TY - JOUR
T1 - Degradation products of crosslinked silk fibroin scaffolds modulate the immune response but not cell toxicity
AU - Sapudom, Jiranuwat
AU - Kongsema, Mesayamas
AU - Methachittipan, Apipon
AU - Damrongsakkul, Siriporn
AU - Kanokpanont, Sorada
AU - Teo, Jeremy C.M.
AU - Khongkow, Mattaka
AU - Tonsomboon, Khaow
AU - Thongnuek, Peerapat
N1 - Publisher Copyright:
© 2023 The Royal Society of Chemistry.
PY - 2023/3/23
Y1 - 2023/3/23
N2 - Silk fibroin (SF) scaffolds have widely been used as functional materials for tissue engineering and implantation. For long-term applications, many cross-linking strategies have been developed to enhance the stability and enzymatic degradation of scaffolds. Although the biocompatibility of SF scaffolds has been investigated, less is known about the extent to which the degradation products of these scaffolds affect the host response in the long term after implantation. In this work, we first studied the effect of two different crosslinkers, namely, 1-ethyl-3-(3-dimethylaminopropyl-carbodiimide hydrochloride) (EDC) and glutaraldehyde (GA), on the topology, mechanical stability and enzymatic degradation of SF scaffolds. We found that the SF scaffolds treated with GA (GA-SF) appeared to show an increase in the sheet thickness and a higher elastic modulus when compared to that treated with EDC (EDC-SF) at a similar level of crosslinking degree. The uncrosslinked and both crosslinked SF scaffolds were completely digested by proteinase K but were not susceptible to degradation by collagenase type IV and trypsin. We next investigated the effect of the degradation of SF on the cytotoxicity, genotoxicity, and immunogenicity. The results demonstrated that the degradation products of the uncrosslinked and crosslinked SFs did not trigger cell proliferation, cell death, or genotoxicity in primary human cells, while they appeared to modulate the phenotypes of macrophages. The degradation products of GA-SF promoted pro-inflammatory phenotypes, while those from EDC-SF enhanced polarization towards anti-inflammatory macrophages. Our results demonstrated that the degradation products of SF scaffolds can mediate the immune modulation of macrophages, which can be implemented as a therapeutic strategy to control the long-term immune response during implantation.
AB - Silk fibroin (SF) scaffolds have widely been used as functional materials for tissue engineering and implantation. For long-term applications, many cross-linking strategies have been developed to enhance the stability and enzymatic degradation of scaffolds. Although the biocompatibility of SF scaffolds has been investigated, less is known about the extent to which the degradation products of these scaffolds affect the host response in the long term after implantation. In this work, we first studied the effect of two different crosslinkers, namely, 1-ethyl-3-(3-dimethylaminopropyl-carbodiimide hydrochloride) (EDC) and glutaraldehyde (GA), on the topology, mechanical stability and enzymatic degradation of SF scaffolds. We found that the SF scaffolds treated with GA (GA-SF) appeared to show an increase in the sheet thickness and a higher elastic modulus when compared to that treated with EDC (EDC-SF) at a similar level of crosslinking degree. The uncrosslinked and both crosslinked SF scaffolds were completely digested by proteinase K but were not susceptible to degradation by collagenase type IV and trypsin. We next investigated the effect of the degradation of SF on the cytotoxicity, genotoxicity, and immunogenicity. The results demonstrated that the degradation products of the uncrosslinked and crosslinked SFs did not trigger cell proliferation, cell death, or genotoxicity in primary human cells, while they appeared to modulate the phenotypes of macrophages. The degradation products of GA-SF promoted pro-inflammatory phenotypes, while those from EDC-SF enhanced polarization towards anti-inflammatory macrophages. Our results demonstrated that the degradation products of SF scaffolds can mediate the immune modulation of macrophages, which can be implemented as a therapeutic strategy to control the long-term immune response during implantation.
UR - http://www.scopus.com/inward/record.url?scp=85152105823&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85152105823&partnerID=8YFLogxK
U2 - 10.1039/d3tb00097d
DO - 10.1039/d3tb00097d
M3 - Article
C2 - 37013997
AN - SCOPUS:85152105823
SN - 2050-7518
VL - 11
SP - 3607
EP - 3616
JO - Journal of Materials Chemistry B
JF - Journal of Materials Chemistry B
IS - 16
ER -