Effect of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide concentrations on the mechanical and biological characteristics of cross-linked collagen fibres for tendon repair

Reconstituted type I collagen fibres have received considerable interest as tendon implant materials due to their chemical and structural similarity to the native tissue. Fibres produced through a semi-continuous extrusion process were cross-linked with different concentrations of the zero-length cross-linker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) in combination with N-hydroxysuccinimide (NHS). Tensile properties of the fibres were considered, along with imaging of both surface structure and fibrillar alignment. Resistance of the fibres to bacterial collagenase was investigated and fibre sections seeded with human tendon cells for biological characterization, including cell adhesion and proliferation. The work clearly demonstrated that whilst the concentration of EDC and NHS had no significant effect on the mechanics, a higher concentration was associated with higher collagenase resistance, but also provided a less attractive surface for cell adhesion and proliferation. A lower cross-linking concentration offered a more biocompatible material without reduction in mechanics and with a potentially more optimal degradability.

[1]  M. Grant,et al.  Investigation into cell growth on collagen/chondroitin-6-sulphate gels: the effect of crosslinking agents and diamines , 1997, Journal of materials science. Materials in medicine.

[2]  S. Badylak,et al.  Extracellular matrix as a biological scaffold material: Structure and function. , 2009, Acta biomaterialia.

[3]  D. Chau,et al.  The cellular response to transglutaminase-cross-linked collagen. , 2005, Biomaterials.

[4]  F. Silver,et al.  Formation of continuous collagen fibres: evaluation of biocompatibility and mechanical properties. , 1990, Biomaterials.

[5]  K. Ghofrani,et al.  Cross-linking by 1-ethyl-3- (3-dimethylaminopropyl)-carbodiimide (EDC) of a collagen/elastin membrane meant to be used as a dermal substitute: effects on physical, biochemical and biological features in vitro , 2001, Journal of materials science. Materials in medicine.

[6]  F. Silver,et al.  A self-assembled collagen scaffold suitable for use in soft and hard tissue replacement , 1995 .

[7]  R. Cameron,et al.  Synthetic collagen fascicles for the regeneration of tendon tissue. , 2012, Acta biomaterialia.

[8]  Min Jung Song,et al.  Characterization of porous collagen/hyaluronic acid scaffold modified by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide cross-linking. , 2002, Biomaterials.

[9]  F H Silver,et al.  Mechanical properties of collagen fibres: a comparison of reconstituted and rat tail tendon fibres. , 1989, Biomaterials.

[10]  R. G. Paul,et al.  Extruded collagen-polyethylene glycol fibers for tissue engineering applications. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[11]  I. Yannas,et al.  Recent advances in tissue synthesis in vivo by use of collagen-glycosaminoglycan copolymers. , 1996, Biomaterials.

[12]  A. Grodzinsky,et al.  Fluorometric assay of DNA in cartilage explants using Hoechst 33258. , 1988, Analytical biochemistry.

[13]  M. Dunn,et al.  Functional evaluation of collagen fiber scaffolds for ACL reconstruction: cyclic loading in proteolytic enzyme solutions. , 2004, Journal of biomedical materials research. Part A.

[14]  B. Mody,et al.  The ABC carbon and polyester prosthetic ligament for ACL-deficient knees. Early results in 31 cases. , 1993, The Journal of bone and joint surgery. British volume.

[15]  R. G. Paul,et al.  Engineering extruded collagen fibers for biomedical applications , 2008 .

[16]  M. Dunn,et al.  Optimization of extruded collagen fibers for ACL reconstruction. , 1993, Journal of biomedical materials research.

[17]  S. Boyce,et al.  EDC cross-linking improves skin substitute strength and stability. , 2006, Biomaterials.

[18]  Dimitrios I Zeugolis,et al.  Cross-linking of extruded collagen fibers--a biomimetic three-dimensional scaffold for tissue engineering applications. , 2009, Journal of biomedical materials research. Part A.

[19]  Jeffrey M. Caves,et al.  Fibrillogenesis in continuously spun synthetic collagen fiber. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[20]  F. O'Brien,et al.  The effect of dehydrothermal treatment on the mechanical and structural properties of collagen-GAG scaffolds. , 2009, Journal of biomedical materials research. Part A.

[21]  G. C. Wood The formation of fibrils from collagen solutions. 2. A mechanism of collagen-fibril formation. , 1960, The Biochemical journal.

[22]  Jeffrey P Spalazzi,et al.  Mechanoactive Scaffold Induces Tendon Remodeling and Expression of Fibrocartilage Markers , 2008, Clinical orthopaedics and related research.

[23]  R. Cameron,et al.  Effect of fiber crosslinking on collagen-fiber reinforced collagen-chondroitin-6-sulfate materials for regenerating load-bearing soft tissues. , 2013, Journal of biomedical materials research. Part A.

[24]  Amit Aurora,et al.  Commercially available extracellular matrix materials for rotator cuff repairs: state of the art and future trends. , 2007, Journal of shoulder and elbow surgery.

[25]  F H Silver,et al.  Self-assembly of collagen fibers. Influence of fibrillar alignment and decorin on mechanical properties. , 1997, Biophysical journal.

