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Bioprinting with collagen
and the final layer of thrombin onto a full-thickness agent. With new materials, the elastic modulus
skin wound (2 × 2 cm ). In 2 weeks, AFS-treated of printed structures was 5.94 MPa. The in vitro
2
mice showed an average of 3% of unclosed evaluation of cellular responses (viability and
wounds, whereas MSC-treated wounds showed proliferation) was comparable to results obtained
an average of 2%. These values were significantly in the pure cell-laden collagen.
lower than those of mice treated with gel only, One of the earliest studies on cartilage bioprinting
which had an average of 13% of unclosed wounds. using pure collagen bioinks was carried out in
Further development of this result was 2016 when primary meniscal fibrochondrocytes
continued by Albanna et al. , where excisional and high-density collagen hydrogels (from 10
[27]
wounds were bioprinted with layered autologous to 20 mg/ml) were bioprinted . In that study,
[20]
dermal fibroblasts and epidermal keratinocytes in the influence of collagen on several parameters,
a fibrinogen/collagen carrier (25 mg/ml fibrinogen, including geometric fidelity, cell viability, and
and 1.1 mg/ml collagen) in two different mechanical properties of printed constructs, was
models: Murine full-thickness wound model evaluated. The concentration of collagen gel had no
(3 × 2.5 cm) and porcine full-thickness wound impact on cell viability, whereas the compressive
model (10 × 10 cm). The obtained results showed modulus of printed gels increased linearly with
a rapid wound closure, reduced contraction, and an increase in collagen concentration. With
accelerated re-epithelialization. the highest printable concentration, the elastic
modulus of the printed structure reached 30 kPa.
3.2 Bone and cartilage These structures maintained cell viability and their
Native bone tissues can withstand heavy loads. geometric fidelity for 10 days while being stored
Therefore, 3D printed structures, ideally must in a culture medium. The geometric accuracy of
possess the same characteristics. In this case, to structures, printed with 15 mg/ml and 17.5 mg/ml
strengthen 3D bioprinted structures, composite collagen solutions, was at 74 – 78%.
[33]
materials are being actively used nowadays, for Shim et al. have printed a construct
example, a mixture of collagen with various types for osteochondral tissue regeneration in the
of bioceramics [28-31] . rabbit knee joint. Pure collagen bio-ink that
Kim et al. have introduced bioceramic-based consisted of atelocollagen, human turbinate-
[29]
cell-printing technique and a cell-laden ceramic derived mesenchymal stromal cells (hTMSCs),
structure. Using 3D bioprinting technology, they and recombinant human bone morphogenetic
created a cell-laden scaffold using α-tricalcium protein-2 (rhBMP-2), was printed into a
phosphate (α-TCP) type I collagen and MC3T3- preprinted polycaprolactone (PCL) scaffold. The
E1 cells. First, they have printed a porous layer prepared cylinder-shaped construct was 5 mm in
consisting of micro-sized α-TCP/collagen struts diameter and 5 mm in height, with a “subchondral
without cells, and then a cell-laden collagen bone layer” (PCL, atelocollagen, hTMSCs, and
bioink was printed onto it. This procedure was rhBMP-2) of 4 mm in thickness, and “superficial
repeated several times to form a 3D porous cell- cartilage layer” (Cucurbit[6]uril, hTMSCs, and
laden ceramic scaffold. The elastic modulus of the TGF-β) of 1 mm in thickness. This construct
α-TCP/collagen scaffold was 550 kPa. However, was in vivo implanted onto the defective part of
this value is much lower than the elastic modulus the rabbit knee joint. Eight weeks later, it was
of a real trabecular bone (around 20 MPa) . shown that the construct possessed a capability
[32]
Nevertheless, it was shown that the designed for osteochondral regeneration. The adjacent
scaffold demonstrated good cellular activities, native cartilage maintained its structure without
including metabolic activity and mineralization. any signs of degeneration. The newly regenerated
In the other work of Kim and Kim , β-TCP, cartilage tissues smoothly integrated themselves
[28]
type I collagen and MC3T3-E1 cells were used as with ends of the host cartilage tissue. The
a bioink, and Genipin was used as a crosslinking immunohistochemical analysis for collagen type
20 International Journal of Bioprinting (2020)–Volume 6, Issue 3
