Biomimetic approaches for rotator cuff repair and regeneration Zizhao Li

Format:

Book

Thesis/Dissertation

Author/Creator:

Li, Zizhao, author.

Contributor:

University of Pennsylvania. Bioengineering., degree granting institution.

Language:

English

Subjects (All):

Bioengineering.

Biomedical engineering.

Physiology.

Biomechanics.

0202.

0541.

0648.

0719.

Local Subjects:

Bioengineering.

Biomedical engineering.

Physiology.

Biomechanics.

0202.

0541.

0648.

0719.

Genre:

Academic theses

Physical Description:

1 online resource (165 pages)

Contained In:

Dissertations Abstracts International 87-12B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2026

Language Note:

English

Summary:

Rotator cuff tears at the tendon-to-bone insertion present a persistent clinical challenge, where current surgical repairs are frequently compromised by high re-tear rates and the formation of mechanically inferior scar tissue. These failures stem primarily from the inability of current treatments to replicate the complex, multi-zonal architecture of the native enthesis, underscoring a critical need for regenerative strategies that can restore this specialized structural and biochemical gradient. This dissertation presents the development of a biomimetic multiphasic scaffold system (BMS) engineered to integrate with conventional suture anchors, delivering spatially organized structural and biological cues to drive functional enthesis regeneration.First, we established a biomimetic structural framework designed to mimic the native stiffness and alignment gradients of the insertion site. The BMS consists of three distinct phases: Phase 1 features an aligned, nanofibrous decellularized tendon extracellular matrix (dECM) combined with 'stiff' methacrylated hyaluronic acid (MeHA) to mimic tendon; Phase 2 incorporates nonaligned, nanofibrous dECM with 'soft' MeHA to replicate the fibrocartilage interface; and Phase 3 utilizes a porous, bioenergetic, citrate-based composite scaffold for bone integration. In vivo, this structural BMS promoted successful integrative healing, forming distinct tendon, fibrocartilage, and bone regions at the repair site while enhancing mechanical fixation through its unique suture-anchor compatible design.To further potentiate this framework with precise biological signaling, we developed a cell-free bio-functionalization strategy using lineage-specific extracellular vesicles (EVs). We isolated high-purity EVs from juvenile bovine tenocytes (T-EVs), chondrocytes (C-EVs), and mesenchymal stem cells (M-EVs) and mapped their distinct proteomic landscapes. Our analysis revealed that while T-EVs and C-EVs act as precise lineage instructors, delivering defined cues for tenogenic and chondrogenic differentiation, respectively, M-EVs operate as unique regulators with "hybrid competency", inducing a dual-lineage transcriptional profile capable of recapitulating the transitional microenvironment. Collectively, integrating these EVs onto the stiffness- and alignment-tunable BMS established a pro-regenerative, bioactive microenvironment. This "EV-BMS" system effectively modulated host cell recruitment and directed spatially defined tissue organization. By coordinating structural anisotropy with lineage-specific vesicular cargo, this work establishes a scalable, cell-free strategy for rotator cuff tissue engineering, offering a versatile solution to restore the structural and functional continuity of complex soft-to-hard tissue interfaces

Notes:

Source: Dissertations Abstracts International, Volume: 87-12, Section: B.

Advisors: Heo, Su Chin Committee members: Dyment, Nathaniel; Mauck, Robert L.; Kuntz, Andrew F.; Ko, Jina

Ph.D. University of Pennsylvania 2026

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798247973072

Access Restriction:

Restricted for use by site license