1. In vivo biofunctional evaluation of hydrogels for disc regeneration
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Britta Kanter, Hans-Joachim Wilke, Anita Ignatius, Joaquim M. Oliveira, Katharina Gruchenberg, Joana Silva-Correia, Ludwika Kreja, Matteo Santin, Sandra Reitmaier, Valeria Perugini, Rui L. Reis, and Universidade do Minho
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Adult ,Hydrostatic pressure ,Angiogenesis Inhibitors ,Biocompatible Materials ,Intervertebral Disc Degeneration ,In Vitro Techniques ,chemistry.chemical_compound ,In vivo ,Hyaluronic acid ,medicine ,Animals ,Humans ,Regeneration ,Diskectomy, Percutaneous ,One-step ,Orthopedics and Sports Medicine ,Hyaluronic Acid ,Bone Marrow Transplantation ,Sheep ,Science & Technology ,business.industry ,Regeneration (biology) ,Mesenchymal stem cell ,technology, industry, and agriculture ,Hydrogels ,Intervertebral disc ,Anatomy ,Large animal model ,Nucleotomy ,Biomechanical Phenomena ,3. Good health ,medicine.anatomical_structure ,chemistry ,Self-healing hydrogels ,Leukocytes, Mononuclear ,Degeneration ,Surgery ,Bone marrow ,business ,EUROSPINE 2013 Full Paper Award ,Biomedical engineering - Abstract
Purpose Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model. Methods In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted. Results Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration. Conclusions None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioning, This work was supported by the EU-project Disc Regeneration (NMP3-LA-2008-213904). Technical assistance of Iris Baum and the whole animal surgery team of the Institute of Orthopaedic Research and Biomechanics, Ulm, are gratefully acknowledged. DDAHA hydrogels were kindly provided by Cristina Longinotti (DDAHA, Anika Therapeutics, Abano Therme, Italy).
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