Localized delivery of growth factors for bone repair

• Published in: European Journal of Pharmaceutics and Biopharmaceutics Vol. 58; no. 2; pp. 197 - 208
• Main Authors: Luginbuehl, Vera, Meinel, Lorenz, Merkle, Hans P, Gander, Bruno
• Format: Book Review Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2004
• Subjects: Animals; Bone Diseases - drug therapy; Bone Morphogenetic Proteins - administration & dosage; Bone Morphogenetic Proteins - genetics; Bone Regeneration - drug effects; Bone repair; Clinical safety; Controlled delivery; Dose effects; Dose-Response Relationship, Drug; Drug Carriers; Drug delivery; Drug Delivery Systems; Growth factors; Growth Substances - administration & dosage; Growth Substances - adverse effects; Growth Substances - pharmacology; Humans; Kinetics; Localized delivery; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - genetics; Release kinetics; Transforming Growth Factor beta - genetics; ECM, extracellular matrix; TGF-β, transforming growth factor β; PLA, poly( d, l-lactide); Drug delivery; aFGF, acidic fibroblast growth factor; TCP, tricalcium phosphate; IGF, insulin-like growth factor; BMP, bone morphogenetic protein; Growth factors; Localized delivery; PEG, polyethyleneglycol; PLGA, poly( d, l-lactide-co-glycolide); Clinical safety; BSA, bovine serum albumin; pI, isoelectic point; VEGF, vascular endothelial growth factor; Bone repair; FDA, Food and Drug Administration; HBGF, heparin-binding growth factor; Controlled delivery; Dose effects; Release kinetics; bFGF, basic fibroblast growth factor; MMP, matrix metalloproteinase; PDGF, platelet-derived growth factor
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2004.03.004

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.