Wesley A Anderson1, Alicia R Willenberg2, Alexander J Bosak2, Bradley J Willenberg3, Stephen Lambert4. 1. Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA. 2. Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL, USA. 3. Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL, USA; Saisijin Biotech, LLC, St. Cloud, FL, USA. 4. Department of Medical Education, College of Medicine, University of Central Florida, Orlando, FL, USA. Electronic address: stephen.lambert@ucf.edu.
Abstract
BACKGROUND: Peripheral neuropathies affect approximately 20 million people in the United States and often stem from other chronic conditions, such as diabetes. In vitro methodologies to facilitate the understanding and treatment of these disorders often lack the cellular and functional complexity required to accurately model peripheral neuropathies. In particular, they are often 2D and fail to faithfully reproduce the 3D in vivo microenvironment. NEW METHOD: Embryonic dorsal root ganglion (DRG) explants were inserted into laminin derivatized capillary alginate gel (Capgel™), a bioabsorbable, self-assembling biomaterial, possessing parallel microchannel architecture, and cultured to mimic normal nerve development, including Schwann cell myelination. RESULTS: Laminin derivatization of the microchannels improved nerve growth through the gel. Axon bundles containing myelinating Schwann cells migrated through the gel and were ensheathed by rudimentary perineurium up to 1 mm from the DRG explant site. COMPARISON WITH EXISTING METHODS: Other nerve models are two-dimensional in nature and/or fail to conserve the complicated architecture and cellular milieu observed in vivo. Our nerve model shows the simple culture technique of cells grown in 3D, which allows for a more advanced structural organization that more accurately mimics the in vivo nerve fascicle. CONCLUSIONS: When embryonic DRG explants are cultured in this system, they show a striking resemblance to in vivo peripheral nerve fascicles, including myelinated axons and the formation of a rudimentary perineurium, suggesting that both neuronal and non-neuronal cells within the DRG explant are capable of recreating the 3D structure of a developing sensory fascicle within the microchannel architecture.
BACKGROUND:Peripheral neuropathies affect approximately 20 million people in the United States and often stem from other chronic conditions, such as diabetes. In vitro methodologies to facilitate the understanding and treatment of these disorders often lack the cellular and functional complexity required to accurately model peripheral neuropathies. In particular, they are often 2D and fail to faithfully reproduce the 3D in vivo microenvironment. NEW METHOD: Embryonic dorsal root ganglion (DRG) explants were inserted into laminin derivatized capillary alginate gel (Capgel™), a bioabsorbable, self-assembling biomaterial, possessing parallel microchannel architecture, and cultured to mimic normal nerve development, including Schwann cell myelination. RESULTS: Laminin derivatization of the microchannels improved nerve growth through the gel. Axon bundles containing myelinating Schwann cells migrated through the gel and were ensheathed by rudimentary perineurium up to 1 mm from the DRG explant site. COMPARISON WITH EXISTING METHODS: Other nerve models are two-dimensional in nature and/or fail to conserve the complicated architecture and cellular milieu observed in vivo. Our nerve model shows the simple culture technique of cells grown in 3D, which allows for a more advanced structural organization that more accurately mimics the in vivo nerve fascicle. CONCLUSIONS: When embryonic DRG explants are cultured in this system, they show a striking resemblance to in vivo peripheral nerve fascicles, including myelinated axons and the formation of a rudimentary perineurium, suggesting that both neuronal and non-neuronal cells within the DRG explant are capable of recreating the 3D structure of a developing sensory fascicle within the microchannel architecture.
Authors: Andrew Philip Panarello; Corey Edward Seavey; Mona Doshi; Andrew K Dickerson; Thomas J Kean; Bradley Jay Willenberg Journal: Gels Date: 2022-06-14
Authors: Wesley A Anderson; Alexander Bosak; Helena T Hogberg; Thomas Hartung; Michael J Moore Journal: In Vitro Cell Dev Biol Anim Date: 2021-01-12 Impact factor: 2.416
Authors: Thomas Distler; Ines Lauria; Rainer Detsch; Clemens M Sauter; Farina Bendt; Julia Kapr; Stephan Rütten; Aldo R Boccaccini; Ellen Fritsche Journal: Biomedicines Date: 2021-03-05