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International Journal of Bioprinting OMT-loaded spinal cord scaffold

1. Introduction The ECM of the central nervous system constitutes a
complex 3D network that participates in the regulation
Spinal cord injury (SCI) can result in serious damage to the of cellular functions in the central nervous system and
central nervous system. It is caused mainly by trauma and promotes axonal regeneration after injury . In our
[32]
has an annual global incidence of about 10.4–83 cases per previous study, decellularized spinal cord scaffolds were
million [1,2] . SCI can cause motor, sensory, and autonomic implanted in rats with a spinal cord hemisection with the
dysfunction below the level of the injury [3,4] . The pathological goal of promoting axon regeneration and motor function
process of SCI is complex but can be divided into two recovery . Considering that the spinal cord ECM
[33]
stages: a primary injury that leads to neuronal and axonal hydrogel retains the original extracellular components,
rupture, necrosis, and demyelination; a secondary injury it can act as a desirable microenvironment to induce
that consists of various pathophysiological mechanisms, favorable cellular responses.
including local hemorrhage, ischemia, edema, ion
imbalance, free radical stress, and inflammatory responses. Oxymatrine (OMT) is a quinazoline alkaloid isolated
Ultimately, local inhibitory protein expression increases from the root of Sophora flavescens. It has anti-inflammatory,
local scarring and cystic cavity formation, and this local anti-fibrotic, and anti-tumor activities. It is used to treat
inhibitory microenvironment is detrimental to neural viral hepatitis, cancer, viral myocarditis, gastrointestinal
tissue regeneration [5-9] . Although partial recovery can be bleeding, and skin diseases [34,35] . Researchers have
achieved in patients with SCI, their recovery and quality confirmed that OMT plays an important role in the
of life would still be undesirable due to the high incidence protection and repair of spinal cord injury because it can
of complications, such as urinary tract infections and greatly restore motor function by reducing oxidative stress,
pressure ulcers [10,11] . Current strategies to treat SCI include inflammatory responses, and apoptosis [36,37] . In addition,
traditional drug therapy, cell therapy, gene therapy, and the anti-fibrotic effects of OMT suggest that it has the
tissue engineering scaffold implantation. These strategies potential to prevent local scar formation after SCI.
cannot fully repair SCI, but are only able to alleviate In this study, we fabricated microfiber-reinforced
[12]
symptoms and reduce complications . Therefore, it is spinal cord ECM hydrogel-based scaffolds loaded with
imperative to explore effective therapeutic strategies. OMT by 3D printing technology. The biocompatibility,
Three-dimensional (3D) printing for making degradability, cumulative release of OMT, and mechanical
advanced tissue engineering scaffolds is an emerging property of the composite scaffolds were verified in vitro.
technology. Its advantage is that it endows scaffolds with The composite scaffolds were implanted into a semi-
a customized shape, biomimetic structure, and tailored transected part of the spinal cord in rats to study its repair
porosity. Through this technology, many tissues and effects on SCI and to find a new method for treating SCI.
organs have been made [13,14] . Meanwhile, biomolecules and Our study found that the composite scaffold could guide
even living cells can be encapsulated within 3D-printed the directional growth of axons, reduce scarring, and
scaffolds to obtain enhanced functionality. The selection promote the recovery of motor function in rats.
of biomaterials is crucial for the therapeutic effect, and
a desirable bioscaffold should be based on excellent 2. Materials and methods
biocompatibility, mechanical strength, biodegradability,
and bioactivity. Polycaprolactone (PCL) is a biodegradable 2.1. Fabrication of the bracket
polymer with good mechanical properties that can provide 2.1.1. Spinal cord decellularized scaffold
physical support for spinal cord regeneration. However, the Healthy adult Sprague-Dawley (SD) rats (purchased
biological activity of PCL is relatively poor. The hydrogel from Changsha Tianqin Biotechnology Co., Ltd.)
has good biological activity but poor mechanical strength, were anesthetized with 3% sodium pentobarbital by
so the combination of the two can satisfy the requirements intraperitoneal injection. Each rat was fixed on the
of the scaffold in mechanical strength and biological operating table in the prone position, and about 3 cm of
activity. the thoracic spinal cord was removed for future use. The
spinal cord tissues were frozen at −80°C for 1 h and then
In recent years, decellularized extracellular matrix thawed at room temperature. They were soaked in double-
(ECM) has been widely used as the material matrix or distilled water for 6 h, with water changes every hour. The
additive to fabricate tissue engineering scaffolds with spinal cord tissues were then placed in 1% TritonX-100
improved composition and similarity. They have been used phosphate buffer and shaken at room temperature for 3 h
to repair/regenerate bone [15,16] , cartilage [17,18] , muscle , (25°C, 100 rpm). They were then further shaken and rinsed
[19]
[26]
[25]
[20]
[24]
skin , heart [21-23] , blood vessels , bladder , kidney , with double-distilled water for 3 h with water changes every
vocal cords , nerves , uterus , and esophagus [30,31] . hour. They were placed in 1% sodium deoxycholate buffer
[28]
[29]
[27]
Volume 9 Issue 3 (2023) 106 https://doi.org/10.18063/ijb.692