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Decellularized Dental Pulp Extracellular Matrix as a Biological Scaffold for Dental Pulp Regenerative Therapy

Alqahtani, Qahtan (2018) Decellularized Dental Pulp Extracellular Matrix as a Biological Scaffold for Dental Pulp Regenerative Therapy. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

In the current theme of dental pulp regeneration, biological and synthetic scaffolds are becoming a potential therapy for pulp revitalization. The extracellular matrix has shown success in preclinical models and humans, promoting constructive remodeling and formation of site-appropriate tissue after injury. The use of ECM-based scaffolds has shown an improved tissue remodeling outcome, as it modulates the host response into an anti-inflammatory response that is characterized by the presence of alternatively activated macrophages around the scaffolds. This effect was demonstrated in other studies, yet the underlying mechanism is still largely unknown. There is currently a growing evidence that the source and composition of ECM scaffolds can be responsible for a pro-inflammatory response, while other scaffolds were able to maintain M2 like macrophage response. This phenomenon has led us to the conclusion that host immune cells behavior varies depending on the chemical composition of the matrix. Cathepsin V, K, S, and L have shown collagenolytic ability with cathepsin K being the most potent. We speculate that lysosomal cathepsin K might play a major role in the hydrolysis of collagen in endosomes. In this work, the swine decellularized pulp extracellular matrix (DP-ECM) was used to understand its effect on dental pulp cells and periodontal ligament cells as a candidate for cell-based pulp therapy. The goal is to understand the process of tissue remodeling and cells contribution to this process over the course of 6 and 12 weeks. The generated matrix was analyzed for odontogenic proteins, levels of retained growth factors and bioactive molecules. To simulate the dental model of pulp regeneration, the ECM was placed into the canal space of human tooth root fragment that were implanted subcutaneously in immune compromised mice. The resulting tissue was analyzed for the expression of βIII-Tubulin, CD31, and DSPP. This was followed up with an investigation of macrophage response toward the DP-ECM. We also, investigated the effect of collagen and matrix components on Cathepsin K activity and macrophages polarization.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Alqahtani, Qahtanqma1@pitt.eduqma10000-0003-0609-7141
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSfeir, Charlescsfeir@pitt.edu
Committee MemberElia, Beniashebeniash@pitt.edu
Committee MemberHerbert, Rayhlr21@pitt.edu
Committee MemberBrian, Brownbrownb@upmc.edu
Date: 12 December 2018
Date Type: Publication
Defense Date: 28 November 2018
Approval Date: 12 December 2018
Submission Date: 2 December 2018
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 130
Institution: University of Pittsburgh
Schools and Programs: School of Dental Medicine > Dental Science
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Regenerative Endodontics Pulp Regeneration Bio-materials
Date Deposited: 12 Dec 2018 19:52
Last Modified: 12 Dec 2018 19:52
URI: http://d-scholarship.pitt.edu/id/eprint/35685

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