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From BMPs to hydroxyapatite, biologics and biomaterials benefit wounded soldiers
Surgeons are using these evolving technologies to effectively repair large segmental bone defects.
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Some advances under way in orthopedic basic and clinical science can help soldiers who sustain wartime injuries resulting in segmental bone defects.
During a combined symposium of the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons, Thomas A. Einhorn, MD, presented some of the latest developments in this area that use bone morphogenetic proteins (BMP) and other biologic interventions.
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"[These are] not future technologies, but technologies that are in place and … potentially applicable to the care of these injuries," Einhorn said.
Roy K. Aaron, MD, who co-moderated the war injuries symposium, said, "All wars serve as laboratories in which to identify and develop treatments for new and complex problems."
Experimental model
According to Einhorn, the biggest hindrance to treating bone loss due to musculoskeletal war injuries is the lack of appropriate experimental models for high-velocity injuries from missiles and land mines. Most models he is aware of that address the repair and regeneration of bone apply to civilian injuries.
"I don't think we have the appropriate models, certainly not in animals, for some of the tissue damage we see," he said. Despite that, Einhorn said the current conflicts in Iraq and Afghanistan have spawned a host of innovative ways to use high-tech approaches to generate bone following wartime injuries. These options may be used alone or in combination to repair even large segmental bone defects. They include:
- nonvascularized and vascularized autologous bone transplantation;
- allogenic bone transplantation;
- intercalary prosthetic replacement;
- bone transport through distraction osteogenesis;
- autologous bone marrow;
- recombinant osteoinductive proteins; and,
- synthetic small molecules.
"Any of these may be combined with a resorbable or a nonresorbable scaffold," Einhorn said.
Bone marrow, hydroxyapatite
There is one promising yet evolving therapy: autologous bone marrow, he said.
This regenerative technology involves harvesting stem cells by aspirating bone marrow from under the endosteum, expanding the cells in culture, and implanting them in a defect. Cells obtained from this location are effective because they house most of the osteoprogenitor cells, Einhorn added.
He presented a combat case involving a 32-year-old male with a high-velocity gunshot wound who received standard treatment for a grade IIIb open distal one-third tibia fracture: irrigation and debridement, wound control, external fixation, implantation of antibiotic beads, bone grafting and soft tissue flaps.
The soldier's orthopedic care, though appropriate, could have been significantly improved if a bone-regenerative technology like autologous bone marrow were used to intervene, Einhorn said.
He cited a promising study by Scott Bruder, PhD, who filled a 16-mm canine defect with hydroxyapatite cubes soaked in autologous bone marrow. Although the new bone was mechanically inferior, it healed end-to-end. "It is possible that the cells themselves secreted paracrine signals, which recruited more cells to the site," Einhorn said.
BMP on a collagen sponge combined with allogenic bone graft is yet another treatment option. It represents an advance over first-generation BMPs. To treat significant bone defects in 13 civilians, Alan Jones, MD, et al combined rhBMP-2 on a collagen sponge with allogenic bone graft and saw healing of the defect at 12 months that surpassed that with BMP and autograft.
Beyond segmental defects
When surgeons are faced with major parts of the anatomy to reconstruct, "There are technologies evolving that may be able to help," Einhorn said.
One example being looked at: Investigators could use a polylactic/polyglycolic acid polymer with bovine periosteum, autologous chondrocytes and osteoblasts to roughly form an anatomical structure that could later be implanted in humans. In a clinical study, other investigators used this construct in a patient following a partial amputation of a digit. Gene therapy might also play a key role in future bone defect treatments since it avoids the high doses and concentrations that BMP-based therapies require and may aid sustained release of osteogenic proteins at the injury site.
"The patient's own cells can become bioreactors for synthesizing their own endogenous growth factor and releasing it at the appropriate time and in the appropriate way, and also preventing the material from being cleared too rapidly and exposing nontarget tissues," he said.
Further research should yield more information about how to apply many of these concepts to battlefield injuries, Einhorn added.
Images: Einhorn TA, Casey D |
For more information:
- Thomas A. Einhorn, MD, chairman of orthopedic surgery, Boston University Medical Center, Doctor's Office Building, Suite 808, 720 Harrison Ave., Boston, MA 02118; 617-638-8435; Thomas.Einhorn@bmc.org. He has received research support from and is a consultant to Stryker, Biotech, Glaxo-Smith Kline, Pfizer, Zelos and Osteotech.
- Einhorn TA. Orthopaedic war injuries from combat casualty care to definitive treatment: A current review of the basic science, clinical advances and research opportunities: Evolving technologies for enhancement of the repair of segmental bone defects. AAOS/ORS Combined Symposium #1. Presented at the Orthopaedic Research Society Annual Meeting/American Academy of Orthopaedic Surgeons 74th Annual Meeting. Feb. 14-18, 2007. San Diego.
- Jones AL, Bucholz RW, Bosse MJ, et al. Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects. J Bone Joint Surg. 2006;88A:1431-1441.