2014
DOI: 10.1002/adhm.201400277
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An Enzyme‐Sensitive PEG Hydrogel Based on Aggrecan Catabolism for Cartilage Tissue Engineering

Abstract: A new cartilage-specific degradable hydrogel based on photoclickable thiol-ene PEG hydrogels is presented. The hydrogel crosslinks are composed of the peptide, CRDTEGE-ARGSVIDRC, derived from the aggrecanase-cleavable site in aggrecan. This new hydrogel is evaluated for use in cartilage tissue engineering by encapsulating bovine chondrocytes from different cell sources (skeletally immature (juvenile) and mature (adult) donors and adult cells stimulated with pro-inflammatory lipopolysaccharide (LPS)) and cultur… Show more

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Cited by 77 publications
(67 citation statements)
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“…A 10% w/w macromer solution of eight-arm PEG-norbornene3536 was mixed with appropriate crosslinker and adhesive peptide where indicated in αMEM supplemented with 1% v/v antibiotic/Antimycotic (A/A; Invitrogen, UK). For the bioinert hydrogel, PEG-dithiol (MW 1,000, Sigma) was used as the crosslinker at a thiol:norbornene molar ratio of 0.8:1.…”
Section: Methodsmentioning
confidence: 99%
“…A 10% w/w macromer solution of eight-arm PEG-norbornene3536 was mixed with appropriate crosslinker and adhesive peptide where indicated in αMEM supplemented with 1% v/v antibiotic/Antimycotic (A/A; Invitrogen, UK). For the bioinert hydrogel, PEG-dithiol (MW 1,000, Sigma) was used as the crosslinker at a thiol:norbornene molar ratio of 0.8:1.…”
Section: Methodsmentioning
confidence: 99%
“…PEG hydrogels were formed by a photoclickable reaction between 8-arm PEG amine (MW 10k and 20k) that was functionalized with norbornene [3] and CVPLS-LYSGC in the presence of a photoinitiator (0.05 wt% Irgacure 2959) and 352 nm light at 6 mW cm −2 for 8 minutes. Hydrogels were formed with varying monomer concentration, monomer molecular weights, and thiol:ene ratios (Table S1).…”
Section: Methodsmentioning
confidence: 99%
“…To date, there has been significant progress towards demonstrating the feasibility of this type of hydrogel platform for a wide range of tissue engineering applications. [1,2,3] However, selecting a hydrogel design a priori to achieve desired hydrogel properties that evolve in space and time is challenging. Soft hydrogels (e.g., ≤ 1 kPa) are often employed such that a relatively low enzyme concentration is required to locally cleave the hydrogel crosslinks.…”
mentioning
confidence: 99%
“…Here, we observe this indirectly by changes in the chondrocyte morphology (Figure 3a); however, there are alternate ways to design systems that might respond to chondrocyte-secreted enzymes. One idea would be to include an aggrecanase-based cleavable peptide linker [52]. We selected the full-length protein gelatin for this study, as we hypothesized that its multiple MMP-cleavable sites would lead to more facile cleavage by chondrocytes than small peptide sequences as suggested by other groups [18].…”
Section: Discussionmentioning
confidence: 99%