Abstract
Introduction: Bioprinting, using “bio-inks” consisting of living cells, supporting structures, and biological motifs to create customized constructs, is an emerging technique that aims to overcome the challenges of cartilaginous reconstruction of head and neck structures. Several living cell lines and culturing methods have been explored as bio-inks with varying efficacy. Coculture of primary chondrocytes and stem cells (SCs) is one technique well established for degenerative joint disease treatment, with potential for use in expanding chondrocyte populations for bio-inks. This study aimed to evaluate the techniques for coculture of primary chondrocytes and SCs for head and neck cartilage regeneration. Methods: A literature review was performed through OVID/Web of Science/MEDLINE/BIOSIS Previews/Embase. Studies reporting on chondrocytes and SCs in conjunction with coculture or cartilage regeneration were included. Studies not reporting on findings from chondrocytes/SCs of the head and neck were excluded. Extracted data included cell sources, coculture ratios, and histological, biochemical, and clinical outcomes. Results: Fifteen studies met inclusion criteria. Auricular cartilage was the most common chondrocyte source (n = 10), then nasal septum (n = 5), articular (n = 1), and tracheal cartilage (n = 1). Bone marrow was the most common SC source (n = 9) then adipose tissue (n = 7). Techniques varied, with coculture ratios ranging from 1:1 to 1:10. All studies reported coculture to be superior to SC monoculture by all outcomes. Most studies reported superiority or equivalence of coculture to chondrocyte monoculture by all outcomes. When comparing clinical outcomes, coculture constructs were equivalent to chondrocyte monoculture in diameter and equivalent or inferior in wet weight and height. Conclusion: Coculture of primary chondrocytes and SCs is a promising technique for expanding chondrocyte populations, with at least equivalence to chondrocyte monoculture and superior to SC monoculture when seeded at the same chondrocyte densities. However, there remains a lack of consensus regarding the optimal cell sources and coculture ratios.
References
1.
Lovice
D
, Mingrone
M
, Toriumi
D
. Grafts amd implants in rhinoplasty and nasal reconstruction
. Otolaryngol Clin North Am
. 1999
;32
(1
):113
–41
. 2.
Lan
M
, Park
J
, Jang
J
. Donor site morbidities resulting from conchal cartilage harvesting in rhinoplasty
. J Laryngol Otol
. 2017
;131
(6
):529
–33
. 3.
Mischkowski
R
, Domingos-Hadamitzky
C
, Siessegger
M
, Zinser
M
, Zoller
J
. Donor-site morbidity of ear cartilage autografts
. Plast Reconstr Surg
. 2008
;121
(1
):79
–87
. 4.
Uppal
R
, Sabbagh
W
, Chana
J
, Gault
D
. Donor-site morbidity after autologous costal cartilage harvest in ear reconstruction and approaches to reducing donor-site contour deformity
. Plast Reconstr Surg
. 2008
;121
(6
):1949
–55
. 5.
Constantine
K
, Gilmore
J
, Lee
K
, Leach
JJ
. Comparison of microtia reconstruction outcomes using rib cartilage vs porous polyethylene implant
. JAMA Facial Plast Surg
. 2014
;16
(4
):240
–4
. 6.
Chung
J
, Kade
J
, Jeiranikhameneh
A
, Ruberu
K
, Mukherjee
P
, Yue
Z
, et al. 3D hybrid printing platform for auricular cartilage reconstruction
. Biomed Phys Eng Express
. 2020
;6
(3
):035003
. 7.
Posniak
S
, Chung
J
, Liu
X
, Mukherjee
P
, Wallace
GG
. The importance of elastin and its role in auricular cartilage tissue engineering
. Bioprinting
. 2023
;32
:e00276
. 8.
Von Der Mark
K
, Gauss
V
, Von Der Mark
H
, Muller
P
. Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture
. Nature
. 1977
;267
(5611
):531
–2
. 9.
Pittenger
MF
, Mackay
AM
, Beck
SC
, Jaiswal
RK
, Douglas
R
, Mosca
JD
, et al. Multilineage potential of adult human mesenchymal stem cells
. Science
. 1999
;284
(5411
):143
–7
. 10.
Hendriks
J
, Riesle
J
, van Blitterswijk
CA
. Co-culture in cartilage tissue engineering
. J Tissue Eng Regen Med
. 2007
;1
(3
):170
–8
. 11.
