Localized delivery of growth factors for bone repair.
Delivery of growth factors for tissue (e.g. bone, cartilage) or cell repair (e.g. nerves) is about to gain important potential as a future therapeutic tool. Depending on the targeted cell type and its state of differentiation, growth factors can activate or regulate a variety of cellular functions. Therefore, strictly localized delivery regimens at well-defined kinetics appear to be logical prerequisites to assure safe and efficacious therapeutic use of such factors and avoid unwanted side effects and toxicity, a major hurdle in the clinical development of growth factor therapies so far. This review summarizes various approaches for localized growth factor delivery as focused on bone repair. Similar considerations may apply to other growth factors and therapeutic indications. Considering the vast number of preclinical studies reported in the area of growth factor-assisted bone repair, it surprises though that only two medical products for bone repair have so far been commercialized, both consisting of a collagen matrix impregnated with a bone morphogenetic protein. The marked diversity of the reported growth factors, delivery concepts and not yet standardized animal models adds to the complexity to learn from past preclinical studies presented in the literature. Nonetheless, it is now firmly established from the available information that the type, dose and delivery kinetics of growth factors all play a decisive role for the therapeutic success of any such approach. Very likely, all of these parameters have to be adapted and optimized for each animal model or clinical case. In the future, systems for localized growth factor delivery thus need to be designed in such a way that their modular components are readily adaptable to the individual pathology. To make such customized systems feasible, close cooperative networks of biomedical and biomaterials engineers, pharmaceutical scientists, chemists, biologists and clinicians need to be established.
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland.
Vera
V
Luginbuehl
Lorenz
L
Meinel
Hans P
HP
Merkle
Bruno
B
Gander
D000818:Animals; D001847:Bone Diseases / Q000188:drug therapy*; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000235:genetics; D001861:Bone Regeneration / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006133:Growth Substances / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D006133:Growth Substances; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta