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Bradford L Currier

Publications and source records attributed to Bradford L Currier.

At least 19 recordsLinked to original sources
PubMed2006

Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate).

The ideal biomaterial for the repair of bone defects is expected to have good mechanical properties, be fabricated easily into a desired shape, support cell attachment, allow controlled release of bioactive factors to induce bone formation, and biodegrade into nontoxic products to permit natural bone formation and remodeling. The synthetic polymer poly(propylene fumarate) (PPF) holds great promise as such a biomaterial. In previous work we developed poly(DL-lactic-co-glycolic acid) (PLGA) and PPF microspheres for the controlled delivery of bioactive molecules. This study presents an approach to incorporate these microspheres into an injectable, porous PPF scaffold. Model drug Texas red dextran (TRD) was encapsulated into biodegradable PLGA and PPF microspheres at 2 microg/mg microsphere. Five porous composite formulations were fabricated via a gas foaming technique by combining the injectable PPF paste with the PLGA or PPF microspheres at 100 or 250 mg microsphere per composite formulation, or a control aqueous TRD solution (200 microg per composite). All scaffolds had an interconnected pore network with an average porosity of 64.8 +/- 3.6%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy and confocal microscopy. The composite scaffolds exhibited a sustained release of the model drug for at least 28 days and had minimal burst release during the initial phase of release, as compared to drug release from microspheres alone. The compressive moduli of the scaffolds were between 2.4 and 26.2 MPa after fabrication, and between 14.9 and 62.8 MPa after 28 days in PBS. The scaffolds containing PPF microspheres exhibited a significantly higher initial compressive modulus than those containing PLGA microspheres. Increasing the amount of microspheres in the composites was found to significantly decrease the initial compressive modulus. The novel injectable PPF-based microsphere/scaffold composites developed in this study are promising to serve as vehicles for controlled drug delivery for bone tissue engineering.

Bone Cements↗
PubMed2005

Multiple-channel scaffolds to promote spinal cord axon regeneration.

As molecular, cellular, and tissue-level treatments for spinal cord injury are discovered, it is likely that combinations of such treatments will be necessary to elicit functional recovery in animal models or patients. We describe multiple-channel, biodegradable scaffolds that serve as the basis for a model to investigate simultaneously the effects on axon regeneration of scaffold architecture, transplanted cells, and locally delivered molecular agents. Poly(lactic-co-glycolic acid) (PLGA) with copolymer ratio 85:15 was used for these initial experiments. Injection molding with rapid solvent evaporation resulted in scaffolds with a plurality of distinct channels running parallel along the length of the scaffolds. The feasibility of creating scaffolds with various channel sizes and geometries was demonstrated. Walls separating open channels were found to possess void fractions as high as 89%, with accessible void fractions as high as 90% through connections 220 microm or larger. Scaffolds degraded in vitro over a period of 30 weeks, over which time-sustained delivery of a surrogate drug was observed for 12 weeks. Primary neonatal Schwann cells were distributed in the channels of the scaffold and remained viable in tissue culture for at least 48 h. Schwann-cell containing scaffolds implanted into transected adult rat spinal cords contained regenerating axons at one month post-operation. Axon regeneration was demonstrated by three-dimensional reconstruction of serial histological sections.

Absorbable Implants↗
PubMed2005

Synthesis and characterizations of biodegradable and crosslinkable poly(epsilon-caprolactone fumarate), poly(ethylene glycol fumarate), and their amphiphilic copolymer.

A series of self-crosslinkable and biodegradable polymers, poly(caprolactone fumarate) (PCLF), poly(ethylene glycol fumarate) (PEGF), and their copolymer PEGF-co-PCLF, has been developed for tissue engineering applications using a novel synthesis method. The current method employs potassium carbonate (K2CO3), other than the previously reported triethylamine, as the proton scavenger. The new synthetic route is more convenient and less time-consuming to carry out, and the synthesized polymers have a much lighter color, which renders them more suitable for self-crosslinking via photo-initiation. This group of polymers are essentially copolymers of fumaryl chloride, which contains double bonds for in situ crosslinking, with poly(epsilon-caprolactone) (PCL) or/and poly(ethylene glycol) (PEG) that has a flexible chain to facilitate self-crosslinking. Both PCLF and PEGF, and their amphiphilic copolymer PEGF-co-PCLF could be self-crosslinked or photocrosslinked to produce scaffolds without the use of a crosslinking agent. Our results suggest that these polymers are potentially useful as injectable, self-crosslinkable, and photo-crosslinkable materials for diverse tissue engineering applications.

Biocompatible Materials↗
PubMed2004

Quantitative analysis of interconnectivity of porous biodegradable scaffolds with micro-computed tomography.

