title: In situ forming collagen-hyaluronic acid membrane structures: mechanism of self-assembly and applications in regenerative medicine.
abstract: Bioactive, in situ forming materials have the potential to complement minimally invasive surgical procedures and enhance tissue healing. For such biomaterials to be adopted in the clinic, they must be cost-effective, easily handled by the surgeon and have a history of biocompatibility. To this end, we report a novel and facile self-assembling strategy to create membranes and encapsulating structures using collagen and hyaluronic acid (HA). Unlike membranes built by layer-by-layer deposition of oppositely charged biomolecules, the collagen-HA membranes described here form a diffusion barrier upon electrostatic interaction of the oppositely charged biomolecules, which is further driven by osmotic pressure imbalances. The resulting membranes have a nanofibrous architecture, a thicknesses of 130 μm and a tensile modulus (0.59±0.06 MPa) that can increase 7-fold using carbodiimide chemistry (4.42±1.46 MPa). Collagen-HA membranes support mesenchymal stem cell proliferation and have a slow and steady protein release profile (7% at day 28), offering opportunities for targeted tissue regeneration. We demonstrate the capacity to encapsulate cells by injecting HA into the collagen solution, and enhance allograft and implant biocompatibility through a coating technique. This study describes a novel mechanism of collagen-HA membrane formation and provides the groundwork to apply these membranes in a variety of tissue engineering applications.
authors.affiliation: Institute for BioNantechnology in Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Chung
authors.forename: Adam E
authors.initials: AE
authors.lastname: Jakus
authors.forename: Ramille N
authors.initials: RN
authors.lastname: Shah
mesh_terms: D000818:Animals; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D003094:Collagen / Q000737:chemistry* / Q000648:ultrastructure; D017886:Durapatite / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D008567:Membranes, Artificial; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D044968:Regenerative Medicine / Q000379:methods*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012996:Solutions; D055672:Static Electricity; D013710:Tendons / Q000187:drug effects; D014184:Transplantation, Homologous
chemical_list: D020099:Coated Materials, Biocompatible; D008567:Membranes, Artificial; D012996:Solutions; D012710:Serum Albumin, Bovine; D006820:Hyaluronic Acid; D003094:Collagen; D017886:Durapatite