Page 59 - IJB-3-1

3D bioprinting of stem cells and polymer/bioactive glass composite scaffolds for bone tissue engineering

(AM), or popularly known as 3D printing, is a cess, cells, hydrogels, and other materials are depo-
layer-by-layer material deposition process in which sited using one or multiple syringes with a pressure
functional parts with complex shapes can be made system. The pressure system consists of either a me-
which are otherwise difficult to manufacture. AM chanical piston or a pneumatic pressure source (most-
of biomaterials has shown that complex and strong ly compressed air) that is computer controlled. The
implants can be made to treat different regions of bone, material is extruded through a nozzle tip and the pro-
including load-bearing bone [5–7] . However, enginee- cess can deposit hydrogels with high cell density and
red bone scaffolds have not been as successful as au- minimal wastage in comparison to laser-assisted and
tologous grafts thus far, largely due to insufficient vas- ink-jet bioprinting techniques. Recent research has
cularization and reduced biomechanical function [8–9] . focused on creating living or cell-laden grafts for tis-
The choices of materials and fabrication process are sues including bone, cartilage, and skeletal musc-
two significant factors that determine the success of le [18–20] . In extrusion bioprinting, one syringe is typi-
engineered scaffolds. Many synthetic polymers and callly devoted to melt the polymer and deposit the
bioceramic materials have been used to make scaf- melt for scaffolding structure. However, research to
folds for bone tissue engineering based on different date has only considered the melt-deposition process
AM techniques [10,11] . Since polymers are only bio- to print scaffolding and is limited to low melting point
compatible, attempts have been made to improve polymers. Therefore, it is essential to investigate alter-
their bioactivity by adding different bioceramics to nate approaches for printing other materials in order to
make polymer composites. Typically, such composites develop more promising approaches in 3D bioprinting.
are prepared by mixing an inorganic bioceramic ma- The addition of bioactive glass to a biocompatible
terial (in particle or fiber form) with a polymer which polymer transforms the 3D environment with its dis-
has been either heat melted or dissolved in an organic solution products by up-regulating the cell-cell and
solvent [12] . The bioactivity of the eventual composite cell-matrix interactions, which promotes vasculariza-
material not only depends on the choice of bioceramic tion. In the current study, we use a highly angiogen-
(including bioactive glass, hydroxyapatite, etc.) but ic bioactive 13-93B3 borate glass because of its osteo
also depends on the method of composite preparation stimulatory/conductive nature and anti-microbial pro-
itself. Composite foams and films made by traditional perties [21] . In comparison to the more comm.on bioac-
fabrication methods such as solvent casting and par- tive silicate glass, such as 45S5 or 13-93 glass, 13-
ticle leaching (SCPL) and thermally induced phase 93B3 has a higher reaction rate (5–10 times faster than
separation (TIPS) have reported improved water ab- silicate glasses) and resorbs (60 to 70% wt. loss) in a
[9]
sorption and formation of hydroxyapatite [13] . However, few days to weeks . Ion release from the borate glass
it is difficult to control the scaffold porosity and shape has been linked to the wound healing nature of this
using such methods. Scaffolds made with AM tech- glass, with the boron ions in particular leading to the
niques such as selective laser sintering and ink-jet angiogenic effects, which are marginal in the silicate
printing have also shown improved bioactivity, but glasses [22] . The borate glass was recently approved by
incorporating cells during fabrication akin to bio- the Food and Drug Administration of the United
printing is not feasible due to processing limitations. States for human use with trade name Mirragen™
3D bioprinting is a process that fabricates a “living” Advanced Wound Matrix.
construct in a layer-by-layer fashion using a “bio-ink” Mesenchymal stem/progenitor cells (MSCs) have be-
(cells suspended in a medium) with or without addi- en used for cell therapy and in tissue engineering be-
tional materials. Creation of a 3D environment with cause of their ability to differentiate into multiple me-
spatial arrangement of cells and materials is essential senchymal lineages in vitro, immune modulatory ef-
for vascularization and complete implant integration fects, and angiogenic capacity [23,24] . MSCs have been
with the surrounding tissue. 3D bioprinting techniques isolated from several tissues, including the bone mar-
can be broadly classified into three categories: (i) la- row (BMSCs), adipose tissue (ASCs), and skin tis-
ser-assisted [14,15] , (ii) inkjet-based [16] , and (iii) extru- sue [25–28] . The frequency of MSCs in adipose tissue is
sion-based printing [17] . Extrusion-based 3D bioprint- much higher than the more commonly studied source
ing is the most successful biofabrication process to of bone marrow, yielding 100 to 500 times more cells
date with a range of materials compatible with the per tissue volume [29–30] . ASCs have similar self-ren-
process [17,18] . In an extrusion-based bioprinting pro- ewal abilities, common surface epitopes, growth ki-

International Journal of Bioprinting (2017)–Volume 3, Issue 1 55