Pore interconnectivity within scaffolds is an important parameter influencing cell migration and tissue ingrowth needed to promote tissue regeneration. Methods for assessment of interconnectivity are usually qualitative, restricted to two-dimensional images, or are destructive. Microcomputed tomography nondestructively provides three-dimensional (3D) images of intact specimens at high spatial resolutions. We describe an image analysis technique for quantitative assessment of scaffold interconnectivity. Scaffolds were made via a particulate leaching process with 75%, 80%, 85%, and 88% volumetric porogen fractions. Specimens were scanned and resulting 3D, digital images were analyzed with a custom algorithm. A series of virtual, idealized scaffolds were also created for illustration of the algorithm's analysis approach and for its validation. The program calculated accessible void fractions over a range of minimum connection sizes. In real specimens, nearly 100% of the porous volume was connected with outside air for connections greater than or equal to 20 microm in their smallest dimension. In scaffolds made with 75% porogen, the accessible void fraction decreased to 78% if only those connections greater than or equal to 260 microm were considered. The relationship between accessible void fraction and connection size varied as a function of porogen content. The interconnectivity parameter described here may have implications for cell migration and tissue growth into scaffolds.

Algorithms↗
PubMed2004

Successful treatment of disseminated nonmeningeal coccidioidomycosis with voriconazole.

A 31-year-old Jamaican man with disseminated nonmeningeal coccidioidomycosis that involved the spine, ribs, pelvis, liver, and spleen did not clinically respond to a prolonged course of both amphotericin B deoxycholate and liposomal amphotericin B therapy. After institution of voriconazole monotherapy, the patient had a favorable (albeit slow) radiological and clinical response without adjunctive surgical intervention.

Adult↗
PubMed2004

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. I. Preparation and characterization.

We developed poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres and investigated the effects of various processing parameters on the characteristics of these microspheres. The advantage of these blend microspheres is that the carbon-carbon double bonds along the PPF backbone could be used for their immobilization in a PPF scaffold. Microspheres containing the model drug Texas red dextran were fabricated using a double emulsion-solvent extraction technique. The effects of the following six processing parameters on the microsphere characteristics were investigated: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) (PVA) in the internal aqueous phase, and PVA concentration in the external aqueous phase. Our results showed that the microsphere surface morphology was affected most by the viscosity of the polymer solution. Microspheres fabricated with a kinematic viscosity of 39 centistokes had a smooth, nonporous surface. In most microsphere formulations, the model drug was dispersed uniformly in the polymer matrix. For all fabricated formulations, the average microsphere diameter ranged between 19.0 and 76.9 microm. The external PVA concentration and vortex speed had most effect on the size distribution. Entrapment efficiencies varied from 60 to 98% and were most affected by the amount of internal aqueous phase, vortex speed, and polymer viscosity. Overall, we demonstrated the ability to fabricate PPF/PLGA blend microspheres with similar surface morphology, entrapment efficiency, and size distribution as conventional PLGA microspheres.

Biocompatible Materials↗
PubMed2004

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. II. Controlled drug release and microsphere degradation.

This article describes the effects of six processing parameters on the release kinetics of a model drug Texas red dextran (TRD) from poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres as well as the degradation of these microspheres. The microspheres were fabricated using a double emulsion-solvent extraction technique in which the following six parameters were varied: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) in the internal aqueous phase, and poly(vinyl alcohol) concentration in the external aqueous phase. We have previously characterized these microspheres in terms of microsphere morphology, size distribution, and TRD entrapment efficiency. In this work, the TRD release profiles in phosphate-buffered saline were determined and all formulations showed an initial burst release in the first 2 days followed by a decreased sustained release over a 38-day period. The initial burst release varied from 5.1 (+/-1.1) to 67.7 (+/-3.4)% of the entrapped TRD, and was affected most by the viscosity of the polymer solution used for microsphere fabrication. The sustained release between day 2 and day 38 ranged from 7.9 (+/-0.8) to 27.2 (+/-3.1)% of the entrapped TRD. During 11 weeks of in vitro degradation, the mass of the microspheres remained relatively constant for the first 3 weeks after which it decreased dramatically, whereas the molecular weight of the polymers decreased immediately upon placement in phosphate-buffered saline. Increasing the PPF content in the PPF/PLGA blend resulted in slower microsphere degradation. Overall, this study provides further understanding of the effects of various processing parameters on the release kinetics from PPF/PLGA blend microspheres thus allowing modulation of drug release to achieve a wide spectrum of release profiles.

Biocompatible Materials↗
PubMed2004

Cervical spine and spinal cord injuries: recognition and treatment.

Cervical spine injuries are frequently encountered in any practice treating patients in the emergency department or outpatient trauma victims. When upper or lower cervical spine injuries are suspected, immediate immobilization, physical and neurologic examination, and radiographic evaluation are imperative. For spinal cord injuries, knowledge of microscopic and cellular pathology helps to determine appropriate management.

