Electrospun Fiber Mesh for High-Resolution Measurements of Oxygen Tension in Cranial Bone Defect Repair

• Type of Material: Article
• Authors: Kevin Schilling, University of Rochester; Mirna El Khatib, University of Pennsylvania; Shane Plunkett, University of Pennsylvania; Jiajia Xue, Georgia Institute of Technology; Younan Xia, Emory University; Sergei A. Vinogradov, University of Pennsylvania; Edward Brown, University of Rochester; Xinping Zhang, University of Rochester
• Language: English
• Date: 2019-09-18
• Publisher: American Chemical Society
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Copyright © 2019 American Chemical Society.
• Final Published Version (URL): http://dx.doi.org/10.1021/acsami.9b08341
• Title of Journal or Parent Work: ACS Applied Materials and Interfaces
• ISSN: 1944-8244
• Volume: 11
• Issue: 37
• Start Page: 33548
• End Page: 33558
• Grant/Funding Information: This study is supported by grants NIH R01AR067859, R01DE019902, R21DE02656 to XZ; NIH R21CA208921 and DoD BCRP W81XWH-17-1-0011 to EB; NIH R01EB018464, R24NS092986 and R21EB027397 to SAV; and NIH R01AR067859 diversity supplement awarded to KS.
• Keywords: coaxial electrospinning; Oximetry; two-photon phosphorescence lifetime microscopy; phosphorescence quenching; Mice; Mice, Transgenic; Oxygen; oxygen tension; Animals; Skull; bone repair; two-photon laser scanning microscopy; Bone Regeneration
• Research Categories: Health Sciences, Medicine and Surgery; Engineering, Biomedical

Abstract

Tissue oxygenation is one of the key determining factors in bone repair and bone tissue engineering. Adequate tissue oxygenation is essential for survival and differentiation of the bone-forming cells and ultimately the success of bone tissue regeneration. Two-photon phosphorescence lifetime microscopy (2PLM) has been successfully applied in the past to image oxygen distributions in tissue with high spatial resolution. However, delivery of phosphorescent probes into avascular compartments, such as those formed during early bone defect healing, poses significant problems. Here, we report a multifunctional oxygen-reporting fibrous matrix fabricated through encapsulation of a hydrophilic oxygen-sensitive, two-photon excitable phosphorescent probe, PtP-C343, in the core of fibers during coaxial electrospinning. The oxygen-sensitive fibers support bone marrow stromal cell growth and differentiation and at the same time enable real-Time high-resolution probing of partial pressures of oxygen via 2PLM. The hydrophilicity of the probe facilitates its gradual release into the nearby microenvironment, allowing fibers to act as a vehicle for probe delivery into the healing tissue. In conjunction with a cranial defect window chamber model, which permits simultaneous imaging of the bone and neovasculature in vivo via two-photon laser scanning microscopy, the oxygen-reporting fibers provide a useful tool for minimally invasive, high-resolution, real-Time 3D mapping of tissue oxygenation during bone defect healing, facilitating studies aimed at understanding the healing process and advancing design of tissue-engineered constructs for enhanced bone repair and regeneration.