Design and characterization of a biodegradable composite scaffold for ligament tissue engineering.

Herein we report on the development and characterization of a biodegradable composite scaffold for ligament tissue engineering based on the fundamental morphological features of the native ligament. An aligned fibrous component was used to mimic the fibrous collagen network and a hydrogel component to mimic the proteoglycan-water matrix of the ligament. The composite scaffold was constructed from cell-adherent, base-etched, electrospun poly(epsilon-caprolactone-co-D,L-lactide) (PCLDLLA) fibers embedded in a noncell-adherent photocrosslinked N-methacrylated glycol chitosan (MGC) hydrogel seeded with primary ligament fibroblasts. Base etching improved cellular adhesion to the PCLDLLA material. Cells within the MGC hydrogel remained viable (72 +/- 4%) during the 4-week culture period. Immunohistochemistry staining revealed ligament ECM markers collagen type I, collagen type III, and decorin organizing and accumulating along the PCLDLLA fibers within the composite scaffolds. On the basis of these results, it was determined that the composite scaffold design was a viable alternative to the current approaches used for ligament tissue engineering and merits further study.

[1]  Ivan Martin,et al.  Silk matrix for tissue engineered anterior cruciate ligaments. , 2002, Biomaterials.

[2]  O. Smidsrod,et al.  Degradation of fully water-soluble, partially N-acetylated chitosans with lysozyme , 1994 .

[3]  M. Ishihara,et al.  Photocrosslinkable chitosan as a biological adhesive. , 2000, Journal of biomedical materials research.

[4]  Masatoshi Sato,et al.  Reconstruction of rabbit Achilles tendon with three bioabsorbable materials: histological and biomechanical studies , 2000, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[5]  D. Bader,et al.  Influence of external uniaxial cyclic strain on oriented fibroblast-seeded collagen gels. , 2003, Tissue engineering.

[6]  R. Guidoin,et al.  Analysis of retrieved polymer fiber based replacements for the ACL. , 2000, Biomaterials.

[7]  Takashi Ushida,et al.  Collagen hybridization with poly(l-lactic acid) braid promotes ligament cell migration , 2001 .

[8]  C. Siedlecki,et al.  Submicron poly(L-lactic acid) pillars affect fibroblast adhesion and proliferation. , 2007, Journal of biomedical materials research. Part A.

[9]  Vincent Chan,et al.  Adhesion contact dynamics of fibroblasts on biomacromolecular surfaces. , 2005, Macromolecular bioscience.

[10]  Casey K Chan,et al.  Long-term viability of coronary artery smooth muscle cells on poly(l-lactide-co-ε-caprolactone) nanofibrous scaffold indicates its potential for blood vessel tissue engineering , 2008, Journal of The Royal Society Interface.

[11]  H. Lee,et al.  Interaction of different types of cells on physicochemically treated poly(L-lactide-co-glycolide) surfaces , 2002 .

[12]  A. U. Daniels,et al.  Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products. , 1994, Journal of applied biomaterials : an official journal of the Society for Biomaterials.

[13]  J. Kohn,et al.  Preliminary development of a novel resorbable synthetic polymer fiber scaffold for anterior cruciate ligament reconstruction. , 2004, Tissue engineering.

[14]  C. Murphy,et al.  Epithelial contact guidance on well-defined micro- and nanostructured substrates , 2003, Journal of Cell Science.

[15]  B. Amsden,et al.  Methacrylated glycol chitosan as a photopolymerizable biomaterial. , 2007, Biomacromolecules.

[16]  K. Leong,et al.  The design of scaffolds for use in tissue engineering. Part I. Traditional factors. , 2001, Tissue engineering.

[17]  Y. Nam,et al.  Adhesion behaviours of hepatocytes cultured onto biodegradable polymer surface modified by alkali hydrolysis process. , 1999, Journal of biomaterials science. Polymer edition.

[18]  S. Teoh,et al.  Characterization of anterior cruciate ligament cells and bone marrow stromal cells on various biodegradable polymeric films , 2002 .

[19]  Karl Grosh,et al.  Engineering of functional tendon. , 2004, Tissue engineering.

[20]  Shanta Raj Bhattarai,et al.  Novel biodegradable electrospun membrane: scaffold for tissue engineering. , 2004, Biomaterials.

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

[22]  Jun Hu,et al.  Alignment of osteoblast-like cells and cell-produced collagen matrix induced by nanogrooves. , 2005, Tissue engineering.

[23]  Kwangsok Kim,et al.  Control of degradation rate and hydrophilicity in electrospun non-woven poly(D,L-lactide) nanofiber scaffolds for biomedical applications. , 2003, Biomaterials.

[24]  S. Teoh,et al.  Knitted poly-lactide-co-glycolide scaffold loaded with bone marrow stromal cells in repair and regeneration of rabbit Achilles tendon. , 2003, Tissue engineering.

[25]  Ali Khademhosseini,et al.  Micromolding of photocrosslinkable chitosan hydrogel for spheroid microarray and co-cultures. , 2006, Biomaterials.

[26]  Ivan Martin,et al.  The FASEB Journal express article 10.1096/fj.01-0656fje. Published online December 28, 2001. Cell differentiation by mechanical stress , 2022 .

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

[28]  O. Damour,et al.  Influence of the degree of acetylation on some biological properties of chitosan films. , 2001, Biomaterials.

[29]  J. Karlsson,et al.  Donor-site morbidity and anterior knee problems after anterior cruciate ligament reconstruction using autografts. , 2001, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[30]  D. H. R. Jenkins.  Ligament Injuries and Their Treatment , 1985 .

