Administration of the insulin into the scaffold atelocollagen for tissue‐engineered cartilage

Abstract

Three-dimensional culture of the tissue-engineered cartilage constructs may increase the matrix production, but central necrosis must occur if the construct becomes large. To increase the cell viability in the middle part of constructs and to enhance the in vivo cartilage regeneration, we attempted to administer the insulin into the scaffold. Insulin is known to strongly enhance the matrix production in the chondrocytes. The pellets of human auricular chondrocytes with atelocollagen hydrogel were 3D-cultured in the medium. The comparison among three groups (insulin mixed in the atelocollagen, insulin added to the medium, and control group, i.e.; insulin in neither atelocollagen nor medium) revealed that both insulin mixed in the atelocollagen and that in the medium could effectively promoted the cell viability and matrix synthesis of the chondrocytes. The daily assay also showed the gradual release of insulin from the atelocollagen hydrogel, suggesting that this material may work as a control release of insulin. We actually transplanted the poly-L-lactide porous scaffolds carrying the chondrocytes and the atelocollagen mixed with or without insulin, into the nude mice, showing that glycosaminoglycan accumulation was evident in the group with insulin although less without insulin. We thus showed the possibility to enhance the in vivo cartilage regeneration, when administered insulin into the atelocollagen hydrogel.

Chitosan‐based injectable hydrogel as a promising in situ forming scaffold for cartilage tissue engineering

“…Others found insulin to enhance strongly the redifferentiation of chondrocytes, which inevitably dedifferentiate during cell expansion, to increase the cell viability in the middle part of the constructs and induce the in vivo cartilage regeneration (Ko et al, 2011). Indeed, the feasibility of using the CH-GP-HEC gels as a stem cell carrier vehicle as well as an insulin delivery vehicle has been shown.…”

“…The GAG density in the scaffold increased considerably from day 14 to 28 ( Figure 5A and B). Administration of insulin into atelocollagen hydrogel enhances the in vivo cartilage regeneration (Ko et al, 2011). Others have demonstrated enhanced MSC chondrogenesis following delivery of TGF-b3 from alginate microspheres within hyaluronic acid hydrogels in vitro and in vivo (Bian et al, 2011).…”

“…Insulin is structurally analogous to IGF-1 (insulin-like growth factor 1), which binds to the IGF-1 receptor, and thus elicits similar effects on cartilage (Maor et al, 1993;Schmid, 1995;Gaissmaier et al, 2008). Some have described cartilage tissue engineering approaches based on insulin release using atelocollagen scaffolds (Ko et al, 2011), chitosan particles (Malafaya et al, 2010) and poly(D,L-lactide-co-glycolide) (PLGA) microspheres (Andreas et al, 2011). Some have described cartilage tissue engineering approaches based on insulin release using atelocollagen scaffolds (Ko et al, 2011), chitosan particles (Malafaya et al, 2010) and poly(D,L-lactide-co-glycolide) (PLGA) microspheres (Andreas et al, 2011).…”

“…This suggests that insulin may be an appropriate and inexpensive alternative to IGF-1 as a growth factor to improve the cartilage tissue engineering and was thus chosen as a model protein (Kellner et al, 2001). Insulin is also a potent survival factor (Loeser and Shanker, 2000), which can prevent central necrosis, induce redifferentiation of dedifferentiated chondrocytes, and promote matrix accumulation (Ko et al, 2011). Insulin is also a potent survival factor (Loeser and Shanker, 2000), which can prevent central necrosis, induce redifferentiation of dedifferentiated chondrocytes, and promote matrix accumulation (Ko et al, 2011).…”

“…This suggests that insulin may be an appropriate and inexpensive alternative to IGF-1 as a growth factor to improve the cartilage tissue engineering and was thus chosen as a model protein (Kellner et al, 2001). Some have described cartilage tissue engineering approaches based on insulin release using atelocollagen scaffolds (Ko et al, 2011), chitosan particles (Malafaya et al, 2010) and poly(D,L-lactide-co-glycolide) (PLGA) microspheres (Andreas et al, 2011). Insulin is also a potent survival factor (Loeser and Shanker, 2000), which can prevent central necrosis, induce redifferentiation of dedifferentiated chondrocytes, and promote matrix accumulation (Ko et al, 2011).…”