Orthopedic Reconstruction Research Articles

Preparation, characterization, and in vitro cytotoxicity evaluation of a novel anti-tuberculosis reconstruction implant.

BackgroundReconstruction materials currently used in clinical for osteoarticular tuberculosis (TB) are unsatisfactory due to a variety of reasons. Rifampicin (RFP) is a well-known and highly effective first-line anti-tuberculosis (anti-TB) drug. Poly-DL-lactide (PDLLA) and nano-hydroxyapatite (nHA) are two promising materials that have been used both for orthopedic reconstruction and as carriers for drug release. In this study we report the development of a novel anti-TB implant for osteoarticular TB reconstruction using a combination of RFP, PDLLA and nHA.MethodsRFP, PDLLA and nHA were used as starting materials to produce a novel anti-TB activity implant by the solvent evaporation method. After manufacture, the implant was characterized and its biodegradation and drug release profile were tested. The in vitro cytotoxicity of the implant was also evaluated in pre-osteoblast MC3T3-E1 cells using multiple methodologies.ResultsA RFP/PDLLA/nHA composite was successfully synthesized using the solvent evaporation method. The composite has a loose and porous structure with evenly distributed pores. The production process was steady and no chemical reaction occurred as proved by Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD). Meanwhile, the composite blocks degraded and released drug for at least 12 weeks. Evaluation of in vitro cytotoxicity in MC3T3-E1 cells verified that the synthesized composite blocks did not affect cell growth and proliferation.ConclusionIt is feasible to manufacture a novel bioactive anti-TB RFP/PDLLA/nHA composite by the solvent evaporation method. The composite blocks showed appropriate properties such as degradation, drug release and biosafety to MC3T3-E1 cells. In conclusion, the novel composite blocks may have great potential for clinical applications in repairing bone defects caused by osteoarticular TB.

Local Foreign-Body Reaction to Commercial Biodegradable Implants: An in Vivo Animal Study

Biodegradable plates have been used extensively in fracture fixation since the 1960s. They rarely cause stress-protection atrophy or problems requiring secondary plate removal, common complications seen with metallic plates. However, aseptic foreign-body reactions have been reported, sometimes years after the original implantation. Both inadequate polymer degradation and debris accumulation have been implicated as causes. The current generation of commercial biodegradable plates is formulated to minimize this complication by altering the ratio of polylactic and polyglycolic acids. This in vivo study compares the degree of local foreign-body reaction of two commercially available resorbable plates in rabbits. Two types of biodegradable plates were examined: poly(D/L)lactide acid (PDLLA) and polylactide-co-glycolide acid (PLGA). Each plate was placed into a periosteal pericalvarial pocket created beneath the anterior or posterior scalp of a rabbit. Humane killing occurred at 3, 6, and 12 months postoperatively. Foreign-body reaction was evaluated histologically. The PDLLA plates demonstrated marked local foreign-body reactions within the implant capsule as early as 3 months after implantation, with presence of inflammatory cells and granulomatous giant cells in close association with the implant material. All local foreign-body reactions were subclinical with no corresponding tissue swelling requiring drainage. PLGA plates did not demonstrate any signs of inflammatory reactions. In addition, the PLGA plates did not appear to resorb or integrate at 12 months. Neither PDLLA nor PLGA plates demonstrated inflammation of the soft tissue or adjacent bone outside the implant capsule. In our study, the PDLLA plates demonstrated histological evidence of foreign-body reaction that is confined within the implant capsule, which was not seen with the PLGA plates. This finding may be attributable to the lack of significant resorption seen in the PLGA plates. Both PDLLA and PLGA plates were biocompatible with the rabbit tissue environment and should be considered for continued use in craniofacial, maxillofacial, and orthopedic reconstruction.

