Abstract
Although autologous chondrocyte transplantation can be effective in articular cartilage repair, negative side effects limit the utility of the treatment, such as long recovery times, poor engraftment or chondrogenic dedifferentiation, and cell leakage. Peptide-based supramolecular polymers have emerged as promising bioactive systems to promote tissue regeneration through cell signaling and dynamic behavior. We report here on the development of a series of glycopeptide amphiphile supramolecular nanofibers with chondrogenic bioactivity. These supramolecular polymers were found to have the ability to boost TGFβ-1 signaling by displaying galactosamine moieties with differing degrees of sulfation on their surfaces. We were also able to encapsulate chondrocytes with these nanostructures as single cells without affecting viability and proliferation. Among the monomers tested, assemblies of trisulfated glycopeptides led to elevated expression of chondrogenic markers relative to those with lower degrees of sulfation that mimic chondroitin sulfate repeating units. We hypothesize the enhanced bioactivity is rooted in specific interactions of the supramolecular assemblies with TGFβ-1 and its consequence on cell signaling, which may involve elevated levels of supramolecular motion as a result of high charge in trisulfated glycopeptide amphiphiles. Our findings suggest that supramolecular polymers formed by the ultra-sulfated glycopeptide amphiphiles could provide better outcomes in chondrocyte transplantation therapies for cartilage regeneration. Statement of significance: This study prepares glycopeptide amphiphiles conjugated at their termini with chondroitin sulfate mimetic residues with varying degrees of sulfation that self-assemble into supramolecular nanofibers in aqueous solution. These supramolecular polymers encapsulate chondrocytes as single cells through intimate contact with cell surface structures, forming artificial matrix that can localize the growth factor TGFβ-1 in the intercellular environment. A high degree of sulfation on the glycopeptide amphiphile is found to be critical in elevating chondrogenic cellular responses that supersede the efficacy of natural chondroitin sulfate. This work demonstrates that supramolecular assembly of a unique molecular structure designed to mimic chondroitin sulfate successfully boosts chondrocyte bioactivity by single cell encapsulation, suggesting a new avenue implementing chondrocyte transplantation with supramolecular nanomaterials for cartilage regeneration.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 103-115 |
| Number of pages | 13 |
| Journal | Acta Biomaterialia |
| Volume | 189 |
| DOIs | |
| State | Published - Nov 2024 |
Funding
This research was primarily supported by a gift from Mike and Mary Sue Shannon to the Simpson Querrey Institute at Northwestern University for research on musculoskeletal regeneration. Additional support was provided by the Center for Regenerative Nanomedicine at the Simpson Querrey Institute. The study resulting in this publication was also assisted by a grant from the Undergraduate Research Grant Program which is administered by Northwestern University's Office of Undergraduate Research. We acknowledge the support by the following core facilities at Northwestern University: the Peptide Synthesis Core Facility and Analytical bioNanoTechnology Equipment Core (ANTEC) Facility of the Simpson Querrey Institute, which has current support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), Keck Biophysics Facility, a shared resource of the Robert H. Lurie Comprehensive Cancer Center supported in part by the NCI Cancer Center Support Grant #P30 CA060553, Biocryo facility of NUANCE Center and IMSERC facility which have received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern's MRSEC program (NSF DMR-1720139), High Throughput Analysis Laboratory, and Flow Cytometry Core Facility. X-ray experiments were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University, The Dow Chemical Company, and DuPont de Nemours, Inc. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Data was collected using an instrument funded by the National Science Foundation under Award Number 0960140. Research reported in this publication was supported by the Chemistry of Life Processes Predoctoral Training Program at Northwestern University. The content is solely the responsibility of the authors and does not necessarily represent the official views of Northwestern University.
Keywords
- Articular cartilage degeneration
- Chondrocyte transplantation
- Peptide amphiphile
- Single-cell encapsulation
- Supramolecular polymerization
ASJC Scopus subject areas
- Biotechnology
- Biomaterials
- Biochemistry
- Biomedical Engineering
- Molecular Biology