title: The proangiogenic potential of a novel calcium releasing biomaterial: Impact on cell recruitment.
abstract: In current bone tissue engineering strategies the achievement of sufficient angiogenesis during tissue regeneration is still a major limitation in order to attain full functionality. Several strategies have been described to tackle this problem, mainly by the use of angiogenic factors or endothelial progenitor cells. However, when facing a clinical scenario these approaches are inherently complex and present a high cost. As such, more cost effective alternatives are awaited. Here, we demonstrate the potential of electrospun poly(lactic acid) (PLA) fiber-based membranes, containing calcium phosphate ormoglass (CaP) particles, to elicit angiogenesis in vivo, in a subcutaneous model in mice. We show that the current approach elicited the local expression of angiogenic factors, associated to a chemotactic effect on macrophages, and sustained angiogenesis into the biomaterial. As both PLA and CaP are currently accepted for clinical application these off-the-shelf novel membranes have great potential for guided bone regeneration applications.
  
  
  CONCLUSIONS
  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, our group has found that calcium ions released by the degradation of calcium phosphate ormoglasses (CaP) are effective angiogenic promoters. Based on this, in this work we successfully produced hybrid fibrous mats with different contents of CaP nanoparticles and thus with different calcium ion release rates, using an ormoglass - poly(lactic acid) blend approach. We show that these matrices, upon implantation in a subcutaneous site, could elicit the local expression of angiogenic factors, associated to a chemotactic effect on macrophages, and sustained angiogenesis into the biomaterial, in a CaP dose dependent manner. This off-the-shelf cost effective approach presents great potential to translate to the clinics.
authors.affiliation: Inserm, U1026, Tissue Bioengineering, University Bordeaux Segalen, Bordeaux Cedex 33076, France. Electronic address: hugo.de-oliveira@inserm.fr.
authors.forename: Hugo
authors.initials: H
authors.lastname: Oliveira
authors.affiliation: Inserm, U1026, Tissue Bioengineering, University Bordeaux Segalen, Bordeaux Cedex 33076, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Catros
authors.affiliation: Inserm, U1026, Tissue Bioengineering, University Bordeaux Segalen, Bordeaux Cedex 33076, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Boiziau
authors.affiliation: Inserm, U1026, Tissue Bioengineering, University Bordeaux Segalen, Bordeaux Cedex 33076, France.
authors.forename: Robin
authors.initials: R
authors.lastname: Siadous
authors.affiliation: Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain; CIBER-BBN, Zaragoza, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Marti-Munoz
authors.affiliation: Inserm, U1026, Tissue Bioengineering, University Bordeaux Segalen, Bordeaux Cedex 33076, France.
authors.forename: Reine
authors.initials: R
authors.lastname: Bareille
authors.affiliation: Inserm, U1026, Tissue Bioengineering, University Bordeaux Segalen, Bordeaux Cedex 33076, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rey
authors.affiliation: Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain; CIBER-BBN, Zaragoza, Spain; Materials Science and Metallurgical Engineering, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Castano
authors.affiliation: Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain; CIBER-BBN, Zaragoza, Spain; Materials Science and Metallurgical Engineering, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Planell
authors.affiliation: Inserm, U1026, Tissue Bioengineering, University Bordeaux Segalen, Bordeaux Cedex 33076, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Amédée
authors.affiliation: Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain; CIBER-BBN, Zaragoza, Spain; Dpt. Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya, Barcelona, Spain.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Engel
mesh_terms: D000328:Adult; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002130:Calcium Phosphates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D008567:Membranes, Artificial; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); C020243:calcium phosphate; D002118:Calcium
keywords: Angiogenesis; Bone regeneration; Calcium phosphate ormoglass