Influence of calcium chloride and aprotinin in the in vivo biological performance of a composite combining biphasic calcium phosphate granules and fibrin sealant.
ABSTRACT Highly bioactive biomaterials have been developed to replace bone grafts in orthopedic revision and maxillofacial surgery for bone augmentation. A mouldable, self-hardening material can be obtained by combining TricOs Biphasic Calcium Phosphate Granules and Tissucol Fibrin Sealant. Two components, calcium chloride and antifibrinolytic agents (aprotinin), are essential for the stability of the fibrin clot. The ingrowth of cells in composites combining sealants without calcium chloride or with a low concentration of aprotinin was evaluated in vivo in an experiment on rabbits. Bone colonization was compared using TricOs alone or with the composite made from TricOs and the standard fibrin sealant. Without the addition of calcium chloride, the calcium ions released by the ceramic component interacted with the components of the sealant too late to stabilize the clot. With a low concentration of aprotinin, the degradation of the clot occurred more quickly, leading to the absence of a scaffold on which the bone cells could colonize the composite. Our results indicate that a stable fibrin scaffold is crucial for bone colonization. The low calcium chloride and low aprotinin groups have shown lower bone growth. Further studies will be necessary to determine the minimal amount of antifibrinolytic agent (aprotinin) necessary to allow the same level of osteogenic activity as the TricOs-fibrin glue composite.
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ABSTRACT: The limited intrinsic repair capacity of articular cartilage has led to the investigation of different treatment options to promote its regeneration. The delivery of hydrogels containing stem or progenitor cells and growth factor releasing microspheres represents an attractive approach to cartilage repair. In this study, the influence of the encapsulating hydrogel on the ability of progenitor cells coupled with TGF-β3 releasing microspheres to form cartilaginous tissue was investigated. Fibrin, agarose and gellan gum hydrogels containing TGF-β3 loaded gelatin microspheres and progenitor cells derived from the infrapatellar fat-pad of the knee were cultured for 21 days in a chemically defined media. In the presence of TGF-β3 releasing microspheres, gellan gum hydrogels were observed to facilitate greater cell proliferation than fibrin or agarose hydrogels. Histological and biochemical analysis of the hydrogels indicated that fibrin was the least chondro-inductive of the three hydrogels, while agarose and gellan gum appeared to support more robust cartilage formation as demonstrated by greater sGAG accumulation within these constructs. Gellan gum hydrogels also stained more intensely for collagen type II and collagen type I, suggesting that although total collagen synthesis was higher in these constructs, that the phenotype may be more fibrocartilaginous in nature than normal hyaline cartilage. This study demonstrates how the encapsulating hydrogel can have a significant impact on the ability of stem cells to form cartilage when incorporated into a growth factor delivery system.Biomedical Materials 03/2013; 8(3):035004. DOI:10.1088/1748-6041/8/3/035004 · 2.92 Impact Factor
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ABSTRACT: A versatile method for preparing spherical, micro- and macroporous (micro: 2-10 and macro: 150-550 microm pores), carbonated apatitic calcium phosphate (Ap-CaP) granules (2-4 mm in size) was developed by using NaCl crystals as the porogen. The entire granule production was performed between 21 and 37 degrees C. A CaP cement powder, comprising alpha-Ca3(PO4)2 (61 wt.%), CaHPO4 (26%), CaCO3 (10%) and precipitated hydroxyapatite, Ca10(PO4)6(OH)2 (3%), was dry mixed with NaCl crystals varying in size from 420 microm to 1 mm. Cement powder (35 wt.%) and NaCl (65 wt.%) mixture was kneaded with an ethanol-Na2HPO4 initiator solution, and the formed dough was immediately agitated on an automatic sieve shaker for a few minutes to produce the spherical granules. Embedded NaCl crystals were then leached out of the granules by soaking them in deionized water. CaP granules were micro- and macroporous with a total porosity of 50% or more. Granules were composed of carbonated, poorly crystallized, apatitic CaP phase. These were the first spherical and porous CaP granules ever produced from a self-setting calcium phosphate cement. The granules reached their final handling strength at the ambient temperature through the cement setting reaction, without having a need for sintering.Journal of Materials Science Materials in Medicine 06/2008; 19(5):2231-9. DOI:10.1007/s10856-007-3326-9 · 2.38 Impact Factor
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ABSTRACT: The state-of-the-art of biocomposites and hybrid biomaterials based on calcium orthophosphates that are suitable for biomedical applications is presented in this review. Since these types of biomaterials offer many significant and exciting possibilities for hard tissue regeneration, this subject belongs to a rapidly expanding area of biomedical research. Through successful combinations of the desired properties of matrix materials with those of fillers (in such systems, calcium orthophosphates might play either role), innovative bone graft biomaterials can be designed. Various types of biocomposites and hybrid biomaterials based on calcium orthophosphates, either those already in use or being investigated for biomedical applications, are extensively discussed. Many different formulations, in terms of the material constituents, fabrication technologies, structural and bioactive properties as well as both in vitro and in vivo characteristics, have already been proposed. Among the others, the nanostructurally controlled biocomposites, those containing nanodimensional compounds, biomimetically fabricated formulations with collagen, chitin and/or gelatin as well as various functionally graded structures seem to be the most promising candidates for clinical applications. The specific advantages of using biocomposites and hybrid biomaterials based on calcium orthophosphates in the selected applications are highlighted. As the way from the laboratory to the hospital is a long one, and the prospective biomedical candidates have to meet many different necessities, this review also examines the critical issues and scientific challenges that require further research and development.07/2011; 1(1):3-56. DOI:10.4161/biom.1.1.16782