Issue: July 2008
July 01, 2008
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New biomaterials, conductive substrates among strategies used to re-grow bone

Vascularized membranes may contain specific growth factors, induce stromal cell differentiation.

Issue: July 2008
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Surgeons have a host of biologic strategies to restore bone. At the American Academy of Orthopaedic Surgeons 75th Annual Meeting, J. Tracy Watson, MD, discussed current and emerging technologies used to re-grow bone in challenging fracture cases.

“I think that the future is happening now,” Watson said during his presentation. “We are using every available technology alone and in combination to maximize our union rates. For smaller bone defects composite graft therapies utilize cellular bone marrow aspirates, concentrating the colony forming units. These cellular components are then combined with BMP cocktails, and conductive substrates which offer the surgeon a powerful bone graft tool. Other restorative techniques utilize rapid bone transport techniques as well as biomaterial segmental bone replacement and reconstruction of massive defects.”

Metaphyseal defects

Surgeons can typically treat metaphyseal subchondral defects with simple calcium ceramic conductive substrates. These defects often need subchondral support to prevent articular collapse, Watson said. Sulphate ceramics give initial compressive strength and function as bone graft extenders and also act as a delivery vehicle for other adjuvants such as antibiotics. Because these materials osteointegrate through a chemically mediated event, sulphate ceramics rapidly degrade leading to a potential loss of articular support just at the time the patient may begin full weight-bearing. This crucial loss of support may lead to premature articular subsidence, he said.

Phosphate ceramics are very porous by nature and have a tremendous surface area that serves as a site for cellular attachment, thus these materials osteointegrate via a cellular-mediated event which extends the osteointegration period. These materials have a higher compressive strength compared to the sulfate materials, he told Orthopedics Today.

“The problem with all Calcium ceramics is that these materials resist tension very poorly,” Watson said. “They are very weak in shear stress, so they are not indicated as a solitary bone graft supplement or replacement for diaphyseal locations.”

Composite ceramic materials seek to combine the best elements of sulphate and phosphate materials. In a prospective multicenter trial, Watson and his co-investigators from Saint Louis University and Washington University in Saint Louis found vigorous subchondral remodeling at 6 months without articular subsidence

“We see that these composite materials provide support past the transition period to full weight-bearing, which is important for beginning earlier weight-bearing without fear of jeopardizing your articular reconstruction,” Watson said. These combination materials will certainly become more prevalent as the technology of these materials continues to expand.

Post-injury CT scan
Post-injury CT scan demonstrating a bicondylar tibial plateau fracture with lateral subchondral bone loss. Images: Watson JT

One-month postoperative X-ray
One-month postoperative X-ray image demonstrating lateral subchondral location of composite calcium sulfate/phosphate bone graft substitute to support the lateral articular surface.

Six-month image postoperative X-ray demonstrating osteointegration
Six-month image postoperative X-ray demonstrating osteointegration of graft material with surrounding bone hypertrophy and maintenance of articular reduction.

Six-month postoperative CT image with articular reduction
Six-month postoperative CT image with articular reduction maintained and subchondral remodeling noted.

Images: Watson JT

Diaphyseal defects

Diaphyseal defects often occur in watershed areas of poor biology and treating the biology is paramount. “These adjuvants do not grow bone on a sidewalk,” Watson said. “You have to reconstruct the biology in an effort to allow these graft materials to work. You can’t forget the basic tenants of soft tissue care and fracture management.

Emerging research indicates that composite grafts may be valuable for treating subcritical defects. However, Watson cautioned against using percutaneous injections of centrifuged aspirate alone. His review of a series of nonunion patients treated using Connolly’s percutaneous injection technique revealed a 70% failure rate. Watson said that surgeons must selectively concentrate marrow aspirates to achieve a critical mass of colony-forming units (CFU’s) and combine them with carrier materials. These composite grafts are then applied utilizing percutaneous injection techniques in very select populations of patients. Alternatively, in long standing defects these materials are best applied in an open fashion.

