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

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

doi:10.1097/01.GOX.0000769980.35543.2a

Plastic and Reconstructive Surgery, Global Open (Jul 2021)

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

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

Affiliations

Dominic Henn, MD: 1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,
Katharina S. Fischer, MD: 1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,
Kellen Chen, PhD: 1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,
Autumn H. Greco, BS: 1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,
Russell A. Martin, PhD: 2 Department of Materials Science & Engineering, Whiting School of Engineering, and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA,
Dharshan Sivaraj, BS: 1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,
Artem A. Trotsyuk, BS: 1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,
Hai-Quan Mao, PhD: 2 Department of Materials Science & Engineering, Whiting School of Engineering, and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA,
Sashank K. Reddy, MD, PhD: 1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,
Ulrich Kneser, MD: 3 Department of Hand, Plastic, and Reconstructive Surgery, BG Trauma Center Ludwigshafen, Ruprecht-Karls-University of Heidelberg, Heidelberg, Heidelberg, Germany,
Geoffrey C. Gurtner, MD: 1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,
Volker J. Schmidt, MD: 1 Hagey Laboratory for Pediatric Regenerative Medicine, Div. of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA, USA,
Justin M. Sacks, MD: 4 Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.

DOI: https://doi.org/10.1097/01.GOX.0000769980.35543.2a
Journal volume & issue: Vol. 9, no. 7S
pp. 10 – 11

Abstract

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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.

Published in Plastic and Reconstructive Surgery, Global Open

ISSN: 2169-7574 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://www.prsgo.com

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