Page 431 - IJB-9-3

International Journal of Bioprinting Gelatin-PVA crosslinked genipin bioinks for skin tissue engineering

1. Introduction Three-dimensional (3D) bioscaffolds can be developed
using conventional and advanced 3D bioprinting
The skin is the outermost layer of the human body. It technologies . It uses an additive manufacturing-based
[16]
significantly protects tissues from external harm by approach to create intricate 3D structures by depositing
microorganisms while maintaining body dehydration living cells, biomaterials, and other elements to form a 3D
and preventing electrolyte loss [1,2] . The skin is the most bioscaffold. Different bioprinting techniques are available,
susceptible organ in direct contact with the external including extrusion-based bioprinting, inkjet bioprinting,
environment . Certain groups of people may be exposed to laser-assisted bioprinting, and microfluidic-based
[3]
highly risky infections or hazards, with severe consequences bioprinting. However, extrusion-based bioprinting is the
in common individuals, patients, and servants working in most widely used bioprinting technology with the excellent
the healthcare sector . A skin wound occurs due to the advantage of enabling rapid deposition of bioinks . It
[4]
[17]
deterioration of the skin’s normal anatomical structure and offers excellent flexibility and reproducibility by fabricating
function . According to the healing timeline, the wounds 3D structures with a layer-by-layer deposition of bioinks
[5]
are classified as acute or chronic [6,7] . Surgical incisions and through a virtual design through computer-aided design
lacerations are common causes of acute wounds as well as software [18,19] . Moreover, extrusion-based bioprinting
abrasions. However, chronic wounds usually necessitate also allows the deposition of high-viscosity bioinks, but
long-term care, and place a significant financial burden on typically it has lower printing precision.
the patients . By 2027, the advanced wound care market
[8]
is anticipated to reach a value of $18.7 billion, expanding Natural polymers, such as collagen, gelatin, and
at a compound annual growth rate of 6.6% from 2020 to fibrinogen are commonly used as bioinks due to their
[20]
2027 . Optimal wound healing in adults should comprise excellent biodegradability and printability . Gelatin,
[9]
four overlapping, continuous phases: inflammation, a collagen hydrolysis product, displays notable benefits
proliferation, remodeling, and hemostasis. However, for tissue engineering applications, including high
chronic wounds with aberrant pathological characteristics biocompatibility, biodegradability, and the capability of
result in a slow healing rate, prolonged inflammatory preserving natural cell adhesion patterns. Depending on
phase, and extensive scar development following the source of the collagen and the hydrolytic treatment
recovery . An ideal wound treatment should have better technique, there are several varieties of gelatin, such
[10]
reproducibility, biocompatibility, cell adherence, and as Type A (porcine) and Type B (bovine), with various
[21]
acceptable mechanical qualities. compositions . In addition, gelatin is widely used
An autologous split-thickness skin graft remains in pharmaceutic and biomedical areas due to its low
[22]
the gold-standard treatment for wounds of larger sizes. antigenicity and low in vivo inflammatory response . The
However, it has significant drawbacks due to donor behavior of the gelatin solution depends on several factors,
such as temperature, pH, concentration, and preparation
site morbidity and the scarcity of donor tissue. Besides, method. A typical property of the gelatin solution is its
allogeneic transplants carry significant risks due to graft
versus host disease and persistent immunosuppression . capability to be gelled at low temperatures (about 20 – 30°C)
[11]
Previously, skin replacements failed due to contamination by cooling to form hydrogels. The use of thermoresponsive
gelatin-based hydrogels in extrusion-based 3D bioprinting
and flaws, with additional drawbacks of autologous and has improved the ability to create solid 3D microstructures
allografts treatments. Moreover, a clinical trial used an
allogenic treatment with skin fibroblasts, keratinocytes, with a wide range of material as well as with a wide array
and polyglycolic/polylactic acids (DermaGraft ) that of biological, chemical, physiological, and therapeutic
TM
[21]
supply growth factors and extracellular matrix (ECM) functions . It can be printed as a solid construct for cell
survival accommodations or as sacrificial (or fugitive)
to wounds with no immune rejection . However, the
[12]
instability of the ECM structure makes it susceptible to “bioinks” for channel or pore designs. Several factors
cellulitis and infections. Thus, tissue substitutes may be a influence the gelatin-based hydrogels that are created
potential strategy categorized under acellular and cellular and deposited during 3D printing procedures, including
skin substitutes . Skin tissue engineering entails the mechanical properties and stability of the hydrogels for
[13]
creation of bioscaffolds resembling the microstructure of in vitro and in vivo testing. However, gelatin has several
the native ECM. The bioscaffold provides a substrate for the drawbacks, such as low mechanical properties, rapid
cells to develop into solid tissue form, with biomolecules degradation rate, and limited thermostability, which
that serve as enhancers or supplements . They have restrict its future applications for wound treatment.
[14]
sufficient aquatic mobility and exceptional adhesion to Polyvinyl alcohol (PVA) is a synthetic polymer
host locations . that dissolves in water and is frequently used for 3D
[15]

Volume 9 Issue 3 (2023) 423 https://doi.org/10.18063/ijb.677