Emerging 2D Nanomaterials for Biomedical Applications

Abstract

Two-dimensional (2D) nanomaterials are an emerging class of biomaterials with remarkable potential for biomedical applications. The planar topography of these nanomaterials confers unique physical, chemical, electronic and optical properties, making them attractive candidates for therapeutic delivery, biosensing, bioimaging, regenerative medicine, and additive manufacturing strategies. The high surface-to-volume ratio of 2D nanomaterials promotes enhanced interactions with biomolecules and cells. A range of 2D nanomaterials, including transition metal dichalcogenides (TMDs), layered double hydroxides (LDHs), layered silicates (nanoclays), 2D metal carbides and nitrides (MXenes), metal-organic framework (MOFs), covalent organic frameworks (COFs) and polymer nanosheets have been investigated for their potential in biomedical applications. Here, we will critically evaluate recent advances of 2D nanomaterial strategies in biomedical engineering and discuss emerging approaches and current limitations associated with these nanomaterials. Due to their unique physical, chemical, and biological properties, this new class of nanomaterials has the potential to become a platform technology in regenerative medicine and other biomedical applications.

Keywords: bioengineering; drug delivery; nanomaterials; regenerative medicine; two dimensional (2D).

Figure 1.. 2D nanomaterials in biomedical engineering.

(A) Exponential increase in the field of 2D nanomaterials as evident from number of publications in past decade (2010-2020). Data obtained from ISI Web of Science using “2D nanomaterials” and “Biomedical applications” (obtained till December 2020). (B) Contribution of individual 2D nanomaterials for biomedical applications in the last decade. Data obtained from ISI Web of Science using “2D nanomaterials” AND “Biomedical applications” OR “TMD”, “LDH”, “Nanoclay”, “MXene”, “Polymer nanosheets” (obtained November 2020). (C) Different types of 2D nanomaterials for various biomedical applications.

Figure 2.. Characteristics of various 2D nanomaterials.

(A) Schematic representation of top and side view of the atomic framework of TMDs and TMOs. (B) Schematic representation of the LDHs atomic structure. (C) Atomic structure of nanoclay showcasing the tetrahedral and octahedral arrangement of atoms which imparts a dual charge nature to the nanomaterials. (D) Schematic representation of biophysical and biochemical characteristics of nanoclay.

Figure 3.. Characteristics of various 2D nanomaterials.

(A) Atomic structure of polymer nanosheets with lattice-defined interaction between sheets. (B) Factors affecting toxicity and unique characteristics of polymer nanosheets. (C) Schematic representation of MXenes synthesis. Evolution in the formation of MXenes on the atomic scale and its various different configurations are shown.

Figure 4.. Biological interaction of 2D nanomaterials.

(A) Top down and bottom up fabrication approach of 2D nanomaterials.(B) Mechanism of interaction and (C) internalization of 2D nanomaterials in cells. The surface charge and size of these nanomaterials determines their mode of interaction. Once internalized, these 2D nanomaterials are prone to accumulate in the lysosome. (D) In vitro and in vivo evaluation of 2D nanomaterials.

Figure 5.. 2D nanomaterials for tissue regeneration.

(A) Schematic representation of the anti-bacterial mechanism of TMDs and TMOs. When internalized, a burst of ROS generation within the bacterial cell results in apoptosis.(B) TMD-based nanocomposites are capable of inducing differentiation in stem cells by various mechanisms. (C) LDH nanosheets are able to sequester small molecule drugs and large proteins, resulting in sustained delivery. (D) Therapeutic loaded LDHs directing stem cell differentiation.

Figure 6.. 2D nanomaterials for tissue regeneration.

(A) Various biomedical applications of nanoclay. (B) Applications of polymer nanosheets for regenerating various tissues. (C) Applications of MXenes in biomedical engineering.

Figure 7.. 2D nanomaterials in cancer therapy.

(A) Different application modalities of TMDsand TMOs for cancer therapeutics. (B) Application of LDHs for tumor-targeting and imaging applications. (C) Surface functionalization of MXenes and NIR mediated PDT/PTT effect exhibited by MXenes. (D) Applications of 2D MOFs for targeting cancer cells to cause oxidative stress resulting in apoptosis.

Figure 8.. 2D nanomaterials for biosensing applications.

(A)Principle of biosesensing using 2D nanomaterials. (B) Range of analytes detecteable using 2D nanomaterials. (C) Functional capabilities of 2D nanomaterials. (D) Signal transduction principles achieved while designing 2D nanomaterial based biosensors.

Figure 9.. Emerging 2D nanomaterials.

Schematic representation of the structure, properties and biomedical applications of new and emerging 2D nanomaterials (A) 2D covalent and metal organic frameworks, (B) sequence-defined nucleic acid, and (C) sequence defined 2D nanomaterials based on peptide, protein and peptoid.