Tissue engineering a composite graft for surgical reconstruction

PhD Thesis


Boodhun, Wali Sholeh. (2019). Tissue engineering a composite graft for surgical reconstruction [PhD Thesis]. Australian Catholic University
AuthorsBoodhun, Wali Sholeh
TypePhD Thesis
Qualification nameDoctor of Philosophy
Abstract

Soft tissue reconstruction remains a clinical challenge for plastic surgeons. Currently flaps are the only reliable option but they are associated with a high morbidity. Adipose tissue engineering remains a promising alternative for soft tissue reconstruction. Cells, scaffolds and regulatory proteins form the basis of tissue engineering. This study investigated the use of two porous synthetic scaffolds: NovoSorb™ and Poly (ethylene Glycol) (PEG) to tissue engineer a subcutaneous adipose (fat) layer. Autologous fat graft (lipoaspirate) provided the cellular component and a decellularized matrix (Adipogel) was used as a source of adipogenic promoting proteins. Different combinations of the scaffolds with lipoaspirate and Adipogel were prepared in vitro and implanted into a rat using a back wound pocket model. These scaffolds were harvested at eight weeks. Histological and immunohistochemical staining was performed to assess the general morphology of the construct, formation of connective tissue, blood vessels and new adipose tissue in the scaffolds. The scaffolds allowed good vascularised connective tissue infiltration, although the formation of fat was limited. The study demonstrated that for adipose tissue formation a fine balance between inflammation and adipogenesis is required.

Poly (ethylene Glycol) (PEG) allowed good infiltration of vascularised connective tissue. A two stage experiment was carried out to investigate if the scaffold could be used as a potential dermal substitute to support a skin graft as used clinically. PEG scaffolds were implanted in a wound pocket on a rodent’s back. After 2 weeks the skin overlying the scaffold was resected and a split skin graft was placed over the scaffold. A protective dressing was placed over the graft. The construct was harvested 10 days after the skin graft was placed over the scaffold in the wound. Macroscopic and histological assessments were performed to assess the percentage of graft take and integration of the scaffold and graft. The results showed the average graft take was greater than 70%. PEG scaffold supported a skin graft and can be used as a promising dermal substitute.

An alternative approach to tissue engineering is the stimulation of adipose tissue growth directly by placement of a pedicled fat graft in vivo within a chamber. In the second arm of this project, a vascularised pedicled fat flap based on the epigastric artery and vein was transplanted into a polycarbonate chamber. Previous studies have shown that a foreign body reaction occurs in response to the chamber, which causes a fibrotic capsule to form around the flap. This capsule mechanically inhibits tissue growth of the flap. In this study, a chemical antifibrotic agent, Tranilast was used to reduce the fibrous capsule and investigate its effects on the volume of the fat flap. The experimental group was given Tranilast orally for seven days. The control group received an oral placebo drug. The flaps were harvested at 10 weeks. The volume of the fat flap and the thickness of the fibrous capsule around the fat flap were measured. The fibrous capsule in the Tranilast group was thinner when compared to the experimental group but it was not statistically different from the Control Group. There was no difference in flap volume in the two groups.

In conclusion, NovoSorb and PEG porous scaffolds were able to support excellent host derived vascularization and connective tissue ingrowth, but the addition of an inductive matrix Adipogel to the scaffolds did not support increased adipogenesis. The addition of lipoaspirate to the scaffold pores marginally increased the degree of adipose tissue forming or surviving at 8 weeks. Both NovoSorb and PEG porous scaffolds have additional properties appropriate for skin reconstruction: NovoSorb induces neighboring host site adipose tissue to grow within its pores at the scaffold edges, and PEG is less inflammatory than NovoSorb and induces excellent collagen infiltration and is able to support the survival of a covering skin graft. Both scaffolds offer promise in skin reconstitution, but further advanced studies are required to promote adipose tissue formation within these scaffolds to tissue engineer the subcutaneous fat tissue layer.

Year2019
PublisherAustralian Catholic University
Page range1-364
Final version
License
All rights reserved
File Access Level
Open
Supplementary Files (Layperson Summary)
File Access Level
Controlled
Output statusPublished
Publication dates
Print02 Jun 2021
Online21 Mar 2022
Publication process dates
Completed2019
Deposited21 Mar 2022
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https://acuresearchbank.acu.edu.au/item/8x94x/tissue-engineering-a-composite-graft-for-surgical-reconstruction

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Final version


Supplementary Files (Layperson Summary)

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