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New Technology

The Effects of a Soluble Polymer and Bone Wax on Sternal Healing in an Animal Model

^a Division of Plastic and Reconstructive Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California
^b Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
^c Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Medical University of South Carolina, Charleston, South Carolina

Accepted for publication November 14, 2007.

^_* Address correspondence to Dr Wellisz, 536 S Rimpau Blvd, Los Angeles CA 90020 (Email: tadeusz{at}wellisz.com).

Drs Wellisz, Armstrong, and Cambridge, and Mr Fisher disclose that they have a financial relationship with Ceremed Inc.

 

	Abstract

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Purpose: This study compares the effects of a soluble polymer hemostatic material and bone wax on sternal bone healing.

Description: Median sternotomies were performed on 20 New Zealand White rabbits, and sufficient polymer (Ostene; Ceremed Inc, Los Angeles CA) or bone wax (Bone Wax; Ethicon Inc, Somerville, NJ) was applied to achieve bone hemostasis. After 6 weeks, sternal healing was assessed using roentgenograms, histology, and mechanical strength testing.

Evaluation: Roentgenograms revealed normal bone healing in the polymer-treated group and nonunion in the bone wax group. Histology showed normal bone healing in the polymer group, with fibrotic scar tissue and the absence of new bone formation in the bone wax group. Mechanical strength testing showed that polymer-treated sternal segments were twice as strong as those treated with bone wax. They had a significantly higher flexural strength (2.53 ± 0.43 vs. 1.29 ± 0.37 megapascal [MPa]; p < 0.001) and Young's modulus (0.315 ± 0.056 vs 0.146 ± 0.031 MPa; p < 0.001).

Conclusions: The application of the polymer hemostatic material to the sternum resulted in significantly stronger union compared with the use of bone wax.

	Technology

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Sternal nonunion has been estimated to occur in 2% to 8% of patients who undergo cardiac operations [1]. Postoperative mediastinitis with sternal dehiscence is a dreaded complication. The estimated incidence of sternal nonunion without a concomitant infection is 0.2% to 5% [2]. Clinical manifestations of late sternal nonunion can range from feelings of chest motion, clicking, and chronic discomfort to respiratory embarrassment due to the cycle of pain, tachypnea, and hypoventilation [1].

Bone wax, which is made of softened beeswax, has been associated with complications after sternotomy [1]. Although effective in stopping bone bleeding, bone wax is not cleared from the operative site and has been shown to inhibit bone healing, increase infection rates, and elicit chronic inflammatory reactions [3, 4]. The continued use of bone wax in cardiac surgery despite its known adverse effects may be in part the result of the absence of a suitable alternative.

A synthetic bone hemostasis material, made of water-soluble alkylene oxide copolymers, has recently become available [3]. The use of alkylene oxide copolymers for bone hemostasis was first described by Wang and colleagues [5]. These soluble copolymers have a long history in the medical field, and they have been used as an additive in cardiopulmonary bypass pump oxygenators [5]. They do not interfere with coagulation and are considered inert because they are eliminated from the body unchanged, without being metabolized. Because these copolymers are hydrophilic and stick well to wet surfaces, they are well suited for bone hemostasis.

Our study was designed to compare the effects of the two bone hemostasis materials on sternal bone healing in an animal model. The objective of this study was to determine if the use of the polymer would improve sternal bone healing compared with the use of bone wax.

	Technique

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Twenty female New Zealand White rabbits (3.75 ± 0.25 kg) were randomly divided into two equal groups of 10 animals. They underwent median sternotomy with the application of either synthetic polymer (Ostene; Ceremed Inc, Los Angeles, CA) or bone wax (Bone Wax; Ethicon Inc, Somerville, NJ). Rabbits were anesthetized using ketamine (30 mg/kg), xylazine (5 mg/kg), and atropine (1 to 3 mg/kg) intramuscularly and maintained on isoflurane after intubation.

The sternotomy was performed using standard aseptic techniques. A 5-cm midline chest incision was made and a circular saw was used to divide the lower three segments of the sternum. Equal amounts of the polymer or bone wax were applied to cover the cut bone surface, and hemostasis was assessed. The sternal halves were secured with 2-0 monofilament suture, and the incision was closed in layers. Animals were sacrificed after 6 weeks using intravenous pentobarbital. All animals received humane care in compliance with the Guide for the Care and Use of Laboratory Animals (National Institutes of Health Publication 85-23, revised 1996). All procedures were approved by the Institutional Animal Care and Use Committee at the Medical University of South Carolina.

