Mahoney, Christopher
(2018)
Composite Adipose Derived Delivery Systems for Soft Tissue Restoration.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Musculoskeletal injuries inflicted by wars, congenital deformities, tumor resection, and general traumatic injuries often require soft tissue reconstruction. Damages to soft tissue not only affect cosmetic appearance, but also hinder function and emotional well-being. Autologous adipose grafting using processed lipoaspirate is a safe, resourceful, and minimally invasive option gaining tremendous momentum in clinical practice due to potential applications in trauma and reconstructive surgery, especially for breast cancer reconstruction. However, results can be unpredictable due to graft resorption rates reaching as high as 90%. These limitations serve as motivation for the development of new therapies to regenerate adipose tissue. We examined the use of an injectable adipose derived extracellular matrix (AdECM) combined with dexamethasone encapsulated polymer microspheres (Dex MS) as a scaffold for soft tissue restoration. First, we implemented a decellularization process to remove lipids and cellular content from discarded adipose tissue. The remaining material, known as AdECM, was thoroughly characterized. Triglycerides and residual DNA content were significantly reduced to ensure biomaterial safety. Adipose matrix proteins and glycosaminoglycans were evident and measurable following the decellularization process. Additionally, polymer microsphere encapsulation techniques were used to release dexamethasone in a controlled fashion.
Hydrogels derived from AdECM have shown potential in the ability to generate new adipose tissue in vivo. To further enhance adipogenesis, a composite adipose derived delivery system (CADDS) containing single- and double-walled dexamethasone encapsulated microspheres (SW and DW Dex MS) was developed. Previously, our laboratory has published the use of Dex MS as an additive to enhance adipogenesis and angiogenesis in adipose tissue grafts. In the current work, AdECM and CADDS are extensively characterized, in addition to conducting in vitro cell culture analysis. Characterization studies indicate the AdECM used for the CADDS has minimal cellular and lipid content allowing for gelation of its collagen structure under physiological conditions. Human adipose-derived stem cell (hASC) culture studies confirmed viability with the CADDS, and adipogenesis was increased in experimental groups containing the hydrogel scaffold. In vitro studies of AdECM hydrogel containing microspheres demonstrated a controlled release of dexamethasone from SW and DW formulations. In vivo studies indicated increased volume retention from CADDS material implants with Dex MS. Additionally, in vitro studies comparing hASCs to rat ASCs (rASCs) showed that hASCs differentiate and accumulate lipids on CADDS material at a higher capacity than rASCs. The comparison offers an explanation to the low retention rates seen from the animal studies. The delivery of Dex MS via an injectable hydrogel scaffold combines two biologically responsive components to develop a minimally invasive, off-the-shelf biomaterial for adipose tissue engineering.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
25 September 2018 |
| Date Type: |
Publication |
| Defense Date: |
13 July 2018 |
| Approval Date: |
25 September 2018 |
| Submission Date: |
10 July 2018 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
109 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
adipose, drug delivery, extracellular matrix |
| Date Deposited: |
25 Sep 2018 14:50 |
| Last Modified: |
08 Mar 2019 22:20 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/34865 |
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