Page 234 - IJB-9-6

International Journal of Bioprinting Bioprinting in diabetic foot disease

structure and functionality, excellent biocompatibility, 3. Functional improvements in chronic
and printability . However, how to eliminate the wound treatment facilitated by bioprinting
[49]
immunogenicity of heterologous dECM while preserving applications
the microstructure and biological activity of dECM as
much as possible remains a challenge . More natural Wound healing is a complex dynamic process. Generally,
[50]
mixtures of microenvironmental factors, such as platelet- wounds that encompass the superficial layer of the
[63]
rich plasma and exosomes, have also gradually attracted epidermis or dermis quickly reach an ideal healing state .
attention with regard to bioprinting [51-52] . However, scar repair often occurs in wounds that reach into
the deep dermis and subcutaneous tissue . When wounds
[64]
2.4. Current applications and challenges are subject to repeated infection, excessive inflammatory
The most anticipated clinical application of skin reactions, circulatory dysfunction, and immune imbalance,
bioprinting is the quick replacement of damaged skin in the formation of a skin barrier with a complete structure
partial- and full-thickness wounds, such as burn wounds and a set of functions during the repair process becomes
and diabetic wounds [25,52] . With the development of difficult . Thus, acute wounds become chronic wounds,
[63]
vascularized bioprinted skin and hair follicle models [30,53] , and it is difficult to achieve ideal healing .
[65]
the structure of bioprinted skin has become increasingly [66]
similar to the structure of real skin. A recently developed DFU wounds are usually chronic and persistent , and
full-thickness skin equivalent was applied to construct skin other common chronic wounds include venous leg ulcers
[63,67]
equivalents with real skin structural features, such as the (VLUs) and pressure ulcers (PU) . These wounds share
subcutaneous layer and accessories [54-55] . Jorgensen et al. the common pathophysiological characteristics of chronic
[55]
[68]
used a composite hydrogel bioink containing gel, glycerin, wounds . Conventional therapy cannot effectively restore
and hyaluronic acid (HA) to construct a skin equivalent chronic wounds due to their complex pathophysiological
[68]
and suspended a variety of cells in the fibrinogen bioink mechanisms . However, the ability of bioprinting to
to print a three-layer patch structure. After 21 days, accurately arrange cells and the functional diversity of
layered epidermis, mature dermis, and angiogenesis were bioprinting ink have shown good application prospects in
[69-70]
observed . Their results confirmed that the full-thickness the treatment of diabetic chronic wounds . Here, the
[55]
skin equivalent was more similar to normal skin than the pathological and physiological characteristics of chronic
hydrogel of the control group . wounds and the functional improvements in chronic
[55]
wound treatment facilitated by bioprinting are introduced.
While skin bioprinting is used in wound healing
and production of skin equivalent grafts based on a 3.1. Molecular mechanisms of difficult-to-heal
clear medical need, it also has great application value in chronic wounds
skin modeling for the study of some diseases and drug The development of multiomics and the subsequent in-
transdermal effects in vitro . Compared to conventional depth research on its mechanisms have revealed the
[56]
skin models, 3D-printed skin models exhibit a higher level pathophysiological characteristics of chronic wounds and
of biological complexity to increase the level of information their environments as well as aided in the exploration of
that can be obtained on drug–skin interactions . therapeutic targets [70-71] . The main skin structures involved
[57]
include the epidermis, dermis, and extracellular matrix,
However, optimal materials for scaffolds and bioinks, as well as resident cells, such as keratinocytes, fibroblasts,
especially intelligent materials for four dimensional immune cells, and endothelial cells . Understanding the
[65]
(4D) printing, are still being developed, and achieving pathophysiological changes and therapeutic targets of these
skin heterogeneity remains a challenge in the design of structures at the cellular level can facilitate the development
bioprinted skin . Product deformation after printing of novel bioprinted scaffolds and ink materials tailored to
[58]
with respect to the printed design is difficult to prevent the characteristics of chronic wounds .
[70]
due to the softness of skin . Currently, there are still
[59]
structural and functional differences between bioprinted 3.1.1. Keratinocytes
skin and natural skin . Achieving a balance between As the main cells that constitute the epidermal structure,
[60]
the proliferation and differentiation of various types of keratinocytes are activated on wound surfaces and restore
cells can help solve the cocultural challenges posed by the the epidermal barrier through migration, proliferation,
introduction of multiple cell types . Further development and differentiation [63,65] . In addition, a large number of
[61]
of new design methods related to bioprinting processes or growth factors and cytokines secreted by keratinocytes
a hybrid system of two or more bioprinting methods may recruit other cells, promoting matrix formation and
be a solution for overcoming the design challenges of skin angiogenesis . In chronic wounds, keratinocytes
[65]
bioprinting . become ineffective in the process of re-epithelialization
[62]
Volume 9 Issue 6 (2023) 226 https://doi.org/10.36922/ijb.0142