Abstract
Regeneration of hyaline cartilage in human-sized joints remains a clinical challenge, and it is a critical unmet need that would contribute to longer healthspans. Injectable scaffolds for cartilage repair that integrate both bioactivity and sufficiently robust physical properties to withstand joint stresses offer a promising strategy. We report here on a hybrid biomaterial that combines a bioactive peptide amphiphile supramolecular polymer that specifically binds the chondrogenic cytokine transforming growth factor β-1 (TGFβ-1) and crosslinked hyaluronic acid microgels that drive formation of filament bundles, a hierarchical motif common in natural musculoskeletal tissues. The scaffold is an injectable slurry that generates a porous rubbery material when exposed to calcium ions once placed in cartilage defects. The hybrid material was found to support in vitro chondrogenic differentiation of encapsulated stem cells in response to sustained delivery of TGFβ-1. Using a sheep model, we implanted the scaffold in shallow osteochondral defects and found it can remain localized in mechanically active joints. Evaluation of resected joints showed significantly improved repair of hyaline cartilage in osteochondral defects injected with the scaffold relative to defects injected with the growth factor alone, including implantation in the load-bearing femoral condyle. These results demonstrate the potential of the hybrid biomimetic scaffold as a niche to favor cartilage repair in mechanically active joints using a clinically relevant large-animal model.
| Original language | English (US) |
|---|---|
| Article number | e2405454121 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 121 |
| Issue number | 33 |
| DOIs | |
| State | Published - Aug 13 2024 |
Funding
(IIN); the Keck Foundation; and the State of Illinois, through the IIN. Imaging was carried out at the Center for Advanced Microscopy at Northwestern University, which is supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. X-ray scattering experiments were carried out at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the APS. DND-CAT is supported by Northwestern University, E.I. DuPont de Nemours & Co., and The Dow Chemical Company. Use of APS, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. This research was supported through a gift from the Shannon Family Fund for Bio-Inspired and Bioactive Materials Systems for Musculoskeletal Regeneration. J.A.L. acknowledges financial support from an NSF Graduate Research Fellowship (grant DGE-1324585). Portions of this article were used in the PhD dissertation of J.A.L. We thank Alex Glittenberg and Anne Pankowski for assistance in animal care, animal surgery, and data analysis. We also acknowledge Hiroaki Sai for advice relating to SAXS experiments data analysis and Charlotte Chen for providing fluorescently tagged PA molecules. Materials synthesis and characterization were performed at the Peptide Synthesis Core Facility and the Analytical BioNanoTechnology Core at the Simpson Querrey Institute at Northwestern University. The Simpson Querrey Institute, Northwestern University Office for Research, U.S. Army Research Office, and the U.S. Army Medical Research and Materiel Command have provided funding to develop both of these facilities and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS \u2013 1542205). Histological samples were prepared by the UW Translational Research Initiatives in Pathology laboratory, supported by the UW Department of Pathology and Laboratory Medicine, UW Carbone Cancer Center (P30 CA014520). Electron microscopy was performed at the EPIC facility of the Northwestern NUANCE center and chemical characterization was performed at IMSERC at Northwestern University, which have received support from ShyNE Resource (NSF ECCS\u20141542205); the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. Imaging was carried out at the Center for Advanced Microscopy at Northwestern University, which is supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. X-ray scattering experiments were carried out at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the APS. DND-CAT is supported by Northwestern University, E.I. DuPont de Nemours & Co., and The Dow Chemical Company. Use of APS, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. ACKNOWLEDGMENTS. This research was supported through a gift from the Shannon Family Fund for Bio-Inspired and Bioactive Materials Systems for Musculoskeletal Regeneration. J.A.L. acknowledges financial support from an NSF Graduate Research Fellowship (grant DGE-1324585). Portions of this article were used in the PhD dissertation of J.A.L. We thank Alex Glittenberg and Anne Pankowski for assistance in animal care, animal surgery, and data analysis. We also acknowledge Hiroaki Sai for advice relating to SAXS experiments data analysis and Charlotte Chen for providing fluorescently tagged PA molecules. Materials synthesis and characterization were performed at the Peptide Synthesis Core Facility and the Analytical BioNanoTechnology Core at the Simpson Querrey Institute at Northwestern University.The Simpson Querrey Institute,Northwestern University Office for Research,U.S.Army Research Office, and the U.S. Army Medical Research and Materiel Command have provided funding to develop both of these facilities and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS \u2013 1542205). Histological samples were prepared by the UW Translational Research Initiatives in Pathology laboratory, supported by the UW Department of Pathology and Laboratory Medicine, UW Carbone Cancer Center (P30 CA014520). Electron microscopy was performed at the EPIC facility of the Northwestern NUANCE center and chemical characterization was performed at IMSERC at Northwestern University, which have received support from ShyNE Resource (NSF ECCS\u20141542205); the International Institute for Nanotechnology
Keywords
- cartilage regeneration
- peptide amphiphiles
- self-assembly
- supramolecular biomaterials
ASJC Scopus subject areas
- General
