Alexandria Digital Research Library

Engineering biomimetic scaffolds to encapsulate adipose-derived stem cells : a cell biology approach to regenerative treatments

Author:
Clevenger, Tracy N.
Degree Grantor:
University of California, Santa Barbara. Molecular, Cellular & Developmental Biology
Degree Supervisor:
Dennis O. Clegg
Place of Publication:
[Santa Barbara, Calif.]
Publisher:
University of California, Santa Barbara
Creation Date:
2016
Issued Date:
2016
Topics:
Biology, Cellular biology, and Molecular biology
Keywords:
Adipose stem cells
Tissue engineering
Soft tissue regeneration
3D cell culture
RGD
Biomimetic
Genres:
Dissertations, Academic and Online resources
Dissertation:
Ph.D.--University of California, Santa Barbara, 2016
Description:

The last decade has seen tremendous advances in the use of stem cell-based therapies to treat injury and disease, yet there are many hurdles still to overcome. Tissue or organ-specific strategies have begun to emerge as our knowledge of stem cell biology and transplant biology increases. This thesis presents results aimed at understanding and improving cell based therapies for soft tissue repair. Defects in soft-tissue can occur by many means, including traumatic injury, tumor resection, and congenital causes. Current approaches to the treatment of these deficiencies include autologous fat transplantation, which falls short of optimal. There are numerous negative outcomes associated with this procedure, the most common of which is loss of transplanted volume; which occurs in 92% of cases.

This thesis describes efforts to improve autologous treatments by utilizing the stem cell population present in transplanted tissue, adipose-derived stem cells (ASCs), and encapsulating them in an environment that supports survival, improving treatment options. The following chapters provide an in-depth overview of the development of a synthetic scaffolding system that supports the survival and differentiation of ASCs in vitro. By utilizing poly(ethylene) glycol (PEG) we were able to model a biomimetic environment and demonstrate that functionalization of inert PEG with different Arg-Gly-Asp (RGD)-containing peptides resulted in different levels of adhesion.

After the development of the scaffolding system we sought to further engineer capabilities of the system to provide the possibility for numerous applications using the same basic chemistry. Capitalizing on what is known about the remodeling of natural extracellular matrix (ECM) we were able to incorporate peptides that permit the degradation of the scaffolding after the stem cells differentiate. Selecting a cleavage sequence that is sensitive to proteinases that are secreted by mature adipocyte and not by undifferentiated ASCs we succeeded in creating a hydrogel that mimics a natural environment and is degradable upon the differentiation of ASCs to the desired cell types. We have further demonstrated that ASCs encapsulated in this system are viable for 12 weeks, both in vitro and in vivo. Although we examined just adipogenic differentiation in this work, due to the simple nature of the system it should be possible to systematically alter the incorporated components for applications of other cell types. This affords extensive possible targets for tissue regeneration utilizing a basic scaffolding system. Collectively, the work described here advances the understanding and application of stem cell based therapies for soft tissue repair and regeneration.

Physical Description:
1 online resource (105 pages)
Format:
Text
Collection(s):
UCSB electronic theses and dissertations
ARK:
ark:/48907/f3xw4jxc
ISBN:
9781369339901
Catalog System Number:
990047189210203776
Rights:
Inc.icon only.dark In Copyright
Copyright Holder:
Tracy Clevenger
File Description
Access: Public access
Clevenger_ucsb_0035D_13120.pdf pdf (Portable Document Format)