A Cadaveric Study Addressing the Feasibility of Remote Patient Monitoring Prosthesis for Total Knee Arthroplasty.

BACKGROUND: Since the COVID-19 pandemic of 2020, there has been a marked rise in the use of telemedicine to evaluate patients after total knee arthroplasty (TKA). The purpose of our study was to assess a novel stem with an embedded sensor that can remotely and objectively monitor a patient's mobility after TKA. METHODS: A single anatomically designed knee system was implanted in concert with an interconnected tibial stem extension containing 3D accelerometers, 3D gyroscopes, a power source, and a telemetry transmission capability in 3 cadaveric pelvis to toe specimens. The legs were moved by hand to preset tibial positions at full knee extension, midflexion, flexion, and back to midflexion and extension for a total of 16 trials across 6 knees. RESULTS: Sensor data were successfully transmitted with good quality of signal to an external base station. Good correlation to the range of motion of the tibia was found (mean error 0.1 degrees; root mean square error 3.8 degrees). The signal from the heel drop tests suggests the sensor could detect heel strike during activities of daily living in vivo and the potential for additional signal processing to analyze vibratory and motion patterns detected by the sensors. A frequency domain analysis of a properly cemented and poorly cemented implant during the heel drop test suggests a difference in accelerometer signal in these implant states. CONCLUSION: The results confirm signals generated from an embedded TKA sensor can transmit through bone and cement, providing accurate range of motion data and may be capable of detecting changes in prosthesis fixation remotely.

Maxillary sinusitis resulting from ostium plugging by dislodged bone graft: case report.

PURPOSE: To report an unusual case of severe maxillary sinusitis resulting from ostial plugging by dislodged bone graft material used for sinus elevation procedure. PATIENTS AND METHODS: A 49-year-old female presented to the oral surgery clinic with severe right maxillary sinusitis after a sinus elevation procedure and placement of a dental implant. She had completed an extended course of multiple antibiotics without culture and sensitivity studies or resolution of sinusitis. RESULTS: A CT scan was obtained which showed a dental implant protruding into the right maxillary sinus, sinusitis of the right ethmoid and maxillary sinuses, and dislodged bone graft material obstructing the ostium into the middle nasal meatus. The dental implant was removed, the patient was referred for functional endoscopic sinus surgery, and her sinusitis subsequently rapidly resolved. CONCLUSIONS: Surgeons performing this or similar procedures should be aware of the possible complications that can arise from foreign debris introduced into the maxillary sinuses. Also, the avoidance of empirically changing antibiotic regimens and the early use of CT scans should be considered.

Drug-eluting stents: beyond the hyperbole.

Drug-eluting stents (DES) promised to reduce the clinical and economic cost of failed bare metal stents (BMS) by locally delivering a therapeutic agent to the injured artery, reducing or eliminating the development of neointimal hyperplasia and reducing the need for repeat interventions to re-open the obstructed artery. Data from initial large-scale, comparable, U.S. pivotal trials of the first two DES to reach the American market, CYPHER from J&J using the drug rapamycin (sirolimus) and TAXUS from Boston Scientific using the drug paclitaxel (taxol), seemed to warrant the enthusiasm. By reducing the failure rate of BMS by about 4-fold, DES have changed clinical practice, reduced the rate of coronary bypass surgery, had a significant economic impact, and triggered extensive research in the areas of stent design, restenosis biology, polymeric drug-delivery and local pharmacology and toxicology.

Drug-eluting stents: a multidisciplinary success story.

Coronary stenting is the most common form of interventional treatment for symptomatic coronary artery disease. In-stent restenosis following bare metal stent (BMS) placement is the most common cause of procedural failure and occurs as a result of vessel wall trauma secondary to balloon angioplasty and stent deployment that results in an overly aggressive healing response (neointimal hyperplasia) that overgrows the stent lumen and causes vascular narrowing. Drug-eluting stents (DES) are specialized vascular stents capable of delivering drugs to the arterial wall in a controlled manner such that neointimal hyperplasia is reduced or prevented, luminal patency is preserved, coronary blood flow is maintained and the patient is spared a repeat procedure to re-open the vessel. The objectives of the review are to provide an overview of the major contributions that a broad range of disciplines have made to the design and development of drug-eluting stents and to summarize future directions of these fields of research. