1. The proangiogenic potential of a novel calcium releasing composite biomaterial: Orthotopic in vivo evaluation
- Author
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Hugo Oliveira, J.A. Planell, Marc Batista, Reine Bareille, Joan Marti-Munoz, Douglas A. Clift, Robin Siadous, Elisabeth Engel, Oscar Castaño, Sylvie Rey, Joëlle Amédée, Sylvain Catros, Chassande, Olivier, Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Universitat Autònoma de Barcelona (UAB), Universitat Politècnica de Catalunya [Barcelona] (UPC), Universitat Politècnica de Catalunya. Departament de Ciència dels Materials i Enginyeria Metal·lúrgica, and Universitat Politècnica de Catalunya. IMEM-BRT- Innovation in Materials and Molecular Engineering - Biomaterials for Regenerative Therapies
- Subjects
Angiogenesis ,[SDV]Life Sciences [q-bio] ,Drug Evaluation, Preclinical ,02 engineering and technology ,Bone tissue ,Biochemistry ,Mice ,Osteogenesis ,Endothelial Progenitor Cells ,Biomaterial ,General Medicine ,021001 nanoscience & nanotechnology ,3. Good health ,Bone regeneration ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Enginyeria de teixits ,Materials biomèdics ,Heterografts ,0210 nano-technology ,Biotechnology ,Materials science ,Polyesters ,Ossos -- Regeneració ,0206 medical engineering ,Biomedical Engineering ,chemistry.chemical_element ,Neovascularization, Physiologic ,Bone healing ,Calcium ,Enginyeria dels materials [Àrees temàtiques de la UPC] ,Biomaterials ,In vivo ,medicine ,Animals ,Humans ,Tissue engineering ,Rats, Wistar ,Molecular Biology ,Calcium phosphate ormoglasses ,Regeneration (biology) ,020601 biomedical engineering ,Rats ,chemistry ,Delayed-Action Preparations ,Ciments ossis ,Biophysics ,Biomedical materials ,Biomedical engineering - Abstract
Insufficient angiogenesis remains a major hurdle in current bone tissue engineering strategies. An extensive body of work has focused on the use of angiogenic factors or endothelial progenitor cells. However, these approaches are inherently complex, in terms of regulatory and methodologic implementation, and present a high cost. We have recently demonstrate the potential of electrospun poly(lactic acid) (PLA) fiber-based membranes, containing calcium phosphate (CaP) ormoglass particles, to elicit angiogenesis in vivo , in a subcutaneous model in mice. Here we have devised an injectable composite, containing CaP glass-ceramic particles, dispersed within a (Hydroxypropyl)methyl cellulose (HPMC) matrix, with the capacity to release calcium in a more sustained fashion. We show that by tuning the release of calcium in vivo , in a rat bone defect model, we could improve both bone formation and increase angiogenesis. The bone regeneration kinetics was dependent on the Ca 2+ release rate, with the faster Ca 2+ release composite gel showing improved bone repair at 3 weeks, in relation to control. In the same line, improved angiogenesis could be observed for the same gel formulation at 6 weeks post implantation. This methodology allows to integrate two fundamental processes for bone tissue regeneration while using a simple, cost effective, and safe approach. Statement of Significance In current bone tissue engineering approaches the achievement of sufficient angiogenesis, during tissue regeneration, is a major limitation in order to attain full tissue functionality. Recently, we have shown that calcium ions, released by the degradation of calcium phosphate ormoglasses (CaP), are effective angiogenic promoters, in both in vitro and in a subcutaneous implantation model. Here, we devised an injectable composite, containing CaP glass-ceramic particles, dispersed within a HPMC matrix, enabling the release of calcium in a more sustained fashion. We show that by tuning the release of calcium in vivo , in a rat bone defect model, we could improve both bone formation and increase angiogenesis. This simple and cost effective approach holds great promise to translate to the clinics.
- Published
- 2017
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