Theranostic biomaterials for tissue engineering

Abstract

Tissue engineering strategies, notably biomaterials, can be modularly designed and tuned to match specific patient needs. Although many challenges within tissue engineering remain, the incorporation of diagnostic strategies to create theranostic (combined therapy and diagnostic) biomaterials presents a unique platform to provide dual monitoring and treatment capabilities and advance the field toward personalized technologies. In this review, we summarize recent developments in this young field of regenerative theranostics and discuss the clinical potential and outlook of these systems from a tissue engineering perspective. As the need for precision and personalized medicines continues to increase to address diseases in all tissues in a patient-specific manner, we envision that such theranostic platforms can serve these needs.

Keywords: Biomaterials; Cell-based devices; Nanoparticles; Scaffolds; Theranostics; Tissue engineering.

Figure 1. Theranostic nanoparticles and microparticles.

Nanoparticles and microparticles can be synthesized using a wide range of suitable biomaterials ranging from metals and graphenes to polymers and lipids. These particles can be functionalized with targeting entities and loaded with therapeutic cargos for systemic or localized delivery. The particles themselves can also serve as contrast agents for various techniques such as ultrasound, bioluminescence, MRI, Positron emission tomography (PET)/Single-photon emission computerized tomopgrahy (SPECT), and CT to achieve the theranostic objectives. AuNP, gold nanoparticle; CT, computed tomography; MRI, magnetic resonance imaging.

Figure 2. Applications of theranostic nanoparticles, scaffolds, and cell-derived platforms.

(a.1) Schematic representation of a polymer nanoparticle (PNP) conjugated with an antirheumatic targeted drug, tocilizumab (TCZ), for near-infrared (NIR) II photoacoustic (PA) imaging and treatment of rheumatoid arthritis (RA). (a.2) Maximum amplitude projection PA (top) and micro-CT (bottom) images of RA animal forepaws at day 57 with and without TCZ PNP treatment (adapted with permission from Go et al. [27]. Copyright (2021) John Wiley and Sons.). (b.1) Representative images of cornea collagen implants, gold nanoparticles (GNPs), and GNPs conjugated with acyclovir (ACV). (b.2) Cross-sectional backscattered electron images of unmodified implants (Bx) and implants with ACV-conjugated GNPs (Tx) (white arrows). (b.3). Immunostained herpes simplex virus type 1 treated with Tx implants, Bx + ACV, or Bx. (b.4) Scans of Bx and Tx implants with MRI in transverse relaxivity (R2), proton density–weighted, and transverse relaxation (T2)–weighted modes with and without ACV (bottom arrow) (adapted with permission from Moroni et al. [39]. Copyright (2021) John Wiley and Sons.). (c.1) Representative transmission electron images of extracellular vesicles (EVs) without aggregation-induced emission luminogens (AIEgens) and with AIEgens (AIE-EVs) (yellow arrowheads) to treat renal ischemia-reperfusion injury (I/IR-kidney). (c.2) In vivo imaging of AIE-EVs in a mouse model of acute kidney injury over 72 h. (c.3) Quantification of AIEgens and AIE-EVs from the I/IR-kidney. (c.4) Micrograph for hematoxylin and eosin staining of kidney sections on day 5 after treatment with AIEgens or AIE-EVs. Black arrowheads indicate tubular protein cast and the necrotic area (adapted with permission from Saxena et al. [59]. Copyright (2021) American Chemical Society.). CT, computed tomography; MRI, magnetic resonance imaging.

Figure 3. Scaffolds and hydrogel platforms.

Scaffolds and hydrogels can be made from a multitude of suitable biomaterials including natural and synthetic polymers, components of the extracellular matrix, ceramics, and metals. The scaffolds by themselves and in combination with engineered cells, nanomaterials/micromaterials, and therapeutic molecules can be used as theranostic tissue-engineered grafts. They, in turn, can track and monitor for any anomalies associated with grafts, intervene by releasing therapeutic molecules, and perform the therapeutic course correction. These real-time monitoring approaches guide the decision-making process of whether to continue or discontinue the grafted tissue.

Figure 4. Cell and biomolecular platforms.

Cells and biomolecules can be engineered to provide diagnostic output alongside their innate biological capacity. This can be achieved by through genetic engineering in fluorescent or radionucleotide reporters, building synthetic gene circuits, or using exosomes loaded with intervening nucleotide sequences or proteins. These platforms allow for synchronous diagnostics and autonomous regulation of corrective therapeutic actions.