David S. Margolis

A novel biomimetic polymer scaffold design enhances bone ingrowth

There has been recent interest in treating large bone defects with polymer scaffolds because current modalities such as autographs and allographs have limitations. Additionally, polymer scaffolds are utilized in tissue engineering applications to implant and anchor tissues in place, promoting integration with surrounding native tissue. In both applications, rapid and increased bone growth is crucial to the success of the implant. Recent studies have shown that mimicking native bone tissue morphology leads to increased osteoblastic phenotype and more rapid mineralization. The purpose of this study was to compare bone ingrowth into polymer scaffolds created with a biomimetic porous architecture to those with a simple porous design. The biomimetic architecture was designed from the inverse structure of native trabecular bone and manufactured using solid free form fabrication. Histology and muCT analysis demonstrated a 500-600% increase in bone growth into and adjacent to the biomimetic scaffold at five months post-op. This is in agreement with previous studies in which biomimetic approaches accelerated bone formation. It also supports the applicability of polymer scaffolds for the treatment of large tissue defects when implanting tissue-engineering constructs. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009.

Biomechanical evaluation of suture-augmented locking plate fixation for proximal third fractures of the olecranon.

Objectives: To describe a method of suture augmentation of locking plate fixation (PF) of proximal olecranon fractures and to evaluate the biomechanical effectiveness of the suture augmentation using a human cadaveric model. Methods: Six matched pairs of cadaveric elbows were used. Proximal one-third fractures of the olecranon were simulated via a transverse osteotomy. Identical locking PF was performed on each elbow using olecranon locking plates. One elbow of each pair was assigned to suture augmentation of the construct. The choice of left/right specimen for augmentation was performed in an alternating fashion. Augmentation was performed using a no. 2 ultra-high–molecular weight polyethylene–braided suture attaching the triceps to the plate via a modified Krackow stitch. The elbows were mounted into a custom jig and linearly loaded to failure using a hydraulic testing machine. Load to and modes of failure were recorded for each sample. The data were analyzed using the Wilcoxon signed-rank test for nonparametric distributions. Results: Suture augmentation improved the single load-to-failure strength in all pairs. One pair was excluded due to failure of the triceps attachment to the test machine. A median 398 N (P = 0.04 range, 197–633 N) or a median 48% (range, 30%–130%) improvement in strength was seen. The most common mode of failure was loss of fixation of the proximal olecranon fragment. Conclusions: Suture augmentation can significantly increase the single load-to-failure strength of locking PF for proximal olecranon fractures.

Evaluation of the Osteogenic Performance of Calcium Phosphate-Chitosan Bone Fillers

ABSTRACT There has been recent interest in utilizing calcium phosphates (CaPs) that set in situ for treating bone defects due to the limitations associated with morselized autografts and allografts. However, CaP cements have long setting times, poor mechanical properties, and poor osteoinductivity. This has prompted research toward finding a nonprotein-based compound, such as chitosan, to accelerate setting times and increase osteoinductivity. The purpose of this study was to compare bone growth rates during the early bone healing response achieved using conventionally prepared chitosan-CaP bone filler to an extensively purified chitosan-CaP compound. Both compounds set quickly and stimulated bone formation. Histomorphometry demonstrated a 290% increase in new bone formation when using the conventional chitosan-CaP bone filler and a 172% increase with the highly purified chitosan-CaP compound compared to the increase in bone formation seen with the unfilled control group. The results of this study indicate that a highly purified chitosan-CaP paste stimulated less bone formation than a conventionally prepared chitosan-CaP paste but both pastes have the potential to stimulate bone formation.

