Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Extracellular matrix bioscaffolds for treatment of volumetric muscle loss

Dziki, Jenna / L (2017) Extracellular matrix bioscaffolds for treatment of volumetric muscle loss. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Download (8MB) | Preview


Overt loss of skeletal muscle tissue, or volumetric muscle loss (VML), overwhelms its inherent regenerative ability and is associated with robust scar tissue deposition and loss of function. VML is a significant problem in both military and civilian medicine. Current treatment options including muscle flaps, grafts, orthotics, and cell-centric strategies remain ineffective. Over the past decade, bioscaffolds composed of mammalian extracellular matrix (ECM) have been investigated as an acellular, inductive template to promote functional myogenesis for VML repair. ECM bioscaffolds obviate the need for exogenous stem cell delivery through the recruitment of endogenous stem / progenitor cells and promote a pro-remodeling microenvironment through modulation of the innate immune response. This immune-stimulatory approach, paired with endogenous stem / progenitor cell recruitment, represents a novel therapeutic strategy for treating VML. Mounting evidence suggests that site-appropriate mechanical loading can contribute to this pro-regenerative microenvironment. The objectives of the present thesis include determination of the spatial and temporal response of macrophages and progenitor cells within the ECM-treated VML injury site, investigation of the effects of ECM bioscaffolds upon macrophage phenotype and function, and determination of the effects of concomitant mechanical loading upon both macrophages and progenitor cells in the context of ECM-mediated VML repair. Results show that ECM bioscaffolds can promote a shift in macrophage phenotype which is associated with downstream stem / progenitor cell recruitment. ECM bioscaffolds activate macrophages towards a pro-remodeling phenotype. Mechanical loading augments a pro-regenerative cross-talk between macrophages and myogenic progenitor cells following exposure to ECM degradation products. These preclinical investigations, among others, have driven the clinical translation of ECM bioscaffolds. Thirteen VML patients have been treated to date, with results that include strength and functional improvement and evidence of new muscle formation and innervation. This strategy which considers the responding innate immune response, stimulates endogenous progenitor cells, and includes early, site-appropriate mechanical loading, represents a promising and translatable approach to VML treatment.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Dziki, Jenna / Ljld141@pitt.edujld141
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBadylak,
Committee MemberDavidson,
Committee MemberStolz,
Committee MemberDearth,
Committee MemberBrown,
Date: 26 September 2017
Date Type: Publication
Defense Date: 27 April 2017
Approval Date: 26 September 2017
Submission Date: 8 June 2017
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 248
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: extracellular matrix, macrophage, volumetric muscle loss
Date Deposited: 26 Sep 2017 16:46
Last Modified: 26 Sep 2017 16:46


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item