Injectable In Situ Crosslinking Hydrogel for Autologous Fat Grafting

Autologous fat grafting is hampered by unpredictable outcomes due to high tissue resorption. Hydrogels based on enzymatically pretreated tunicate nanocellulose (ETC) and alginate (ALG) are biocompatible, safe, and present physiochemical properties capable of promoting cell survival. Here, we compare...

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Main Authors: Kristin Oskarsdotter, Catherine T. Nordgård, Peter Apelgren, Karin Säljö, Anita A. Solbu, Edwin Eliasson, Sanna Sämfors, Henriette E. M. Sætrang, Lise Cathrine Asdahl, Eric M. Thompson, Christofer Troedsson, Stina Simonsson, Berit L. Strand, Paul Gatenholm, Lars Kölby
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Gels
Subjects:
Online Access:https://www.mdpi.com/2310-2861/9/10/813
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author Kristin Oskarsdotter
Catherine T. Nordgård
Peter Apelgren
Karin Säljö
Anita A. Solbu
Edwin Eliasson
Sanna Sämfors
Henriette E. M. Sætrang
Lise Cathrine Asdahl
Eric M. Thompson
Christofer Troedsson
Stina Simonsson
Berit L. Strand
Paul Gatenholm
Lars Kölby
author_facet Kristin Oskarsdotter
Catherine T. Nordgård
Peter Apelgren
Karin Säljö
Anita A. Solbu
Edwin Eliasson
Sanna Sämfors
Henriette E. M. Sætrang
Lise Cathrine Asdahl
Eric M. Thompson
Christofer Troedsson
Stina Simonsson
Berit L. Strand
Paul Gatenholm
Lars Kölby
author_sort Kristin Oskarsdotter
collection DOAJ
description Autologous fat grafting is hampered by unpredictable outcomes due to high tissue resorption. Hydrogels based on enzymatically pretreated tunicate nanocellulose (ETC) and alginate (ALG) are biocompatible, safe, and present physiochemical properties capable of promoting cell survival. Here, we compared in situ and ex situ crosslinking of ETC/ALG hydrogels combined with lipoaspirate human adipose tissue (LAT) to generate an injectable formulation capable of retaining dimensional stability in vivo. We performed in situ crosslinking using two different approaches; inducing Ca<sup>2+</sup> release from CaCO<sub>3</sub> microparticles (CMPs) and physiologically available Ca<sup>2+</sup> in vivo. Additionally, we generated ex situ-crosslinked, 3D-bioprinted hydrogel-fat grafts. We found that in vitro optimization generated a CMP-crosslinking system with comparable stiffness to ex situ-crosslinked gels. Comparison of outcomes following in vivo injection of each respective crosslinked hydrogel revealed that after 30 days<i>,</i> in situ crosslinking generated fat grafts with less shape retention than 3D-bioprinted constructs that had undergone ex situ crosslinking. However, CMP addition improved fat-cell distribution and cell survival relative to grafts dependent on physiological Ca<sup>2+</sup> alone. These findings suggested that in situ crosslinking using CMP might promote the dimensional stability of injectable fat-hydrogel grafts, although 3D bioprinting with ex situ crosslinking more effectively ensured proper shape stability in vivo.
