Biopolymer-based growth factor delivery for tissue repair: from natural concepts to engineered systems

The extracellular matrix of tissues is regarded as a physiological depot for various growth factors (GFs), from where they are to be released into the surrounding tissue and play their natural roles in tissue regulation. In addition to autocrine and paracrine cell signaling, they provide specific extracellular information necessary to conduct tissue homeostasis and (re)generation. This review will detail on various physiological concepts that have evolved during evolution to control the activity of GFs in a specific manner through interaction with biopolymers of the extracellular matrix, and how such interactions may respond to systemic or cellular signals. A fundamental understanding of the extracellular storage and control of GFs could provide important cues about the nature of GF interactions and improve the potency of current implantable biopolymer systems for GF delivery in tissue repair. Therefore, in a second part of this review, current nature-derived biopolymers will be discussed with respect to their availability, suitability for scaffolding, mechanical properties, and efficiency to sustain the activity and release of GFs. Further, we will detail on rational modifications and engineering approaches to improve their applicability as delivery systems. In particular, we discuss biotechnology and chemical engineering strategies to adapt natural concepts of GF depots for delivery purposes. In conclusion, the engineering of novel biopolymer platforms holds promise to enhance the biological performance of GF-loaded artificial tissue substitutes to replace autologous and allogenous tissue grafts for the treatment of critical tissue defects.