Measurements of microwave spectra and structural parameters for methylferrocene

Rotational transitions for methylferrocene were measured, in the 4–12 GHz range, using a Flygare–Balle type, pulsed-beam Fourier transform spectrometer. Mono-substituted ferrocenes are nearprolate asymmetric tops with a and b dipole moment components, providing numerous possible transitions in this frequency range. Eighteen rotational constants were calculated from the data for six isotopomers. 59 transitions were measured for the normal isotopomer, and much smaller data sets were obtained for the 54Fe, and four 13C isotopomers. Despite the small data sets for 13C and 54Fe transitions, good fits were obtained with small standard deviations ranging from 2 to 5 kHz. The eighteen A, B, and C rotational constants were used to determine the structural parameters for methylferrocene. Measured rotational constants for the normal isotopomer are: A=1592.6050(6), B=957.2565(4), and C=825.9892(4) MHz. The values for the averaged structural parameters are: r1(Fe–C)=2.050(7) A, r2(C–C)(cyclopentadienyl ligands)=1.433(...

Load Measurement Accuracy from Sensate Scaffolds with and without a Cartilage Surface

ABSTRACT The use of “sensate” scaffolds covered with tissue-engineered cartilage has emerged as a possible treatment option for focal articular cartilage defects. The ability to monitor joint loading provides several benefits that can be useful in both clinical and research situations. Previous studies have shown that these scaffolds can accurately monitor in vivo joint loading during various activities. However, the effect that an articular cartilage layer or soft tissue overgrowth has on scaffold sensitivity has not been tested. Eight scaffolds were tested with cartilage samples taken from four hounds. Three strain gauges were attached to each scaffold and a servo hydraulics system was used to test sensitivity while the scaffold was in contact with cartilage, metal, or silicone surfaces. Strain gauge sensitivity was calculated from load and strain measurements collected during testing. There was no significant difference between the mean strain gauge sensitivities when the scaffolds were in contact with the different surfaces: cartilage 30.9 ± 16.2 με/N, metal 31.8 ± 18.6 με/N, and silicone 30.6 ± 12.3 με/N. These results indicate that “sensate” scaffolds can be calibrated and used to monitor load with the presence of an articular cartilage layer.

Axonal Loss in Murine Peripheral Nerves Following Exposure to Recombinant Human Bone Morphogenetic Protein-2 in an Absorbable Collagen Sponge

BACKGROUND With the proven efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) to treat open tibial fractures and promote spine fusion, there has been an increase in its off-label use. Recent studies have shown that BMPs play a role in nerve development and regeneration. Little is known about changes that result when rhBMP-2 is used in the vicinity of peripheral nerves. The purpose of this study is to characterize changes in peripheral nerves following exposure to rhBMP-2-soaked collagen sponges. METHODS rhBMP-2 on an absorbable collagen sponge (ACS) was implanted directly on the sciatic nerves of Wistar rats. One and three weeks following surgery, the nerves were harvested and histological analysis was performed to evaluate inflammatory and structural changes. RESULTS rhBMP-2-soaked collagen sponges induced ectopic bone formation in muscle tissue in all animals after three weeks, but did not cause bone formation within the nerve. Axonal swelling and splitting of the myelin sheath were observed in both experimental and control nerves and may be a result of surgical manipulation. The overall incidence of axonal loss was 15.8% in the rhBMP-2/ACS-exposed nerves and was 0% in control nerves (p < 0.05). CONCLUSIONS rhBMP-2-soaked collagen sponges may adversely affect the axons of peripheral nerves by causing axonal dropout and loss of axons. Ectopic bone formation occurs within muscle tissues and not within the peripheral nerve. The axonal dropout may be a direct effect of rhBMP-2-soaked collagen sponges and not nerve compression as it was observed prior to ectopic bone formation.