Bone embrittlement and collagen modifications due to high-dose gamma-irradiation sterilization

Bone allografts are often used in orthopedic reconstruction of skeletal defects resulting from trauma, bone cancer or revision of joint arthroplasty. γ-Irradiation sterilization is a widely-used biological safety measure; however it is known to embrittle bone. Irradiation has been shown to affect the post-yield properties, which are attributed to the collagen component of bone. In order to find a solution to the loss of toughness in irradiated bone allografts, it is important to fully understand the effects of irradiation on bone collagen. The objective of this study was to evaluate changes in the structure and integrity of bone collagen as a result of γ-irradiation, with the hypothesis that irradiation fragments collagen molecules leading to a loss of collagen network connectivity and therefore loss of toughness.Using cortical bone from bovine tibiae, sample beams irradiated at 33kGy on dry ice were compared to native bone beams (paired controls). All beams were subjected to three-point bend testing to failure followed by characterization of the decalcified bone collagen, using differential scanning calorimetry (DSC), hydrothermal isometric tension testing (HIT), high performance liquid chromatography (HPLC) and gel electrophoresis (SDS-PAGE). The carbonyl content of demineralized bone collagen was also measured chemically to assess oxidative damage. Barium sulfate staining after single edge notch bending (SEN(B)) fracture testing was also performed on bovine tibia bone beams with a machined and sharpened notch to evaluate the fracture toughness and ability of irradiated bone to form micro-damage during fracture.Irradiation resulted in a 62% loss of work-to-fracture (p≤0.001). There was significantly less micro-damage formed during fracture propagation in the irradiated bone. HPLC showed no significant effect on pentosidine, pyridinoline, or hydroxypyridinoline levels suggesting that the loss of toughness is not due to changes in these stable crosslinks. For DSC, there was a 20% decrease in thermal stability (p<0.001) with a 100% increase (p<0.001) in enthalpy of denaturation (melting). HIT testing also showed a decrease in thermal stability (20% lower denaturation temperature, p<0.001) and greatly reduced measures of collagen network connectivity (p<0.001). Interestingly, the increase in enthalpy of denaturation suggests that irradiated collagen requires more energy to denature (melt), perhaps a result of alterations in the hydrogen bonding sites (increased carbonyl content detected in the insoluble collagen) on the irradiated bone collagen.Altogether, this new data strongly indicates that a large loss of overall collagen connectivity due to collagen fragmentation resulting from γ-irradiation sterilization leads to inferior cortical bone toughness. In addition, notable changes in the thermal denaturation of the bone collagen along with chemical indicators of oxidative modification of the bone collagen indicate that the embrittlement may be a function not only of collagen fragmentation but also of changes in bonding.

CAD Method for Profiling Helical Surfaces of Parts Used in the Orthopaedic Reconstruction Surgery

In orthopedics are used a lot of specialized tools and reconstructive elements. Many of these are tools bounded by helical surfaces, significantly different from those used in similarly constructions with general character. There are analyzed, in a comparative way, two methods for profiling side mill tools for generation of specific threads used in the construction of the orthopaedic prosthetic screw. It is proposed an analytical method, based on the fundamental theorem of the surfaces enveloping versus a graphical method, developed in CATIA.

Bioactivation of calcium deficient hydroxyapatite with foamed gelatin gel. A new injectable self-setting bone analogue

An alternative approach to bone repair for less invasive surgical techniques, involves the development of biomaterials directly injectable into the injury sites and able to replicate a spatially organized platform with features of bone tissue. Here, the preparation and characterization of an innovative injectable bone analogue made of calcium deficient hydroxyapatite and foamed gelatin is presented. The biopolymer features and the cement self-setting reaction were investigated by rheological analysis. The porous architecture, the evolution of surface morphology and the grains dimension were analyzed with electron microscopy (SEM/ESEM/TEM). The physico-chemical properties were characterized by X-ray diffraction and FTIR analysis. Moreover, an injection test was carried out to prove the positive effect of gelatin on the flow ensuing that cement is fully injectable. The cement mechanical properties are adequate to function as temporary substrate for bone tissue regeneration. Furthermore, MG63 cells and bone marrow-derived human mesenchymal stem cells (hMSCs) were able to migrate and proliferate inside the pores, and hMSCs differentiated to the osteoblastic phenotype. The results are paving the way for an injectable bone substitute with properties that mimic natural bone tissue allowing the successful use as bone filler for craniofacial and orthopedic reconstructions in regenerative medicine.

