]  Geraldine M Mitchell,et al.  Engineering the microcirculation. , 2008, Tissue engineering. Part B, Reviews.

[18]  N. Gellrich,et al.  En bloc prefabrication of vascularized bioartificial bone grafts in sheep and complete workflow for custom-made transplants. , 2014, International journal of oral and maxillofacial surgery.

[19]  T. Mittlmeier,et al.  Osteogenic capacity of nanocrystalline bone cement in a weight-bearing defect at the ovine tibial metaphysis , 2012, International journal of nanomedicine.

[20]  A. Boos,et al.  Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model , 2014, International journal of nanomedicine.

[21]  Jeroen Rouwkema,et al.  Endothelial cells assemble into a 3-dimensional prevascular network in a bone tissue engineering construct. , 2006, Tissue engineering.

[22]  Andreas Hess,et al.  De novo generation of axially vascularized tissue in a large animal model , 2009, Microsurgery.

[23]  Werner Götz,et al.  Nanostructuring of Biomaterials—A Pathway to Bone Grafting Substitute , 2006, European Journal of Trauma.

[24]  T. He,et al.  Cross-talk between EGF and BMP9 signalling pathways regulates the osteogenic differentiation of mesenchymal stem cells , 2013, Journal of cellular and molecular medicine.

[25]  A. Arkudas,et al.  Combination of BMP2 and MSCs significantly increases bone formation in the rat arterio-venous loop model. , 2015, Tissue engineering. Part A.

[26]  R. Singer,et al.  Combination of Extrinsic and Intrinsic Pathways Significantly Accelerates Axial Vascularization of Bioartificial Tissues , 2012, Plastic and reconstructive surgery.

[27]  A. Wenzel,et al.  Remodeling of cortical and corticocancellous fresh-frozen allogeneic block bone grafts--a radiographic and histomorphometric comparison to autologous bone grafts. , 2015, Clinical oral implants research.

[28]  M. Kasai,et al.  A bone substitute with high affinity for vitamin D-binding protein―relationship with niche of osteoclasts , 2013, Journal of cellular and molecular medicine.

[29]  R. Rao,et al.  Effects of hydroxyapatite on endothelial network formation in collagen/fibrin composite hydrogels in vitro and in vivo. , 2014, Acta biomaterialia.

[30]  W. Grayson,et al.  Platelet-derived growth factor and spatiotemporal cues induce development of vascularized bone tissue by adipose-derived stem cells. , 2013, Tissue engineering. Part A.

[31]  R. Jung,et al.  Bone regeneration in the presence of a synthetic hydroxyapatite/silica oxide-based and a xenogenic hydroxyapatite-based bone substitute material. , 2011, Clinical oral implants research.

[32]  A. Hess,et al.  De novo Generation of an Axially Vascularized Processed Bovine Cancellous-Bone Substitute in the Sheep Arteriovenous-Loop Model , 2011, European Surgical Research.

[33]  T. Gedrange,et al.  A preliminary study in osteoinduction by a nano-crystalline hydroxyapatite in the mini pig. , 2011, Folia histochemica et cytobiologica.

[34]  Kyongbum Lee,et al.  Vascularization strategies for tissue engineering. , 2009, Tissue engineering. Part B, Reviews.

[35]  Andreas Hess,et al.  Engineering of vascularized transplantable bone tissues: induction of axial vascularization in an osteoconductive matrix using an arteriovenous loop. , 2006, Tissue engineering.

[36]  A. Boccaccini,et al.  Evaluation of angiogenesis of bioactive glass in the arteriovenous loop model. , 2013, Tissue engineering. Part C, Methods.

[37]  P. Cui,et al.  Tissue-engineered larynx using perfusion-decellularized technique and mesenchymal stem cells in a rabbit model , 2011, Acta oto-laryngologica.

[38]  E. Sherry,et al.  Comparison of in vitro biocompatibility of NanoBone(®) and BioOss(®) for human osteoblasts. , 2011, Clinical Oral Implants Research.

[39]  S. Bai,et al.  Prefabrication of vascularized bone grafts using a combination of bone marrow mesenchymal stem cells and vascular bundles with β-tricalcium phosphate ceramics. , 2012, Oral surgery, oral medicine, oral pathology and oral radiology.

[40]  G. Vunjak‐Novakovic,et al.  Tissue engineered bone grafts: biological requirements, tissue culture and clinical relevance. , 2008, Current stem cell research & therapy.

[41]  Andreas Hess,et al.  Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model , 2010, Journal of tissue engineering and regenerative medicine.

[42]  A. Boos,et al.  A novel early precursor cell population from rat bone marrow promotes angiogenesis in vitro , 2014, BMC Cell Biology.

[43]  D. Mooney,et al.  Combined Angiogenic and Osteogenic Factor Delivery Enhances Bone Marrow Stromal Cell‐Driven Bone Regeneration , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[44]  Ulrich Kneser,et al.  Fibrin Gel-Immobilized VEGF and bFGF Efficiently Stimulate Angiogenesis in the AV Loop Model , 2007, Molecular medicine.

[45]  Andreas Hess,et al.  Automatic quantitative micro-computed tomography evaluation of angiogenesis in an axially vascularized tissue-engineered bone construct. , 2010, Tissue engineering. Part C, Methods.

[46]  R. Guldberg,et al.  Vascularization Strategies for Bone Regeneration , 2014, Annals of Biomedical Engineering.

[47]  G. Pierer,et al.  Spatial and temporal patterns of bone formation in ectopically pre-fabricated, autologous cell-based engineered bone flaps in rabbits , 2008, Journal of cellular and molecular medicine.

[48]  Christopher S. Chen,et al.  Cell adhesion and mechanical stimulation in the regulation of mesenchymal stem cell differentiation , 2013, Journal of cellular and molecular medicine.

[49]  M. Barbeck,et al.  Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation , 2013, Head & Face Medicine.

[50]  R A Perez,et al.  Therapeutic bioactive microcarriers: co-delivery of growth factors and stem cells for bone tissue engineering. , 2014, Acta biomaterialia.

[51]  M. Barbeck,et al.  Nanocrystalline hydroxyapatite bone substitute leads to sufficient bone tissue formation already after 3 months: histological and histomorphometrical analysis 3 and 6 months following human sinus cavity augmentation. , 2013, Clinical implant dentistry and related research.

[52]  L. Gottlieb,et al.  Autologous Immediate Cranioplasty with Vascularized Bone in High-Risk Composite Cranial Defects , 2013, Plastic and reconstructive surgery.

[53]  B. Vollmar,et al.  In vivo analysis of biocompatibility and vascularization of the synthetic bone grafting substitute NanoBone. , 2009, Journal of biomedical materials research. Part A.

[54]  M. Hammon,et al.  Endothelial progenitor cells are integrated in newly formed capillaries and alter adjacent fibrovascular tissue after subcutaneous implantation in a fibrin matrix , 2011, Journal of cellular and molecular medicine.