QS8: Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Pro-regenerative Macrophage Polarization and Angiogenesis for Soft Tissue Engineering

Purpose: Fractionated fat (FF) has been shown to promote dermal regeneration; however, the use of fat grafting for reconstruction of soft tissue defects is limited due to volume loss over time. We have developed a novel approach for engineering of vascularized soft tissue using an injectable nanofib...

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Main Authors: Dominic Henn, MD, Katharina S. Fischer, MD, Kellen Chen, PhD, Autumn H. Greco, BS, Russell A. Martin, PhD, Dharshan Sivaraj, BS, Artem A. Trotsyuk, BS, Hai-Quan Mao, PhD, Sashank K. Reddy, MD, PhD, Ulrich Kneser, MD, Geoffrey C. Gurtner, MD, Volker J. Schmidt, MD, Justin M. Sacks, MD
Format: Article
Language:English
Published: Wolters Kluwer 2021-07-01
Series:Plastic and Reconstructive Surgery, Global Open
Online Access:http://journals.lww.com/prsgo/fulltext/10.1097/01.GOX.0000769980.35543.2a
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author Dominic Henn, MD
Katharina S. Fischer, MD
Kellen Chen, PhD
Autumn H. Greco, BS
Russell A. Martin, PhD
Dharshan Sivaraj, BS
Artem A. Trotsyuk, BS
Hai-Quan Mao, PhD
Sashank K. Reddy, MD, PhD
Ulrich Kneser, MD
Geoffrey C. Gurtner, MD
Volker J. Schmidt, MD
Justin M. Sacks, MD
spellingShingle Dominic Henn, MD
Katharina S. Fischer, MD
Kellen Chen, PhD
Autumn H. Greco, BS
Russell A. Martin, PhD
Dharshan Sivaraj, BS
Artem A. Trotsyuk, BS
Hai-Quan Mao, PhD
Sashank K. Reddy, MD, PhD
Ulrich Kneser, MD
Geoffrey C. Gurtner, MD
Volker J. Schmidt, MD
Justin M. Sacks, MD
QS8: Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Pro-regenerative Macrophage Polarization and Angiogenesis for Soft Tissue Engineering
Plastic and Reconstructive Surgery, Global Open
author_facet Dominic Henn, MD
Katharina S. Fischer, MD
Kellen Chen, PhD
Autumn H. Greco, BS
Russell A. Martin, PhD
Dharshan Sivaraj, BS
Artem A. Trotsyuk, BS
Hai-Quan Mao, PhD
Sashank K. Reddy, MD, PhD
Ulrich Kneser, MD
Geoffrey C. Gurtner, MD
Volker J. Schmidt, MD
Justin M. Sacks, MD
author_sort Dominic Henn, MD
title QS8: Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Pro-regenerative Macrophage Polarization and Angiogenesis for Soft Tissue Engineering
title_short QS8: Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Pro-regenerative Macrophage Polarization and Angiogenesis for Soft Tissue Engineering
title_full QS8: Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Pro-regenerative Macrophage Polarization and Angiogenesis for Soft Tissue Engineering
title_fullStr QS8: Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Pro-regenerative Macrophage Polarization and Angiogenesis for Soft Tissue Engineering
title_full_unstemmed QS8: Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Pro-regenerative Macrophage Polarization and Angiogenesis for Soft Tissue Engineering
title_sort qs8: enrichment of nanofiber hydrogel composite with fractionated fat promotes pro-regenerative macrophage polarization and angiogenesis for soft tissue engineering
publisher Wolters Kluwer
series Plastic and Reconstructive Surgery, Global Open
issn 2169-7574
publishDate 2021-07-01
description Purpose: Fractionated fat (FF) has been shown to promote dermal regeneration; however, the use of fat grafting for reconstruction of soft tissue defects is limited due to volume loss over time. We have developed a novel approach for engineering of vascularized soft tissue using an injectable nanofiber hydrogel (NHC) enriched with FF. Methods: FF was generated by emulsification of groin fat pads from rats and mixed in a 3:1 ratio with NHC (NHC-FF). NHC-FF or NHC alone were placed into isolation chambers together with arteriovenous (AV) loops, which were subcutaneously implanted into the groin of rats (n=8 per group). After 21 days, animals were euthanized, systemically perfused with ink, and tissue was explanted for histological analysis. Immunofluorescent staining (IF) and confocal laser scanning microscopy were used to quantify CD34+ progenitor cells and macrophage subpopulations. Results: NHC-FF tissue maintained its shape without shrinking and showed a significantly stronger functional neovascularization compared to NHC alone at 21 days after implantation (mean vessel count: 833.5 ± 206.1 vs. 296.5 ± 114.1, p = 0.04). Tissue remodeling and cellular infiltration were greater in NHC-FF (mean cell count: 49,707 ± 18,491 vs. 9,263 ± 3,790, p = 0.005) with a significantly higher amount of progenitor cells and regenerative CD163+ macrophages compared to NHC alone. Conclusion: FF-enriched NHC transforms into highly vascularized soft tissue over 21 days without signs of shrinking and promotes macrophage polarization toward regenerative phenotypes. Enrichment of injectable NHC with FF represents a promising approach for durable reconstruction of soft tissue defects.
