Musculoskeletal Allograft in the U.S. Research Report - Sample Chapter
BY EDITOR, NOVEMBER 8, 2006
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Processing and Manufacturing of Tissues
There is a broad range of processing that can be applied to musculoskeletal tissue. With the FDA regulatory focus on tissue, many steps are necessary to decrease the incoming bioburden (the number of contaminating microbes on a certain amount of material prior to that material being processed) of recovered tissues: processing tissue aseptically into grafts for surgical use, packaging, and in most cases, applying some form of terminal sterilization.
Until the late 1970s, the vast majority of graft preparation and processing was actually performed by the surgeon in the operating room. The first tissue banks to process and package allografts were also the same non-profits doing procurement. Today the demand for allograft consistently processed in terms of size, shape and appearance -- as well as the novel forms of allografts such as gels, putties and machined grafts -- calls for sophisticated, controlled environments and a device-manufacturing approach (e.g. document control, process validation, staff training, etc.)
FDA regulations and the prevailing industry standard permit only single-donor processing for musculoskeletal tissues (meaning only one donor may be present and processed in a controlled environment at a given time.) This limit helps prevent cross contamination of tissues during processing. Tissue is processed in environments that are climate and bacterially controlled, called "clean rooms." Most clean rooms push significant amounts of air through that has been cleaned by HEPA filters capable of capturing particles just a few microns in size.
Typically the first steps in tissue processing are designed to remove blood product and lipids from the tissue. This involves the removal of muscle and connective tissues from the bone followed by washing in various solutions.
This initial cleaning step is followed by any of several cutting, grinding or crushing operations, depending on the type of bone and the surgical application for the bone. This cutting and shaping can be accomplished with a variety of tools including scalpels, osteotomes, hand saws, table saws and drills. With the increased use and demand for precision-cut allografts, many tissue processors use Computer Numerical Control (CNC) machines to finish the grafts. These are software-driven machines capable of utilizing several drilling or cutting mechanisms during the same processing session. These allow the addition of features to a graft beyond standard sizes. These features could include slots to facilitate alignment and insertion with surgical instruments, which permit a closer fit of the graft into the patient and minimize time in surgery.
Another complex process is used to produce demineralized bone matrix (DBM.) This product starts with the grinding of cortical bone into a powder. The ground bone is then placed in a reagent such as hydrochloric acid to remove the calcium, leaving behind other proteins, bone growth factors and collagen. DBM has both osteoconductive and osteoinductive properties, and it is available in the form of granules, gels and putties.
After bone has been cut and shaped and processed, the final step is to preserve (fresh, frozen, or freeze-dried), sterilize and package the allograft. Soft tissue is essentially processed, preserved and sterilized in the same manner as bone, perhaps differing in that a higher percentage tends to be preserved fresh or frozen. It is rarely freeze-dried. The methods vary by type of graft and even among tissue processors. Many tissue processors package and then sterilize grafts while some have sterilization processes that must be completed before final packaging. In these cases, the treated grafts are then aseptically packaged.
