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Optimized Repopulation of Tendon Hydrogel: Synergistic Effects of Growth Factor Combinations and Adipose-Derived Stem Cells
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. VA Palo Alto Health Care System, Livermore, CA, USA.
Stanford University, CA, USA.
VA Palo Alto Health Care System, Livermore, CA, USA; Stanford University, CA, USA.
VA Palo Alto Health Care System, Livermore, CA, USA; Stanford University, CA, USA.
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2017 (English)In: Hand (New York, N.Y.), ISSN 1558-9447, Vol. 12, no 1, p. 68-77Article in journal (Refereed) Published
Abstract [en]

Background: Tendon-derived extracellular matrix (ECM) hydrogel has been shown to augment tendon healing in vivo. We hypothesized that reseeding of the gel with adipose-derived stem cells (ASCs) could further assist repopulation of the gel and that combinations of growth factors (GFs) would improve the survival of these cells after reseeding. Methods: A tendon-specific ECM solution was supplemented with varying concentrations of basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF-1), and platelet-derived growth factor-BB (PDGF-BB). Gels were then seeded with ASCs transfected with a green fluorescent protein/luciferin construct. Cell proliferation was determined using the MTT assay and histology, and GF and ASC augmented gels were injected into the back of Sprague Dawley rats. Bioluminescence of seeded gels was continuously followed after reseeding, and cell counts were performed after the gels were explanted at 14 days. Results: Synergistic effects of the GFs were seen, and an optimal combination was determined to be 10 ng/mL bFGF, 100 ng/mL IGF-1, and 100 ng/mL PDGF-BB (2.8-fold increase; P amp;lt; .05). In vivo bioluminescence showed an improved initial survival of cells in gels supplemented with the optimal concentration of GF compared with the control group (10.6-fold increase at 8 days; P amp;lt; .05). Cell counts of explants showed a dramatic endogenous repopulation of gels supplemented by GF + ASCs compared with both gels with GF but no ASCs (7.6-fold increase) and gels with ASCs but no GF (1.6-fold increase). Conclusion: Synergistic effects of GFs can be used to improve cellular proliferation of ASCs seeded to a tendon ECM gel. Reseeding with ASCs stimulates endogenous repopulation of the gel in vivo and may be used to further augment tendon healing.

Place, publisher, year, edition, pages
Sage Publications, 2017. Vol. 12, no 1, p. 68-77
Keyword [en]
ECM; flexor tendon; hydrogel; reconstructive hand surgery; tissue engineering
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-145067DOI: 10.1177/1558944715628005PubMedID: 28082847OAI: oai:DiVA.org:liu-145067DiVA: diva2:1181250
Available from: 2018-02-08 Created: 2018-02-08 Last updated: 2018-02-08

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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Hand and Plastic Surgery
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