July 2025

ORTHOPAEDICS

PEPTIDE AMPHIPHILES AS A NEW CLASS OF BIOLOGICS FOR BONE REGENERATIVE MEDICINE

At a recent Grand Rounds, Erin L. K. Hsu, PhD, discussed a novel class of biologics — peptide amphiphiles (PAs)— as a promising solution for improving bone regeneration, particularly in challenging environments such as spinal fusion surgeries.
Dr. Hsu’s research, supported by NIH and NSF grants, focuses on improving healthspan through regenerative nanomedicine.

Addressing the Challenges of Spinal Disorders
As scientists continue to explore regenerative solutions, spinal deformities remain a significant concern. In establishing the context for her study, Dr. Hsu drew upon existing literature that underscores the prevalence and significance of postoperative complications in adult spinal deformity patients: a retrospective review of 695 patients with adult spinal deformity highlights the impact of readmissions, with a 24% readmission rate due to postoperative complications.

The data reveal staggering increases in the financial costs of readmission:
  • Pseudarthrosis: 105% increase
  • Infection: 72% increase
  • Proximal junctional kyphosis: 63% increase

These findings emphasize the urgent need for advanced therapeutic strategies that reduce costs and improve patient outcomes. The success of spine fusion is highly variable, demanding more robust osteoinductive responses to overcome challenging healing environments.

Minimally Invasive Surgery: Redefining Indications in Spine Care
Minimally invasive surgery offers innovative possibilities in spinal treatments but comes with limitations:
  • Restricted access to affected areas
  • Decreased surface area for bone bridging
  • Lack of autograft availability
  • Challenging healing environment, reducing margin for error
  • Biologic handling properties that play a critical role in surgical success

These constraints necessitate biologics that can overcome structural and regenerative challenges to enhance spinal fusion success rates.

Self-Assembled PA Nanofibers for Bone Repair
A major breakthrough in regenerative medicine, led by the laboratory of Samuel L. Stupp,PhD, involves self-assembled peptide nanofibers, which mimic the structure, dynamics and bioactivity of natural extracellular matrices. These nanofiber solutions transform into gels when injected into lesion sites, localizing regenerative signals and fostering osteoinductive properties crucial for bone repair. The Hsu group has collaborated with the Stupp research team over the past decade, translating this platform technology to develop materials for bone regenerative medicine, with a focus on spinal fusion. 

The development of BMP-2 binding peptide amphiphile nanofibers for spinal arthrodesis further underscores PAs’ potential to improve tissue regeneration. When implanted in the spine, the bone regenerative material spontaneously forms a scaffold which mimics the natural matrix on which cells grow.  The PAs in that synthetic matrix deliver signals to local stem cells, directing them to become bone-forming osteoblast cells.  Over a period of weeks, the PAs biodegrade into harmless amino acids and lipids, while new bone is mineralized in its place.  

Unlike other products which require high doses of recombinant BMP-2 in order to achieve clinical success, the PA material promotes successful fusion without the side effects associated with high doses of growth factor proteins. The team is now working with the FDA to translate this material into the clinic through their startup company, Amphix Bio.

Driving Research Convergence
Northwestern Medicine Center for Regenerative Nanomedicine, formerly Simpson Querrey Institute, fosters interdisciplinary collaboration to develop novel regenerative medicine approaches and breakthroughs for degenerative diseases.

As PAs pave the way for more effective biologic solutions, the convergence of scientific research and clinical application is poised to significantly improve the treatment of spinal disorders and bone repair. By harnessing nanotechnology and synthetic extracellular matrices, regenerative medicine is inching closer to a reality where patients not only live longer — but live better.
 
For more information, visit the Hsu Lab.
Erin L K Hsu, PhD
Research Associate Professor, Orthopaedic Surgery
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