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 RCCC Limb Salvage and Regeneration Bone Projects

Clinical Challenges Project Proposed Therapies
Segmental bone loss Advanced degradable scaffolds for repair of bone defects Biodegradable polymeric scaffolds and composites of polymers with inorganic fillers
Bone defects Optimizing cell sources for repair of bone defects Bone marrow excavation; separation methods; selective retention in scaffolds of above project
Bone injury
Molecular Surface Design (MSD) for controlled cell- and tissue-scaffold interactions Protein-based growth factor- molecular surface design; Peptide-based- molecular surface design



Advanced Degradable Scaffolds for Repair of Bone Defects

Sometimes, the body’s natural processes are not enough to repair a fracture site.  This project seeks to repair fractured bone by implanting a scaffold to support growth of both adjacent bone cells and transferred bone marrow cells and more effectively bridge bone defects.

The scaffolds are fabricated from new synthetic biomaterials that are specifically selected and designed to stimulate and guide the attachment and migration of bone forming cells and new blood vessels into the repair site. As the bone regenerates, the scaffolds are designed to degrade harmlessly, leaving only natural tissue behind.  Enhancements to the scaffolds include new polymer materials, new three dimensional structures that mimic natural bone.


Scaffolds to Aid the Formation
of
New Bone in Injury Sites

Cleveland Clinic, Orthopaedic and Rheumatologic Research Center and the Clinical Tissue Engineering Center, George Muschler, MD

Mayo Clinic, Tissue Engineering and Biomaterials Laboratory, Michael Yaszemski, MD, PhD  

Rutgers, New Jersey Center for Biomaterials, Joachim Kohn,  PhD

MIT, Biotech/Pharma Engineering Center, Linda Griffith, PhD


Trident Biomedical, Inc.


Integra Spine, Akron, OH


BonWrx, Inc., Phoenix, AZ




Optimizing Cell Sources for Repair of Bone Defects

Cells that are capable of forming new bone tissue, called osteogenic connective tissue progenitors (CTP-Os), are essential to successful bone formation.  This project focuses on developing new practical clinical tools for the harvesting, processing, selection and concentration of osteogenic connective tissue progenitor cells (CTP-Os) which are critical for bone repair.  The researchers are comparing current techniques for harvesting and manipulating CTP-Os from bone marrow, developing new methods, and determining which practices provide the most effective source of CTP-Os for combination with existing scaffolds and for new scaffolds being developed in related AFIRM projects.


Machine used for rapid concentration and selection of stem cells in the operating room

Cleveland Clinic, Orthopaedic and Rheumatologic Research Center and the Clinical Tissue Engineering Center, George Muschler, MD


Integra Spine, Akron, OH





Molecular Surface Design (MSD) for Controlled Cell- and Tissue-Scaffold Interactions

The goal of this project is to develop a molecular surface design method to improve control over the response of cells and tissues to implanted materials.  Specifically, these researchers attach bioactive materials to the surface of bone scaffolds.
The surface coatings involve attaching molecules that stimulate the attachment, growth and survival of bone forming cells (osteogenic connective tissue progenitors, aka CTP-Os) and offer a potent method for further improvement upon the advanced scaffolds being developed in other AFIRM projects.


Protein molecules tethered to
the surface of a scaffold

Cleveland Clinic, Orthopaedic and Rheumatologic Research Center and the Clinical Tissue Engineering Center, George Muschler, MD

MIT, Biotech/Pharma Engineering Center, Linda Griffith, PhD

Stony Brook University, Center of Tissue Engineering,
Director, Richard Clark, MD

Rutgers, New Jersey Center for Biomaterials, Joachim Kohn,  PhD

Integra Spine, Akron, OH