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spelling doaj.art-d4d2e4cd729246f8996c88b38a6d393a2023-11-19T16:35:44ZengMDPI AGGels2310-28612023-10-0191081310.3390/gels9100813Injectable In Situ Crosslinking Hydrogel for Autologous Fat GraftingKristin Oskarsdotter0Catherine T. Nordgård1Peter Apelgren2Karin Säljö3Anita A. Solbu4Edwin Eliasson5Sanna Sämfors6Henriette E. M. Sætrang7Lise Cathrine Asdahl8Eric M. Thompson9Christofer Troedsson10Stina Simonsson11Berit L. Strand12Paul Gatenholm13Lars Kölby14Department of Plastic Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, SwedenDepartment of Biotechnology and Food Science, Norwegian Biopolymer Laboratory (NOBIPOL), Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Plastic Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, SwedenDepartment of Plastic Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, SwedenDepartment of Biotechnology and Food Science, Norwegian Biopolymer Laboratory (NOBIPOL), Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Chemistry and Chemical Engineering, Chalmers University of Technology, 412 96 Gothenburg, SwedenDepartment of Chemistry and Chemical Engineering, Chalmers University of Technology, 412 96 Gothenburg, SwedenDuPont Nutrition Norge AS d/b/a NovaMatrix, Postboks 223, 1377 Billingstad, NorwayDuPont Nutrition Norge AS d/b/a NovaMatrix, Postboks 223, 1377 Billingstad, NorwayOcean TuniCell AS, 5258 Blomsterdalen, NorwayOcean TuniCell AS, 5258 Blomsterdalen, NorwayDepartment of Medicinal Chemistry & Cell Biology, Institution of Biomedicine, Sahlgrenska University Hospital, 405 30 Gothenburg, SwedenDepartment of Biotechnology and Food Science, Norwegian Biopolymer Laboratory (NOBIPOL), Norwegian University of Science and Technology, 7491 Trondheim, NorwayCELLHEAL AS, 2636 Sandvika, NorwayDepartment of Plastic Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, SwedenAutologous fat grafting is hampered by unpredictable outcomes due to high tissue resorption. Hydrogels based on enzymatically pretreated tunicate nanocellulose (ETC) and alginate (ALG) are biocompatible, safe, and present physiochemical properties capable of promoting cell survival. Here, we compared in situ and ex situ crosslinking of ETC/ALG hydrogels combined with lipoaspirate human adipose tissue (LAT) to generate an injectable formulation capable of retaining dimensional stability in vivo. We performed in situ crosslinking using two different approaches; inducing Ca<sup>2+</sup> release from CaCO<sub>3</sub> microparticles (CMPs) and physiologically available Ca<sup>2+</sup> in vivo. Additionally, we generated ex situ-crosslinked, 3D-bioprinted hydrogel-fat grafts. We found that in vitro optimization generated a CMP-crosslinking system with comparable stiffness to ex situ-crosslinked gels. Comparison of outcomes following in vivo injection of each respective crosslinked hydrogel revealed that after 30 days<i>,</i> in situ crosslinking generated fat grafts with less shape retention than 3D-bioprinted constructs that had undergone ex situ crosslinking. However, CMP addition improved fat-cell distribution and cell survival relative to grafts dependent on physiological Ca<sup>2+</sup> alone. These findings suggested that in situ crosslinking using CMP might promote the dimensional stability of injectable fat-hydrogel grafts, although 3D bioprinting with ex situ crosslinking more effectively ensured proper shape stability in vivo.https://www.mdpi.com/2310-2861/9/10/813soft tissue reconstructionin situ crosslinking3D bioprintingnanocellulosealginate
spellingShingle Kristin Oskarsdotter
Catherine T. Nordgård
Peter Apelgren
Karin Säljö
Anita A. Solbu
Edwin Eliasson
Sanna Sämfors
Henriette E. M. Sætrang
Lise Cathrine Asdahl
Eric M. Thompson
Christofer Troedsson
Stina Simonsson
Berit L. Strand
Paul Gatenholm
Lars Kölby
Injectable In Situ Crosslinking Hydrogel for Autologous Fat Grafting
Gels
soft tissue reconstruction
in situ crosslinking
3D bioprinting
nanocellulose
alginate
title Injectable In Situ Crosslinking Hydrogel for Autologous Fat Grafting
title_full Injectable In Situ Crosslinking Hydrogel for Autologous Fat Grafting
title_fullStr Injectable In Situ Crosslinking Hydrogel for Autologous Fat Grafting
title_full_unstemmed Injectable In Situ Crosslinking Hydrogel for Autologous Fat Grafting
title_short Injectable In Situ Crosslinking Hydrogel for Autologous Fat Grafting
title_sort injectable in situ crosslinking hydrogel for autologous fat grafting
topic soft tissue reconstruction
in situ crosslinking
3D bioprinting
nanocellulose
alginate
url https://www.mdpi.com/2310-2861/9/10/813
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