title: Photoactivated composite biomaterial for soft tissue restoration in rodents and in humans.
abstract: Soft tissue reconstruction often requires multiple surgical procedures that can result in scars and disfiguration. Facial soft tissue reconstruction represents a clinical challenge because even subtle deformities can severely affect an individual's social and psychological function. We therefore developed a biosynthetic soft tissue replacement composed of poly(ethylene glycol) (PEG) and hyaluronic acid (HA) that can be injected and photocrosslinked in situ with transdermal light exposure. Modulating the ratio of synthetic to biological polymer allowed us to tune implant elasticity and volume persistence. In a small-animal model, implanted photocrosslinked PEG-HA showed a dose-dependent relationship between increasing PEG concentration and enhanced implant volume persistence. In direct comparison with commercial HA injections, the PEG-HA implants maintained significantly greater average volumes and heights. Reversibility of the implant volume was achieved with hyaluronidase injection. Pilot clinical testing in human patients confirmed the feasibility of the transdermal photocrosslinking approach for implantation in abdomen soft tissue, although an inflammatory response was observed surrounding some of the materials.
authors.affiliation: Department of Otolaryngology, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Hillel
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Shimon
authors.initials: S
authors.lastname: Unterman
authors.affiliation: Department of Ophthalmology, Stanford University, Palo Alto, CA 94305, USA.
authors.forename: Zayna
authors.initials: Z
authors.lastname: Nahas
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Branden
authors.initials: B
authors.lastname: Reid
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Jeannine M
authors.initials: JM
authors.lastname: Coburn
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Axelman
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Jemin J
authors.initials: JJ
authors.lastname: Chae
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Qiongyu
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Energist North America, Nyack, NY 10960, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Trow
authors.affiliation: Energist North America, Nyack, NY 10960, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Department of Radiology, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Kythera Biopharmaceuticals, Calabasas, CA 91301, USA.
authors.forename: Serge
authors.initials: S
authors.lastname: Lichtsteiner
authors.affiliation: Kythera Biopharmaceuticals, Calabasas, CA 91301, USA.
authors.forename: Damon
authors.initials: D
authors.lastname: Sutton
authors.affiliation: Kythera Biopharmaceuticals, Calabasas, CA 91301, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Matheson
authors.affiliation: Kythera Biopharmaceuticals, Calabasas, CA 91301, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Walker
authors.affiliation: Kythera Biopharmaceuticals, Calabasas, CA 91301, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: David
authors.affiliation: Department of Radiology, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Dermatology, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Janis M
authors.initials: JM
authors.lastname: Taube
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000494:pharmacology*; D024042:Collagen Type I / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D020405:Dermis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D020007:Implants, Experimental; D008027:Light; D008422:Materials Testing; D009928:Organ Specificity / Q000187:drug effects / Q000528:radiation effects; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D012212:Rheology / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D024042:Collagen Type I; D003432:Cross-Linking Reagents; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid