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International Journal of Bioprinting Biomaterials for vascularized and innervated tissue regeneration

Figure 4. 3D-bioprinted biomimetic multicellular scaffolds promoting vascularized skin regeneration. (A) The specific bilayered distribution of human
dermal fibroblasts (HDFs) and HUVECs in the 3D-bioprinted scaffolds. (B) Live/dead staining of the cells within the scaffolds after co-cultured for 1 day
and 10 days. (C) Images of acute wounds at different times. (D) Images of chronic wounds at different times. (E) Immunohistochemical staining images
of CD31 antibody . Reprinted from Ma J, Qin C, Wu J, et al., Advanced Healthcare Materials, 2021, 2100523. Copyright © 2021 John Wiley and Sons.
[85]
of electroactive materials is a feasible approach to endowing and functions of sensory nerves through binding with
3D-printed scaffolds with bioelectrical properties, which its specific receptors . Recently, Chinese traditional
[23]
enables to stimulate innervation and accelerate wound medicine ginseng-derived exosomes have been proven to
healing . For example, Peng et al. prepared a self- stimulate the neurogenic differentiation and maturation
[91]
adaptive delivery chip by 3D coaxial printing technique, of MSCs, possessing huge potential in cutaneous nerves
which allows stepwise release of multiple biochemical and regeneration . Moreover, increasing evidence indicated
[94]
bioelectrical components to promote rapid skin nerves that bioactive ions play important roles in nerve tissue
restoration and excitation (Figure 5) . Electroactive regeneration by participating in many biological processes
[92]
materials GO-polyethyleneimine (CGP) and GO- (such as DNA/RNA synthesis and enzyme activation) .
[95]
polypyrrole-alginate (GPA) were distributed in the core In a recent study of our group, we found that zinc silicate
and shell of the 3D-printed scaffolds, respectively, which nanoparticles exhibited outstanding neurogenic activity by
could provide a conductive microenvironment to promote releasing bioactive Zn and Si ions in a sustainable manner .
[97]
cutaneous nerve regeneration. The bioelectrical signals Besides, the positive effects of zinc silicate nanoparticles
and released plasmid DNAs (pDNAs) synergistically on cutaneous innervation were also confirmed in a deep
directed the neural differentiation of mesenchymal stem second-degree skin burn model. Therefore, integrating
cells (MSCs), which could further differentiate into neural these bioactive agents into 3D-printed scaffolds would be
cells with electrophysiological activities. The in vivo results ideal for the regeneration of skin nerves.
further confirmed that this 3D-printed self-adaptive
scaffold can stimulate the cutaneous nerves regeneration 4. Bone tissues
with excitation function recovery within 23 days.
4.1. 3D printing for bone tissue engineering
Apart from electroactive materials, biological factors, Due to the limited self-healing ability of bone tissues,
mRNA, platelet, and exosomes have been demonstrated numerous bone regenerative biomaterials were developed
to promote neurogenesis and wound healing [93-96] . and applied to repair large-scale bone defects, such as
For example, neurotrophic factors (NGF, BDNF, etc.) bioceramics, metals, and polymers [98,99] . 3D printing
play significant roles in the survival, differentiation, possesses the capacity to repair bone defects via simulating

Volume 9 Issue 3 (2023) 222 https://doi.org/10.18063/ijb.706