*2.2.1.2 Selection of an appropriate immobilization method*

Biological molecule must be attached to the surface of a transducer to function consistently as a biological receptor. Immobilization is the term for this procedure. This goal has been accomplished using a variety of techniques including adsorption, entrapment, covalent attachment, microencapsulation, and crosslinking [45, 46].

### *2.2.1.3 Transducer element selection*

The efficiency of the biosensor device is heavily influenced by the transducer element. The use of an effective transducer will result in a device with greater efficiency, whereas the use of an ineffective transducer will result in a device with reduced efficiency [45, 47].

#### **2.3 Recent advances in biosensing**

#### *2.3.1 Tissue engineering*

Biosensors are particularly useful in tissue engineering applications, such as maintaining three-dimensional (3D)-printed cell cultures [48] and developing "organs-onchips" models, where biomolecule concentrations such as glucose, adenosines, and hydrogen peroxide levels play a key role in determining the fate of cells and tissues. Changes in oxygen consumption, pH, membrane potentials, ion concentrations, and the release of numerous metabolic chemicals and proteins are all well-known physical and chemical signals that living cells communicate [49]. Monitoring these analytes in real time can provide insight into cellular activity.

#### *2.3.1.1 Application of biosensors in tissue engineering*

## *2.3.1.1.1 3D-bioprinted sensing devices*

The deposition of a bioink (living cells and biomaterials) onto a printing surface is described as bioprinting, and it is a new approach for fabricating tissues and organs by accurately controlling the periodic arrangement of diverse biological materials, such as biomolecules and biocells. It has a wide range of characteristics that can be used in biosensing applications, such as fast deposition and patterning of proteins and other biomolecules [50]. A typical illustration of a 3D-printed tissue construct can be seen in **Figure 8**.

There are a variety of bioprinting technologies that can be used to make biosensors, and they are basically grouped into two methods, namely contact-based and noncontact-based printing. Both biomaterials and bioinks are essential for biological signal transduction. For advanced extrusion-based bioprinting such as coaxial or triaxial, optimization of the bioink viscosity is a major consideration to prevent clogging. Other properties including pore size and cellular behavior may influence biosensing [52]. Using an electric field, some printing processes, such as electrodeposition, may be able to transfer thin films of metal nanoparticles [50] or nanowires [53] to a substrate. Creating circuits that could be an intrinsic part of a biosensor, as well as some immunoassays or microarrays, can be done by printing thin metal sheets [54, 55]. Even thin films of biological material, such as proteins, enzymes, nucleic acids, polysaccharides, and bacterial cells, have been printed using electrodeposition

*Recent Advances in Biosensing in Tissue Engineering and Regenerative Medicine DOI: http://dx.doi.org/10.5772/intechopen.104922*

#### **Figure 8.**

*Stages in submerged bioprinting of a 3D tissue construct. A) The cell-laden hydrogel bioink is printed in droplets, layer by layer following the provided model. The printing nozzle is submerged in high-density perfluorocarbons that are immiscible in water and oil. Perfluorocarbons are suitable for submerged cells due to the presence of oxygen and carbon dioxide transport capability. B) The hydrogel droplets are printed in a vertical or lateral dimension to produce branching constructs without solid support [51].*

[56–58]. More work needs to be done on bioprinting techniques that may be utilized to deposit a wide range of biologics and mammalian cells in precise spatial positions, rather than thin films, which have been used for biosensing applications.

### *2.3.1.1.2 Biosensors for diabetes*

Diabetes is a serious chronic metabolic illness that affects over 400 million people globally. Uncontrolled chronic hyperglycemia damages and destroys various organs, resulting in significant morbidity and mortality [59]. Blood glucose control can help to reduce the frequency and severity of these problems [60]. By putting the glucose oxidase enzyme on an oxygen electrode, Clark and Lyons created the first biosensor for monitoring glucose levels in 1962 [61]. The care of diabetic patients was transformed when the first self-monitoring blood glucose (SMBG) gadget based on the glucose dehydrogenase enzyme was introduced in 1987 [62]. SMBG in **Figure 9** is now widely used in the treatment of diabetes, particularly type I [64, 65].

#### *2.3.1.1.3 Biosensors for wound healing*

Wound healing is a multistep process that necessitates the collaboration of numerous tissues and biochemical pathways [66]. Chronic wounds result from the failure of these processes to proceed in a timely and organized manner, possibly putting a huge financial strain on healthcare systems [67]. Uncontrolled inflammatory processes, bacterial infections, alterations in the acidic pH of the skin, oxygen levels, and matrix

**Figure 9.** *Various parts of an electrochemical glucose biosensor for diabetes care [63].*

metalloproteinases (MMPs) are all involved in such failures [67, 68]. Biosensors are being researched to allow doctors to closely monitor the healing process, as regular monitoring is crucial in chronic wound management [67]. Screen-printing electrodes with Ag/AgCl-conductive ink were used to create a wearable pH sensor [69]. Wearable sensors for biomarkers detection for wound infections can be shown in **Figure 10**.
