Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine

Abstract

Polymer hydrogels have been widely explored as therapeutic delivery matrices because of their ability to present sustained, localized and controlled release of bioactive factors. Bioactive factor delivery from injectable biopolymer hydrogels provides a versatile approach to treat a wide variety of diseases, to direct cell function and to enhance tissue regeneration. The innovative development and modification of both natural-(e.g., alginate (ALG), chitosan, hyaluronic acid (HA), gelatin, heparin (HEP), etc.) and synthetic-(e.g., polyesters, polyethyleneimine (PEI), etc.) based polymers has resulted in a variety of approaches to design drug delivery hydrogel systems from which loaded therapeutics are released. This review presents the state-of-the-art in a wide range of hydrogels that are formed though self-assembly of polymers and peptides, chemical crosslinking, ionic crosslinking and biomolecule recognition. Hydrogel design for bioactive factor delivery is the focus of the first section. The second section then thoroughly discusses release strategies of payloads from hydrogels for therapeutic medicine, such as physical incorporation, covalent tethering, affinity interactions, on demand release and/or use of hybrid polymer scaffolds, with an emphasis on the last 5 years.

Light-Triggered RNA Release and Induction of Hmsc Osteogenesis Via Photodegradable, Dual-Crosslinked Hydrogels

“…siRNA suppresses gene activity by binding to one specific complementary Light-triggered RNA release and induction of hMSC osteogenesis via photodegradable, dual-crosslinked hydrogels future science group Research Article Huynh, Nguyen, Naris, Tonga, Rotello & Alsberg messenger RNA (mRNA) target and inactivating it through enzymatic cleavage [33][34][35][36][37], while miRNA regulates gene expression by binding to multiple mRNA targets and inhibiting their translation [17,18]. These RNAs possess great therapeutic potential due to their ability to regulate the production of specific proteins associated, for example, with the progression of a specific disease or the inhibition of tissue regeneration [6,20,[32][33][34][35][36][37][38].…”

“…Despite the promise of siRNA and miRNA-based therapy, their effective delivery to target cells remains a significant challenge [1,6,[32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. Efficacy of naked siRNA/miRNA is limited due to their short half-lives in vivo, ranging from several minutes to an hour, which is largely a consequence of their susceptibility to degradation by ribonucleases (RNases) [36].…”

“…For example, nanocomplexes of anionic siRNA and miRNA with cationic macromers, such as polyethylenimines (PEIs) [46], chitosan [34,49], poly(β-amino ester) [21], and others [27,50,51] have been shown to increase their stability and cellular internalization. However, locally delivering these nanocarriers to specific regions in the body is hampered by their rapid dispersion in vivo as a result of their small size [6,[32][33][34][35][36][37][38]47,[52][53][54]. Consequently, repeated or high doses are generally necessary to achieve sustained gene knockdown at a target tissue.…”

“…Polymeric hydrogel biomaterials are three-dimentional chemically or physically crosslinked hydrophilic polymer networks that can absorb and retain large quantities of water [2,38,[55][56][57][58]. Hydrogels hold great potential in biomedical and pharmaceutical applications because bioactive factors can be encapsulated within them and subsequently delivered in a localized and controlled manner at desired anatomic locations [38,[55][56][57].…”

“…Hydrogels hold great potential in biomedical and pharmaceutical applications because bioactive factors can be encapsulated within them and subsequently delivered in a localized and controlled manner at desired anatomic locations [38,[55][56][57]. For example, they have been employed as depots for the delivery of anticancer drugs [59][60][61], genetic materials [62], and proteins [63][64][65].…”