Novel biomaterial strategies for controlled growth factor delivery for biomedical applications

Growth factors (GFs) are soluble proteins secreted by cells that have the ability to regulate a variety of cellular processes and tissue regeneration. However, their translation into clinical applications is limited due to their short effective half-life, low stability, and rapid inactivation by enzymes under physiological conditions. To maximize the effectiveness of GFs and their biologically relevant applicability, a wide variety of sophisticated bio-inspired systems have been developed that augment tissue repair and cellular regeneration by controlling how much, when, and where GFs are released. Recently, protein immobilization techniques combined with nanomaterial carriers have shown promise in mimicking the natural healing cascade during tissue regeneration by augmenting the delivery and effectiveness of GFs. This review evaluates the latest techniques in direct immobilization and relevant biomaterials used for GF loading and release, including synthetic polymers, albumin, polysaccharides, lipids, mesoporous silica-based nanoparticles (NPs), and polymeric capsules. Specifically, we focus on GF-encapsulated NPs in functionalized microporous scaffolds as a promising alternative with the ability to mimic extracellular matrix (ECM) hierarchical architectures and components with high cell affinity and bioactivity. Finally, we discuss how these next-generation, advanced delivery systems have been used to enhance tissue repair and regeneration and consider future implications for their use in the field of regenerative medicine.