Each sternum was harvested for radiographic, histologic, and mechanical analysis. Standardized lateral roentgenograms of the sternum were taken under the same conditions, using the same x-ray intensity and duration, from the same constant object-to-film-to-x-ray-source distance, and with the same batch of ultra-high-contrast mammography film.

Each fresh specimen was sectioned, and the uppermost treated sternal segment was fixed in 10% neutral buffered formalin and processed for routine undecalcified sectioning. The specimens were embedded in Spurr media and cut using a slow-speed diamond saw. Sections were ground to a thickness of 50 µm and stained with Sanderson rapid bone stain, which stains bone a red color.

Microscopic images of the bone sections were obtained courtesy of the Tissue Procurement Core Laboratory (University of California, Los Angeles School of Medicine, Los Angeles, CA) using MetaMorph software in the scan slide module (Molecular Devices Corp, Downington, PA) installed on a personal computer with a dual Xeon processor (Integrated Electronics [Intel] Corporation, Santa Clara, CA). The software drove an automated Proscan moterized stage (Prior Scientific Inc, Rockland, MA) installed on an Olympus BX50 microscope (Olympus America Inc, Center Valley, PA). Images were captured with a Spot Insight 4 MP camera (Diagnostic Instruments Inc, Sterling Heights, MI).

The lower portion of each treated segment was used for mechanical strength testing. The mechanical strength of each sternal segment was measured on a MTS Synergie 100 material tester (MTS Systems Corp, Eden Prairie, MN) using three-point testing with a 0.2 mm/s crosshead speed. Statistical analysis of the measured flexural strength and the Young modulus were performed using a t test.

	Results

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During the procedure, equivalent bone hemostasis was achieved using bone wax and the alkylene oxide copolymer. At the time of sacrifice 6 weeks after the operation, roentgenograms of two groups showed differences in bone fusion. In the polymer group, the two halves of each sternum were consistently fused (Fig 1A). In contrast, every sternum segment treated with bone wax exhibited areas of radiolucency indicating sternal nonunion (Fig 1B).

View larger version (165K): [in this window] [in a new window]   Fig 1. (A) A roentgenogram taken 6 weeks after a sternotomy in which the soluble polymer was used for hemostasis. Bone fusion occurred consistently in every animal. (B) A roentgenogram taken 6 weeks after operation in which the sternal segments were treated with bone wax, all of which exhibited areas of radiolucency indicating nonunion.

View larger version (137K): [in this window] [in a new window]   Fig 2. (A) The polymer-treated sternum shown in horizontal section. The bone is stained red. New bone has been formed within normal bone marrow, and intact cartilage is present between the sternal segments. (B) Sternum treated with bone wax shown in horizontal section. The bone is stained red. Bone wax is still present at the site (BW), with fibrotic scar in the area of the bone wax (F). There is scant new bone and minimal normal bone marrow. Intact cartilage is present between the sternal segments. (Sanderson stain, original magnification x5).

View larger version (73K): [in this window] [in a new window]   Fig 3. (A) Schematic representation of the three-point testing used to assess the strength of the healed sternum. (B) One segment of sternum undergoing three-point testing.

View larger version (16K): [in this window] [in a new window]   Fig 4. The flexural strength of the polymer-treated sternal segments (2.53 ± 0.43 megapascal [MPa]) was significantly greater than segments in the group treated with bone wax (1.29 ± 0.37; p < 0.001). The error bars signify the standard deviation.

View larger version (17K): [in this window] [in a new window]   Fig 5. The Young's modulus of the polymer-treated sternal segments (0.315 ± 0.056 megapascal [MPa]) were significantly greater than that of the bone wax group (0.146 ± 0.031 MPa; p < 0.001). The error bars signify the standard deviation.

	Comment

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Bone wax has long been known to interfere with bone healing. In the 1924 edition of Carson's Modern Operative Surgery, the use of bone wax is recommended not for bone hemostasis but for preventing bone healing and for the creation of a pseudoarthrosis [6]. In 1969, Howard and Kelley [7] demonstrated that bone wax prevents bone healing in an animal model and concluded that bone wax is contraindicated in areas where bone fusion is desired. Histologic findings associated with the implantation of bone wax typically include foreign-body reactions characterized by giant cells, plasma cells, fibrous tissue, and a lack of bone formation [3]. In the clinical setting, autopsy studies have demonstrated persistent sternal nonunion and chronic inflammatory reactions with the presence of residual bone wax up to 10 years after operation [8].

