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Composite Adipose Derived Delivery Systems for Soft Tissue Restoration

Mahoney, Christopher (2018) Composite Adipose Derived Delivery Systems for Soft Tissue Restoration. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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:
CreatorsEmailPitt UsernameORCID
Mahoney, Christophercmm237@pitt.educmm237
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMarra, Kaceymarrak@upmc.edukgm5
Rubin, J. Peterrubipj@upmc.edujpr5
Yates, Ceceliacecelia.yates@pitt.educecelia.yates
Almarza, Alejandroalejandro.almarza@pitt.edualejandro.almarza
Soto-Gutierrez, Alejandroals208@pitt.eduals208
Date: 25 September 2018
Date Type: Publication
Defense Date: 13 July 0018
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: 25 Sep 2018 14:50
URI: http://d-scholarship.pitt.edu/id/eprint/34865

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