title: Functional fabrication of recombinant human collagen-phosphorylcholine hydrogels for regenerative medicine applications.
abstract: The implant-host interface is a critical element in guiding tissue or organ regeneration. We previously developed hydrogels comprising interpenetrating networks of recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) as substitutes for the corneal extracellular matrix that promote endogenous regeneration of corneal tissue. To render them functional for clinical application, we have now optimized their composition and thereby enhanced their mechanical properties. We have demonstrated that such optimized RHCIII-MPC hydrogels are suitable for precision femtosecond laser cutting to produce complementing implants and host surgical beds for subsequent tissue welding. This avoids the tissue damage and inflammation associated with manual surgical techniques, thereby leading to more efficient healing. Although we previously demonstrated in clinical testing that RHCIII-based implants stimulated cornea regeneration in patients, the rate of epithelial cell coverage of the implants needs improvement, e.g. modification of the implant surface. We now show that our 500μm thick RHCIII-MPC constructs comprising over 85% water are suitable for microcontact printing with fibronectin. The resulting fibronectin micropatterns promote cell adhesion, unlike the bare RHCIII-MPC hydrogel. Interestingly, a pattern of 30μm wide fibronectin stripes enhanced cell attachment and showed the highest mitotic rates, an effect that potentially can be utilized for faster integration of the implant. We have therefore shown that laboratory-produced mimics of naturally occurring collagen and phospholipids can be fabricated into robust hydrogels that can be laser profiled and patterned to enhance their potential function as artificial substitutes of donor human corneas.
authors.affiliation: Swedish Medical Nanoscience Center, Dept. of Neurosciences, Karolinska Institutet, S-17177 Stockholm, Sweden; Integrative Regenerative Medicine Centre, Dept. of Clinical and Experimental Medicine, Cell Biology Bldg. - Level 10, Linköping University, S-58185 Linköping, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Mirazul Islam
authors.affiliation: Dept. of Nanoengineering, Center for Physical Sciences and Technology, Savanorių 231, LT-02300 Vilnius, Lithuania.
authors.forename: Vytautas
authors.initials: V
authors.lastname: Cėpla
authors.affiliation: Ottawa Hospital Research Institute - Vision, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.
authors.forename: Chaoliang
authors.initials: C
authors.lastname: He
authors.affiliation: Integrative Regenerative Medicine Centre, Dept. of Clinical and Experimental Medicine, Cell Biology Bldg. - Level 10, Linköping University, S-58185 Linköping, Sweden.
authors.forename: Joel
authors.initials: J
authors.lastname: Edin
authors.affiliation: Dept. of Nanoengineering, Center for Physical Sciences and Technology, Savanorių 231, LT-02300 Vilnius, Lithuania.
authors.forename: Tomas
authors.initials: T
authors.lastname: Rakickas
authors.affiliation: Clinic of Ophthalmology, Klinikum rechts der Isar, Technische Universität München, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Kobuch
authors.affiliation: Dept. of Nanoengineering, Center for Physical Sciences and Technology, Savanorių 231, LT-02300 Vilnius, Lithuania.
authors.forename: Živilė
authors.initials: Ž
authors.lastname: Ruželė
authors.affiliation: Ottawa Hospital Research Institute - Vision, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Bruce Jackson
authors.affiliation: Ottawa Hospital Research Institute - Vision, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada; Integrative Regenerative Medicine Centre, Dept. of Clinical and Experimental Medicine, Cell Biology Bldg. - Level 10, Linköping University, S-58185 Linköping, Sweden; Dept. of Biomedical Engineering, Linköping University, S-58185 Linköping, Sweden.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Rafat
authors.affiliation: Clinic of Ophthalmology, Klinikum rechts der Isar, Technische Universität München, Germany.
authors.forename: Chris P
authors.initials: CP
authors.lastname: Lohmann
authors.affiliation: Dept. of Nanoengineering, Center for Physical Sciences and Technology, Savanorių 231, LT-02300 Vilnius, Lithuania. Electronic address: valiokas@ftmc.lt.
authors.forename: Ramūnas
authors.initials: R
authors.lastname: Valiokas
authors.affiliation: Swedish Medical Nanoscience Center, Dept. of Neurosciences, Karolinska Institutet, S-17177 Stockholm, Sweden; Ottawa Hospital Research Institute - Vision, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada; Integrative Regenerative Medicine Centre, Dept. of Clinical and Experimental Medicine, Cell Biology Bldg. - Level 10, Linköping University, S-58185 Linköping, Sweden. Electronic address: May.Griffith@liu.se.
authors.forename: May
authors.initials: M
authors.lastname: Griffith
mesh_terms: D002448:Cell Adhesion; D002460:Cell Line; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels; D010767:Phosphorylcholine / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D044968:Regenerative Medicine
chemical_list: D020100:Hydrogels; D011994:Recombinant Proteins; D010767:Phosphorylcholine; D003094:Collagen
keywords: Collagen; Cornea; Hydrogel; Laser profiling; Surface modification