Page 239 - IJB-9-1

International Journal of Bioprinting 3D printing of smart constructs for precise medicine

structures into specific shapes, sizes, and compositions to be readily used as external stimuli for biological devices
perform tasks, such as tissue repair, drug release, or signal and medicines to realize precise, customized health care .
[11]
acquisition, when implanted in patients. These constructs However, the human body is a sophisticated system that
can serve as supportive bio-scaffolds that escort cells and naturally and continuously experiences complex stress
biomolecules toward the target sites , or as stiff sensors and and changes in temperature, moisture, pH, enzymes, ion
[2]
transducers placed in the vicinity of biological substances concentrations, and electrical activity, which can be used
(e.g., sweat, tears, and blood) to detect pathophysiological as internal impulses . These physical, chemical, and
[12]
changes of these substances in the body . However, biological cues can be utilized to control various aspects
[3]
conventional 3D-printed constructs are restricted to rigid, of the smart constructs by triggering shape-morphing ,
[13]
static, and passive processes because they cannot promote navigating targeted delivery , programming release
[14]
regeneration, achieve targeted drug delivery, and monitor kinetics , and controlling the degradation rate . Due
[15]
[16]
physiological changes, making it difficult for them to meet to their flexibility, 3D-bioprinted smart constructs have
the demands of biomedical and clinical applications. To great potential as next-generation therapeutic tools and
fill this gap, the focus has been on smart constructs that biomedical devices (Figure 1).
can detect environmental conditions and stimuli (e.g., This review focuses on the progress of 3D-bioprinted
mechanical, chemical, electrical, or magnetic signals) and smart constructs using stimuli-responsive biomaterials
react to them by performing specific functions.
for biomedical and clinical applications. It explains the
To achieve smart performance, 3D-bioprinted definition and classification of 3D-printable biomaterials
constructs are fabricated with specific microstructures, and bioinks, outlines prevalent 3D printing and bioprinting
topology, geometry, and composition; therefore, under techniques, and elaborates on the advantages of 3D printing
a given stimuli, a designed transformation, specific and bioprinting in creating smart constructs. Subsequently,
property, or programmed functionality of the responsive various advanced responsive biomaterials that have been
biomaterials is triggered. Recently developed intelligent explored for fabricating smart constructs are discussed,
materials include stimuli-responsive hydrogels , shape- and typical applications of these 3D-bioprinted smart
[4]
memory polymers , liquid crystal polymers , and constructs, such as in regenerative medicine, drug delivery,
[5]
[6]
responsive additives (e.g., graphene oxide , magnetic and biosensors, are systematically summarized.
[7]
medium , and electroconductive compounds ). The
[9]
[8]
emergence of intelligent biomaterials has opened new 2. Biomaterials and 3D bioprinting
avenues for engineering various smart structures (such techniques
as self-control mechanics, soft robots, adaptive optics, 2.1. Biomaterials and bioinks
and actuators) that have been utilized in the fields of
defense, aerospace, and industry. However, to build smart For a long time, confusion regarding the definitions of
bioproducts, the selected biomaterials must fulfill several “biomaterials” and “bioinks” has led to incorrect use of
critical requirements so that they can be adapted to 3D these two terms for quite some time. Biomaterials have been
printing/bioprinting techniques. extensively studied over the past 50 years. Biomaterials
are defined as substances engineered to interact with the
The fundamental requirement for biomedical
applications is that the biomaterial used for building biological systems for biomedical applications, mainly
for therapeutic (treatment, augmentation, repair, or
smart constructs should be non-toxic, biocompatible, and replacement) or diagnostic purposes . Biomaterials is,
[17]
biodegradable. The flexibility of the 3D printing techniques therefore, a broad term that includes biocompatible metals,
can facilitate the fabrication of biological structures with ceramics, glass, polymers, biomolecules, and biological
intricate designs (e.g., microstructure, topology, geometry, products, such as enzymes, growth factors, DNA, and
and composition). Although many printing techniques exosomes.
are available, it is not possible to bioprint all types of
biomaterials, and the materials used require several suitable Groll et al. defined bioinks as “a formulation of cells
[18]
properties, including viscosity, rheological features, and suitable for processing by an automated biofabrication
polymerization . Furthermore, to impart 3D-bioprinted technology that may also contain biologically active
[10]
products with intelligence, biomaterials must show components and biomaterials. ” This definition
prompt and tunable responses to specific stimuli that can distinguishes bioinks from other types of biomaterials.
be endured by patients. These stimuli can be exogenous or Although biomaterials must support cellular behaviors and
autogenous signals. Due to the advancements in modern functions, they are not designated to encapsulate cells for
medical instrumentation, diverse signals, including the fabrication of constructs. Bioinks must contain living
magnetism, electricity, irradiation, heat, and acoustics, can cells as a fundamental element, irrespective of the other

Volume 9 Issue 1 (2023) 231 https://doi.org/10.18063/ijb.v9i1.638