In Memoriam: George Cierny, III MD (1947-2013)

The Musculoskeletal Infection Society (MSIS) joins the entire orthopaedic community in mourning the loss of George Cierny, III MD (Fig. 1), an orthopaedic leader and legend. Dr. Cierny died on June 24, 2013 following a 7-month-long battle with pancreatic cancer. Fig. 1 A superb clinician-scientist, Dr. Cierny’s contributions to the field of orthopaedics number more than 100 scientific papers and book chapters. Dr. Cierny was born on Dec. 12, 1947 in San Diego, CA. He graduated from the University of California, Berkeley in 1969, and attended medical school at the University of California, Los Angeles, receiving his doctorate in 1974. Dr. Cierny completed his surgical internship and orthopaedic residency in 1979 at the University of Texas, Parkland in Dallas. There, he took an interest in the treatment of high-energy open fractures and the study of wound environment. From his experiences, he went on to coauthor landmark papers on open fracture management. After residency, Dr. Cierny continued his education in a Musculoskeletal Oncology and Pathology fellowship at the University of Florida, Gainesville, with Dr. William Enneking who described Dr. Cierny in a conversation with Dr. Richard “Dickey” Jones (June 2013) as “a truly remarkable individual, a really unique thinker.” After joining the Department of Orthopaedic Surgery at the University of Texas, Galveston, Dr. Cierny combined his expertise of oncology and orthopaedic reconstruction, and applied the principles to musculoskeletal infections. His pioneering work with Infectious Disease specialist Dr. Jon Mader, led to the landmark paper describing the Cierny-Mader classification, staging system, and treatment algorithm for osteomyelitis, which has been accepted worldwide. Dr. Cierny then moved to Atlanta, GA and joined the faculty of Orthopaedic Surgery at Emory University, where he served as Associate Professor and later as full Professor. There, he continued his work on musculskeletal infections. In 1989, Dr. Cierny became a founding member of the MSIS, which is a multidisciplinary educational and scientific forum for the advancement of knowledge in bone and joint infection. An active member from the society’s inception, Dr. Cierny served two terms as President—in 1999 and 2006. Deciding to move back to his childhood hometown, he and his wife and practice partner, Dr. Doreen DiPasquale, relocated from Atlanta to San Diego in 2006. Back in California, they established REOrthopaedics—a practice dedicated to the care of patients with musculoskeletal infections. A superb clinician-scientist, his contributions to the field of orthopaedics include more than 100 scientific papers and book chapters. In 2009, he coedited Orthopaedic Knowledge Update: Musculoskeletal Infection, published by the American Academy of Orthopaedic Surgeons. Dr. Cierny has been a guest speaker at numerous national and international meetings, and he was honored as presidential speaker for many orthopaedic organizations where he graced the audience with informative and concise lectures. Dr. Cierny’s contributions to the MSIS have been numerous and impactful. His enthusiasm, energy, and dedication to excellence serve as a role model for everyone to emulate. To encourage research investigating the treatment of orthopaedic infections, the Orthopaedic Research and Education Foundation established the George Cierny III, MD Bone and Joint Musculoskeletal Infection Fund, accessible at on.oref.org/Cierny. We all will greatly miss Dr. Cierny, a true orthopaedic legend, who leaves a lasting legacy.

Paediatric extremity vascular injuries – Experience from a large urban trauma centre in India

IntroductionPaediatric extremity vascular injuries are infrequent, and management protocols draw significantly from adult vascular trauma experience necessitating a continuous review of evidence. Materials and methodsA retrospective registry review of all consecutive patients younger than 18 years age treated for extremity vascular trauma from 2007 to 2012 was carried out. Diagnostic algorithm relied little on measurement of pressure indices. Data was collected about demographics, time since injury, pattern of injury, ISS, initial GCS and presence of shock, results of diagnostic modality and treatment given with associated complications. Patients completing 2 years follow up were assessed for functional disability and vascular patency. A multivariable regression model was used to evaluate effects of – ISS, presence of orthopaedic injury, soft tissue injury, neural injury and arterial patency at the end of 2 years – on outcome of functional disability. ResultsPaediatric extremity vascular injuries accounted for 0.68% hospital admissions with a median delay of 8h from injury. 82 patients were included with 50 cases examined for long term outcome. Patient cohort was overwhelmingly male, with ‘fall’, ‘road traffic injury’ and ‘glass cut’ being most common injury mechanisms. CT angiography and duplex scan based diagnostic algorithm performed satisfactorily further identifying missed injuries and aiding complex orthopaedic reconstruction. Brachial and femoral vessels were most commonly injured. Lower extremity vascular injury was found associated with significantly higher ISS and requirement for fasciotomy. Upper extremity vascular injury was associated with higher odds of neural injury. Younger children were at higher risk of combined radial and ulnar vessel injury. No patient satisfactorily complied with post-operative anticoagulant/antithrombotic prophylaxis. 28 patients had good functional outcome with unsatisfactory functional outcome found associated with significantly higher ISS, presence of orthopaedic and neural injury, along with absence of arterial patency. ConclusionThe epidemiology of paediatric peripheral vascular injury differs in India compared to west. Certain traditional management principles of extremity vascular trauma may stand uniquely challenged in the paediatric population.

