three main types of bone grafting techniques: (1) In the autologous bone graft: The graft is taken from bones of the same individual requiring the procedure. The bones used for harvesting of the graft include the mandible, ribs, iliac crest, and the fibula. (2) In the allograft, the graft is obtained from an individual other than the beneficiary. An allograft can also be taken from bone donors after their death. There are three types of an allograft; namely, fresh or fresh-frozen bone, freeze-dried bone, and demineralized freeze-dried bone. (3) The xenograft requires the use of a bone graft taken from an animal source other than the human species.
Distraction Osteogenesis. This method is applicable when there is a large skeletal defect or a fractured bone with separated ends. External fixators, intra-medullary nails, and intra-medullary lengthening devices are all devices that are surgically fixed to the damaged bone, but this is a prolonged treatment and technically is quite demanding.
Mesenchymal Stem Cell Implantation. There is a possibility of utilizing autologous MSCs in regeneration of bones. The process involves isolating and then purifying the MSCs of an individual, expanding them in vitro by producing cultures, and then implanting them into the bone defect with the help of a suitable carrier.
Ammara Iftikhar
Aaiza Iftikhar
Aamir Aslam
Pakistan Medical and Dental Council
See Also: Bone: Cell Types Composing the Tissue; Bone: Existing or Potential Regenerative Medicine Strategies; Bone: Stem and Progenitor Cells in Adults.
Further Readings
Dimitriou, Jones, et al. “Bone Regeneration: Current Concepts and Future Directions.” BMC Medicine, v.9 (2011).
Saladin, Kenneth. “Anatomy and Physiology: The Unity of Form and Function.” New York: McGraw-Hill, 2012.
Soucacos, P. N., E. O. Johnson, and G. Babis. “An Update on Recent Advances in Bone Regeneration.” Injury, v.39/2 (September 2008).
Bone: Existing or Potential Regenerative Medicine Strategies
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Bone: Existing or Potential Regenerative Medicine Strategies
Bone is a supporting tough tissue that provides structure to the body and aids movement by cooperating with the muscles. We have over 200 bones in our bodies, forming the skeletal structure and weighing approximately 2 kilograms (kg). Bone is a unique tissue that constantly undergoes remodeling through the period of adult life. Bone defects result from tumor resection, congenital malformations, trauma, fractures, periodontitis, and diseases such as arthritis and osteoporosis. Clinically, healing of fractures is a natural phenomenon in which bone regeneration occurs as part of the healing process. Bone is the only tissue where there is no scar tissue formation in the healing process, and the constant remodeling of the bone is one of the factors that facilitate this regeneration.
Other than the liver, bone is the only organ in the human body that can regenerate. As mentioned above, the ability to regenerate is demonstrated in the human body when a fractured bone uses its potential to regrow and heal itself. Fracture healing takes place in three phases: (1) the reactive phase, in which there is inflammation and granular tissue forms; (2) the reparative phase, in which there is cartilage callus formation and lamellar bone deposition, and (3) the remodeling phase, in which the lamellar bone is remodeled to the original bone contour.
Regeneration of the bone in fractured tissue involves this three-step process. The granular tissue is a small mass of cells that contains fibroblasts and blood vessels. While learning about the different stages in the formation of bone, it is extremely important to understand the terminology. Most of the nomenclature associated with bone either starts or ends with “osteo”—meaning “bone” in Greek. The periosteum is a layer of cells that surrounds the bone. In the fractured tissue, the periosteal cells differentiate into osteoblasts, which are cellular precursors of the cartilage tissue. Once the cartilage is formed on the proximal and distal end of the bone, it grows until it unites to form a single callus tissue. The next phase in this cascade is the mineralization of the extracellular matrix in the callous tissue. Osteoblasts in the callus tissue form the lamellar bone when they come in contact with the mineralized matrix, and this process is called ossification. This stage in bone regeneration is the trabecular bone or the spongy bone. This bone is then reabsorbed by osteoclasts, a class of bone macrophages that reabsorb bone, to create the reabsorption pit. The osteoblast then deposits compact bone into this pit, which closely resembles the original structure.
In some fractures, the healing process is impaired because of delayed union or nonunion of the bones, and 13 percent of fractures do not heal due to this impaired process. Bone regeneration is necessary in situations of skeletal reconstruction in events of trauma and injury. The gold standard until now is autologous or autogenous bone grafting, meaning bone graft from the same individual’s body. The difficulty in this method is the availability of bone tissue to be grafted. To solve this issue, bone from cadavers was resorted to, but this resulted in immunogenic graft rejection. Stem cells and their potential to differentiate into different cell types was an alternate solution to these challenges. The initial solution to this problem was to directly administer BMP—bone morphogenic proteins—to the site of the wound where the stem cell progenitors would use this hormone to differentiate into the bone. Another solution was to directly administer stem cells obtained from the patient to the site of the wound, where the stem cells would use the local systemic cues to differentiate into bone cells that would lead to wound closure. All of these options did not result in successful union of the fracture and resulted in formation of scar tissue. Though this attempt was not as successful, it led to expansion of the knowledge base whereby scientists discovered that the site of the wound needed to be closed off from the surrounding environment to facilitate efficient closure. The current methods include extracting stem cells from the patient’s bone marrow, differentiating them into osteogenic progenitors outside the body, and packaging them appropriately to insert into the body later. The technology used, the potential therapeutic solutions, and the drawbacks of those technologies are discussed below. Several of these therapies have reached the stage of clinical trials in which the therapeutic option is tested on human patients. Some of the options are outlined in the following paragraphs.
Percutaneous Injection
Percutaneous injections are those in which the stem cells derived from the bone marrow of a patient are injected directly at the wound site and the stem cells enhance the healing of the bone by differentiating. A drawback to this method is obtaining a sufficient number of cells that can differentiate to actually heal the bone. To circumvent this technical difficulty, the cells are spun down and the mononuclear cells are isolated. This helps to concentrate the cells before they can be injected. Other methods are to differentiate and populate the cell in vitro in culture.
In addition to bone marrow, pluripotent adipose tissue is also capable of differentiating into cells that are progenitors for bone. The adipose tissue can be derived from the skin layers of the patient. Another popular source is by the liposuction of fat. The stem cells in that aspirate are pluripotent, with differentiating capacities that are useful. Frozen adipose tissue is also a great source of adipose pluripotent stem cells.
Guided Bone Regeneration (GBR)
Guided bone regeneration is defined as the process whereby the wounded region is closed off from the surrounding soft tissue with the use of barrier membranes. This mechanically impedes the growing soft tissue and provides an enclosed socket for the new regenerating tissue. Expanded polytetra-fluorothylene (e-PTFE) is one of the materials that has been used until now to facilitate GBR. Acceptance of an external foreign material and association of the human body with these biomaterials is one of the significant issues. e-PTFE is regularly used