Bone Marrow Used as Graft or Adjuvant to Grafting
Dr. Muschler is an orthopaedic surgeon specializing in adult reconstruction and treatment of fracture nonunions. He also heads the Orthopaedic Research Center's Bone Biology Laboratory in the Department of Biomedical Engineering.
In the next few years, cell therapy is likely to become important, if not critical, to optimizing the performance of bone grafting procedures in the operating room.
Today, autologous cancellous bone is the gold standard of graft materials. However, it poses several drawbacks which have fueled interest in orthopaedic tissue engineering of cells and matrices. Significant morbidity is associated with the harvest of iliac crest bone graft. Also, the amount and availability of autogenous bone may be insufficient for many clinical problems.
As a result of these disadvantages, many surgeons have begun supplementing graft sites with aspirated bone marrow, an effective osteogenic graft that is probably underused in current clinical practice. Bone marrow aspirates obtained from the iliac crest will contain an average of about 1,000 osteoblastic progenitor stem cells per milliliter, as well as other cells rich in cytokines. They also contain fibrin that may facilitate rapid revascularization.
In our laboratory in The Cleveland Clinic Department of Biomedical Engineering, we have developed a method to increase the concentration and selection of connective tissue progenitor cells from bone marrow.
This method can supply five to 20 times the number of progenitor cells than routine bone marrow aspirates provide. Higher concentrations of osteoblastic progenitor cells have resulted in significant improvements in the quality and reliability of posterior spinal fusions in an animal model using both mineralized and demineralized allograft bone as a carrier.
Methods of bone marrow concentration are now being evaluated in prospective clinical trials in the Department of Orthopaedic Surgery as an alternative to autogenous cancellous bone graft for inducing spinal fusion and for treatment of non-union of long-bone fractures.
Tissue Engineering in Operating Rooms
Today the term "tissue engineering" can be broadly applied to all of our biologic efforts to grow a specific tissue in a specific location. Orthopaedic surgeons have an increasing array of options for enhancing the repair and regeneration of tissues. These options include bone grafting, cartilage regeneration and tendon and ligament repair.
Our armamentarium for bone grafting includes a wide variety of preparations of allograft bone and bone matrix (whole bones, segments, blocks, chips, granules, fibers, paste, putties, gels). Similarly, we have many other matrices and bone-void fillers in the form of calcium phosphate, ceramics and calcium sulfate, as well as three-dimensional scaffolds of degradable and non-degradable polymers. Growth factors, such as bone morphogenetic proteins, are being used in clinical trials and may become available in the next few years.
The availability of this wide array of materials places upon us an increasing demand to understand their biologic properties and the basis for their effectiveness in enhancing tissue repair.
One of the central paradigms of tissue engineering is a central paradigm of life. Stated simply: "Cells do all the work." Furthermore, it is unlikely that any matrix or growth factor can be used to its best advantage if the local environment in which the material is placed is deficient in stem cells or progenitors.
(Above) No growth factor, no matrix, no cytokine, no protein, no material of any kind can have a beneficial or functional effect in a wound site or graft bed except through its effect on the behavior of cells. It is often forgotten that perhaps the most critical determinants of success in any tissue engineering construct is the presence of a sufficient number of healthy and viable stem cells or progenitor cells.
(Above) The iliac crest provides a broad area from which marrow can be aspirated safely.
(Above) Two small incisions large enough to pass an aspiration needle provides access to the entire iliac crest.
(Above) Bone regeneration requires cells capable of forming bone and an environment in which these cells can survive, proliferate, migrate and differentiate.
