RT Journal Article
T1 Optimization of Collagen Chemical Crosslinking to Restore Biocompatibility of Tissue-Engineered Scaffolds
A1 Islam, Mohammad Mirazul
A1 AbuSamra, Dina B.
A1 Chivu, Alexandru
A1 Argüeso, Pablo
A1 Dohlman, Claes H.
A1 Patra, Hirak K.
A1 Chodosh, James
A1 González-Andrades, Miguel
K1 Cornea
K1 Collagen
K1 Double-crosslinking
K1 Carbodiimide
K1 Glutaraldehyde
K1 Sodium metabisulfite
K1 Sodium borohydride
K1 EDC/NHS
K1 Tissue engineering
K1 Macrophages
K1 Córnea
K1 Colágeno
K1 Carbodiimidas
K1 Glutaral
K1 Borohidruros
K1 Ingeniería de tejidos
K1 Materiales biocompatibles
AB Collagen scaffolds, one of the most used biomaterials in corneal tissue engineering, are frequently crosslinked to improve mechanical properties, enzyme tolerance, and thermal stability. Crosslinkers such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) are compatible with tissues but provide low crosslinking density and reduced mechanical properties. Conversely, crosslinkers such as glutaraldehyde (GTA) can generate mechanically more robust scaffolds; however, they can also induce greater toxicity. Herein, we evaluated the effectivity of double-crosslinking with both EDC and GTA together with the capability of sodium metabisulfite (SM) and sodium borohydride (SB) to neutralize the toxicity and restore biocompatibility after crosslinking. The EDC-crosslinked collagen scaffolds were treated with different concentrations of GTA. To neutralize the free unreacted aldehyde groups, scaffolds were treated with SM or SB. The chemistry involved in these reactions together with the mechanical and functional properties of the collagen scaffolds was evaluated. The viability of the cells grown on the scaffolds was studied using different corneal cell types. The effect of each type of scaffold treatment on human monocyte differentiation was evaluated. One-way ANOVA was used for statistical analysis. The addition of GTA as a double-crosslinking agent significantly improved the mechanical properties and enzymatic stability of the EDC crosslinked collagen scaffold. GTA decreased cell biocompatibility but this effect was reversed by treatment with SB or SM. These agents did not affect the mechanical properties, enzymatic stability, or transparency of the double-crosslinked scaffold. Contact of monocytes with the different scaffolds did not trigger their differentiation into activated macrophages. Our results demonstrate that GTA improves the mechanical properties of EDC crosslinked scaffolds in a dose-dependent manner, and that subsequent treatment with SB or SM partially restores biocompatibility. This novel manufacturing approach would facilitate the translation of collagen-based artificial corneas to the clinical setting.
PB MDPI
YR 2021
FD 2021-06-03
LK http://hdl.handle.net/10668/4457
UL http://hdl.handle.net/10668/4457
LA en
NO Islam MM, AbuSamra DB, Chivu A, Argüeso P, Dohlman CH, Patra HK, et al. Optimization of Collagen Chemical Crosslinking to Restore Biocompatibility of Tissue-Engineered Scaffolds. Pharmaceutics. 2021 Jun 3;13(6):832.
DS RISalud
RD Feb 14, 2025