TY - JOUR
T1 - The effects of crosslinking of scaffolds engineered from cartilage ECM on the chondrogenic differentiation of MSCs
AU - Rowland, Christopher R.
AU - Lennon, Donald P.
AU - Caplan, Arnold I.
AU - Guilak, Farshid
N1 - Funding Information:
This study was supported by the Collaborative Research Center , AO Foundation, Davos, Switzerland , the Arthritis Foundation , and NIH grants AG15768 , AR50245 , AR48182 , AR48852 , and AR53622 . We thank Lina Colucci, Katherine Glass, and Jonathan Brunger for assistance with various aspects of the project.
PY - 2013/7
Y1 - 2013/7
N2 - Scaffolds fabricated from cartilage extracellular matrix provide a chondroinductive environment that stimulates cartilaginous matrix synthesis in a variety of cell types. A limitation of these cartilage-derived matrix (CDM) scaffolds is that they contract during invitro culture, which unpredictably alters their shape. The current study examined the hypothesis that collagen crosslinking techniques could inhibit cell-mediated contraction of CDM scaffolds. We analyzed the effects of dehydrothermal (DHT) treatment, ultraviolet light irradiation (UV), and the chemical crosslinker carbodiimide (CAR) on scaffold contraction and chondrogenic differentiation of adult human bone marrow-derived stem cells (MSCs). Both physical and chemical crosslinking treatments retained the original scaffold dimensions. DHT and UV treatments produced significantly higher glycosaminoglycan and collagen contents than CAR crosslinked and non-crosslinked constructs. Crosslinking treatments influenced the composition of newly synthesized matrix, and DHT treatment best matched the composition of native cartilage. DHT, UV, and non-crosslinked CDM films supported cell attachment, while CAR crosslinking inhibited cell adhesion. These results affirm that collagen crosslinking treatments can prevent cell-mediated contraction of CDM scaffolds. Interestingly, crosslinking treatments influence chondrogenic differentiation. These effects seem to be mediated by modifications to cell-matrix interactions between MSCs and the CDM; however, further work is necessary to elucidate the specific mechanisms involved in this process.
AB - Scaffolds fabricated from cartilage extracellular matrix provide a chondroinductive environment that stimulates cartilaginous matrix synthesis in a variety of cell types. A limitation of these cartilage-derived matrix (CDM) scaffolds is that they contract during invitro culture, which unpredictably alters their shape. The current study examined the hypothesis that collagen crosslinking techniques could inhibit cell-mediated contraction of CDM scaffolds. We analyzed the effects of dehydrothermal (DHT) treatment, ultraviolet light irradiation (UV), and the chemical crosslinker carbodiimide (CAR) on scaffold contraction and chondrogenic differentiation of adult human bone marrow-derived stem cells (MSCs). Both physical and chemical crosslinking treatments retained the original scaffold dimensions. DHT and UV treatments produced significantly higher glycosaminoglycan and collagen contents than CAR crosslinked and non-crosslinked constructs. Crosslinking treatments influenced the composition of newly synthesized matrix, and DHT treatment best matched the composition of native cartilage. DHT, UV, and non-crosslinked CDM films supported cell attachment, while CAR crosslinking inhibited cell adhesion. These results affirm that collagen crosslinking treatments can prevent cell-mediated contraction of CDM scaffolds. Interestingly, crosslinking treatments influence chondrogenic differentiation. These effects seem to be mediated by modifications to cell-matrix interactions between MSCs and the CDM; however, further work is necessary to elucidate the specific mechanisms involved in this process.
KW - Articular cartilage
KW - Cell-mediated contraction
KW - Crosslink
KW - Decellularized tissue
KW - Mesenchymal stem cell
KW - Tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=84877803299&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2013.04.027
DO - 10.1016/j.biomaterials.2013.04.027
M3 - Article
C2 - 23642532
AN - SCOPUS:84877803299
SN - 0142-9612
VL - 34
SP - 5802
EP - 5812
JO - Biomaterials
JF - Biomaterials
IS - 23
ER -