Bone wax is known to increase infection rates and impair the ability of bone to clear bacteria. In a rat tibia model, the presence of bone wax reduced the amount of Staphylococcus aureus needed to produce osteomyelitis by a factor of 10,000 [9].

Bone wax is known to remain as a foreign body indefinitely, causing giant cell reactions and inflammation at the site of application. In a human study, Sorrentini and colleagues [10] evaluated the reactions to bone wax in the tibias of 12 patients who had undergone tibial tubercle elevation. The patients underwent reoperation after 5 to 13 months and bone biopsies were performed. The authors observed a progression from foreign body giant cell reaction, with giant cells containing vacuoles filled with bone wax, to the formation of mature fibrous tissue. Reactions consisted mainly of pain and swelling, often exacerbated by infection.

The alkylene oxide copolymer material used by Wang and colleagues [5] was shown not to interfere with bone healing. New bone grew into rat femur defects within 10 days after treatment with the polymer, compared with the defects filled with bone wax, which showed no bone formation after 48 days. The polymer material dissolved from the site of application within 24 to 48 hours, allowing the early phases of bone healing to occur [5]. The polymer material used in this study dissolves in the body and has been shown not to interfere with bone healing or cause inflammation in animal models [3]. The use of the soluble polymer also significantly decreased the incidence of osteomyelitis compared with that seen with the use of bone wax in a tibial defect model [6].

In our study, the soluble polymer did not demonstrate the interference with bone healing that was observed with the use of bone wax. When the polymer was used, significantly stronger sternal healing occurred compared with bone wax. The use of this polymer in place of bone wax may help reduce the occurrence of postoperative sternal nonunion and its associated complications.

	Disclosure and Freedom of Investigation

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Research funding was provided by Ceremed Inc. The polymer was donated to the study, and the bone wax was purchased. The authors had full control of the design of the study, methods used, outcome parameters, analysis of data, and production of the written report.

	Acknowledgments

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We would like to thank Drs Sarah Dry and Dorina Gui from the Tissue Procurement Core Laboratory, Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, California.

	Footnotes

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^Disclaimer The Society of Thoracic Surgeons, the Southern Thoracic Surgical Association, and The Annals of Thoracic Surgery neither endorse nor discourage use of the new technology described in this article.

	References

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1. Robicsek F, Fokin A, Cook J, Bhatia D. Sternal instability after midline sternotomy Thorac Cardiovasc Surg 2000;48:1-8.[Medline]
2. Olbrecht VA, Barreiro CJ, Bonde PN, et al. Clinical outcomes of noninfectious sternal dehiscence after median sternotomy Ann Thorac Surg 2006;82:902-907.[Abstract/Free Full Text]
3. Wellisz T, Armstrong JK, Cambridge J, Fisher TC. Ostene, a new water-soluble bone hemostasis agent J Craniofac Surg 2006;17:420-425.[Medline]
4. Angelini GD, el-Ghamari FA, Butchart EG. Poststernotomy pseudo-arthrosis due to foreign body reaction to bone wax Eur J Cardiothorac Surg 1987;1:129-130.[Abstract]
5. Wang MY, Armstrong JK, Fisher TC, et al. A new, pluronic-based, bone hemostatic agent that does not impair osteogenesis Neurosurgery 2001;49:962-967discussion 968.[Medline]
6. Wellisz T, An YH, Wen X, et al. Infection rates and healing using bone wax and a soluble polymer material Clin Orthop Relat Res 2008;466:481-486.[Medline]
7. Howard TC, Kelley RR. The effect of bone wax on the healing of experimental rat tibial lesions Clin Orthop Relat Res 1969;63:226-232.[Medline]
8. Sudmann B, Bang G, Sudmann E. Histologically verified bone wax (beeswax) granuloma after median sternotomy in 17 of 18 autopsy cases Pathology 2006;38:138-141.[Medline]
9. Nelson DR, Buxton TB, Luu QN, Rissing JP. The promotional effect of bone wax on experimental Staphylococcus aureus osteomyelitis J Thorac Cardiovasc Surg 1990;99:977-980.[Abstract]
10. Sorrenti SJ, Cumming WJ, Miller D. Reaction of the human tibia to bone wax Clin Orthop Relat Res 1984:293-296.

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This Article Abstract Full Text (PDF) Correction Correction (v86,p1403) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wellisz, T. Articles by Fisher, T. C. Search for Related Content PubMed PubMed Citation Articles by Wellisz, T. Articles by Fisher, T. C. Related Collections Chest wall Related Article