Ultrahigh-strength and tough hyaluronic acid hydrogel for cartilage repair
Description: Articular cartilage tissue lacks an intrinsic capacity for self-regeneration and chondral lesions often progress to osteoarthritis, eventually requiring total joint replacement. Although many strategies to repair cartilage defects have been developed, there is currently no treatment available to recreate instantaneously the mechanical properties of healthy adjacent articular cartilage. New regenerative approaches have emerged to address this rising clinical need to generate functional cartilage substitutes. One approach utilizes hydrogels (water-swollen polymer networks) for cell encapsulation and delivery; however, it remains an unmet challenge to design ultrahigh-strength and tough injectable hydrogels for functional repair. We hypothesize that a double-network hyaluronic acid hydrogel utilizing both reversible supramolecular guest-host interactions and covalently crosslinking can provide a unique cell encapsulating microenvironment and thus has the potential to meet the clinical need of a simple yet effective approach for cartilage repair. Double-network hydrogels composed of a supramolecular and a covalently crosslinked hyaluronic acid (HA) will be formed by: reversible physical crosslinking of adamantine-HA and cyclodextrin-HA, followed by an irreversible chemical crosslinking of methacrylated HA by Michael-addition with dithiothreitol. In the first aim of this project I will investigate various compositions of an ultrahigh-strength and tough double-network hyaluronic acid hydrogel that is mechanically stable under extreme biomechanical loading similar to the knee joint. My second aim is to quantitatively determine how the matrix properties and injection of the hydrogel affect the viability, self-renewal and differentiation of encapsulated mesenchymal stem cells (MSC) in vitro. The third aim will comprise the assessment of injectability and degradation of MSC-laden hydrogels in a subcutaneous mouse model and identification of an optimal formulation for cell delivery and maturation in vivo.In a broader perspective, this approach will be very useful to physically protect encapsulated cells from the repeated articular loading in vivo. To our knowledge, there is no existing double-network hydrogel that has the benefits of being both injectable and cytocompatible; thus, this system would be beneficial not only to cartilage repair, but also to other tissue environments.
Amount: CHF 75,970
Funding type: fellowship
Funder scheme: Early Postdoc.Mobility
Start date: 2017-01-01
End date: 2018-06-30
Investigator: Loebel, Claudia
Institution: Department of Bioengineering University of Pennsylvania
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 168819
OpenAlex ID: G3672495905