Biomaterial-assisted biotherapy: A brief review of biomaterials used in drug delivery, vaccine development, gene therapy, and stem cell therapy

Abstract

Biotherapy has recently become a hotspot research topic with encouraging prospects in various fields due to a wide range of treatments applications, as demonstrated in preclinical and clinical studies. However, the broad applications of biotherapy have been limited by critical challenges, including the lack of safe and efficient delivery systems and serious side effects. Due to the unique potentials of biomaterials, such as good biocompatibility and bioactive properties, biomaterial-assisted biotherapy has been demonstrated to be an attractive strategy. The biomaterial-based delivery systems possess sufficient packaging capacity and versatile functions, enabling a sustained and localized release of drugs at the target sites. Furthermore, the biomaterials can provide a niche with specific extracellular conditions for the proliferation, differentiation, attachment, and migration of stem cells, leading to tissue regeneration. In this review, the state-of-the-art studies on the applications of biomaterials in biotherapy, including drug delivery, vaccine development, gene therapy, and stem cell therapy, have been summarized. The challenges and an outlook of biomaterial-assisted biotherapies have also been discussed.

Keywords: Biomaterial; Biotherapy; Drug delivery system; Gene therapy; Stem cell therapy; Vaccine development.

Graphical abstract

Fig. 1

Four targeting strategies for systemic drug delivery. EPR, enhanced permeability and retention; NanoEL, nanomaterial-induced endothelial leakiness; DDS, drug delivery system; NP, nanoparticle; ROS, reactive oxygen species; GSH, glutathione; FA, folic acid; HA, hyaluronic acid; and R, receptor.

Fig. 2

Application of biomaterials for the delivery of different nucleic acids. Biomaterials, such as lipid or lipid-like materials, polymeric materials, dendrimers, inorganic materials, and exosomes, are under intensive investigations for the delivery of different genes, including double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), small interfering RNA (siRNA), microRNA (miRNA), messenger RNA (mRNA), etc.

Fig. 3

Schematic illustration of in-situ T cells reprogramming to express the disease-specific CARs or TCRs using IVT mRNA carried by polymeric nanoparticles. Reproduced under the CC-BY license terms [153].

Fig. 4

Three strategies for the delivery of the CRISPR-Cas9 system. Cas9 nuclease can be delivered in plasmid DNA (A), mRNA (B), or protein (C) forms. Each of these delivery approaches has its pros (red) and cons (black). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 5

Application of biomaterials in stem cell therapy. By altering the tunable matrix properties of 3D cell culture, the cellular behaviors, including proliferation, differentiation, migration, attachment, and adhesion, can be controlled. The 3D culture with tunable properties can be spatiotemporally controlled to mimic the native ECM for the further guidance of stem cell behaviors to form desired organoids or organ-on-a-chip (OOC). Organoids and OOC have a wide range of applications, such as disease modeling, drug screening, etc. These properties of 3D culture can also be incorporated into designing the injectable hydrogels and stem cell patches for the delivery of stem cells. These cell delivery vehicles possess outstanding advantages, such as low invasiveness, high efficiency, decreased cell death, etc. ECM, extracellular matrix; and RPE, retinal pigment epithelium.