Association of human growth hormone and calcium phosphate by dynamic compaction: in vitro biocompatibility and bioactivity.

The association of therapeutic agents with biomaterials has been achieved through various techniques, such as coating of the ceramic block surface or drug incorporation into ceramics. The dynamic compaction method recently was developed to consolidate drug-loaded calcium phosphate powder without a sintering step. In the present work, human recombinant growth hormone was loaded on biphasic calcium phosphate powder and consolidated by a specific process of cold sintering (dynamic compaction). Analyses of the biocompatibility of compacted pellets (mouse L929 fibroblastic cell culture) and the bioactivity of the drugs released by them (growth hormone bioassay) were performed. This report demonstrates the biocompatibility of the compacts prepared by dynamic compaction. L929 cell proliferation was maintained and the capacity to secrete fibronectin was conserved in the presence of compacted materials. Comparison of released growth hormone integrity, revealed by radioimmunoassay and eluted stain bioassay, has shown that the biological activity of growth hormone was totally preserved after dynamic compaction. However, 35% of loaded growth hormone was not released in our experimental conditions, probably because of the inaccessibility of growth hormone within the granulated compacts. Dynamic compaction shows good potential for the production of biomaterials capable of releasing therapeutic agents in situ.

[1]  G. Daculsi,et al.  Apatite as carrier for growth hormone: in vitro characterization of loading and release. , 1997, Journal of biomedical materials research.

[2]  K. Chihara,et al.  Stimulatory effect of growth hormone on bone resorption and osteoclast differentiation. , 1996, Endocrinology.

[3]  G. Daculsi,et al.  Dynamic compaction of calcium phosphate biomaterials , 1995 .

[4]  M. Dattani,et al.  The measurement of growth hormone bioactivity in patient serum using an eluted stain assay. , 1995, The Journal of clinical endocrinology and metabolism.

[5]  S. J. Holt,et al.  A critical assessment of the use of microculture tetrazolium assays to measure cell growth and function. , 1995, Growth regulation.

[6]  S. J. Holt,et al.  The development of an eluted stain bioassay (ESTA) for human growth hormone. , 1995, Growth regulation.

[7]  M. Grégoire,et al.  Comparative effect of calcium hydroxide and hydroxyapatite on the cellular activity of human pulp fibroblasts in vitro. , 1994, Archives of oral biology.

[8]  C. Löwik,et al.  Ceramic hydroxyapatite implants for the release of bisphosphonate. , 1994, Bone and mineral.

[9]  A Pizzoferrato,et al.  Cell culture methods for testing biocompatibility. , 1994, Clinical materials.

[10]  J. Kaufman,et al.  Short and long‐term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone‐deficient males * , 1993, Clinical endocrinology.

[11]  M. Slootweg,et al.  Growth Hormone and Bone , 1993, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[12]  N. Araki,et al.  Calcium hydroxyapatite ceramic used as a delivery system for antibiotics. , 1992, The Journal of bone and joint surgery. British volume.

[13]  B. Alliot-Licht,et al.  Cellular activity of osteoblasts in the presence of hydroxyapatite: an in vitro experiment. , 1991, Biomaterials.

[14]  S. Downes,et al.  Growth-hormone loaded bioactive ceramics , 1991 .

[15]  T. Martin,et al.  Growth hormone (GH) receptors in clonal osteoblast-like cells mediate a mitogenic response to GH. , 1991, Endocrinology.

[16]  G. Daculsi,et al.  Macroporous calcium phosphate ceramic for long bone surgery in humans and dogs. Clinical and histological study. , 1990, Journal of biomedical materials research.

[17]  H. Benghuzzi,et al.  Ceramic systems for long-term delivery of chemicals and biologicals. , 1988, Journal of biomedical materials research.

[18]  A. Lindahl,et al.  Mechanism of the stimulatory effect of growth hormone on longitudinal bone growth. , 1987, Endocrine reviews.

[19]  A. Schulz,et al.  Effect of growth hormone on osteoblasts and demonstration of somatomedin-C/IGF I in bone organ culture. , 1984, Acta endocrinologica.

[20]  O. Isaksson,et al.  Growth hormone stimulates the proliferation of cultured chondrocytes from rabbit ear and rat rib growth cartilage , 1983, Nature.

[21]  R. Noble,et al.  Prolactin-stimulated growth of cell cultures established from malignant Nb rat lymphomas. , 1980, Cancer research.