Injectable In Situ Crosslinking Hydrogel for Autologous Fat Grafting
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
Affiliations
Kristin Oskarsdotter
Department of Plastic Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden
Catherine T. Nordgård
Department of Biotechnology and Food Science, Norwegian Biopolymer Laboratory (NOBIPOL), Norwegian University of Science and Technology, 7491 Trondheim, Norway
Peter Apelgren
Department of Plastic Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden
Karin Säljö
Department of Plastic Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden
Anita A. Solbu
Department of Biotechnology and Food Science, Norwegian Biopolymer Laboratory (NOBIPOL), Norwegian University of Science and Technology, 7491 Trondheim, Norway
Edwin Eliasson
Department of Chemistry and Chemical Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden
Sanna Sämfors
Department of Chemistry and Chemical Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden
Henriette E. M. Sætrang
DuPont Nutrition Norge AS d/b/a NovaMatrix, Postboks 223, 1377 Billingstad, Norway
Lise Cathrine Asdahl
DuPont Nutrition Norge AS d/b/a NovaMatrix, Postboks 223, 1377 Billingstad, Norway
Eric M. Thompson
Ocean TuniCell AS, 5258 Blomsterdalen, Norway
Christofer Troedsson
Ocean TuniCell AS, 5258 Blomsterdalen, Norway
Stina Simonsson
Department of Medicinal Chemistry & Cell Biology, Institution of Biomedicine, Sahlgrenska University Hospital, 405 30 Gothenburg, Sweden
Berit L. Strand
Department of Biotechnology and Food Science, Norwegian Biopolymer Laboratory (NOBIPOL), Norwegian University of Science and Technology, 7491 Trondheim, Norway
Paul Gatenholm
CELLHEAL AS, 2636 Sandvika, Norway
Lars Kölby
Department of Plastic Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden
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 Ca2+ release from CaCO3 microparticles (CMPs) and physiologically available Ca2+ 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, 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 Ca2+ 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.