Cervical Vertebrae↗
PubMed2003

Anatomic relationship of the internal carotid artery to the C1 vertebra: A case report of cervical reconstruction for chordoma and pilot study to assess the risk of screw fixation of the atlas.

STUDY DESIGN: A case of internal carotid artery impingement by the tip of a well-positioned C1-C2 transarticular screw is presented along with a pilot study involving radiologic and anatomic evaluation of human cadaveric specimens. OBJECTIVE: To raise awareness that the internal carotid artery may be in close proximity to the anterior aspect of the atlas and at risk of injury during placement of C1-C2 transarticular screws or C1 lateral mass screws. SUMMARY OF BACKGROUND DATA: To our knowledge, no cases of internal carotid artery injury or impingement have been reported with screw fixation of the atlas. METHODS: A case of internal carotid artery impingement by a C1-C2 transarticular screw is presented. The C1-C2 rotation appeared to place the internal carotid artery in the path of the screw, prompting a pilot study. Three fresh-frozen human cadaveric head and neck specimens were fixed in different degrees of rotation. Thin-section computed tomography of the specimens was obtained in the plane of the atlas. The frozen specimens were sectioned in the same plane as the computed tomography images. Measurements were taken to assess the location of the internal carotid artery relative to the anterior aspect of the atlas. RESULTS: Cervical rotation does not have a predictable effect on the location of the internal carotid artery. Medial angulation of a screw placed in the lateral mass of C1 appears to increase the margin of safety for the internal carotid artery. The internal carotid artery varies in location and may be within 1 mm of the ideal exit point of a bicortical transarticular screw or a C1 lateral mass screw. CONCLUSIONS: The internal carotid artery is at risk during bicortical screw fixation of the atlas. We recommend a contrast-enhanced computed tomography to assess the location of the internal carotid artery before screw fixation of the atlas.

Adolescent↗
PubMed2003

Biomechanical evaluation of posterior screw fixation in cadaveric cervical spines.

Sixteen fresh-frozen spines from cadavers (C4-T1) were randomized on the basis of dual energy xray absorptiometry analysis of bone mineral density. The specimens were subjected to physiologic loads (<or= 1.5 N-m) in a device that applied pure unconstrained, flexion and extension, lateral bending, and torsional moments. After a major injury, including a wide C6 laminectomy, bilateral capsulectomies, and 65% facetectomy at C6-C7, four constructs were applied to each specimen in a balanced sequence, and the stability tests were repeated. All the constructs were identical posterior cervical rods secured to the spine with lateral mass screws in C5 and pedicle screws in C7. The constructs differed only in the presence or absence of a transverse connector between the rods, presence or absence of lateral mass screws in C6, and unicortical or bicortical lateral mass screws. Insertional screw torque was higher in specimens with greater bone mineral density. Pedicle screws had greater torque than lateral mass screws. Posterior cervical spine rod fixation provided an equivalent stability by use of either unicortical or bicortical lateral mass screws. A transverse stabilizer between the rods reduces the number of lateral mass screws needed in posterior cervical spinal rod systems. Repeated stability tests, even when done with physiologic loads, may compromise the screw-bone interface. This effect is most pronounced in specimens that have low bone mineral density.

Adult↗
PubMed2003

Biomechanical evaluation of new posterior occipitocervical instrumentation system.

Twelve fresh-frozen cadaveric occipitocervical specimens were randomized based on dual energy xray absorptiometry analysis of bone mineral density. The specimens were subjected to physiologic loads in a device that applied pure unconstrained flexion and extension, lateral bending, and axial rotational moments. The spines were tested intact and after major injury simulating transoral decompression of the dens. Biomechanical testing using pure moments with physiologic loads (< 1.5 N-m) was used to compare stability of posterior occipitocervical plates and screws, loop and cable construct, and new cervical rod and screw system. The injury created significantly less stiffness and greater range of motion and neutral zone at C1-C2 in flexion and extension and lateral bending and greater range of motion and neutral zone in axial rotation than the intact state. In lateral bending, the new rod construct had significantly lower mean values for range of motion than the loop and the plate construct. In axial rotation, the rod construct had a significantly higher mean value for stiffness than the other two devices and a significantly lower mean value for range of motion than the loop. The new rod-based instrumentation system for occipitocervical fixation is biomechanically equivalent or superior to a plate and screw construct and a rod and cable system.

Absorptiometry, Photon↗
PubMed2003

Metastatic disease of the spine: evaluation and treatment.

