Nonunion of a fracture refers to the absence of healing in a fracture.
Nonunion is a serious complication of a fracture and may occur when the fracture moves too much, has a poor blood supply or gets infected. Patients who smoke have a higher incidence of nonunion. The normal process of bone healing is interrupted or stalled. More commonly the tissue between the un-united fragments is scar tissue.
Since the process of bone healing is quite variable, a nonunion may go on to heal without intervention in a very few cases. In general, if a nonunion is still evident at 6 months post injury it will remain unhealed without specific treatment, usually orthopedic surgery. A non-union which does go on to heal is called a delayed union.
Types of Non-Union
1. Hypertrophic non-union Callus is formed, but the bone fractures have not joined. This can be due to inadequate fixation of the fracture, and treated with rigid immobilization.
2. Atrophic non-union No callus is formed. This is often due to impaired bony healing, for example due to vascular causes (e.g. impaired blood supply to the bone fragments) or metabolic causes (e.g. diabetes or smoking). Failure of initial union, for example when bone fragments are separated by soft tissue may also lead to atrophic non-union.
Cause of a nonunion:
Determining the cause of a nonunion is critical to determining the proper treatment. The most common causes of nonunion are:
2. Inadequate blood flow to the bone
3. Separation of the fractured ends of the bone
4. Inadequate stabilization of the fracture .
Treatment of Non-Union Fracture using Stem Cell Therapy:-
The primary bone-forming cell in the body is the osteoblast and its precursor is the MSC. Bone formation occurs as the extracellular matrix, which is produced by the osteoblast, becomes mineralized. Osteoprogenitors refer to all the cell stages stemming from Mesenchymal stem cells up to the osteoblast. This naturally occurring differentiation process is regulated by a series of naturally occurring proteins, or growth factors, that eventually guide the MSC to form osteoblast.
Protocol Outline for Non-Union Treatment:-
1. We transplant bone marrow stem cells concentrate by mixing with Synthetic/Autologous graft with/without cultured Mesenchymal stem cells (based on the patient/fracture gap) between the fracture gap to make new bone formation.
2. “Bone marrow-derived stem cells concentrate (BMSCs)” provide a rich growth factor environment that may enhance the bone healing response in spinal fusion cases. Complete bone formation is dependent on the all the cell types contained in Bone marrow stem cells concentrate. The iliac crest contains bone marrow which is a rich source of the regenerative cells needed for bone formation, including:-
Mesenchymal Stem Cells (MSCs):- MSCs which differentiate into many types of cells such as bone, cartilage, neuron and so more.
Hematopoietic Stem Cells (HSCs):- HSCs which differentiate into all types of blood cells and also provide enhance environment for MSCs activation.
Endothelial Stem Cells (ESCs):- ESCs which differentiate into all types of blood vessels also release BMP-2 and BMP-6 which is very important growth factor for bone formation.
1. To modulate the regeneration process
2. Recruit bone marrow progenitor cells to loci of injury
3. Provides adhesion site for stem cells
4. Platelets fibrin provides migration highway at the site of injury
3. Autologous adult stem cells concentrated from bone marrow harvested from the iliac crest may become a viable alternative to iliac crest bone grafting and its inherent associated morbidity. Previous reports (Connolly, Gangji, Hernigou et al) have shown that high concentrations of adult stem cells from iliac crest bone marrow can enhance the rate and amount of bone formation.
4. Sometimes we refer to transplant cultured mesenchymal stem cells (MSCs) isolated from bone marrow, cord tissue after evaluation of complete case study because MSCs has the property to differentiate into many types of cells such as bone, cartilage, neuron and so more.
5. Non-union fracture should always be fixated for some fix period of time after stem cells transplantation.
6. We also start stem cell supplement (Stem-Kine) during and after stem cell transplantation to get better improvement.
Follow-up with patients:-
Our medical staff members will be in contact with patients to get complete follow-up at 1, 3, 6 month intervals to monitor all the evaluation.
1. Hendrich et al. 2009, Orthopaedics Review. Safety of autologous bone marrow aspiration concentrates transplantation: initial experiences in 101 patients
2. Chanchai et al. 2009. Journal of Cranio-Maxillofacial Surgery. Application of a new chair-side method for the harvest of mesenchymal stem cells in a patient with nonunion of a fracture of the atrophic mandible case report
3. Hernigou et al. 2005, The Journal of Bone & Joint Surgery. Percutaneous Autologous Bone-Marrow Grafting for Nonunions: Influence of the Number and Concentration of Progenitor Cells.