Page 231 - IJB-9-6

International Journal of Bioprinting Bioprinting in diabetic foot disease

mechanistic research in vitro . Although most studies Traditional skin engineering typically involves
[1]
are still in the preclinical research stage, their application the creation of a simplified model consisting of two
prospects are beyond doubt . The emergence of new compartments based on the two major structures of the
[3]
technologies and concepts, such as hydrogels and stem skin (epidermis and dermis) . The polymer or protein
[18]
cells, provides new material choices for bioprinting [4-5] . scaffold is combined with fibroblasts to form a construct
The combination of these biotechnologies and bioprinting that is immersed in a culture medium to simulate the
will accelerate the development of regenerative dermis, and then keratinocytes are added to the upper layer
medicine . of the construct and exposed to the gas–liquid interface to
[6]
Bioprinting has attracted much attention with regard to form a fully keratinized epidermis [18-19] . This construction
skin regeneration and repair of refractory chronic wounds method can endow the product with morphology and
because it has the potential to produce three-dimensional biological functions that have a certain degree of similarity
[19]
(3D) skin equivalents . Chronic wound healing has been a to those of human skin .
[7]
difficult problem for decades . Especially, with an increase However, to act as a barrier to damages from external
[8]
of diabetes incidence rate, a growing number of patients factors, such as pathogenic toxins and ultraviolet rays,
become troubled by one of the complications of diabetes, the skin, as the largest human organ, is equipped with
i.e., diabetic foot ulcers (DFUs) . Wounds in patients with a complex structure that includes the hypodermis,
[9]
diabetes usually heal poorly due to inflammation, infection, namely, the subcutaneous tissue, in addition to the
immune dysfunction, and impaired angiogenesis [8-10] . epidermis and dermis [19,20] . Not only are keratinocytes
Usually, amputation is required in DFU patients because and fibroblasts formed in the epidermis and dermis, but
of chronic, severe, and intractable skin ulcers [9-10] . The pain immune cell populations, nerve endings, and glands are
inflicted by chronic and difficult-to-heal DFU wounds, as also formed [20,21] . Due to the lack of natural skin features,
well as the corresponding medical burden on society, is such as hair follicles, innervation, and vascularization,
difficult to be neglected [10-11] . existing skin tissue equivalents are considered functionally
inadequate .
[21]
Some studies have shown that bioprinting has
unique advantages in improving wound healing in DFU Bioprinting allows the accurate arrangement of cells
patients by means of producing antibacterial and anti- and biomaterials, which can facilitate the construction
inflammatory materials and promoting angiogenesis [12-14] . of complex multilayer structures . The primary goal
[22]
However, bioprinting for diabetic wound treatment is still of skin bioprinting is to improve the tissue authenticity
far from clinical application . The use of bioprinting in of traditional skin equivalents, allowing the accurate
[13]
diabetic wound management should be more targeted . placement of multiple cell types and skin accessories .
[14]
[23]
In this review, we introduce the current applications of 3D printing technology has, at the very least, been proven
bioprinting technology, including the bioprinting of skin in vivo to be capable of producing skin substitutes for
equivalents for wound repair, functional improvements diabetic wounds [12,14,24] .
in the treatment of chronic wounds facilitated by
bioprinting applications, and bioprinting applications in 2.1. Skin bioprinting process
addressing unique diabetic foot disease characteristics, The current skin bioprinting process mainly includes
[18]
so that guidance can be provided for future research and the following four steps : preprocessing, printing,
translational applications of bioprinting in the field of postprocessing, and evaluation (Figure 1). In the
diabetic foot wound treatment. preprocessing stage, cell and ink bioprinting materials
should be selected properly, and the whole design of the
2. Bioprinting of skin equivalents for printing process, including the printing method, imaging
promoting wound healing technology, blueprinting, and organization of the toolpath,
needs to be preset . In the following step, a 3D conduct
[23]
DFUs are usually accompanied by wounds that are difficult is created by layering cell-laden bioinks [2,23] . The common
to heal. There are various clinical management methods bioprinting methods include laser-assisted bioprinting,
for promoting wound healing [10,15] . Skin transplantation is droplet-based bioprinting, and extrusion bioprinting [23,25] .
an option, but the insufficient supply of autologous split These methods can be integrated into a bioprinting
skin transplantation materials is a global challenge [13,16] . system . After that, dermal fibroblast proliferation and
[26]
Skin equivalents can also be used to promote wound epidermal keratinocyte differentiation are induced in the
healing [16-17] . Hence, good skin equivalents become a postprocessing step to attain the mechanical properties
major demand in wound repair, and producing them via and structure of the printed conduct . This 3D conduct is
[25]
bioprinting seems to be feasible. usually cultured in Petri dishes at an air–liquid interface .
[23]
Volume 9 Issue 6 (2023) 223 https://doi.org/10.36922/ijb.0142