Meretoja
VV
, Dahlin
RL
, Wright
S
, Kasper
FK
, Mikos
AG
. Articular chondrocyte redifferentiation in 3D Co-cultures with mesenchymal stem cells
. Tissue Eng Part C Methods
. 2014
;20
(6
):514
–23
. 12.
Lee
M
, Mukherjee
P
, Steffens
D
, Chung
J
, Wallace
G
, Lee
M
. Co-culture of chondrocytes and mesenchymal stem cells for cartilage regeneration in the head and neck (search protocol)
. Available from: https://osf.io/UM95Y/.13.
Moher
D
, Liberati
A
, Tetzlaff
J
, Altman
DG
; PRISMA Group
. Preferred reporting Items for systematic reviews and meta-analyses: the PRISMA statement
. PLoS Med
. 2009
;6
(7
):e1000097
. 14.
Acharya
C
, Adesida
A
, Zajac
P
, Mumme
M
, Riesle
J
, Martin
I
, et al. Enhanced chondrocyte proliferation and mesenchymal stromal cells chondrogenesis in coculture pellets mediate improved cartilage formation
. J Cell Physiol
. 2012
;227
(1
):88
–97
. 15.
Anderson-Baron
M
, Liang
Y
, Kunze
M
, Mulet-Sierra
A
, Osswald
M
, Ansari
K
, et al. Suppression of hypertrophy during in vitro chondrogenesis of cocultures of human mesenchymal stem cells and nasal chondrocytes correlates with lack of in vivo calcification and vascular invasion
. Front Bioeng Biotechnol
. 2020
;8
:572356
. 16.
Apelgren
P
, Amoroso
M
, Lindahl
A
, Brantsing
C
, Rotter
N
, Gatenholm
P
, et al. Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo
. PLoS One
. 2017
;12
(12
):e0189428
. 17.
Cai
Z
, Pan
B
, Jiang
H
, Zhang
L
. Chondrogenesis of human adipose-derived stem cells by in vivo Co-graft with auricular chondrocytes from microtia
. Aesthet Plast Surg
. 2015
;39
(3
):431
–9
. 18.
Cohen
B
, Bernstein
J
, Morrison
K
, Spector
J
, Bonassar
L
. Tissue engineering the human auricle by auricular chondrocyte-mesenchymal stem cell co-implantation
. PLoS One
. 2018
;13
(10
):e0202356
. 19.
Goh
B
, Che Omar
SN
, Ubaidah
M
, Saim
L
, Sulaiman
S
, Chua
K
. Chondrogenesis of human adipose derived stem cells for future microtia repair using co-culture technique
. Acta Otolaryngol
. 2017
;137
(4
):432
–41
. 20.
Kang
N
, Liu
X
, Yan
L
, Wang
Q
, Cao
Y
, Xiao
R
. Different ratios of bone marrow mesenchymal stem cells and chondrocytes used in tissue-engineered cartilage and its application for human ear-shaped substitutes in vitro
. Cells Tissues Organs
. 2013
;198
(5
):357
–66
. 21.
Kang
N
, Liu
X
, Guan
Y
, Wang
J
, Gong
F
, Yang
X
, et al. Effects of co-culturing BMSCs and auricular chondrocytes on the elastic modulus and hypertrophy of tissue engineered cartilage
. Biomaterials
. 2012
;33
(18
):4535
–44
. 22.
Lv
X
, Zhou
G
, Liu
X
, Liu
H
, Chen
J
, Liu
K
, et al. Chondrogenesis by Co-culture of adipose-derived stromal cells and chondrocytes in vitro
. Connect Tissue Res
. 2012
;53
(6
):492
–7
. 23.
Ma
X
, Ma
X
, Qian
W
, Zhao
H
, Ding
J
, Zhao
T
. Co-culture of adipose-derived stem cells and chondrocytes with transforming growth factor-beta 3 promotes chondrogenic differentiation
. J Craniofac Surg
. 2020
;31
(8
):2355
–9
. 24.
Möller
T
, Amoroso
M
, Hägg
D
, Brantsing
C
, Rotter
N
, Apelgren
P
, et al. In vivo chondrogenesis in 3D bioprinted human cell-laden hydrogel constructs
. Plast Reconstr Surg Glob Open
. 2017
;5
(2
):e1227
. 25.
Morrison
R
, Nasser
H
, Kashlan
K
, Zopf
D
, Milner
D
, Flanangan
C
, et al. Co-culture of adipose-derived stem cells and chondrocytes on three-dimensionally printed bioscaffolds for craniofacial cartilage engineering
. Laryngoscope
. 2018
;128
(7
):E251
–7
. 26.
