Collagen-hydroxyapatite composite substitute and bone marrow nuclear cells on posterolateral spine fusion in sheep

The effects of a large collagen-hydroxyapatite (COL-HA) substitute with or without isolated bone marrow nuclear cells (BMNC) on spine fusion were evaluated using a two-level posterolateral spinal fusion model in sheep. Six sheep each were included in both the COL-HA and autograft groups. In each animal, spine fusions were performed at two levels by randomization with or without BMNC. After an observation period of 4.5 months, the fusion blocks (length = 50 mm) were harvested and evaluated by micro-CT with respect to fusion rate and microarchitecture, and histology was performed to qualitatively assess new bone morphology. BMNC supplementation did not lead to significant differences in fusion rates or microarchitectural properties in the both groups (p = 0.56). Porosity decreased significantly in the COL-HA group (p = 0.002), suggesting a relatively fast degradation of COL-HA. Qualitative histology assessment revealed quick reabsorption of COL-HA replaced by newly formed bone, and this new bone morphology was similar to autograft. Interestingly, COL-HA generated significant amounts of new bone in vivo which were similar to autograft, and the presence of BMNC seemed to enhance this process. Apart from porosity, the comparable fusion rate and similar microarchitectural parameters suggested equal performance of COL-HA and autograft with respect to spine fusion and bone quality. In conclusion, the COL-HA with BMNC demonstrated comparable fusion rates as the autograft. COL-HA was capable of forming new bone and was revealed to be similar to the autograft with respect to microarchitectural properties apart from porosity of the fusion blocks.

[1]  F. Luyten,et al.  Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. , 2018, Biomaterials.

[2]  Woojin Cho,et al.  Bone graft materials for posterolateral fusion made simple: a systematic review , 2018, European Spine Journal.

[3]  F. O'Brien,et al.  Controlled release of vascular endothelial growth factor from spray‐dried alginate microparticles in collagen–hydroxyapatite scaffolds for promoting vascularization and bone repair , 2017, Journal of tissue engineering and regenerative medicine.

[4]  Alan H. Daniels,et al.  Mesenchymal stromal cells in spinal fusion: Current and future applications. , 2017, Journal of orthopaedics.

[5]  Zunpeng Liu,et al.  Enhancement of posterolateral lumbar spine fusion using recombinant human bone morphogenetic protein-2 and mesenchymal stem cells delivered in fibrin glue , 2016, Journal of biomaterials applications.

[6]  E. Figallo,et al.  Collagen-Hydroxyapatite Scaffolds Induce Human Adipose Derived Stem Cells Osteogenic Differentiation In Vitro , 2016, PloS one.

[7]  Jeffrey C. Wang,et al.  Clinical and radiographic outcomes of concentrated bone marrow aspirate with allograft and demineralized bone matrix for posterolateral and interbody lumbar fusion in elderly patients , 2015, European Spine Journal.

[8]  G. Logroscino,et al.  Bone substitutes in orthopaedic surgery: from basic science to clinical practice , 2014, Journal of Materials Science: Materials in Medicine.

[9]  S. Berven,et al.  Cell Based Therapies as Compared to Autologous Bone Grafts for Spinal Arthrodesis , 2013, Spine.

[10]  D. Wendt,et al.  Effects of a perfusion bioreactor activated novel bone substitute in spine fusion in sheep , 2012, European Spine Journal.

[11]  Alberto Diaspro,et al.  Order versus Disorder: in vivo bone formation within osteoconductive scaffolds , 2012, Scientific Reports.

[12]  T. Yoshii,et al.  Hybrid Grafting Using Bone Marrow Aspirate Combined With Porous &bgr;-Tricalcium Phosphate and Trephine Bone for Lumbar Posterolateral Spinal Fusion: A Prospective, Comparative Study Versus Local Bone Grafting , 2012, Spine.

[13]  F. Luyten,et al.  Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology , 2011, Journal of cellular and molecular medicine.

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

[15]  Andrea Augello,et al.  Mesenchymal stem cells: a perspective from in vitro cultures to in vivo migration and niches. , 2010, European cells & materials.

[16]  M. Ding.  Microarchitectural adaptations in aging and osteoarthrotic subchondral bone issues , 2010, Acta orthopaedica. Supplementum.

[17]  C. V. van Blitterswijk,et al.  Relevance of bone graft viability in a goat transverse process model , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[18]  Warren D. Yu,et al.  Pseudarthrosis of the Spine , 2009, The Journal of the American Academy of Orthopaedic Surgeons.

[19]  Ivan Martin,et al.  Design of graded biomimetic osteochondral composite scaffolds. , 2008, Biomaterials.

[20]  Munish C. Gupta,et al.  Efficacy of Mesenchymal Stem Cell Enriched Grafts in an Ovine Posterolateral Lumbar Spine Model , 2007, Spine.

[21]  J T Czernuszka,et al.  Collagen-hydroxyapatite composites for hard tissue repair. , 2006, European cells & materials.

[22]  G. Falini,et al.  Biologically inspired synthesis of bone-like composite: self-assembled collagen fibers/hydroxyapatite nanocrystals. , 2003, Journal of biomedical materials research. Part A.

[23]  Safdar N. Khan,et al.  Animal Models for Preclinical Assessment of Bone Morphogenetic Proteins in the Spine , 2002, Spine.

[24]  A. Turner,et al.  The sheep as a model for osteoporosis in humans. , 2002, Veterinary journal.

[25]  A. Ka.  Effect of adding resorbable calcium sulfate to grafting materials on early bone regeneration in osseous defects in rabbits. , 2000 .

[26]  S. Ludwig,et al.  Osteoinductive bone graft substitutes , 2000, European Spine Journal.

[27]  M Ding,et al.  Accuracy of cancellous bone volume fraction measured by micro-CT scanning. , 1999, Journal of biomechanics.

[28]  P. Rüegsegger,et al.  A new method for the model‐independent assessment of thickness in three‐dimensional images , 1997 .

[29]  D. R. Sumner,et al.  Biologic issues in lumbar spinal fusion. Introduction. 1995 Focus Issue Meeting on Fusion. , 1995, Spine.

[30]  D. R. Sumner,et al.  Biologic Factors Affecting Spinal Fusion and Bone Regeneration , 1995, Spine.

[31]  H. Gundersen,et al.  Quantification of connectivity in cancellous bone, with special emphasis on 3-D reconstructions. , 1993, Bone.

[32]  V. Goldberg,et al.  Osteogenic potential of culture-expanded rat marrow cells as assayed in vivo with porous calcium phosphate ceramic. , 1991, Biomaterials.

[33]  H J Gundersen,et al.  Estimation of structural anisotropy based on volume orientation. A new concept , 1990, Journal of microscopy.

[34]  L. Dolcini,et al.  Effects of different crosslinking conditions on the chemical–physical properties of a novel bio-inspired composite scaffold stabilised with 1,4-butanediol diglycidyl ether (BDDGE) , 2012, Journal of Materials Science: Materials in Medicine.

[35]  K. A. A. Ruhaimi.  Effect of Adding Resorbable Calcium Sulfate to Grafting Materials on Early Bone Regeneration in Osseous Defects in Rabbits , 2000 .

[36]  TOR Hildebrand,et al.  Quantification of Bone Microarchitecture with the Structure Model Index. , 1997, Computer methods in biomechanics and biomedical engineering.