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A novel hyaluronic acid hydrogel as an extracellular matrix to improve graft survival in autologous adipose tissue transfer
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Bechar, Janak (2022) A novel hyaluronic acid hydrogel as an extracellular matrix to improve graft survival in autologous adipose tissue transfer. PhD thesis, University of Warwick.
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WRAP_THESIS_Bechar_2022.pdf - Submitted Version - Requires a PDF viewer. Download (5Mb) | Preview |
Official URL: http://webcat.warwick.ac.uk/record=b3869830
Abstract
Introduction
Adipose tissue transfer is used for correcting breast defects after cancer surgery and reconstruction after trauma or congenital defects. Graft survival can be as poor as 15%. Modified hyaluronic acid (HA) hydrogels can be used to suspend adipocytes to aid survival. The study aims were to synthesise a HA hydrogel with robust mechanical properties to support injection, and to assess adipocyte viability with HA hydrogel in vitro and in vivo.
Methods
A HA hydrogel with cross-linked aldehyde and hydrazine groups allowing self-healing around cells was engineered, with rheology and degradation properties characterised. Per2-dLuc 3T3-L1 murine pre-adipocytes expressing luciferase, CAG-luc-eGFP murine and human adipocytes were grown under, on, and encapsulated within HA hydrogel, with cell survival and gene expression investigated. A murine animal model underwent subcutaneous injection of primary murine adipocytes mixed with HA hydrogel, with cell survival and gene expression of mature adipocyte markers investigated.
Results
HA hydrogel can be degraded by tissue hyaluronidases in 4-5 days. Self-healing occurred in 30 minutes and is robust enough to resist deformation forces.
Per2-dLuc 3T3-L1 and CAG-luc-eGFP murine adipocytes were encapsulated within HA hydrogel and showed a <15% reduction in photon emission compared to control. Mature adipocyte markers gene expression levels in HA hydrogel encapsulated murine and human cells were similar to those of control (no HA hydrogel) cells. Primary murine adipocytes injected subcutaneously with HA hydrogel in wild type mice showed no difference in survival at higher gel volumes compared to control. Gene expression markers of differentiation in injected primary adipocytes mixed with HA hydrogel showed no difference compared to control cells.
Conclusion
The novel engineered HA hydrogel has suitable mechanical characteristics for injection and can support adipocyte survival in vitro and in vivo. A human pilot trial may be the next step in development of the novel HA hydrogel.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QD Chemistry Q Science > QP Physiology R Medicine > RD Surgery |
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Library of Congress Subject Headings (LCSH): | Colloids, Skin-grafting, Adipose tissues -- Transplantation, Fat cells, Hyaluronic acid | ||||
Official Date: | June 2022 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Hardwicke, Joseph ; Bastie, Claire ; Homer-Vanniasinkam, Shervanthi | ||||
Sponsors: | Medical and Life Sciences Research Fund ; Wellcome Trust (London, England) ; National Health Service. Research Development Fund | ||||
Format of File: | |||||
Extent: | 33 pages : illustrations, charts | ||||
Language: | eng |
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