A Physiological Dynamic Testing Machine for the Elbow Joint

Background: The aim of our study was to develop a test setup combining realistic force transmission with physiological movement patterns at a frequency that mimicked daily use of the elbow, to assess implants in orthopedic joint reconstruction and trauma surgery.Methods:In a multidisciplinary approach, an in vitro biomechanical testing machine was developed and manufactured that could simulate the repetitive forceful movement of the human elbow joint. The construction involved pneumatic actuators. An aluminum forearm module enabled movements in 3 degrees of freedom, while motions and forces were replicated via force and angular sensors that were similar to in vivo measurements.Results:In the initial testing, 16 human elbow joint specimens were tested at 35 Nm in up to 5000 cycles at a range of 10° extension to 110° flexion. The transmitted forces led to failure in 9 out of the 16 tested specimens, significantly more often in females and small specimens.Conclusions:It is possible to construct a testing machine to simulate nearly physiological repetitive elbow motions. The prototype has a number of technical deficiencies that could be modified. When testing implants for the human elbow with cadaver specimens, the specimen has to be chosen according to the intended use of the implant under investigation.

Orthopaedic Reconstruction of Complex Pelvic Bone Defects. Evaluation of Various Treatment Methods

Despite major developments in the field of revision surgery in recent decades, the management of severe acetabular deficiency at revision arthroplasty, complex primary total hip replacement or after pelvic tumour resection remains a complex problem. The options available for the management of severe bone loss include the use of uncemented press-fit cups with or without metal augments, impaction allografts, allograft-prosthesis composites, custom-made triflange cups, hip transposition, reconstruction prostheses or various combinations of these. This paper describes defect classification, various treatment options, clinical outcomes, survival of reconstruction, and typical complications in relation to treatment.

Decision Making in Limb Salvage

Optimal decision making in reconstruction of soft tissues after massive orthopedic trauma is mission-critical to a favorable outcome. In the broadest definition this reconstruction does not just mean a large soft-tissue placed on the bony injury—but rather that the injured patient regains as full a functional recovery, is not narcotic or antibiotic dependent (as many patients with recurring osteomyelitis, plate infection are) and has as little of a disfigurement of the donor and recipient sites as possible. Many argue this is a tall order—and perhaps so. But given where we are in 2012, with advances in all trauma-related fields including imaging, injury scoring, orthopedic reconstruction, it is not too much to expect that plastic and reconstructive methods too run with the winners. An optimal result depends heavily on the following key reconstructive elements described below. (1) timing of reconstruction, (2) choice of soft tissue, (3) anticipated functional outcomes, (4) composite orthoplastic team. Critics may argue that this approach is oversimplified. But on further and more thorough examination it becomes amply clear that these 4 factors play a sentinel role: Here, we describe these aspects in detail.

PHEMA-nHA Encapsulation and Delivery of Vancomycin and rhBMP-2 Enhances its Role as a Bone Graft Substitute

