ARRA IMPACT REPORT:
Regenerative Medicine in Musculoskeletal Diseases
Public Health Burden
Regenerative medicine, a field of study focused on stimulating the natural healing processes of the body or regenerating tissues in laboratory conditions for subsequent implantation, holds considerable promise as treatments for debilitating bone, joint, and muscle disorders. Most recently, approaches have focused on the potential of stem cells and biomolecules, as well as new bioengineering technologies developed by multi-disciplinary teams, to mend complex fractures, heal torn cartilage or connective tissues, or regenerate skeletal muscle.
Molecular and Cellular Approaches to Regenerative Medicine
A better understanding of molecular and cellular processes, as well as the biological, chemical, and mechanical conditions that affect cell behavior, will allow scientists to guide and enhance tissue repair. Approaches have focused on particular cells that can renew themselves, as well as differentiate into more specialized cells. Examples of ARRA-funded research include:
- Bone Regeneration Strategies: Characterizing the relative regenerative capacity of stem cells from fetal and adult tissue, and assessing the effectiveness of different strategies for their delivery for bone regeneration.1 This project has led to several papers that could set a foundation for new strategies to repair large sections of damaged bone or control bone formation as part of spinal fusion surgery.
- Characterization of Factors Related to the Development of Bone Cells: Identifying specific biomaterial surface characteristics and biophysical signals that cause stem cells to become bone cells.2 In addition to permitting researchers to expand their original line of inquiry to better understand factors that influence cell responses, the ARRA award enabled a high school biology teacher to obtain hands-on laboratory training that he is now incorporating into his classroom curriculum.
- RNA Molecules and Bone Formation: Identifying how fragments of RNA influence the development and maturation of bone-forming cells.3 In addition to supporting initial efforts to characterize an intricate system of genes, proteins, and RNA molecules that control bone formation and maintenance, the two-year ARRA award sustained the research team until they could apply for a second five-year NIH grant.
- Mechanisms for Cartilage Repair: Defining the cellular, molecular, and mechanical processes that control cartilage repair following an injury.4 This project is providing information about the factors that control whether cells become bone or cartilage, and the differences between newly repaired and more mature tissue.
- Effects of Mechanical Environment on Tissue Development: Developing strategies to monitor and maintain cartilage and meniscal tissue development during movement and weight-bearing activities.5,6 Such research is an essential component of efforts to engineer tissue replacements that can survive and function in the complex and demanding mechanical environment of the native tissue.
Biomaterial and Scaffold Development
In addition to basic research focused on the molecules and cells involved in the healing process, the creation of biomaterials and scaffolds that support the structural and functional development and maintenance of regenerated or repaired tissues is also important. Examples of ARRA-funded research on the development of new regenerative medicine technologies include:
- Implantable Micropump to Support Long-Term Muscle Regeneration: Mass-producing an implantable micropump prototype to determine if it can effectively deliver molecules that control muscle regeneration on a long-term basis.7 Published results will inform the development of related pumps that can be used when testing potential regenerative therapies.
- Insights into Bone Graft Integration: Examining a cell process thought to influence how grafts are integrated into damaged bone to improve the healing of complex fractures.8 The research has demonstrated that a pathway involved in limb development also participates in bone healing, and is providing other insights that might be leveraged to develop new cell-based therapies.
- Scaffolding to Direct Appropriate Tissue Architecture Development: Producing a multi-component scaffold that can maintain structural integrity and direct appropriate tissue architecture, while promoting tissue formation throughout the regeneration period.9 Scaffolds that are amenable to the addition of different kinds of compounds will assist researchers as they engineer hard-to-heal musculoskeletal tissues.
- Knee Joint Bioengineering: Engineering a meniscus that cushions the knee joint and more closely mimics native tissue.10 Published findings from this ARRA-funded grant will provide a basis for subsequent efforts.
Contributing NIH Institutes & Centers
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)