A copper sulfate and hydroxylysine treatment regimen for enhancing collagen cross-linking and biomechanical properties in engineered neocartilage

Eleftherios A. Makris, Regina F. MacBarb, Donald J. Responte, Jerry C. Hu, Kyriacos A. Athanasiou

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The objective of this study was to improve the biomechanical properties of engineered neotissues through promoting the development of collagen cross-links. It was hypothesized that supplementing medium with copper sulfate and the amino acid hydroxylysine would enhance the activity of lysyl oxidase enzyme to form collagen cross-links, increasing the strength and integrity of the neotissue. Neocartilage constructs were generated using a scaffoldless, selfassembling process and treated with copper sulfate and hydroxylysine, either alone or in combination, following a 2-factor, full-factorial study design. Following a 6-wk culture period, the biomechanical and biochemical properties of the constructs were measured. Results found copper sulfate to significantly increase pyridinoline (PYR) cross-links in all copper sulfate-containing groups over controls. When copper sulfate and hydroxylysine were combined, the result was synergistic, with a 10-fold increase in PYR content over controls. This increase in PYR cross-links manifested in a 3.3- fold significant increase in the tensile properties of the copper sulfate + hydroxylysine group. In addition, an 123% increase over control values was detected in the copper sulfate group in terms of the aggregate modulus. These data elucidate the role of copper sulfate and hydroxylysine toward improving the biomechanical properties of neotissues through collagen cross-linking enhancement.

Original languageEnglish (US)
Pages (from-to)2421-2430
Number of pages10
JournalFASEB Journal
Volume27
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

Hydroxylysine
Copper Sulfate
Collagen
Protein-Lysine 6-Oxidase
Tensile properties
Amino Acids
Control Groups

Keywords

  • Articular cartilage regeneration
  • Covalent intermolecular bonds
  • Scaffoldless self-assembly

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

A copper sulfate and hydroxylysine treatment regimen for enhancing collagen cross-linking and biomechanical properties in engineered neocartilage. / Makris, Eleftherios A.; MacBarb, Regina F.; Responte, Donald J.; Hu, Jerry C.; Athanasiou, Kyriacos A.

In: FASEB Journal, Vol. 27, No. 6, 06.2013, p. 2421-2430.

Research output: Contribution to journalArticle

Makris, Eleftherios A. ; MacBarb, Regina F. ; Responte, Donald J. ; Hu, Jerry C. ; Athanasiou, Kyriacos A. / A copper sulfate and hydroxylysine treatment regimen for enhancing collagen cross-linking and biomechanical properties in engineered neocartilage. In: FASEB Journal. 2013 ; Vol. 27, No. 6. pp. 2421-2430.
@article{814d185734654eff8cd4931ba580ff74,
title = "A copper sulfate and hydroxylysine treatment regimen for enhancing collagen cross-linking and biomechanical properties in engineered neocartilage",
abstract = "The objective of this study was to improve the biomechanical properties of engineered neotissues through promoting the development of collagen cross-links. It was hypothesized that supplementing medium with copper sulfate and the amino acid hydroxylysine would enhance the activity of lysyl oxidase enzyme to form collagen cross-links, increasing the strength and integrity of the neotissue. Neocartilage constructs were generated using a scaffoldless, selfassembling process and treated with copper sulfate and hydroxylysine, either alone or in combination, following a 2-factor, full-factorial study design. Following a 6-wk culture period, the biomechanical and biochemical properties of the constructs were measured. Results found copper sulfate to significantly increase pyridinoline (PYR) cross-links in all copper sulfate-containing groups over controls. When copper sulfate and hydroxylysine were combined, the result was synergistic, with a 10-fold increase in PYR content over controls. This increase in PYR cross-links manifested in a 3.3- fold significant increase in the tensile properties of the copper sulfate + hydroxylysine group. In addition, an 123{\%} increase over control values was detected in the copper sulfate group in terms of the aggregate modulus. These data elucidate the role of copper sulfate and hydroxylysine toward improving the biomechanical properties of neotissues through collagen cross-linking enhancement.",
keywords = "Articular cartilage regeneration, Covalent intermolecular bonds, Scaffoldless self-assembly",
author = "Makris, {Eleftherios A.} and MacBarb, {Regina F.} and Responte, {Donald J.} and Hu, {Jerry C.} and Athanasiou, {Kyriacos A.}",
year = "2013",
month = "6",
doi = "10.1096/fj.12-224030",
language = "English (US)",
volume = "27",
pages = "2421--2430",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "6",