Bone grafts are widely used in orthopaedic procedures. Autografts are limited by donor site morbidity while allografts are known for considerable infection and failure rates. A synthetic composite bone graft substitute poly(2-hydroxyethyl methacrylate)-nanocrystalline hydroxyapatite (pHEMA-nHA) was previously developed to stably press-fit in and functionally repair critical-sized rat femoral segmental defects when it was preabsorbed with a single low dose of 300 ng recombinant human bone morphogenetic protein-2/7 (rhBMP-2/7). To facilitate clinical translation of pHEMA-nHA as a synthetic structural bone graft substitute, we examined its ability to encapsulate and release rhBMP-2 and the antibiotic vancomycin. We analyzed the compressive behavior and microstructure of pHEMA-nHA as a function of vancomycin incorporation doses using a dynamic mechanical analyzer and a scanning electron microscope. In vitro release of vancomycin was monitored by ultraviolet-visible spectroscopy. Release of rhBMP-2 from pHEMA-nHA-vancomycin was determined by ELISA. Bioactivity of the released vancomycin and rhBMP-2 was examined by bacterial inhibition and osteogenic transdifferentiation capabilities in cell culture, respectively. Up to 4.8 wt% of vancomycin was incorporated into pHEMA-nHA without compromising its structural integrity and compressive modulus. Encapsulated vancomycin was released in a dose-dependent and sustained manner in phosphate-buffered saline over 2 weeks, and the released vancomycin inhibited Escherichia coli culture. The pHEMA-nHA-vancomycin composite released preabsorbed rhBMP-2 in a sustained manner over 8 days and locally induced osteogenic transdifferentiation of C2C12 cells in culture. pHEMA-nHA can encapsulate and deliver vancomycin and rhBMP-2 in a sustained and localized manner with reduced loading doses. The elasticity, osteoconductivity, and rhBMP-2/vancomycin delivery characteristics of pHEMA-nHA may benefit orthopaedic reconstructions or fusions with enhanced safety and efficiency and reduced infection risk.

Guided Growth for Deformity Correction

Abnormal or injured physes, with or without pathologic loading, may result in a wide variety of limb deformities that require orthopaedic reconstruction to correct angular problems and equalize limb lengths. For neglected cases, or upon reaching skeletal maturity, osteotomies may be required for correction. However, in the skeletally immature patient with angular deformity, reversible hemi-epiphysiodesis, or guided growth, may be used to correct the mechanical axis, gain length, and restore function. In addition, for unilateral deformities, epiphysiodesis of the contralateral extremity, be it temporary or “definitive,” may be useful to correct modest limb length discrepancy (ie, 2-5 cm). Epiphysiodesis via physeal ablation, be it by open (Phemister) or percutaneous drilling, has the disadvantages of inexact timing and permanence. Although Blount staples were used for decades to achieve reversible epiphysiodesis, problems with staple migration or breakage led to the development of the nonlocking plate/screw construct, in order reduce complications and provide more reliable outcomes. This article focuses upon the technique and rationale for guided growth, including illustrative case examples.

EARLY COMBINED NEUROSURGERY AND ORTHOPAEDIC SURGERY IN NEONATAL BRACHIAL PLEXUS PALSY

Three cases are presented in which neurosurgical reconstruction of a Neonatal Brachial Plexus Palsy was combined with orthopaedic reconstruction of a posterior glenohumeral dislocation. The authors believe that a combined procedure is indicated if the neurological deficit meets the criteria for neural reconstruction and the complication of a posterior glenohumeral dislocation has occurred prior to nerve surgery. Two children with C5-6 lesions and a third child with a pan-plexus lesion obtained good shoulder function following the combined reconstruction.

Addition of pamidronate to chemotherapy for the treatment of osteosarcoma

This study evaluated the safety and feasibility of the addition of pamidronate to chemotherapy for treatment of osteosarcoma. The authors treated 40 patients with osteosarcoma with cisplatin, doxorubicin, and methotrexate with the addition of pamidronate 2 mg/kg/dose (max dose 90 mg) monthly for 12 doses. Survival, event-free survival (EFS), and durability of orthopedic reconstruction were evaluated. For patients with localized disease, event-free survival (EFS) at 5 years was 72% and overall survival 93%. For patients with metastatic disease, EFS at 5 years was 45% and overall survival 64%. Toxicity was similar to patients treated with chemotherapy alone. Thirteen of 14 uncemented implants demonstrated successful osteointegration. Among allograft reconstructions, there were 2 graft failures, 4 delayed unions, and 6 successful grafts. Overall, 5 of 33 reconstructions failed. There were no stress fractures or growth disturbances. Pamidronate can be safely incorporated with chemotherapy for the treatment of osteosarcoma. It does not impair the efficacy of chemotherapy. Pamidronate may improve the durability of limb reconstruction.

