Bioabsorbable polymer optical waveguides for deep-tissue photomedicine

Advances in photonics have stimulated significant progress in medicine, with many techniques now in routine clinical use. However, the finite depth of light penetration in tissue is a serious constraint to clinical utility. Here we show implantable light-delivery devices made of bio-derived or biocompatible, and biodegradable polymers. In contrast to conventional optical fibres, which must be removed from the body soon after use, the biodegradable and biocompatible waveguides may be used for long-term light delivery and need not be removed as they are gradually resorbed by the tissue. As proof of concept, we demonstrate this paradigm-shifting approach for photochemical tissue bonding (PTB). Using comb-shaped planar waveguides, we achieve a full thickness (>10 mm) wound closure of porcine skin, which represents ∼10-fold extension of the tissue area achieved with conventional PTB. The results point to a new direction in photomedicine for using light in deep tissues.

[1]  Brett E. Bouma,et al.  Tethered capsule endomicroscopy enables less-invasive imaging of gastrointestinal tract microstructure , 2012, Nature Medicine.

[2]  David L. Kaplan,et al.  A new route for silk , 2008 .

[3]  Jeff W. Lichtman,et al.  Clarifying Tissue Clearing , 2015, Cell.

[4]  Hu Tao,et al.  Silk Materials – A Road to Sustainable High Technology , 2012, Advanced materials.

[5]  Seonghoon Kim,et al.  Step‐Index Optical Fiber Made of Biocompatible Hydrogels , 2015, Advanced materials.

[6]  Buddy D. Ratner,et al.  Biomaterials Science: An Introduction to Materials in Medicine , 1996 .

[7]  Anthony J. Johnson,et al.  Light-initiated bonding of amniotic membrane to cornea. , 2011, Investigative ophthalmology & visual science.

[8]  I. Kochevar,et al.  Light‐activated sutureless closure of wounds in thin skin , 2012, Lasers in surgery and medicine.

[9]  S. Jacques Optical properties of biological tissues: a review , 2013, Physics in medicine and biology.

[10]  T. Dougherty Photodynamic therapy. , 1993, Photochemistry and photobiology.

[11]  David Erickson,et al.  Gel-based optical waveguides with live cell encapsulation and integrated microfluidics. , 2012, Optics letters.

[12]  Marco Roffi,et al.  Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial , 2014, The Lancet.

[13]  I. Kochevar,et al.  Light‐activated tissue bonding for excisional wound closure: a split‐lesion clinical trial , 2012, The British journal of dermatology.

[14]  Benjamin A. Rockwell,et al.  A procedure for multiple-pulse maximum permissible exposure determination under the Z136.1-2000 American National Standard for Safe Use of Lasers , 2001 .

[15]  Prashant K. Jain,et al.  Plasmonic photothermal therapy (PPTT) using gold nanoparticles , 2008, Lasers in Medical Science.

[16]  Anna Yaroslavsky,et al.  Phototoxicity is not associated with photochemical tissue bonding of skin , 2010, Lasers in surgery and medicine.

[17]  D. Kaplan,et al.  Materials fabrication from Bombyx mori silk fibroin , 2011, Nature Protocols.

[18]  R. Anderson,et al.  Permanent hair removal by normal-mode ruby laser. , 1998, Archives of dermatology.

[19]  M. Haedersdal,et al.  Evidence‐based review of hair removal using lasers and light sources , 2006, Journal of the European Academy of Dermatology and Venereology : JEADV.

[20]  Jun Q. Lu,et al.  Refractive indices of human skin tissues at eight wavelengths and estimated dispersion relations between 300 and 1600 nm , 2006, Physics in medicine and biology.

[21]  Helmut Schäfer,et al.  Upconverting nanoparticles. , 2011, Angewandte Chemie.

[22]  R. Friedman,et al.  Pre-clinical in vivo evaluation of orthopaedic bioabsorbable devices. , 2000, Biomaterials.

[23]  Markus F Neurath,et al.  Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. , 2007, Gastroenterology.

[24]  Timothy D. Soper,et al.  Scanning fiber endoscopy with highly flexible, 1 mm catheterscopes for wide‐field, full‐color imaging , 2010, Journal of biophotonics.

[25]  Robert C. Wolpert,et al.  A Review of the , 1985 .

[26]  David L. Kaplan,et al.  Biocompatible Silk Printed Optical Waveguides , 2009 .

[27]  Alexandre Albanese,et al.  Biophotonics: Implantable waveguides , 2013 .

[28]  D. Kaplan,et al.  Low-threshold blue lasing from silk fibroin thin films , 2012 .

[29]  Hyunmin Yi,et al.  Facile fabrication of gelatin‐based biopolymeric optical waveguides , 2009, Biotechnology and bioengineering.

[30]  Muthu Kumara Gnanasammandhan,et al.  In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers , 2012, Nature Medicine.

[31]  Kam W Leong,et al.  Peripheral nerve regeneration by microbraided poly(L-lactide-co-glycolide) biodegradable polymer fibers. , 2004, Journal of biomedical materials research. Part A.

[32]  Carmen Alvarez-Lorenzo,et al.  Light‐sensitive Intelligent Drug Delivery Systems † , 2009, Photochemistry and photobiology.

[33]  Euiheon Chung,et al.  In vivo wide-area cellular imaging by side-view endomicroscopy , 2010, Nature Methods.

[34]  Seok Hyun Yun,et al.  Light-guiding hydrogels for cell-based sensing and optogenetic synthesis in vivo , 2013, Nature Photonics.

[35]  Mark Cronin-Golomb,et al.  Bioactive silk protein biomaterial systems for optical devices. , 2008, Biomacromolecules.

[36]  Sergio Fantini,et al.  Implantable, multifunctional, bioresorbable optics , 2012, Proceedings of the National Academy of Sciences.

[37]  David L. Kaplan,et al.  Nano‐ and Micropatterning of Optically Transparent, Mechanically Robust, Biocompatible Silk Fibroin Films , 2008 .

[38]  C. S. Lim,et al.  Simultaneous phase and size control of upconversion nanocrystals through lanthanide doping , 2010, Nature.