}

TY - JOUR

T1 - A copper sulfate and hydroxylysine treatment regimen for enhancing collagen cross-linking and biomechanical properties in engineered neocartilage

AU - Makris, Eleftherios A.

AU - MacBarb, Regina F.

AU - Responte, Donald J.

AU - Hu, Jerry C.

AU - Athanasiou, Kyriacos A.

PY - 2013/6

Y1 - 2013/6

N2 - The objective of this study was to improve the biomechanical properties of engineered neotissues through promoting the development of collagen cross-links. It was hypothesized that supplementing medium with copper sulfate and the amino acid hydroxylysine would enhance the activity of lysyl oxidase enzyme to form collagen cross-links, increasing the strength and integrity of the neotissue. Neocartilage constructs were generated using a scaffoldless, selfassembling process and treated with copper sulfate and hydroxylysine, either alone or in combination, following a 2-factor, full-factorial study design. Following a 6-wk culture period, the biomechanical and biochemical properties of the constructs were measured. Results found copper sulfate to significantly increase pyridinoline (PYR) cross-links in all copper sulfate-containing groups over controls. When copper sulfate and hydroxylysine were combined, the result was synergistic, with a 10-fold increase in PYR content over controls. This increase in PYR cross-links manifested in a 3.3- fold significant increase in the tensile properties of the copper sulfate + hydroxylysine group. In addition, an 123% increase over control values was detected in the copper sulfate group in terms of the aggregate modulus. These data elucidate the role of copper sulfate and hydroxylysine toward improving the biomechanical properties of neotissues through collagen cross-linking enhancement.

AB - The objective of this study was to improve the biomechanical properties of engineered neotissues through promoting the development of collagen cross-links. It was hypothesized that supplementing medium with copper sulfate and the amino acid hydroxylysine would enhance the activity of lysyl oxidase enzyme to form collagen cross-links, increasing the strength and integrity of the neotissue. Neocartilage constructs were generated using a scaffoldless, selfassembling process and treated with copper sulfate and hydroxylysine, either alone or in combination, following a 2-factor, full-factorial study design. Following a 6-wk culture period, the biomechanical and biochemical properties of the constructs were measured. Results found copper sulfate to significantly increase pyridinoline (PYR) cross-links in all copper sulfate-containing groups over controls. When copper sulfate and hydroxylysine were combined, the result was synergistic, with a 10-fold increase in PYR content over controls. This increase in PYR cross-links manifested in a 3.3- fold significant increase in the tensile properties of the copper sulfate + hydroxylysine group. In addition, an 123% increase over control values was detected in the copper sulfate group in terms of the aggregate modulus. These data elucidate the role of copper sulfate and hydroxylysine toward improving the biomechanical properties of neotissues through collagen cross-linking enhancement.

KW - Articular cartilage regeneration

KW - Covalent intermolecular bonds

KW - Scaffoldless self-assembly

UR - http://www.scopus.com/inward/record.url?scp=84878765493&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878765493&partnerID=8YFLogxK

U2 - 10.1096/fj.12-224030

DO - 10.1096/fj.12-224030

M3 - Article

C2 - 23457219

AN - SCOPUS:84878765493

VL - 27

SP - 2421

EP - 2430

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 6

ER -