Traditional iliac autograft still remains the gold standard for smaller noncritical sized defects, with all subsequent materials held to this standard. Studies in the literature report nearly a 100% success rate for stable, uninfected noncritical sized defects with autograft volumes averaging 20 cc. It is worth noting that one anterior iliac crest will reliably only produce 30 cc of graft.

“According to the reported literature, the upper limit of success for the treatment of critical sized defects (up to 4 cm segmental bone loss) basically requires the harvesting of two iliac crests in order to achieve enough graft material to treat a 4-cm defect. That is a lot of intervention on somebody’s pelvic crest,” he said. Systems that ream, irrigate and aspirate the intramedullary canal can collect up to 60 cc to 80 cc of bone graft, but early results only report a 60% union rate for critical sized defects, with many cases requiring a second graft.

A real advancement for open fracture management has been rhBMP-2 (Infuse-Medtronic Sofamor Danek), Watson said. “Implanting BMP-2 at the time of secondary wound closure in combination with allograft augmentation has been shown to achieve reliable incorporation for these critical size defects up to 4 cm.”

Injury to left arm
Injury to left arm with complete loss of elbow joint.

Application of antibiotic spacer
Application of antibiotic spacer at time of wound closure.

One-month postoperative image following graft placement
One-month postoperative image following graft placement into spacer pseudomembrane. Graft consisted of concentrated iliac aspirate with DBM and BMP with exchange of antibiotic spacer.

Large segmental defects

Watson recommends using antibiotic spacers in patients with large defects. “The initial stage in the reconstruction of these massive defects is to apply an antibiotic spacer or antibiotic insert spanning the defect. These spacers will contribute to the development a highly vascularized membrane due in part to the porous nature of these temporary spacers,” he said. It has been shown that these induced membranes secrete endogenous growth factors such as VEGF, TGF-b, and BMP-2. Grafting into these highly vascularized membranes using composite grafting methodologies has demonstrated consolidation of very large defects without the morbidity of massive iliac crest harvesting.

While distraction osteogenesis still plays an important role in the treatment of these defects, problems arise from the prolonged time these patients are in the external fixator. In addition, there are detrimental biologic consequences associated with prolonged transport times, primarily complications associated with nonunion of the docking site and poor bone regenerate sites.

“A significant advancement in distraction osteogenesis has been the addition of orthobiologic augmentation to both the transport and docking sites,” Watson said. These adjuvants have allowed for more rapid distraction rates with the ability to achieve reliable regenerate bone formation and reduction in the number of docking site nonunions.

Research using titanium mesh cages combined with allograft and demineralized bone matrix has shown promise for segmental defects, Watson said. He also highlighted the potential using these replacement materials in combination with bioactive membranes.

“In addition to containing specific growth factors including BMP-2, these well vascularized membranes have been shown to induce marrow stromal cell differentiation into an osteoblastic lineage,” Watson said. “Additionally, these membranes present a significant textured uniform surface area with a specific three dimensional architecture suitable for cellular infiltration and attachment.

“Cellular viability is really the driving factor for any of these new graft modalities. Providing viable bone forming cells is really the engine that drives this entire process,” he said.

For more information:

  • J. Tracy Watson, MD, can be reached at St. Louis University Hospital, 7th Floor Desloge Towers, 3635 Vista Ave., St. Louis, MO 63110; 314-577-8850; watsonjt@slu.edu. He receives research and or institutional support and royalties from Smith & Nephew and DePuy, a Johnson & Johnson Company, research and or institutional support from Zimmer and is a consultant of employee of Wright Medical Technology, Inc.

Reference:

  • Watson JT. Biologic strategies to grow bone in difficult clinical situations. Presented at the American Academy of Orthopaedic Surgeons 75th Annual Meeting. March 5-9, 2008. San Francisco.