[31]  Casey K. Chan,et al.  Tissue-engineering approach to the repair and regeneration of tendons and ligaments. , 2003, Tissue engineering.

[32]  G. Lisignoli,et al.  Analysis of mesenchymal stem cells grown on a three-dimensional HYAFF 11-based prototype ligament scaffold. , 2005, Journal of biomedical materials research. Part A.

[33]  M. Saito,et al.  The “Ligamentization” Process in Human Anterior Cruciate Ligament Reconstruction with Autogenous Patellar and Hamstring Tendons , 2005, The American journal of sports medicine.

[34]  P. Gallop,et al.  Collagen synthesized and modified by aging fibroblasts in culture , 1975, In Vitro.

[35]  Warren King,et al.  The Safe and Effective Use of Allograft Tissue—An Update , 2003, The American journal of sports medicine.

[36]  Frank Emmrich,et al.  Isolation and characterization of rheumatoid arthritis synovial fibroblasts from primary culture — primary culture cells markedly differ from fourth-passage cells , 2000, Arthritis research.

[37]  K. Miyasaka.  The incidece of knee ligament injuries in the general population , 1991 .

[38]  Glen A. Livesay,et al.  Development of Ligament-Like Structural Organization and Properties in Cell-Seeded Collagen Scaffolds in vitro , 2006, Annals of Biomedical Engineering.

[39]  D L Butler,et al.  Comparison of material properties in fascicle-bone units from human patellar tendon and knee ligaments. , 1986, Journal of biomechanics.

[40]  Kwangsok Kim,et al.  Structure and process relationship of electrospun bioabsorbable nanofiber membranes , 2002 .

[41]  Thomas J Webster,et al.  Decreased fibroblast cell density on chemically degraded poly-lactic-co-glycolic acid, polyurethane, and polycaprolactone. , 2004, Biomaterials.

[42]  Paul N Manson,et al.  Variable cytocompatibility of six cell lines with photoinitiators used for polymerizing hydrogels and cell encapsulation. , 2005, Biomaterials.

[43]  D. Mooney,et al.  Hydrogels for tissue engineering: scaffold design variables and applications. , 2003, Biomaterials.

[44]  Wan-Ju Li,et al.  Biological response of chondrocytes cultured in three-dimensional nanofibrous poly(ϵ-caprolactone) scaffolds† , 2003 .

[45]  Dameron Tb,et al.  The untreated anterior cruciate ligament rupture. , 1983 .

[46]  B. Zarins,et al.  Combined intraarticular and extraarticular anterior cruciate ligament reconstruction , 1988 .

[47]  N Schütze,et al.  Anterior cruciate ligament constructs fabricated from human mesenchymal stem cells in a collagen type I hydrogel. , 2005, Cytotherapy.

[48]  R Langer,et al.  Surface hydrolysis of poly(glycolic acid) meshes increases the seeding density of vascular smooth muscle cells. , 1998, Journal of biomedical materials research.

[49]  T. Koob,et al.  Biocompatibility of NDGA-polymerized collagen fibers. II. Attachment, proliferation, and migration of tendon fibroblasts in vitro. , 2001, Journal of biomedical materials research.

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

[51]  Paul G Scott,et al.  A Role for Decorin in the Structural Organization of Periodontal Ligament , 2000, Laboratory Investigation.

[52]  D. W. Jackson,et al.  Donor cell survival and repopulation after intraarticular transplantation of tendon and ligament allografts , 2002, Microscopy research and technique.

[53]  K. Jacobsen,et al.  Osteoarthrosis following insufficiency of the cruciate ligaments in man. A clinical study. , 1977, Acta orthopaedica Scandinavica.

[54]  Joseph P. Zawadsky,et al.  Preliminary development of a collagen‐PLA composite for ACL reconstruction , 1997 .

[55]  Shin-Ichiro Nishimura,et al.  Novel chitosan-based hyaluronan hybrid polymer fibers as a scaffold in ligament tissue engineering. , 2005, Journal of biomedical materials research. Part A.

[56]  A F von Recum,et al.  Orientation of ECM protein deposition, fibroblast cytoskeleton, and attachment complex components on silicone microgrooved surfaces. , 1998, Journal of biomedical materials research.

[57]  Il Keun Kwon,et al.  Electrospun nano- to microfiber fabrics made of biodegradable copolyesters: structural characteristics, mechanical properties and cell adhesion potential. , 2005, Biomaterials.

[58]  G. Pasquinelli,et al.  Functionalization of poly-L-lactic-co-ε-caprolactone: effects of surface modification on endothelial cell proliferation and hemocompatibility , 2003 .

[59]  G. Stevens,et al.  Controllable surface modification of poly(lactic-co-glycolic acid) (PLGA) by hydrolysis or aminolysis I: physical, chemical, and theoretical aspects. , 2004, Biomacromolecules.

[60]  B. Stanulis-Praeger.  Cellular Senescence revisited: a review , 1987, Mechanisms of Ageing and Development.

[61]  J. Jansen,et al.  Contact guidance of rat fibroblasts on various implant materials. , 1999, Journal of biomedical materials research.

[62]  L. Creemers,et al.  Phagocytosis and intracellular digestion of collagen, its role in turnover and remodelling , 1996, The Histochemical Journal.

[63]  S J Bryant,et al.  Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro , 2000, Journal of biomaterials science. Polymer edition.