Do locking plates have a role in orthopaedic oncological reconstruction

Role of locking plate in skeletal reconstruction after resection of bone tumours in Indian patients. Retrospective evaluation of skeletal reconstruction using locking plate in 20 cases of long bone tumours was done. Reconstruction was done in 12 patients following limb salvage surgery, internal fixation of pathological fracture in seven bone tumours and one angiomatous tumour. There were 12 females and 8 male patients. Average age at the time of surgery was 30.1 years (range 10-58). Minimum follow-up was 11 months (range 11-38). Average time for union in pathological fractures was 4 weeks and 120 days after limb salvage surgery. Vicryl mesh was used to contain the morcellized allograft and cancellous iliac crest in 17 cases. Eighteen reconstructions were intact at an average follow-up of 17 months. Two failed reconstructions included one plate breakage and one screw pull out. Use of locking plate does not ensure the bony union at the site of reconstruction but it expedite it and allow early mobilization of joints and weight bearing particularly in Indian patients with late presentations. Careful selection of patients and proper preoperative planning including length of resection are essential for optimal outcomes and to minimize complications. Reconstruction should be supported by cortico-cancellous autograft/allograft for stabilization and union at junction of host and autograft/allograft bone and should be given adequate protection. Vicryl mesh helps in containing the morcellized grafts along the long axis of reconstruction.

Engineering anatomically shaped human bone grafts

The ability to engineer anatomically correct pieces of viable and functional human bone would have tremendous potential for bone reconstructions after congenital defects, cancer resections, and trauma. We report that clinically sized, anatomically shaped, viable human bone grafts can be engineered by using human mesenchymal stem cells (hMSCs) and a "biomimetic" scaffold-bioreactor system. We selected the temporomandibular joint (TMJ) condylar bone as our tissue model, because of its clinical importance and the challenges associated with its complex shape. Anatomically shaped scaffolds were generated from fully decellularized trabecular bone by using digitized clinical images, seeded with hMSCs, and cultured with interstitial flow of culture medium. A bioreactor with a chamber in the exact shape of a human TMJ was designed for controllable perfusion throughout the engineered construct. By 5 weeks of cultivation, tissue growth was evidenced by the formation of confluent layers of lamellar bone (by scanning electron microscopy), markedly increased volume of mineralized matrix (by quantitative microcomputer tomography), and the formation of osteoids (histologically). Within bone grafts of this size and complexity cells were fully viable at a physiologic density, likely an important factor of graft function. Moreover, the density and architecture of bone matrix correlated with the intensity and pattern of the interstitial flow, as determined in experimental and modeling studies. This approach has potential to overcome a critical hurdle-in vitro cultivation of viable bone grafts of complex geometries-to provide patient-specific bone grafts for craniofacial and orthopedic reconstructions.

Transforming growth factor-β1 modulates insulin-like growth factor binding protein-4 expression and proteolysis in cultured periosteal explants

Objective Periosteum is involved in bone growth and fracture healing and has been used as a cell source and tissue graft for tissue engineering and orthopedic reconstruction including joint resurfacing. Periosteum can be induced by transforming growth factor beta (TGF-β) or insulin-like growth factor-I (IGF-I) alone or in combination to form cartilage. However, little is known about the interaction between IGF and TGF-β signaling during periosteal chondrogenesis. The purpose of this study was to determine the effect of TGF-β1 on IGF binding protein-4 (IGFBP-4) and the IGFBP-4 protease pregnancy-associated plasma protein-A (PAPP-A) expression in cultured periosteal explants. Design Periosteal explants from rabbits were cultured with or without TGF-β1. IGFBP-4 and PAPP-A mRNA levels were determined by real-time quantitative PCR. Conditioned medium was analyzed for IGFBP-4 and PAPP-A protein levels and IGFBP-4 protease activity. Results TGF-β1-treated explants contained lower IGFBP-4 mRNA levels throughout the culture period with a maximum reduction of 70% on day 5 of culture. Lower levels of IGFBP-4 protein were also detected in the conditioned medium from TGF-β1-treated explants. PAPP-A mRNA levels were increased 1.6-fold, PAPP-A protein levels were increased threefold, and IGFBP-4 protease activity was increased 8.5-fold between 7 and 10 days of culture (the onset of cartilage formation in this model) in conditioned medium from TGF-β1-treated explants. Conclusions This study demonstrates that TGF-β1 modulates the expression of IGFBP-4 and PAPP-A in cultured periosteal explants.

