Bioactive hydrogel scaffolds. Advances in cartilage regeneration through controlled drug delivery

The importance of growth factor delivery in cartilage tissue engineering is nowadays widely recognized. However, when growth factors are administered by a bolus injection, they undergo rapid clearance before they could stimulate the cells of interest at promoting cartilage repair. Their short half-lives make growth factors ineffective, unless administered at supraphysiological doses, with potentially harmful consequences on patient safety. Recently, new tissue engineering strategies relying on the combination of biodegradable scaffolds and specific biological cues, such as growth or adhesive factors or genetic material, have demonstrated that controlled release is the key factor for achieving effective cartilage repair at lower drug doses. Among all biomaterials, hydrogels have emerged as promising cartilage tissue engineering scaffolds for simultaneous cell growth and drug delivery. In fact, hydrogels can be easily loaded with cells and drugs, that are subsequently released in a controlled fashion. The success of hydrogels in controlled drug delivery for tissue engineering originates from their biocompatibility and capacity to integrate well with the host tissue. This review overviews the hydrogels technologies now available for the regeneration of cartilage that base their efficacy on the controlled release of bioactive substances able to modulate cellular behavior and to eventually lead to successful tissue repai