|Year : 2016 | Volume
| Issue : 2 | Page : 31-32
Recent trends in bone fracture therapeutics and management
Samiksha Wasnik, Naga B Goparaju
Division of Regenerative Medicine, Loma Linda University, Loma Linda, California, USA
|Date of Web Publication||27-Jun-2016|
Loma Linda University, Loma Linda, CA
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Wasnik S, Goparaju NB. Recent trends in bone fracture therapeutics and management. Dent Med Res 2016;4:31-2
Defects in the bone such as fractures can heal naturally, or spontaneously, in healthy individuals. However, in the cases of aging and osteoporosis, delayed-union or nonunion (fractures) pose a risk for serious secondary health concerns such as infections, pain, multiple surgeries, and prolonged hospitalization. Several therapeutic approaches are aimed at providing the best possible recovery with fewer complications during the treatment of the fracture. In this editorial article, we give our readers a comprehensive understanding of the recent trends of bone fracture management and therapies.
The current gold standard to treat a segmental or critical size defects is autologous bone grafting, which has a success rate considered to be 50-80%. The bone segment taken from patient's body contains osteoconductive and osteoinductive properties that aid in faster bone regeneration. However, the surgical procedure of autologous bone grafting can be laborious and present the risk for inherent postoperative infections, such as bleeding.
The alternative to the grafting approach is the use of a broad range of bone substitutes, which include biomaterials and scaffolds. Biomaterials hold a great potential for clinical application, including the treatment of nonunion fractures, with the use of scaffolds that are commonly constituted with collagen, hydroxyapatite, β-tri-calcium phosphate, bio-ceramics, biopolymer, bioactive glasses, bioactive composites, etc., However, these biological and synthetic scaffolds lack the efficient osteoinductive and osteogenic properties when compared to bone grafts. Alternatively, they provide the structural strength necessary for the regenerating bone by aiding cellular adhesion, proliferation, and differentiation, which over time are replaced by the newly generated bone. Although biomaterials partially mimic the structural microenvironment of the bone, the current challenge is to improve their biological aspects. Next generation biomaterials and scaffolds are being designed to match the topographical and biological features of bone at the nanoscale to achieve maximum biofunctionality and faster recovery.
Stem cell therapy is an alternative platform currently gaining momentum as a therapeutic approach to treat various bone defects, including fractures. Stem cells derived from various sources, such as bone marrow, adipose tissue, and peripheral blood, have the potential for use in regenerating broken bones. Among the different types of stem cells (both embryonic and adult stem cells) mesenchymal stem cells (MSCs) have been shown to have great potential to be used in cell therapies. MSCs, when influenced by the bone microenvironmental cues, can differentiate into functional osteoblastic cells and contribute to new bone formation. The use of MSCs derived from bone marrow has been well accepted in clinical trials. However, more advanced strategies now focus on identifying the precursor cells of the MSCs and understanding the mechanism by which MSCs maintain tissue homeostasis during healing and repair. In this regard, research of specialized subsets purified from total MSC with relatively higher osteogenic potential is being identified and studied. Advance methods of cell-specific lineage tracing are now employed to recognize, MSCs subtypes that have an efficient homing and engraftment potential. Using multichromatic flow cytometry, specific subsets can be purified, expanded in vitro, and subsequently injected systemically to treat the fractures. Certain biomolecules, such as bone morphogenic proteins (BMPs), and growth factors regulate the bone metabolism and stimulate the differentiation of MSCs to osteoblasts. Supplementation with these growth factors further contributes to faster recovery by activation of resident MSCs and increases their osteoinduction properties. Several ongoing clinical trials involve the use of autologous MSCs-loaded with a carrier, or incorporated with BMP2 like factors, for the treatment of fractures and other defects. The next generation of stem cell therapy with MSCs may involve the use of specialized osteogenic precursor cells. The focus would also be in advancing technologies for achieving an improved and maximum engraftment with reduced cell numbers. Stem cell therapies may also be incorporated with bioengineering techniques to modulate the bone microenvironment (cellular, acellular, and molecular factors) and/or induce synthesis and secretion of differentiation/growth factors that facilitate faster bone recovery.
Apart from the cellular and molecular techniques mentioned above to treat bone fractures, several high-throughput technologies involving the use of innovative approaches through cutting edge instruments have begun to receive more attention. Low-intensity pulsed ultrasound (LIPUS) in fracture healing is one such promising new therapy and is found to have a beneficial effect on normal fracture healing. LIPUS accelerates normal fracture healing as well as promotes healing in compromised tissue beds. Treating osteoblasts with LIPUS demonstrated increased calcium incorporation in cultured bone cells, thus contributing to fracture healing. Biophysical techniques such as electric and electromagnetic fields (EMF) have been shown to regulate extracellular matrix synthesis and may be useful in clinical setups in stimulating fracture repairs and nonunions. By regulating proteoglycan and collagen synthesis in endochondral ossification, electric and EMF are found to increase bone formation.
In this article, we have summarized the recent trends and therapeutic approaches applied in the management of bone fracture, which include the use of autografts, potential for stem cell subsets, growth factors, and high-throughput biophysical technologies. In the future, use of these advance therapies in the bone regeneration will have the potential to simulate normal bone formation with reduced morbidity and improved bone union in the long-term, and maximize the overall recovery process.
| Authors|| |
Dr. Samiksha Wasnik