Titanium implants alter endothelial function and vasoconstriction via a protein kinase C-regulated pathway

The application of titanium (Ti) alloy in joint prostheses is a good choice in orthopedic reconstruction. An elevated serum concentration of Ti has been shown in the patients with loosened knee prostheses. The precise actions of elevated Ti on the circulation remain unclear. In this study the maximal contractile responses elicited by phenylephrine in the aortas of rats 4 weeks after Ti alloy implantation and in cultured rat aortas treated with a soluble form of Ti for a period of 18 h were significantly decreased as compared with controls. Aortas isolated from rats with Ti alloy implants or aortas treated with a soluble form of Ti had enhanced protein expression of endothelial nitric oxide synthase (eNOS) and protein kinase C (PKC)-α and enhanced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Treatment of human umbilical vein endothelial cells (HUVECs) with a soluble form of Ti for 24 h dose-dependently increased eNOS protein expression. Short-term treatment of HUVECs with Ti for 1 h effectively enhanced the phosphorylation of eNOS, PKC (pan) and ERK1/2. PKC inhibitors RO320432 and chelerythrine effectively inhibited Ti-enhanced phosphorylation of eNOS and PKC (pan). These results indicate that Ti in the circulation may alter endothelial function and reduce vasoconstriction.

Management of traumatic brachial artery injuries: A report on 49 patients

BACKGROUND AND OBJECTIVE:The brachial artery is the most frequently injured artery in the upper extremity due to its vulnerability. The purpose of our study was to review our experience with brachial artery injuries over a 9-year period, describing the type of injury, surgical procedures, complications, and associated injuries.PATIENTS AND METHODS:Forty-nine patients with brachial artery injury underwent surgical repair procedures at our hospital, from the beginning of May 1999 to the end of June 2008. The brachial artery injuries were diagnosed by physical examination and Doppler ultrasonography. Depending on the mode of presentation, patients were either taken immediately to the operating room for bleeding control and vascular repair or were assessed by preoperative duplex ultrasonography.RESULTS:This study group consisted of 43 males and 6 females, ranging in age from 6 to 65 years with a mean (SD) age of 27.9 (6.7) years. The mechanism of trauma was penetrating in 45 patients and blunt in the remaining 4 patients. Stab injury was the most frequent form of penetrating trauma (24 of 45). Treatment included primary arterial repair in 5 cases, end-to-end anastomosis in 28 cases, interposition vein graft in 15 cases, and interposition-ringed polytetrafluoroethylene graft in 1 case. Associated injuries were common and included venous injury (14), bone fracture (5), and peripheral nerve injury (11). Fifteen patients developed postoperative complications. One patient underwent an above-elbow amputation.CONCLUSIONS:Prompt and appropriate management of the brachial artery injuries, attention to associated injuries, and a readiness to revise the vascular repair early in the event of failure will maximize patient survival and upper extremity salvage.

Manipulating the anabolic and catabolic response in bone graft remodeling: Synergism by a combination of local BMP‐7 and a single systemic dosis of zoledronate

Remodeling of a bone graft can be influenced both by anabolic substances, such as a bone morphogenic protein (BMP) and by anticatabolic substances, such as the bisphosphonates. BMPs are potent bone anabolic substances, but also boost catabolism and cause resorption. Bisphosphonates inhibit osteoclast function and can be used to postpone resorption. In the present study a combination of both drugs was explored in a rat bone chamber model. Cancellous bone grafts were treated with either BMP-7 or saline and placed in a bone chamber implanted in the proximal tibia. After 2 weeks, an injection of either zoledronate 0.1 mg/kg or saline was given subcutaneously. The rats were killed after 6 weeks, and bone ingrowth distance into the graft and graft resorption were measured by histomorphometry. BMP-7 significantly (p = 0.007) increased new bone ingrowth distance into the graft from 2.0 mm (SD = 0.98 mm) in the controls to 3.1 mm (SD = 0.93 mm). If bisphosphonate was not given, most of the newly formed and old graft bone was resorbed. A single injection of zoledronate significantly (p < 0.001) increased the trabecular volume/total volume to 40% (SD = 9%) compared to 14% (SD = 10%) in the nonbisphosphonate treated. In total, the net amount of bone increased by 400% when BMP-7 and zoledronate combined was compared to saline. A bone graft can be treated with BMP-7 to increase new bone formation and at the same time be protected against premature catabolism by a single dose of a bisphosphonate. This combination might be useful in various conditions in orthopedic reconstruction.