Micro-architecture of calcium phosphate granules and fibrin glue composites for bone tissue engineering.

Calcium phosphate ceramics are currently used as bone graft substitutes in various types of clinical applications. Fibrin glue is also used in surgery due to its haemostatic, chemotactic and mitogenic properties. By combining these two biomaterials, new composite scaffolds were prepared. In this study, we attempt to analyse whether thrombin concentration in the fibrin glue could influence the properties of the composite. The association between fibrin glue and calcium phosphate ceramic granules was characterized at the ultra structural level. Micro and macroporous biphasic calcium phosphate ceramic granules with a diameter of 1-2mm composed of hydroxyapatite and beta-tricalcium phosphate (60/40) were associated to fibrin glue. The composites were observed by scanning and transmission electron microscopy and microcomputed tomography. Fibre thickness, porosity and homogeneity of the fibrin clot were modified by increased the thrombin concentration. Mixing fibrin glue with calcium phosphate granules (1:2) did not modify the microstructure of the fibrin clot in the composite. Nevertheless, thrombin interacted with the bioceramic by inducing the nucleation of crystalline precipitate at the ceramic/fibrin glue interface. Combining fibrin sealant and calcium phosphate ceramics could lead to new scaffolds for bone tissue engineering with the synergy of the properties of the two biomaterials.

[1]  R. Pike,et al.  Inhibition of osteoblast apoptosis by thrombin. , 2003, Bone.

[2]  M. Ueda,et al.  Bone regeneration following injection of mesenchymal stem cells and fibrin glue with a biodegradable scaffold. , 2003, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[3]  H. Matras.  Fibrin seal: the state of the art. , 1985, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[4]  M. Mosesson.  Fibrinogen and fibrin structure and functions , 2005, Journal of thrombosis and haemostasis : JTH.

[5]  K. Sueishi,et al.  Effects of fibrin on the angiogenesis in vitro of bovine endothelial cells in collagen gel , 1995, In Vitro Cellular & Developmental Biology - Animal.

[6]  J. Lindhe,et al.  The effect of a fibrin glue on the integration of Bio-Oss with bone tissue. A experimental study in labrador dogs. , 2002, Journal of clinical periodontology.

[7]  G. Daculsi,et al.  Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles. , 2005, Bone.

[8]  L. Currie,et al.  The use of fibrin glue in skin grafts and tissue-engineered skin replacements: a review. , 2001, Plastic and reconstructive surgery.

[9]  J. McDonagh,et al.  Studies on the mechanism of thrombin. Interaction with fibrin. , 1983, The Journal of biological chemistry.

[10]  G. Daculsi,et al.  MBCP® biphasic calcium phosphate granules and tissucol® fibrin sealant in rabbit femoral defects: The effect of fibrin on bone ingrowth , 2005, Journal of materials science. Materials in medicine.

[11]  A. Eslami,et al.  Biphasic calcium phosphate ceramic combined with fibrillar collagen with and without citric acid conditioning in the treatment of periodontal osseous defects. , 1990, Journal of periodontology.

[12]  J. Trouillet,et al.  Osseointegration of macroporous calcium phosphate ceramics having a different chemical composition. , 1993, Biomaterials.

[13]  S. Koutsopoulos,et al.  The calcification of fibrin in vitro , 2000 .

[14]  M. Kaibara.  Dynamic viscoelastic study of the formation of fibrin networks in fibrinogen-thrombin systems and plasma. , 1973, Biorheology.

[15]  H. Varma,et al.  Fibrin glue as an osteoinductive protein in a mouse model. , 2002, Biomaterials.

[16]  I. Juhan-Vague,et al.  Du fibrinogène à la fibrine et sa dissolution , 2003 .

[17]  L Sedel,et al.  A biodegradable fibrin scaffold for mesenchymal stem cell transplantation. , 2003, Biomaterials.

[18]  S. Andreadis,et al.  Fibrin promotes migration in a three-dimensional in vitro model of wound regeneration. , 2002, Tissue engineering.

[19]  R. Doolittle,et al.  Evolution of vertebrate fibrin formation and the process of its dissolution. , 1997, Ciba Foundation symposium.

[20]  A. Wittkampf.  Fibrin glue as cement for HA-granules. , 1989, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[21]  H. Petite,et al.  Experimental vertebroplasty using osteoconductive granular material. , 2000, Spine.

[22]  G. Daculsi,et al.  Formation of carbonate-apatite crystals after implantation of calcium phosphate ceramics , 2007, Calcified Tissue International.

[23]  G. Daculsi,et al.  Role of fibronectin during biological apatite crystal nucleation: ultrastructural characterization. , 1999, Journal of biomedical materials research.

[24]  D. Dhall,et al.  Physiological studies on fibrin network structure. , 1985, Thrombosis research.

[25]  F. Jegoux,et al.  In vivo biological performance of composites combining micro-macroporous biphasic calcium phosphate granules and fibrin sealant , 2005, Archives of Orthopaedic and Trauma Surgery.

[26]  B Kerebel,et al.  Transformation of biphasic calcium phosphate ceramics in vivo: ultrastructural and physicochemical characterization. , 1989, Journal of biomedical materials research.

[27]  T. Koshino,et al.  Osteogenic response of the rabbit femur to a hydroxyapatite thermal decomposition product-fibrin glue mixture. , 1998, Biomaterials.

[28]  A. Wolberg,et al.  Elevated prothrombin results in clots with an altered fiber structure: a possible mechanism of the increased thrombotic risk. , 2003, Blood.

[29]  D. Sierra,et al.  Experimental and clinical applications of fibrin glue. , 1991, Plastic and reconstructive surgery.

[30]  G. Daculsi,et al.  A review of bioceramics and fibrin sealant. , 2004, European cells & materials.

[31]  E. Mackie,et al.  Expression of the Thrombin Receptor in Developing Bone and Associated Tissues , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[32]  E. Harvey,et al.  The Effect of Fibrin Sealant on Spinal Fusions Using Allograft in Dogs , 1996, Spine.

[33]  S. Lindskog,et al.  A clinical histologic study of bovine hydroxyapatite in combination with autogenous bone and fibrin glue for maxillary sinus floor augmentation. Results after 6 to 8 months of healing. , 2001, Clinical oral implants research.