Evidence-based Comprehensive Approach to Forearm Arterial Laceration

Introduction Penetrating injury to the forearm may cause an isolated radial or ulnar artery injury, or a complex injury involving other structures including veins, tendons and nerves. The management of forearm laceration with arterial injury involves both operative and nonoperative strategies. An evolution in management has emerged especially at urban trauma centers, where the multidisciplinary resource of trauma and hand subspecialties may invoke controversy pertaining to the optimal management of such injuries. The objective of this review was to provide an evidence-based, systematic, operative and nonoperative approach to the management of isolated and complex forearm lacerations. A comprehensive search of MedLine, Cochrane Library, Embase and the National Guideline Clearinghouse did not yield evidence-based management guidelines for forearm arterial laceration injury. No professional or societal consensus guidelines or best practice guidelines exist to our knowledge. Discussion The optimal methods for achieving hemostasis are by a combination approach utilizing direct digital pressure, temporary tourniquet pressure, compressive dressings followed by wound closure. While surgical hemostasis may provide an expedited route for control of hemorrhage, this aggressive approach is often not needed (with a few exceptions) to achieve hemostasis for most forearm lacerations. Conservative methods mentioned above will attain the same result. Further, routine emergent or urgent operative exploration of forearm laceration injuries are not warranted and not cost-beneficial. It has been widely accepted with ample evidence in the literature that neither injury to forearm artery, nerve or tendon requires immediate surgical repair. Attention should be directed instead to control of bleeding, and perform a complete physical examination of the hand to document the presence or absence of other associated injuries. Critical ischemia will require expeditious surgical restoration of arterial perfusion. In a well-perfused hand, however, the presence of one intact artery is adequate to sustain viability without long-term functional disability, provided the palmar arch circulation is intact. Early consultation with a hand specialist should be pursued, and follow-up arrangement made for delayed primary repair in cases of complex injury. Conclusion Management in accordance with well-established clinical principles will maximize treatment efficacy and functional outcome while minimizing the cost of medical care.

Brachial Plexopathy Following Use of Recombinant Human BMP-2 for Treatment of Atrophic Delayed Union of the Clavicle

Case:Although recombinant human bone morphogenetic protein-2 (rhBMP-2) is approved for treatment of open tibial fractures and anterior lumbar interbody fusion, off-label use has been associated with complications such as local inflammation, osteolysis, and dysphagia. This case report describes a patient treated with rhBMP-2 for an atrophic delayed union of a clavicular fracture who subsequently developed a profound motor and sensory brachial plexopathy. Conclusion:Use of rhBMP-2 near peripheral nerves may cause neuropathy. This should be considered prior to its use in surgical sites with peripheral nerves in proximity.

213 POROUS POLYBUTYLENE TEREPHTHALATE IMPLANTS ALLOW FOR BONE INGROWTH AND PROVIDE A WELL-ANCHORED SCAFFOLD THAT CAN BE USED TO DELIVER TISSUE-ENGINEERED CARTILAGE.

While joint pain and loss of mobility are common causes of impairment, there are few procedures that can consistently restore the long-term function of damaged articular cartilage. One approach that offers a potential solution for articular cartilage repair is replacement of the damaged cartilage using a tissue-engineered scaffold. The goal of this study was to measure loading and bone attachment in sensate, porous, calcium phosphate ceramic (CPC) coated polybutylene terephthalate (PBT) scaffolds that have been implanted in the medial compartment of the knees of 6 canines. In addition histology, histomorphometry, and scanning electron microscopy (SEM) were used to characterize bone growth into and around the PBT scaffold. In vivo measurements from the calibrated scaffolds indicated that peak loads in the dog knees ranged from 80-120N. Post-sacrifice biomechanical testing indicated that these loads correlated to pressures of 11 ± 1.54 MPa in the medial compartment of the knees. Histology demonstrated a bone volume of 6.8 ± 8.8% within the scaffold pores and an osteoid volume of 64.9 ± 17.2%. Histomorphometry indicated an increased bone formation rate within the scaffold pores, 8.2E-5 ± 5.9E-5 μm3 /μm2 /day, compared to 1.3E-5 ± 0.8E-5 mm3 /μm2 /day in control knees. SEM demonstrated less bone within the scaffold pores compared to the extensive amount of bone surrounding the scaffold and in intimate contact with the CPC particles. These results demonstrate that the scaffold is mechanically coupled to the bone. In addition, the increased bone formation rate and osteoid within the PBT pores demonstrate that bone formation is still occurring 6 months post-op. Currently studies are focused on the integration of PBT scaffolds containing a tissue-engineered cartilage covering into damaged articular cartilage.