url http://journals.lww.com/prsgo/fulltext/10.1097/01.GOX.0000769980.35543.2a
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spelling doaj-eb774fa248704a04ab21a6b79d328f2a2021-07-26T05:34:24ZengWolters KluwerPlastic and Reconstructive Surgery, Global Open2169-75742021-07-0197S101110.1097/01.GOX.0000769980.35543.2a202107001-00015QS8: Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Pro-regenerative Macrophage Polarization and Angiogenesis for Soft Tissue EngineeringDominic Henn, MD0Katharina S. Fischer, MD1Kellen Chen, PhD2Autumn H. Greco, BS3Russell A. Martin, PhD4Dharshan Sivaraj, BS5Artem A. Trotsyuk, BS6Hai-Quan Mao, PhD7Sashank K. Reddy, MD, PhD8Ulrich Kneser, MD9Geoffrey C. Gurtner, MD10Volker J. Schmidt, MD11Justin M. Sacks, MD121 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,2 Department of Materials Science & Engineering, Whiting School of Engineering, and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA,1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,2 Department of Materials Science & Engineering, Whiting School of Engineering, and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA,1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,3 Department of Hand, Plastic, and Reconstructive Surgery, BG Trauma Center Ludwigshafen, Ruprecht-Karls-University of Heidelberg, Heidelberg, Heidelberg, Germany,1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,4 Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.Purpose: Fractionated fat (FF) has been shown to promote dermal regeneration; however, the use of fat grafting for reconstruction of soft tissue defects is limited due to volume loss over time. We have developed a novel approach for engineering of vascularized soft tissue using an injectable nanofiber hydrogel (NHC) enriched with FF. Methods: FF was generated by emulsification of groin fat pads from rats and mixed in a 3:1 ratio with NHC (NHC-FF). NHC-FF or NHC alone were placed into isolation chambers together with arteriovenous (AV) loops, which were subcutaneously implanted into the groin of rats (n=8 per group). After 21 days, animals were euthanized, systemically perfused with ink, and tissue was explanted for histological analysis. Immunofluorescent staining (IF) and confocal laser scanning microscopy were used to quantify CD34+ progenitor cells and macrophage subpopulations. Results: NHC-FF tissue maintained its shape without shrinking and showed a significantly stronger functional neovascularization compared to NHC alone at 21 days after implantation (mean vessel count: 833.5 ± 206.1 vs. 296.5 ± 114.1, p = 0.04). Tissue remodeling and cellular infiltration were greater in NHC-FF (mean cell count: 49,707 ± 18,491 vs. 9,263 ± 3,790, p = 0.005) with a significantly higher amount of progenitor cells and regenerative CD163+ macrophages compared to NHC alone. Conclusion: FF-enriched NHC transforms into highly vascularized soft tissue over 21 days without signs of shrinking and promotes macrophage polarization toward regenerative phenotypes. Enrichment of injectable NHC with FF represents a promising approach for durable reconstruction of soft tissue defects.http://journals.lww.com/prsgo/fulltext/10.1097/01.GOX.0000769980.35543.2a