Abstract
Recombinant bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive growth factor that can promote bone regeneration for challenging skeletal repair and even for ectopic bone formation in spinal fusion procedures. However, serious clinical side effects related to supraphysiological dosing highlight the need for advances in novel biomaterials that can significantly reduce the amount of this biologic. Novel biomaterials could not only reduce clinical side effects but also expand the indications for use of BMP-2, while at the same time lowering the cost of such procedures. To achieve this objective, we have developed a slurry containing a known supramolecular polymer that potentiates BMP-2 signaling and porous collagen microparticles. This slurry exhibits a paste-like consistency that stiffens into an elastic gel upon implantation making it ideal for minimally invasive procedures. We carried out in vivo evaluation of the novel biomaterial in the rabbit posterolateral spine fusion model, and discovered efficacy at unprecedented ultra-low BMP-2 doses (5 μg/implant). This dose reduces the growth factor requirement by more than 100-fold relative to current clinical products. This observation is significant given that spinal fusion involves ectopic bone formation and the rabbit model is known to be predictive of human efficacy. We expect the novel biomaterial can expand BMP-2 indications for difficult cases requiring large volumes of bone formation or involving patients with underlying conditions that compromise bone regeneration.
| Original language | English (US) |
|---|---|
| Article number | 122357 |
| Journal | Biomaterials |
| Volume | 302 |
| DOIs | |
| State | Published - Nov 2023 |
Funding
This work was generously supported by the Center for Regenerative Nanomedicine (CRN) at the Simpson Querrey Institute. Research reported in this manuscript was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Center of the National Institutes of Health under award number R01AR072721. We would like to thank Medtronic (Spine Division) for partial financial support of the in vivo studies. Dr. Wei Ji is a postdoctoral fellow of the Research Foundation Flanders (12G2718 N), and received a Travel Grant of Long Stay Abroad (V468915 N) from the Research Foundation Flanders (FWO-Vlaanderen), Junior Mobility Program (JuMo) of KU Leuven (JUMO-15-0514), and a research grant (No.1721-2022) from International Team of Implantology (ITI). Peptide amphiphile synthesis was performed at the Peptide Synthesis Core Facility, and in vitro data was collected in Analytical bioNanotechnology Equipment Core (ANTEC) of the Simpson Querrey Institute at Northwestern University, which has current support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS – 1542205). This work made use of the EPIC facility of Northwestern University's NUANCE Center which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. Micro CT Imaging was performed by Chad R Haney of Northwestern University's Center for Advanced Molecular Imaging generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. Multiphoton microscopy was performed on a Nikon A1R multiphoton microscope, acquired through the support of NIH 1S10OD010398-01. This work was generously supported by the Center for Regenerative Nanomedicine (CRN) at the Simpson Querrey Institute. Research reported in this manuscript was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Center of the National Institutes of Health under award number R01AR072721 . We would like to thank Medtronic (Spine Division) for partial financial support of the in vivo studies. Dr. Wei Ji is a postdoctoral fellow of the Research Foundation Flanders ( 12G2718 N ), and received a Travel Grant of Long Stay Abroad ( V468915 N ) from the Research Foundation Flanders (FWO- Vlaanderen ), Junior Mobility Program (JuMo) of KU Leuven ( JUMO-15-0514 ), and a research grant (No. 1721-2022 ) from International Team of Implantology (ITI). Peptide amphiphile synthesis was performed at the Peptide Synthesis Core Facility, and in vitro data was collected in Analytical bioNanotechnology Equipment Core (ANTEC) of the Simpson Querrey Institute at Northwestern University , which has current support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource ( NSF ECCS – 1542205 ). This work made use of the EPIC facility of Northwestern University's NUANCE Center which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource ( NSF ECCS-1542205 ); the MRSEC program ( NSF DMR-1121262 ) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. Micro CT Imaging was performed by Chad R Haney of Northwestern University's Center for Advanced Molecular Imaging generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. Multiphoton microscopy was performed on a Nikon A1R multiphoton microscope, acquired through the support of NIH 1S10OD010398-01 .
ASJC Scopus subject areas
- Biophysics
- Bioengineering
- Ceramics and Composites
- Biomaterials
- Mechanics of Materials