Controlled release strategies for bone, cartilage, and osteochondral engineering : Part II : challenges on the evolution from single to multiple bioactive factor delivery

The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interfaceis one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majorityof the developed systems consider only the release of a single growth factor, which is a limiting step for thesuccess of the therapy. More recent studies have been focused on the design and tailoring of appropriatecombinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, consideringthe complexity of extracellular matrix and the diversity of growth factors and cytokines involved in eachbiological response, it is expected that an appropriate combination of bioactive factors could lead to moresuccessful outcomes in tissue regeneration. In this review, the evolution on the development of dual andmultiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specificallythe relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. Acomprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlightingthe increasing impact of platelet-rich plasma as an autologous source of multiple growth factors.The authors thank Fundacaopara a Ciencia e Tecnologia for V.E.Santo's PhD grant (SFRH/BD/39486/2007). This work was carried out under the scope of the European FP7 Project Find and Bind (NMP4-SL-2009-229292) and Project MIT/ECE/0047/2009