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International Journal of Bioprinting Bioprinting in diabetic foot disease
Table 2. Natural polymers for scaffolds
Polymer Advantages Disadvantages
Natural polymer Gelatin Low-cost, good injectability, and possessing Lack of thermal stability, quick degradation
ability to promote cell adhesion and proliferation rate, and poor mechanical properties
Collagen No high temperatures required for pH Poor mechanical properties, low viscosity, and
neutralization and highly permeable time-consuming gelation
Fibrin Good cell adhesion and possessing ability to Time-consuming gelation, poor mechanical
promote wound healing properties, and poor extrusion and shape
fidelity
Alginate Easily modified and maintains moist wound Poor mechanical properties and shear thinning
environment behavior
Synthetic polymer Poly(lactic-co-glycolic Low-cost, widespread use, good mechanical Higher temperatures and pressures needed
acid) properties, and modifiable degradation rate
Polycaprolactone Easy to process, good mechanical properties, and High printing temperatures and pressures,
low degradation rate time-consuming, and low cell adhesion
Polyurethane Low printing temperature, good mechanical Additional crosslinking stage required
properties and elasticity, and possessing ability to
promote cell adhesion and proliferation
Polyethylene glycol Promotes M2 macrophage polarization and Time-consuming, additional processing step
wound healing, good mechanical properties, and required, and other supporting biomaterials
easily modifiable required
In addition, the development of automated-assisted have been widely used as biomaterials in bioprinting [34-37] .
technology has increased the potential of in situ bioprinting Some synthetic polymers, including polyurethane,
technology [30-32] . In situ technology can be used to directly polycaprolactone (PCL), poly(lactic-co-glycolic acids), and
print at specific anatomical locations on living organisms polyethylene glycol, have also been used to complement
and design living cells, growth factors, and biomaterials natural materials to endow them with stable structures and
with precise positioning . Robots and handheld devices controllable mechanical properties by mixing synthetic
[31]
are commonly used to fabricate complex shapes and curved and natural materials together [34-39] . Table 2 summarizes
surfaces in situ . With the help of robotics, bioprinting these polymers in detail [34-41] .
[32]
tasks can be facilitated with high accuracy and automation
levels without exhausting the operator . Typical robotic- 2.3.2. Seed cells
[32]
assisted bioprinting includes Cartesian coordinate robots, The keratinocytes and fibroblasts comprised in the
articulated robots, and parallel robots . Cubo et al. structure of the epidermis and dermis are the preferred
[32]
[33]
[42]
confirmed that a Cartesian printer can produce engineered seed cells for skin bioprinting . Other types of seed cells,
[43]
skin that is very similar to human skin. This group used such as melanocytes, have also been explored . For in vivo
biological ink containing human plasma and primary experiments, stem cells, especially mesenchymal stem
human fibroblasts and keratinocytes obtained from skin cells, adipose-derived stem cells, and induced pluripotent
biopsies to print human bilayered skin and tested the stem cells are favored by researchers due to their valuable
function of this bilayered skin in an immunocompromised differentiation ability and low immunogenicity [44-45] .
mouse model . However, there are still ethical concerns regarding the
[33]
application of stem cell, as well as difficulties in controlling
2.3. Bioinks the direction of differentiation, which could cause
[46]
Bioinks include biomaterials that form temporary tumorigenesis if not properly controlled .
scaffolds, seed cells, and microenvironmental factors that
regulate cells . This bioprinting component determines 2.3.3. Regulation factors
[34]
the printability of scaffolds and can be endowed with Cytokines and chemokines are often added to
[47]
specific functions by adding factors [14,34] . biological inks , but it is difficult to simulate complex
microenvironments and intercellular interactions with
2.3.1. Biomaterials the addition of only one or several regulatory factors . In
[48]
The primary features of biomaterials are nontoxicity and recent years, decellularized extracellular matrix (dECM)
good biocompatibility . Gelatin, collagen, fibrin, alginate, has become a new choice of bioink . It performs well
[49]
[34]
and other natural compounds similar to the outer matrix in skin bioprinting due to its retained partial ECM
Volume 9 Issue 6 (2023) 225 https://doi.org/10.36922/ijb.0142