Treatment of patients with metastatic disease of the spine continues to be a challenging problem. Advances in imaging studies and surgical techniques have improved patient outcomes with operative intervention. However, the lack of a validated set of criteria to determine spinal instability makes patient selection for surgical intervention difficult. Multiple classification systems that assist surgeons in determining appropriate operative candidates have been proposed. We will review current information on the evaluation and treatment of metastatic disease of the spine and discuss classification systems that assist in determining appropriate operative candidates.

Algorithms↗
PubMed2002

Controlled release of NFkappaB decoy oligonucleotides from biodegradable polymer microparticles.

The objective of this study was to evaluate a poly(DL-lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) delivery system for nuclear factor-kappa B (NFkappaB) decoy phosphorothioated oligonucleotides (ODNs). PLGA/PEG microparticles loaded with ODNs were fabricated with entrapment efficiencies up to 70%. The effects of PEG contents (0, 5, and l0 wt%), ODN loading densities (0.4, 4, and 40 microg/mg), and pH of the incubation medium (pH 5, 7.4. and 10) on ODN release kinetics from the PLGA/PEG microparticles were investigated in vitro for up to 28 days. The release profiles in pH 7.4 phosphate buffered saline (PBS) were characterized by an initial burst during the first 2 days, a linear release phase until day 18, and a final release phase for the rest of the period. Up to 85% of the ODNs were released after 28 days in pH 7.4 PBS regardless of the ODN loading density and PEG content. Higher ODN loading densities resulted in lower entrapment efficiencies and greater initial burst effects. The bulk degradation of PLGA was not significantly affected by the PEG content and ODN loading density, but significantly accelerated at acidic buffer pH. Under acidic and basic conditions, the aggregation of microparticles resulted in significantly lower cumulative mass of released ODNs than that released at neutral pH. The effects of pH were reduced by the incorporation of PEG into PLGA microparticles. Since the PLGA degradation products are acidic, PLGA/PEG microparticles might provide a better ODN delivery vehicle than PLGA microparticles. These results suggest that PLGA/PEG microparticles are useful as delivery vehicles for controlled release of ODNs and merit further investigation in cell culture and animal models of glioblastoma.

Biocompatible Materials↗
PubMed2002

Bowel and bladder function after major sacral resection.

Major sacral resection generally is reserved for patients with malignant lesions. Because of the uncommon nature of these diseases, little is known about outcomes of surgical treatment. The current authors describe the retrospective analysis of bowel and bladder function in patients having major sacral resection at their institution during a 10-year period. Fifty-three patients were identified. In patients who had unilateral sacrectomy, in whom the contralateral sacral nerves were preserved, normal bowel and bladder function was retained in 87% and 89%, respectively. In patients who had bilateral S2-S5 nerve roots sacrificed, all had abnormal bowel and bladder function. In patients who had bilateral S3-S5 resection, normal bowel and bladder function was retained in 40% and 25%, respectively. In patients who had bilateral S4-S5 resection, with preservation of the S3 nerves bilaterally, normal bowel and bladder function was retained in 100% and 69%, respectively. In patients who had asymmetric sacral resections, with preservation of at least one S3 nerve root, normal bowel and bladder function was retained in 67% and 60%, respectively. These results show that unilateral resection of sacral roots or preservation of at least one S3 root in bilateral resection preserves bowel and bladder function in the majority of patients.

Adolescent↗
PubMed2002

Relationship between surgical margins and local recurrence in sarcomas of the spine.

The combination of improved resection, stabilization, and fusion techniques allows for more aggressive removal of malignant spinal tumors with acceptable mortality and morbidity. Thirty consecutive patients with primary sarcomas of the mobile spine, who were operated on at the authors' institution from January 1970 to December 2000, were included in the current study. Demographic information, tumor location, type of resection, resection margins, local recurrence, and overall survival data were retrieved and analyzed. Treatment consisted of en bloc resection in 12 patients (40%) and piecemeal resections in 18 patients (60%). The resection was classified as wide in seven patients (23.3%), marginal in three patients (10%), and intralesional in 20 patients (66.7%). Pathology reports showed tumor-free resection margins in 12 patients (40%). In the remaining 18 patients (60%), resection margins were positive and resulted in a fivefold increase in the risk of a local recurrence. Ninety-two percent of the patients with local recurrence died of sequelae associated with the local recurrence. Primary sarcomas of the mobile spine in certain cases, can be removed completely with tumor-free resection margins. En bloc resection with tumor-free margins provides substantial improvement in overall survival.

Adolescent↗
PubMed2002

Vertebra plana caused by primary Ewing sarcoma: case report and review of the literature.

A 7-year-old boy presented with vertebra plana of T11. The presumptive diagnosis suggested by clinical presentation, conventional radiographs, and computed tomographic scans was eosinophilic granuloma. Progressive neurologic symptoms required surgical excision of the lesion and decompression. Histopathologic examination of the surgical specimen confirmed the diagnosis of Ewing sarcoma.

Back Pain↗