Calcium Phosphate Bioceramics: An Alternative to Autograft and Allograft? - Engineered Bone: Tissue Engineering Intelligence Unit - page 68

to be totally appropriate to a drug solution adsorbed onto a solid degradable CaP matrix.
Finally, even if drug release seems too complex to be described by a simple diffusion mecha-
nism (with respect to the Higuchi equation), pharmacokinetic of drug release from CaP ce-
ramic is also dependent on matrix tortuosity and porosity. Both of these ceramic parameters are
affected by precipitation/dissolution process of CaP, which occurs when such ceramics are im-
mersed in release solution or under the influence of the ceramic resorption/degradation process
in bone sites. Thus, drug release in vivo is under the influence of both a diffusion mechanism
and the ceramic resorption/degradation process. A precise knowledge of ceramic dissolution
and resorption properties is therefore of importance to provide clinicians with a valuable CaP
ceramic DDS for bone sites.
Therapeutic Applications of CaP Ceramic-Based Drug Delivery Systems
Preclinical and clinical trials have shown that CaP ceramics were able to induce new bone
formation at their expenses leading to their total replacement by lamellar bone. However,
osteoconductivity of CaP ceramics does not yet allow the filling of large bone defects. Today,
one approach to improve the ceramic bone replacement consists in associating an osteogenic
factor with the material. In this attempt, growth factors such as transforming growth factor,
platelet-derived growth factor, bone morphogenetic proteins, growth hormone and insulin-like
growth factor-1 have been successfully investigated. These promising results have encouraged
the scientific community to consider CaP ceramics as supports for the release of others mol-
ecules potentially implicated in the local treatment of bone pathologies such as infections,
bone tumors and pathological bone loss.
Infections
Therapy of bone infections (osteomyelitis) may easily last two years because of the poor
accessibility of the infection site by commonly systemically administered antibiotics. This is
mainly because bones are moderately perfused organs and likely because of a reduced blood
supply associated to the formation of diffusional barriers in the infected bone tissues. In this
context, to improve therapy, resorbable CaP materials have been contemplated as potential
carriers for antibiotics. They release effective drug amount at the site of infection for several
months, while the systemic drug concentration remains very low. Among the various antibiotics,
vancomycin and gentamycin have been extensively investigated and proved efficacy in human
osteomyelitis. 45
Bone Tumors
A major attempt in treating bone and soft tissue tumors is to maintain local long acting and
effective high concentrations of a chemotherapeutic drug at the site of tumors while producing
minimum systemic side effects. Porous CaP ceramics have been demonstrated to be an efficient
form of local DDS for methotrexate or cis-platinum and successfully used in the clinical treat-
ment of mice osteosarcoma. 46,47 CaP ceramic could therefore play a major role in cancer che-
motherapy in reducing the recurrence of tumors without risk of systemic toxicity.
Bone Loss
Osteoarticular disorders associated with increased osteoclastic bone resorption (as observed
in osteoporosis, Paget's disease of bone, bone lytic tumors, periodontal disease…) often lead to
pathological fractures. They are widely treated by systemic administration of Bisphosphonates,
potent inhibitors of osteoclast activity. Association of CaP materials with bisphosphonates would
allow to increase the efficiency of bisphosphonate by being locally released and decreasing
significantly secondary effects (nephrotoxicity) observed after systemic treatments. In this ob-
jective, ceramic hydroxyapatite implants have been used in dental surgery. Denissen et al 48
have reported that bisphosphonates may be beneficial in preventing alveolar bone destruction
associated with natural and experimental periodontal disease. These authors have demonstrated
the efficiency of Bisphosphonate-complexed hydroxyapatite implants on the repair of alveolar
bone.