[26]  M. Benjamin,et al.  Structure‐function relationships in tendons: a review , 2008, Journal of anatomy.

[27]  S. Andreadis,et al.  Crosslinking of discrete self-assembled collagen threads: Effects on mechanical strength and cell-matrix interactions. , 2007, Journal of biomedical materials research. Part A.

[28]  Neil Rushton,et al.  Collagen fibre implant for tendon and ligament biological augmentation. In vivo study in an ovine model , 2013, Knee Surgery, Sports Traumatology, Arthroscopy.

[29]  J. Feijen,et al.  Cross-linking of dermal sheep collagen using a water-soluble carbodiimide. , 1996, Biomaterials.

[30]  B. Mckibbin Development of a reconstituted collagen tendon prosthesis. , 1990, Journal of Bone and Joint Surgery. American volume.

[31]  F H Silver,et al.  Development of a reconstituted collagen tendon prosthesis. A preliminary implantation study. , 1989, The Journal of bone and joint surgery. American volume.

[32]  R. G. Paul,et al.  Post-self-assembly experimentation on extruded collagen fibres for tissue engineering applications. , 2008, Acta biomaterialia.

[33]  B. Harley,et al.  The effect of anisotropic collagen-GAG scaffolds and growth factor supplementation on tendon cell recruitment, alignment, and metabolic activity. , 2011, Biomaterials.

[34]  Stephen B Doty,et al.  Novel nanofiber-based scaffold for rotator cuff repair and augmentation. , 2009, Tissue engineering. Part A.

[35]  R. Brooks,et al.  Exploring the application of stem cells in tendon repair and regeneration. , 2012, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[36]  R. Cameron,et al.  The process of EDC-NHS Cross-linking of reconstituted collagen fibres increases collagen fibrillar order and alignment. , 2015, APL materials.

[37]  G. C. Wood,et al.  The formation of fibrils from collagen solutions. 1. The effect of experimental conditions: kinetic and electron-microscope studies. , 1960, The Biochemical journal.

[38]  J. Feijen,et al.  Biocompatibility and tissue regenerating capacity of crosslinked dermal sheep collagen. , 1994, Journal of biomedical materials research.

[39]  M. Keech The formation of fibrils from collagen solutions. IV. Effect of mucopolysaccharides and nucleic acids: an electron microscope study. , 1961 .

[40]  Pankaj Sharma,et al.  Tendinopathy and tendon injury: The future , 2008, Disability and rehabilitation.

[41]  J. Feijen,et al.  In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide. , 1996, Biomaterials.

[42]  A. Tria,et al.  Regeneration of Achilles tendon with a collagen tendon prosthesis. Results of a one-year implantation study. , 1991, The Journal of bone and joint surgery. American volume.

[43]  D. Speer,et al.  Effect of tanning agent on tissue reaction to tissue implanted collagen sponge. , 1983, The Journal of surgical research.

[44]  Chunrong Yang Enhanced physicochemical properties of collagen by using EDC/NHS-crosslinking , 2012, Bulletin of Materials Science.

[45]  C. Enwemeka,et al.  Matrix remodeling in healing rabbit Achilles tendon , 1999, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[46]  R. Cameron,et al.  Regeneration and repair of tendon and ligament tissue using collagen fibre biomaterials. , 2011, Acta biomaterialia.

[47]  Kye-Yong Song,et al.  Reinforced bioartificial dermis constructed with collagen threads , 2008 .

[48]  Joseph W Freeman,et al.  Anterior cruciate ligament regeneration using braided biodegradable scaffolds: in vitro optimization studies. , 2005, Biomaterials.

[49]  Benjamin M. Wu,et al.  Tissue engineering for anterior cruciate ligament reconstruction: a review of current strategies. , 2006, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[50]  M. Raspanti,et al.  Crimp morphology in relaxed and stretched rat Achilles tendon , 2007, Journal of anatomy.

[51]  Yang Liu,et al.  Tendon tissue engineering using scaffold enhancing strategies. , 2008, Trends in biotechnology.

[52]  Joseph W Freeman,et al.  Fiber-based tissue-engineered scaffold for ligament replacement: design considerations and in vitro evaluation. , 2005, Biomaterials.

[53]  Young-Mi Kang,et al.  Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast. , 2005, Biomaterials.

[54]  M. Grant,et al.  Chondroitin-6-sulphate incorporated into collagen gels for the growth of human keratinocytes: the effect of cross-linking agents and diamines. , 1996, Biomaterials.

[55]  F. Silver,et al.  Evaluation of collagen crosslinking techniques. , 1983, Biomaterials, medical devices, and artificial organs.

[56]  Neil Rushton,et al.  Extruded collagen fibres for tissue engineering applications: effect of crosslinking method on mechanical and biological properties , 2011, Journal of materials science. Materials in medicine.

[57]  Eric A Nauman,et al.  Mechanical characterization of collagen fibers and scaffolds for tissue engineering. , 2003, Biomaterials.

[58]  Donald O Freytes,et al.  Reprint of: Extracellular matrix as a biological scaffold material: Structure and function. , 2015, Acta biomaterialia.