Page 239 - IJB-9-6

International Journal of Bioprinting Bioprinting in diabetic foot disease

used human umbilical vein endothelial cells (HUVECs) bioprinted biocuratives containing mesenchymal stem
to introduce a vascular structure into the model. By cells (MSCs) to the back wounds of diabetic mice. These
detecting the molecular expression, collagen precipitation, biocuratives containing MSCs and alginate saline gel as
angiogenesis, and other indicators, it was determined the matrix could promote the deposition of mouse skin
that the model had characteristics that were very similar collagen and the wound healing more than the biocuratives
to the skin characteristics of the DFU patients [122] . This without MSCs could [136] . Adipose stem cells are also
patient-derived skin model has good application prospects commonly used as seed cells for bioprinting to promote
in the research on cellular crosstalk mechanisms and the DFU healing [92,137] .
screening of therapeutic drugs [122] . Recently, novel strategies have also been developed that
The use of bioprinting technology to control involve the direct use of stem cells without loading other
hyperglycemic environments is also an application of scaffold materials, such as in situ printing and embedded
bioprinting in the treatment of DFUs [123-128] . A high-glucose printing methods mentioned above. Yastı et al. [138] used
microenvironment not only limits the availability of growth adipose-derived stem cells (ADSCs) to obtain autologous
factors and promotes the expression of inflammatory adipose tissue and then achieved autologous minimally
factors, but also hinders immune cell recruitment, causes manipulated homologous adipose tissue (AMHAT)
microvascular dysfunction, and affects wound healing [123] . transplantation in DFU wounds with customized shapes
Several clinical studies have proven that hypoglycemic through 3D printing in a small sample of patients. This
treatment can improve the healing of DFUs and reduce study demonstrated that transplantation using 3D printing
the risk of amputation [124-125,128] . The use of bioprinted can reduce the total time needed for wound healing and
microneedle technology can improve the delivery efficiency scar formation, although the cost may be higher than that of
of hypoglycemic drugs to help DFU patients control blood ordinary autologous tissue transplantation [138] . Furthermore,
sugar, thus improving the healing of DFU wounds [125-126] . embedded printing technology can be combined with
In addition, loading hypoglycemic drugs into a 3D scaffold organoid technology to accurately combine organoid units
for the local hypoglycemic treatment of wounds can be a into complex biomimetic structures, compensating for the
therapeutic strategy for improving DFU healing [127] . Kamel limitations of existing bioprinting methods with regard to
et al. [127] confirmed that treatment with 3D chitosan composite biomimetic skin size and facilitating the treatment of DFU
scaffolds loaded with pioglitazone hydrochloride (PG) in a wounds with greater degrees of damage [139] . Table 3 shows
rat model significantly improved healing compared to the the recent studies on AMHAT combined with 3D printing
treatment without PG loading. Adding immunomodulators technology in DFU treatment [138-141] .
to bioinks may also improve the external matrix environment Organoid technology can assist embedded in situ
and promote DFU healing [66,128] .
bioprinting in building finer and larger biomimetic skin
4.3. 3D-printed products for DFU prevention and structures [142] , and exosomes and other novel immune
limb prostheses modulators, such as platelet-rich plasma (PRP), can also
The use of foot-assisted devices for gait adjustment can be used as alternative bioprinting materials to produce
help prevent DFUs from occurring [129-131] . Compared functional bioprinted skin substitutes to promote DFU
to traditional customized brackets and insoles made of wound healing [143] . Crosslinking these exosomes with
gypsum and other materials, customized auxiliary devices scaffolds can also help prolong the release of new types of
produced by 3D printing have an adjustable hardness and regulatory factors, such as exosomes and PRP, and solve the
their shape is more suitable for application [132] . In addition, problems of rapid metabolism and short action time [143] .
bioprinting can also be used to customize exquisite Huang et al. [144] used coaxial microfluidic 3D bioprinting
castings to compensate for limb defects caused by DFU technology and the calcium ion chemical dual crosslinking
amputation [133] . Compared to the Paris plaster used in method to load PRP on a multilayer bioactive shell core
clinical practice, customized plaster made using 3D printing fibrous hydrogel, which reduced drug delivery frequency
technology can alleviate skin necrosis caused by inaccurate by 33% compared with that of ordinary hydrogel and
model fitting and improve patient satisfaction [133] . ensured slow but continuous release of growth factors in
PRP. This hydrogel also showed outstanding therapeutic
4.4. Potential applications of bioprinting combined effects on DFUs by reducing inflammation [144] .
with novel technologies
Hydrogels and stem cells are commonly combined with 5. Perspectives
bioprinting [134-135] . Hydrogels are often used as a kind
of bioink in bioprinting [134] . Stem cells are attached to The development of bioprinting methods for the
biological scaffolds as seed cells [135] . Manso et al. [136] applied production of skin equivalents and the adjuvant treatment

Volume 9 Issue 6 (2023) 231 https://doi.org/10.36922/ijb.0142