when implants are drilled into bone, which then heals from the trauma and grows around the membrane. Other options that have been experimented with for this purpose are biodegradable materials such as collagen gels; polyurethane, polyglycolic acid, polyorthoester, and several polymers of polyactic and polygalactic acid were tested. After insertion of the polymer within the tissue, the degradation rate and curve are incumbent on the wound site and cannot be controlled. The rate at which the phagocytes absorb the polymer is a variable that is different every time the therapy is administered. In light of this, e-PTFE was chosen as the most efficient vector for delivery of these stem cells into the site of the wound. The stem cells are a mixture of osteogenic progenitor cells and mitogenic mesenchymal stem cells that are derived from the marrow of the patient. Dentistry is a field that avidly uses GBR for bone regeneration.
GBR was tested first in animal models of bone regeneration of cranofacial skeletal tissue. With e-PTFE and osteogenic progenitor cells, mice were able to complete the union of the bone tissue without the formation of scar tissue. With the success of in vivo models, several clinical trials were approved for testing the GBR technology. In 2009, a clinical trial was approved to test the effect of GBR in the presence of BMP and in the absence of it. Eleven patients were recruited for the trial. They received 34 implants in total at sites exhibiting lateral bone growth. A collagen membrane with xenogenic bone material was used. The use and efficiency of BMP was tested in the process. This is a five-year trial in which the patients were followed for acceptance of the implant and tested to determine if the efficiency of healing was higher in the presence of BMP. It was found that there was no significant difference between the two groups, suggesting that BMP is not essential to GBR.
Scaffolds and Bone Substitutes
Scaffolds and bone substitutes are biomaterials that are similar to bone, which, when inserted at the site of the wound, stimulate regeneration in addition to providing structure for the growing tissue. A significant advantage of this method is that it does not trigger immunogenicity, though it is an invasive process in which the scaffold is inserted surgically. Bone substitutes such as β-TCP, calcium phosphate cement, and glass ceramics are used as bone substitutes because it has been proven that these agents promote cellular proliferation, migration, and differentiation to bone cells. Other non-biological materials used include porous tantalum, which provides structure and a robust substrate for the growth of bone.
The REBORNE project (Regenerating Bone Defects Using New Biomedical Engineering Approaches), funded by the European Commission and coordinated by Inserm, recently gained approval for a clinical trial in which stem cells from patients will be isolated from the bone marrow. These cells will consist of a heterogeneous mixture of mesenchymal stem cells and osteogenic progenitor cells. These cells will be treated with growth hormones in the lab to facilitate the differentiation to bone cells. The cells will then be applied to a scaffold that provides a structure for the progenitor cells to differentiate and proliferate. These scaffolds will be surgically inserted at the wound site and the cells will continue to grow and heal the fracture, resulting in the union of the bone. The trial kicked off in January 2010; it is a five-year trial for which patients with fractures from trauma will be recruited. The effective healing of the wound and union of the fracture will be assessed to ascertain the efficiency of the scaffold.
Clinical Trials
Clinical trials are devised to test the effectiveness of the treatment option that has been developed. The efficiency and robustness of the method is judged based on the healing time, the quality of the regenerated bone, and the efficacy of acceptance of the bone graft/biomaterial in the body. Some of the important considerations are to test patients who have given their informed consent and to determine that the variables that will interfere with the treatment options are constant. Different lengths and periods of time are tested to analyze the best form of therapy administration. When designing clinical trials, it is also important to consider the ethical policies of each country. For example, the policies on the use of human embryos and stem cells derived from them are very different in the United States compared to the European Union (EU). For studies dealing with bone regeneration clinical trials, the period for assessing the immune acceptance of the graft/biomaterial is between six and 12 weeks. The efficacy of the bone regeneration is tested by analyzing the bone density and constitution of the fresh bone. Of course, healing of the fractures is the main goal. Another factor is assessing the formation of scar tissue that might get in the way of function restoration. This is important in dealing with therapies for regeneration of the hip and joints. And, last but not least, infections during the procedure need to be prevented, in addition to targeting a therapy with a reduced pain factor.
Some of the future technologies and patents include use of porous metals that form the basic structure on which the stem cells form the regeneration. The metal provides support and structure to the developing cells.
Sharanya Kumar
Independent Scholar
See Also: Bone: Cell Types Composing the Tissue; Bone: Current Research on Isolation or Production of Therapeutic Cells; Bone: Development and Regeneration Potential; Bone: Major Pathologies; Bone: Stem and Progenitor Cells in Adults; Bone Marrow Transplants.
Further Readings
Dimitriou, R., E. Jones, D. McGonagle, and P. V. Giannoudi. “Bone Regeneration: Current Concepts and Future Directions.” BMC Medicine, v.9/66 (2011).
La, W. G., et al. “Delivery of Bone Morphogenetic Protein-2 and Substance P Using Graphene Oxide for Bone Regeneration.” International Journal of Nanomedicine, v.9/Supp. 1 (2014).
Bone: Major Pathologies
Bone: Major Pathologies
123
126
Bone: Major Pathologies
The bones are multifunctional organs of the body that are a part of the endoskeleton. They are composed of cortical (compact) bone and cancellous (spongy) bone. Cortical bone is the outer hard covering, which gives bones the characteristic white color. Cancellous bone is the inner part of the bone, which is composed of a porous network in which the blood vessels and bone marrow are located. The bones have many essential functions. They act as a protective barrier for vital organs such as the brain and heart. They are required for structure and movement of the human body. The major function of the bone is hematopoiesis, which is the production of red blood cells (RBC) and white blood cells (WBC). Therefore, disorders of the bones can have highly detrimental effects in the body and can lead to death. Stem cells have great potential in the recovery of normal function after treatment of a bone disease. During the course of disease, there is death of essential cells and a decrease in normal function. Hematopoietic stem cells can be implanted after chemotherapy to regain normal WBC and RBC production. This article explains some of the major pathologies affecting bone.
Osteoporosis
Osteoporosis is the most common bone disease. The incidence is much higher in females than in males. In this disease, there is a loss of bone density, resulting in weak bones that are highly susceptible to fractures. Osteoporosis is a disease of age, as it mostly affects elderly humans. This is due to progressive loss of bone composition with age due to decreased locomotion, inadequate nutrition, and decreased production of hormones such as estrogen in the case of postmenopausal women. It can be divided into two types. Primary osteoporosis can be characterized into postmenopausal, senile, and idiopathic. Secondary osteoporosis is associated with underlying disorders such as endocrine, gastrointestinal, use of certain chemotherapeutic drugs, and neoplasia. Pathophysiology includes five major factors. The peak bone mass is influenced by nutrition and physical activity. Individuals with decreased levels of dietary calcium, vitamin D, and increased levels of PTH are at a greater risk of developing osteoporosis. In addition, low levels of physical activity cause a loss of bone because the force associated with activity helps the essential process of bone remodeling. Genetic factors