Pleumeekers
M
, Nimeskern
L
, Koevoet
W
, Karperien
M
, Stok
K
, van Osch
G
. Cartilage regeneration in the head and neck area: combination of ear or nasal chondrocytes and mesenchymal stem cells improves cartilage production
. Plast Reconstr Surg
. 2015
;136
(6
):762e
–74e
. 27.
Zhang
L
, He
A
, Yin
Z
, Yu
Z
, Luo
X
, Liu
W
, et al. Regeneration of human-ear-shaped cartilage by co-culturing human microtia chondrocytes with BMSCs
. Biomaterials
. 2014
;35
(18
):4878
–87
. 28.
Ziegler
M
, Sorensen
A
, Banyard
D
, Evans
G
, Widgerow
A
. Improving in vitro cartilage generation by Co-culturing adipose-derived stem cells and chondrocytes on an allograft adipose matrix framework
. Plast Reconstr Surg
. 2020
;147
(1
):87
–99
. 29.
Johnson
K
, Zhu
S
, Tremblay
M
, Payette
J
, Wang
J
, Bouchez
L
, et al. A stem cell-based approach to cartilage repair
. Science
. 2012
;336
(6082
):717
–21
. 30.
Mianehsaz
E
, Mirzaei
H
, Mahjoubin-Tehran
M
, Rezaee
A
, Sahebnasagh
R
, Pourhanifeh
M
, et al. Mesenchymal stem cell-derived exosomes: a new therapeutic approach to osteoarthritis
. Stem Cell Res Ther
. 2019
;10
(1
):340
. 31.
Chung
J
, Naficy
S
, Yue
Z
, Kapsa
R
, Quigley
A
, Moulton
S
, et al. Bio-ink properties and printability for extrusion printing living cells
. Biomater Sci
. 2013
;1
(7
):763
–73
. 32.
Matsuno
H
, Matsuyama
R
, Yamamoto
A
, Tanaka
K
. Enhanced cellular affinity for poly(lactic acid) surfaces modified with titanium oxide
. Polym J
. 2015
;47
(7
):505
–12
. 33.
Izadifar
Z
, Chang
T
, Kulyk
W
, Chen
X
, Eames
B
. Analyzing biological performance of 3D-printed, cell-impregnated hybrid constructs for cartilage tissue engineering
. Tissue Eng Part C Methods
. 2016
;22
(3
):173
–88
. 34.
Vis
M
, Ito
K
, Hofmann
S
. Impact of culture medium on cellular interactions in in vitro Co-culture systems
. Front Bioeng Biotechnol
. 2020
;8
(8
):911
. 35.
Bian
L
, Zhai
D
, Mauck
R
, Burdick
J
. Coculture of human mesenchymal stem cells and articular chondrocytes reduces hypertrophy and enhances functional properties of engineered cartilage
. Tissue Eng Part A
. 2011
;17
(7–8
):1137
–45
. 36.
Levorson
E
, Santoro
M
, Kasper
F
, Mikos
A
. Direct and indirect Co-culture of chondrocytes and mesenchymal stem cells for the generation of polymer/extracellular matrix hybrid constructs
. Acta Biomater
. 2014
;10
(5
):1824
–35
. 37.
Posniak
S
, Chung
J
, Liu
X
, Mukherjee
P
, Gambhir
S
, Khansari
A
, et al. Bioprinting of chondrocyte stem cell co-cultures for auricular cartilage regeneration
. ACS Omega
. 2022
;7
:5908
–20
. 38.
de Windt
T
, Hendriks
J
, Zhao
X
, Vonk
L
, Creemers
L
, Dhert
W
, et al. Concise review: unraveling stem cell cocultures in regenerative medicine: which cell interactions steer cartilage regeneration and how
. Stem Cells Transl Med
. 2014
;3
(6
):723
–33
. 39.
Mohamed-Ahmed
S
, Fristad
I
, Lie
S
, Suliman
S
, Mustafa
K
, Vindenes
H
, et al. Adipose-derived and bone marrow mesenchymal stem cells: a donor-matched comparison
. Stem Cell Res Ther
. 2018
;9
(1
):168
. 40.
Kim
B
, Kim
J
, Lee
S
. Unleashing the power of undifferentiated induced pluripotent stem cell bioprinting: current progress and future prospects
. Int J Stem Cells
. 2024
;17
(1
):38
–50
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