TISSUE ENGINEERING WITH POROUS CERAMIC BONE GRAFT SUBSTITUTES

Abstract

Tissue engineering is founded on the principle of pro-actively manipulating the triad of tissue regeneration. The triad consists of matrices, pluripotential cells and signaling factors. Our hypothesis is that advances in orthopedic surgery to successfully regenerate bone are accomplished by incorporating optimised matrices into the surgeon’s armamentarium.

Pro Osteon is a bioactive ceramic matrix with interconnected porosity. It has been evaluated in experimental animals and used clinically as a bone graft substitute for more than two decades. It is available in slowly resorbable form composed of hydroxyapatite and as a more rapidly resorbable composite of calcium carbonate and calcium phosphate. Experiments have been conducted in sheep, rats and dogs to demonstrate consistent and predictable bone regeneration when the implant is placed in direct apposition to host bone, the host bone is viable and the interfaces between the bone and implants are biomechanically stable. Most importantly, controlled, multi-center clinical trials showed consistent efficacy and safety in humans. Either as a block or granules, Pro Osteon is biocompatible and osteophilic and osteoconductive. Bone regeneration, as demonstrated radiographically and histologically, occurs directly within the porous ceramic in traumatic defects and tumors. Where surrounding viable bone or mechanical stability is inadequate, such as posterior spinal fusion, the ceramic must be co-mixed with autograft. For indications where autograft is limited or unavailable, bone regeneration within the porosity was enhanced and fusion achieved by supplementing Pro Osteon with bone marrow and/or with growth factors. This was demonstrated experimentally and clinically. Mitogenic and/or morphogenic growth factors were demonstrated to increase the rate or degree of bone formation. Methods and equipment for intra-operative collection of concentrated platelets were shown to be a cost-effective and safe source of autologous mitogens. Using a variety of ectopic and orthotopic animals models, we have shown that autologous, purified xenogenic and recombinant growth factors will bind to the surface of Pro Osteon and initiate or stimulate the bone induction process.

In conclusion, Pro Osteon is an effective matrix for bone formation. It can be used alone or it can be used in combination with pluripotential, osteogenic stem cells or with signaling proteins.