Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: implications for cartilage tissue repair.
Emerging medical technologies for effective and lasting repair of articular cartilage include delivery of cells or cell-seeded scaffolds to a defect site to initiate de novo tissue regeneration. Biocompatible scaffolds assist in providing a template for cell distribution and extracellular matrix (ECM) accumulation in a three-dimensional geometry. A major challenge in choosing an appropriate scaffold for cartilage repair is the identification of a material that can simultaneously stimulate high rates of cell division and high rates of cell synthesis of phenotypically specific ECM macromolecules until repair evolves into steady-state tissue maintenance. We have devised a self-assembling peptide hydrogel scaffold for cartilage repair and developed a method to encapsulate chondrocytes within the peptide hydrogel. During 4 weeks of culture in vitro, chondrocytes seeded within the peptide hydrogel retained their morphology and developed a cartilage-like ECM rich in proteoglycans and type II collagen, indicative of a stable chondrocyte phenotype. Time-dependent accumulation of this ECM was paralleled by increases in material stiffness, indicative of deposition of mechanically functional neo-tissue. Taken together, these results demonstrate the potential of a self-assembling peptide hydrogel as a scaffold for the synthesis and accumulation of a true cartilage-like ECM within a three-dimensional cell culture for cartilage tissue repair.
Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139-4307, USA.
J
J
Kisiday
M
M
Jin
B
B
Kurz
H
H
Hung
C
C
Semino
S
S
Zhang
A J
AJ
Grodzinsky
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001672:Biocompatible Materials / Q000494:pharmacology; D002417:Cattle; D019902:Chondrocytes / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000032:analysis / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D001672:Biocompatible Materials; D009842:Oligopeptides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003094:Collagen