Targeting of Endogenous Stem Cells for Segmental Bone Fracture Repair
Bone tissue, which provides major structural and supportive connective tissue to the body, can be lost due to cancer or trauma. When the edges of a fracture are close to each other, bone repair cells are capable of healing the injury. However, when a large piece of bone is missing, these cells cannot bridge the necessary gap for healing, resulting in the need for bone grafting—the current gold-standard therapy.
Bone grafting can be complicated, as bone cells are not always available and their harvest, usually from the pelvic bone, can lead to prolonged pain. The Gazit Laboratory is developing a novel approach for the treatment of bone fractures without the need for bone grafting. Stem cells are recruited to the fracture site using a collagen matrix and then a bone-forming gene is directly delivered to the stem cells using an ultrasound pulse. This proposed therapy has the potential to generate rapid healing of segmental bone fractures and significantly decrease patient hospitalization, loss of working days and significant healthcare costs. In addition, this therapeutic intervention can be repeated several times when needed in order to deal with severe cases of bone loss. The research is supported by a grant from National Institutes of Health (NIH)/National Institute of Biomedical Imaging and Bioengineering (#R01EB026094) entitled "Ultrasound-Guided DNA Delivery for Regenerative Medicine" and Department of Defense (#W81XWH-18-1-0593) entitled "Ultrasound-Mediated Nanobiomaterial Delivery for Segmental Bone Fracture Repair."
Noninvasive Method for Diagnosing Low Back Pain
More than 85 percent of the United States population suffers from low back pain, much of which is caused by intervertebral disc degeneration. Disc degeneration is a progressive condition, resulting in chronic pain in the back and neck. For some patients, degeneration can occur for years before pain sets in, presenting symptoms, while others are affected almost immediately. Currently, identifying the exact disc that is the source of pain involves painful and invasive diagnostic procedures, in which physicians inject a contrast agent or non-toxic dye into patients’ spinal discs.
Knee Cartilage Resurfacing Utilizing Bio-Scaffolds
The use of implanted devices in orthopedics to alleviate pain and restore joint function has grown dramatically in recent times. Driven by worldwide aging populations and increasing prevalence of physically active lifestyles, the clinical need for orthopedic implants continues to increase.
Knee osteoarthritis continues to pose a major clinical challenge. The Gazit Lab proposes to expand the usability of meniscal allograft-based arthroplasty (MABA) to knee cartilage resurfacing in order to elucidate some of the cellular processes mediating the therapeutic effect of MABA. By improving our understanding of these processes, the Gazit Lab could potentially improve current clinical practice and develop novel therapeutic approaches to treat arthritis, eliminate pain and restore joint function.
Reconstruction of Massive Bone Loss in the Jaws Utilizing Bone Allografts and a Recombinant Hormone
Massive craniofacial bone loss poses a clinical challenge to neurosurgeons and maxillofacial surgeons alike. Structural bone allografts are readily available at tissue banks but are rarely used in such cases due to a high failure rate. Previous studies showed that intermittent administration of recombinant parathyroid hormone (rPTH) enhanced integration of allografts in a murine model of calvarial bone defect. Our studies aim to assess the hypothesis that rPTH would enhance integration of a mandibular allograft in a clinically relevant model of mandibulectomy in a large animal. Porcine bone allografts are generated at a veterinary tissue bank and implanted in a 5-cm-long noncontinuous bone defect that had been created in the mandible of minipigs. To date, our results showed formation of more bone in the animals treated with rPTH, all biomechanical properties of bone were higher in the rPTH group. This is an ongoing study, but at this point we can affirm that a daily dose of rPTH induced integration of mandibular allografts in a large animal model of mandibulectomy.
Human Induced Pluripotent Stem Cells (iPSC) Can Be Differentiated into Notochordal Cells that Reduce Intervertebral Disc Degeneration in a Porcine Model
In a recently published paper, the Gazit Lab reports a stepwise differentiation method to generate notochordal cells (iNCs) from human iPSCs. These cells not only demonstrate a sustainable notochordal cell phenotype in vitro and in vivo, but also show the functionality of notochordal cells and have protective effect in case of induced disc degeneration and prevent the change in the pH level of the injected intervertebral discs (IVD).