Why Allograft Bone?

Bone is a complex material that has a mineralized extracellular matrix built by the bone cells in the body. Removing the cells and mineralization yields an extra cellular matrix that is predominantly collagen but also contains a rich cocktail of signaling proteins that have been identified as a broad family of growth factors. Researchers have identified individual growth factors and products such as Medtronic’s INFUSE have a recombinant version of bone morphogenic protein-2 (BMP-2). Used in isolation these bmps need to be used at concentrations many times greater than the physiologic levels and while good clinical efficacy data exist there are also concerns about possible adverse effects.

TheraCell has identified a process through which allograft bone selected from carefully screened donors can be treated to inactivate viruses, remove the mineral and cellular materials to yield extracellular matrix. The process generates the extracellular material in the form of demineralized bone fibers (DBF™). TheraCell’s DBF fibers provide a scaffold that can be used to generate new bone. The material provides a rich source on bone morphogenic proteins that have been shown to be osteoinductive (induce bone formation). Furthermore the fiber matrix form is osteoconductive, i.e. it acts as a scaffold that allows cells to migrate.

TheraFuze DBF® does not require any additives and the fibers are designed to act as an easy to handle material that the surgeon can use directly, or if required may add autologous bone or bone marrow from the patient at the time of implantation.

TheraFuze DBF® is OsteoInductive and OsteoConductive

Seminal work was performed in 1999 and reported in a study in which TheraCell’s Chief Scientifc Officer, Nelson Scarborough was the senior author. In this work the authors demonstrated significant performance benefits of fibers over DBM powder.

The purpose of the study was to assess the efficacy of a flexible fiber based strip which is akin to our Fiber-Boat product and a malleable fiber based product which is akin to our “Fiber-Ball” product, versus the powder based DBM flowable gel in a posterolateral lumbar spine arthrodesis study using a rabbit model.

108 New Zealand white rabbits underwent bilateral posterolateral intertransverse spine arthrodesis at L5–L6 using autogenous iliac crest bone graft alone (control), and demineralized bone matrix (DBM) fibers made from rabbit bone alone or in combination with autogenous iliac crest bone. Rabbits were killed 6 weeks after surgery. The lumbar spines were excised, and fusion success or failure was determined by manual palpation and radiography. Specimens also were processed for un-decalcified histologic analysis.

Manual palpation of the harvested lumbar spines revealed that the fusion rates of the Fiber Strip/Autograft group (9/9, 100%) and Fiber-Ball/Autograft group (10/10, 100%) were superior (P < 0.01) to those of the Autograft group (8/11, 73%). As a stand-alone graft substitute, the Fiber-Strip performed superiorly with a fusion rate of 11/11 (100%) compared with that of the Fiber-Ball (10/12, 83%) and DBM-Powder (7/12, 58%). The devitalized version of Fiber-Strip where BMPs were removed using guanidine HCl had a fusion rate of 4/11 (36%), which was comparable with the devitalized Fiber-Ball rate of 4/12 (33%). Both were superior (P < 0.05) to the devitalized DBM-Powder rate of 0/12 (0%). More mature fusions with greater amounts of trabecular bone were present radiographically and histologically in rabbits that received all forms of demineralized bone matrix compared to those in which autograft was used.

Products equivalent to TheraCell’s Fiber-Boat and Fiber-Ball forms of demineralized bone matrix fiber were effective as an autograft extender and substitute in this model. The fiber-based products also showed improved handling characteristics compared with the powder form. This is due to the fact that fibers allow entanglement to maintain cohesiveness and give better handling characteristics. No additional additives are needed to make a material that can be placed into the graft site and that will resist being washed out.

TheraFuze DBF® Has A Unique Nanotopography

The topography of a surface can influence cellular response. The surfaces of demineralized allograft products are not the same and are dependent on processing techniques. The process to manufacture the TheraFuze DBF® is designed to conserve the collagen structure of bone while preserving the inductive proteins. This is achieved using patented processing techniques to effectively remove residual lipids from the nanoporous matrix of bone. Followed by gentle cleaving of the bone along the axis of the collagen orientation, using TheraCell Inc.’s patented process. This gentle process provides a nanotopography that is not seen in conventional demineralized bone matrix products. The nanotopography is shown in the scanning electron micrographs below. In contrast the images of a conventional Demineralized Bone Matrix (DBM) particle where the acid treatment of bone particles has smoothed the surface destroying its surface topography.

TheraFuze DBF®