title: Towards autotrophic tissue engineering: Photosynthetic gene therapy for regeneration.
abstract: The use of artificial tissues in regenerative medicine is limited due to hypoxia. As a strategy to overcome this drawback, we have shown that photosynthetic biomaterials can produce and provide oxygen independently of blood perfusion by generating chimeric animal-plant tissues during dermal regeneration. In this work, we demonstrate the safety and efficacy of photosynthetic biomaterials in vivo after engraftment in a fully immunocompetent mouse skin defect model. Further, we show that it is also possible to genetically engineer such photosynthetic scaffolds to deliver other key molecules in addition to oxygen. As a proof-of-concept, biomaterials were loaded with gene modified microalgae expressing the angiogenic recombinant protein VEGF. Survival of the algae, growth factor delivery and regenerative potential were evaluated in vitro and in vivo. This work proposes the use of photosynthetic gene therapy in regenerative medicine and provides scientific evidence for the use of engineered microalgae as an alternative to deliver recombinant molecules for gene therapy.
authors.affiliation: Department of Plastic Surgery and Hand Surgery, University Hospital rechts der Isar, Technische Universität München, Germany; FONDAP Center for Genome Regulation, Faculty of Science, Universidad de Chile, Santiago, Chile.
authors.forename: Myra Noemi
authors.initials: MN
authors.lastname: Chávez
authors.affiliation: Department of Plastic Surgery and Hand Surgery, University Hospital rechts der Isar, Technische Universität München, Germany; Handchirurgie, Plastische Chirurgie, Ästhetische Chirurgie der Ludwig-Maximilians Universität München, Germany.
authors.forename: Thilo Ludwig
authors.initials: TL
authors.lastname: Schenck
authors.affiliation: Department of Plastic Surgery and Hand Surgery, University Hospital rechts der Isar, Technische Universität München, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Hopfner
authors.affiliation: Department of Plastic Surgery and Hand Surgery, University Hospital rechts der Isar, Technische Universität München, Germany; Biotechnology Research Center, Costa Rica Institute of Technology, Cartago, Costa Rica.
authors.forename: Carolina
authors.initials: C
authors.lastname: Centeno-Cerdas
authors.affiliation: Department of Nuclear Medicine, University Hospital rechts der Isar, Technische Universität, München, Germany.
authors.forename: Ian
authors.initials: I
authors.lastname: Somlai-Schweiger
authors.affiliation: Molekulare Pflanzenwissenschaften, Biozentrum Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schwarz
authors.affiliation: Department of Plastic Surgery and Hand Surgery, University Hospital rechts der Isar, Technische Universität München, Germany.
authors.forename: Hans-Günther
authors.initials: HG
authors.lastname: Machens
authors.affiliation: Institute of Virology, Technische Universität München, Germany; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.affiliation: Department of Biology, Faculty of Science, Universidad de Chile, Santiago, Chile.
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Bono
authors.affiliation: FONDAP Center for Genome Regulation, Faculty of Science, Universidad de Chile, Santiago, Chile.
authors.forename: Miguel L
authors.initials: ML
authors.lastname: Allende
authors.affiliation: Molekulare Pflanzenwissenschaften, Biozentrum Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Nickelsen
authors.affiliation: Department of Plastic Surgery and Hand Surgery, University Hospital rechts der Isar, Technische Universität München, Germany; FONDAP Center for Genome Regulation, Faculty of Science, Universidad de Chile, Santiago, Chile; Institute for Medical and Biological Engineering, Schools of Engineering, Biological Sciences and Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: tomasega@gmail.com.
authors.forename: José Tomás
authors.initials: JT
authors.lastname: Egaña
mesh_terms: D000818:Animals; D052818:Autotrophic Processes / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology; D002696:Chlamydomonas / Q000187:drug effects / Q000502:physiology; D020405:Dermis / Q000187:drug effects; D005260:Female; D015316:Genetic Therapy; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology; D051379:Mice; D058086:Microalgae / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D010788:Photosynthesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D015027:Zebrafish
chemical_list: D001672:Biocompatible Materials; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen
keywords: Algae biotechnology; Biomaterials; Drug delivery; Hypoxia; Molecular therapy; Oxygen; Regenerative medicine