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International Journal of Bioprinting Bioprinting in diabetic foot disease
in dysfunctional fibroblasts to alleviate inflammation- developed by combining nicotinamide with human
induced damage, including direct supplementation of dermal fibroblasts had a promoting effect on the healing
cytokines or administration of probiotics that can regulate of infected wounds.
secretion of cytokine [83-85] . Due to the characteristics of chronic wounds such as
Neovascularization provides immune cells, oxygen, insufficient blood oxygen supply and difficult healing,
and nutrients for highly metabolic wound repair and recent studies have proposed a variety of materials and
transport of metabolic waste, which are critical for the methods for improving angiogenesis and local oxygen
healing of chronic wounds in the elderly and those with supply [94-95] . Ma et al. added a uniform strontium silicate
[94]
microcirculation disorders, such as patients with severe (SS) microcylinder to a bioink as a stable inducer of
DFUs . In addition to chronic hypoxia and nutritional angiogenesis in skin substitutes composed of a bioprinted
[85]
disorders, another serious consequence of angiogenesis multicellular system. Inspired by symbiotic relationships,
dysfunction is the inability to recruit sufficient endothelial Wang et al. proposed using in situ microfluidic-
[95]
progenitor cells (EPCs) to the wound surface . Hyperbaric assisted 3D printing to incorporate unicellular microalgae
[86]
oxygen therapy can help improve angiogenesis and EPC (Chlorella pyrenoidosa) into a scaffold to form a live
dysfunction and promote DFU wound healing [86-87] . photosynthetic scaffold, which could alleviate local
hypoxia on the wound surface through the photosynthesis
3.2. Bioprinting applications for wound chronicity of microalgae, promote extracellular matrix synthesis,
Although skin transplantation is still the gold standard for and accelerate wound healing. In addition, 3D-printed
the treatment of chronic wounds , bioprinted scaffolds patches containing angiogenic factors could also improve
[13]
still have unique advantages compared to other skin ischemia and hypoxia on the wound surface and promote
engineering materials in the treatment of chronic wound wound healing [96-97] . Guan et al. developed a bioprintable
[96]
healing . In particular, they can promote healing by peptide patch and promoted the angiogenic properties of
[88]
addressing the angiogenic disorders and inflammation that the patch by covalently coupling the peptide QHREDGS
occur after the healing of chronic wounds, such as DFUs . with GelMA and hyaluronic acid methacryloyl (HAMA)
[88]
Here, we introduce studies that employed bioprinting biological patches. Liao et al. covalently crosslinked
[97]
using different functional materials in the treatment of intravascular growth factor (VEGF) onto a biological patch
chronic wounds. composed of alginate polysaccharide and chondroitin
3.2.1. Different scaffold materials and bioinks for sulfate methacrylic acid groups through calcium ions and
promoting chronic wound healing ultraviolet light, simplifying the single chemical coupling
There are physical and biochemical factors involved in step and extending the VEGF release time.
skin engineering that cannot be accurately controlled
by traditional techniques and cannot be fulfilled by a 3.2.2. Personalized printing and novel printing
single biomaterial . Therefore, bioprinting methods strategies for complex wounds
[89]
rely on programmable microscales to control material The shape of DFU wounds is irregular, the depth varies, and
[98]
and cell deposition, as well as combining a variety of the structure is complex . Bioprinting fulfills the needs of
complex materials, including natural ECM components, personalized and accurate treatment by producing models
[99]
to simulate a repair environment with certain biological in varying designs using different printing strategies .
functions and skin structures, making these methods Embedded bioprinting is a novel type of bioprinting
incomparable to traditional skin engineering methods . that outperforms traditional bioprinting strategies, such
[89]
Especially in inflammatory and infected wounds, some as extrusion bioprinting, in terms of the fineness and
scaffolds eliminate inflammation and infection, thereby complexity of 3D-printed pendants or hollow structures [100] .
promoting wound healing [90-93] . For example, Prasad et al. It has great potential in solving the vascularization problem
[91]
encapsulated curcumin in an oil gel 3D fiber network in 3D-printed scaffold [101] . Embedded printing can better
to treat bacterial biofilm-related infections, such as preserve the shape of hydrogels by printing in a prefilled
Staphylococcus aureus, and promote DFU wound healing. matrix [102] . In addition, a new printing strategy has been
Xia et al. loaded curcumin into gelatin methacryloyl developed that involves printing cell aggregates, without
[92]
(GelMA)-containing adipose-derived stem cells to using hydrogel as a biological ink, into 3D tissue constructs
evaluate its therapeutic effect on DFU wounds through in with a certain spatial structure and then assembling these
vitro experiments. They found that the gel could reduce constructs into integrated tissues [102-103] . Skylar-Scott
apoptosis and reactive oxygen species production, which et al. [103] used this method to construct organ building
could promote DFU wound healing . Ullah et al. blocks (OBBs) derived from patient-specific pluripotent
[93]
[92]
demonstrated through in vivo experiments that a scaffold stem cells and then assembled perfusion-capable vascular
Volume 9 Issue 6 (2023) 228 https://doi.org/10.36922/ijb.0142

