development of biodegradable implantable medical devices. Materials for bioelectronic

devices must be strong enough to withstand massive deformations while being flexible

enough to be compatible with soft tissues. Such devices have made their way not just into

biomedical research, but also into stretchy, flexible, and wearable electronics. To design

an efficient bioelectronic device, the material’s properties such as biocompatibility, shape

conformance, electrical, optical, and mechanical properties must be considered.

3.2.1 Biocompatibility

Biocompatibility and safety are the fundamental concern to utilizing 2D materials–based

bioelectronic devices for in-vivo biomedical applications. Even for in-vitro applications, the

biocompatibility of the materials is also reviewed to find the extent of tolerance of various

cell lines such as HeLa, 4T1, A549, 293T, MCF7, PC3. Typical examinations used to estimate

the cell viability are the methyl thiazolyl tetrazolium, water-soluble tetrazolium, Alamar

Blue, calcein acetoxymethyl/propidium iodide, and dihydroethidine. The toxic effect of

materials on hemo-, histo-, and neuro systems must be examined before using them in

biomedicine. In certain instances, in-vivo toxicity experiments were performed on rats or

mice to understand material’s toxicity in hemo-, histo-, and neuro systems. The composi­

tional biocompatibility of bare transition metal dichalcogenides (TMDs) nanosheets (MoS2,

WS2, and WSe2) was evaluated by employing MTT and WST-8 tests on the A549 cell line

[10]. The results demonstrated that WSe2 was highly toxic (0.2 mg/mL) as compared to the

other two even at a higher concentration (0.4 mg/mL). This designated that the bio­

compatibility of a 2D material also depends on its chemical composition.

The tunning chemical composition provides a possible gateway to modify the surface of

2D materials and improves their biocompatibility. Better biocompatibility was observed

when the surface of molybdenum disulfide was modified through exfoliation in bovine

serum albumin (BSA) (Figure 3.3) [11]. A schematic binding (Figure 3.3a) of BSA on the

molybdenum disulfide layer was observed with benzene rings and disulfides. BSA and

other polymeric compounds affect the biocompatibility, adsorption, and capacitance of

MoS2. BSA-modified MoS2 showed higher biocompatibility (Figure 3.3b) in comparison to

bulk and polymers adsorbed MoS2. In addition, 2,4-D bounding with BSA-modified MoS2

(Figure 3.3c) was better than bulk and other polymers modified MoS2. The MoS2−BSA

nanosheets (Figure 3.3d) demonstrated higher specific capacitance. A similar approach has

been extensively employed using smaller molecules and polymers including polyethylene

glycol (PEG), BSA, poly(vinyl pyrrolidone) (PVP), glutathione, soybean phospholipid, and

polyacrylic acid [11,12]. Surface treatment through these chemicals increases material sta­

bility under physiological conditions and improves biocompatibility at the expense of

toxicity. Furthermore, coatings are used to improve the biocompatibility of TMDs. A me­

soporous Si coating on PEG-modified WS2@Fe3O4 demonstrated superior biocompatibility

through 4T1, HeLa, and 293T cells up to 0.2 mg/mL dosage [13]. In addition, coated TMDs

showed no noticeable damage or abnormalities in the organ. Recently discovered 2D Ti3C2

MXene nanosheets have also shown higher biocompatibility when encapsulated with

soybean phospholipid [14]. The encapsulated MXene nanosheets have no noticeable toxic

impact on 4T1 cells even at a higher dosage of 0.4 mg/mL.

The biocompatibility of black phosphorus (BP) quantum dots can be improved by

modifying the synthesis protocol. Better biocompatibility and stability were observed

when BP was synthesized through the liquid-phase exfoliation method and encapsulated

with poly(lactic-co-glycolic acid) (PLGA) nanospheres [15]. BP encapsulated agarose

hydrogel was tested for breast cancer therapy [16]. The results revealed that encapsulated

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Bioelectronics