Plastic and Reconstructive Surgery • March 2014 Supplement
Conclusion: Endothelial cell-stromal interactions, mediated by SDF-1, play a pivotal role in maintaining ASC niche transcriptional homeostasis and preserving the functional capacity of ASCs. In the absence of SDF-1, ASCs are shunted towards adipogenesis, with reduced proliferative and proangiogenic capacity, impacting their physiological role within the adipose niche environment and their therapeutic potential in treating ischemia. The dysfunction of ASCs in diabetes may be related to downregulation of SDF-1 and subsequent disruption of the physiological cytokine milieu. Further investigation of the role of SDF-1 in ASC homeostasis and function, particularly in the context of diabetes, is ongoing to inform the development of autologous cell based therapies for diabetic wound healing.
9 Selectively Permeable Nanofiber Constructs to Prevent Inflammatory Scarring And Enhance Nerve Regeneration in Peripheral Nerve Injury Karim A Sarhane, MD, MSc; Zuhaib Ibrahim, MD; Kellin Krick, PhD candidate; Russell Martin, PhD candidate; Baohan Pan, MD, PhD; Sami H Tuffaha, MD; Justin M Broyles, MD; Chris Cashman, MD/PhD candidate; Ruifa Mi, MD, PhD; Mohammed Alrakan, MD; Sepher Tehrani, MD candidate; Leah Goldberg, MD candidate; Hai-Quan Mao, PhD; WP Andrew Lee, MD; Gerald Brandacher, MD Johns Hopkins University, Baltimore, MD Purpose: Substantial advances have been made in enhancing nerve regeneration across gaps through the use of conduits and acellular nerve grafts. However, very few therapeutic approaches have been successfully studied in primary endto-end repairs. Post-repair histologic studies commonly demonstrate scar tissue between coapted nerve stumps. In this study, we propose a novel semi-permeable nanofiber nerve wrap prepared from FDA approved biocompatible materials (polycaprolactone) to reduce inflammation at nerve coaptation site through inhibition of inflammatory cell infiltration while allowing diffusion of essential nutrients and growth factors. Methods: Nerve wraps were synthesized by electrospinning of randomly oriented 650-nm nanofibers, and constructs with pores smaller than 10 μm were obtained. Using Thy-1 GFP Sprague-Dawley rats, we performed sciatic nerve transection and epinureal repair (control group) and with wrapping the coaptation site using the neuro-protective nanofiber construct (experimental group). Five weeks later, histologic analysis (Masson’s Trichrome staining, ED1+TUJ1 immunofluorescence co-staining) was performed on nerve sections at the repair site to assess fibrosis (collagen deposition) and inflammation (macrophage invasion) (n=5/group). Additionally, retrograde labeling was performed, and at the same time, the distal stump was harvested for histo-morphometric evaluation (n=8/group). Results: Masson’s Trichrome and double immunofluorescence staining (ED1+TUJ1) of nerve longitudinal sections 5 weeks following repair showed a significantly decreased level of intraneural scarring and inflammation in the nanofiber nerve wrap group, as determined by collagen quantification (7.4% ± 1.3 vs. 3.2% ± 1.3, p
Conclusion: Endothelial cell-stromal interactions, mediated by SDF-1, play a pivotal role in maintaining ASC niche transcriptional homeostasis and preserving the functional capacity of ASCs. In the absence of SDF-1, ASCs are shunted towards adipogenesis, with reduced proliferative and proangiogenic capacity, impacting their physiological role within the adipose niche environment and their therapeutic potential in treating ischemia. The dysfunction of ASCs in diabetes may be related to downregulation of SDF-1 and subsequent disruption of the physiological cytokine milieu. Further investigation of the role of SDF-1 in ASC homeostasis and function, particularly in the context of diabetes, is ongoing to inform the development of autologous cell based therapies for diabetic wound healing.
9 Selectively Permeable Nanofiber Constructs to Prevent Inflammatory Scarring And Enhance Nerve Regeneration in Peripheral Nerve Injury Karim A Sarhane, MD, MSc; Zuhaib Ibrahim, MD; Kellin Krick, PhD candidate; Russell Martin, PhD candidate; Baohan Pan, MD, PhD; Sami H Tuffaha, MD; Justin M Broyles, MD; Chris Cashman, MD/PhD candidate; Ruifa Mi, MD, PhD; Mohammed Alrakan, MD; Sepher Tehrani, MD candidate; Leah Goldberg, MD candidate; Hai-Quan Mao, PhD; WP Andrew Lee, MD; Gerald Brandacher, MD Johns Hopkins University, Baltimore, MD Purpose: Substantial advances have been made in enhancing nerve regeneration across gaps through the use of conduits and acellular nerve grafts. However, very few therapeutic approaches have been successfully studied in primary endto-end repairs. Post-repair histologic studies commonly demonstrate scar tissue between coapted nerve stumps. In this study, we propose a novel semi-permeable nanofiber nerve wrap prepared from FDA approved biocompatible materials (polycaprolactone) to reduce inflammation at nerve coaptation site through inhibition of inflammatory cell infiltration while allowing diffusion of essential nutrients and growth factors. Methods: Nerve wraps were synthesized by electrospinning of randomly oriented 650-nm nanofibers, and constructs with pores smaller than 10 μm were obtained. Using Thy-1 GFP Sprague-Dawley rats, we performed sciatic nerve transection and epinureal repair (control group) and with wrapping the coaptation site using the neuro-protective nanofiber construct (experimental group). Five weeks later, histologic analysis (Masson’s Trichrome staining, ED1+TUJ1 immunofluorescence co-staining) was performed on nerve sections at the repair site to assess fibrosis (collagen deposition) and inflammation (macrophage invasion) (n=5/group). Additionally, retrograde labeling was performed, and at the same time, the distal stump was harvested for histo-morphometric evaluation (n=8/group). Results: Masson’s Trichrome and double immunofluorescence staining (ED1+TUJ1) of nerve longitudinal sections 5 weeks following repair showed a significantly decreased level of intraneural scarring and inflammation in the nanofiber nerve wrap group, as determined by collagen quantification (7.4% ± 1.3 vs. 3.2% ± 1.3, p
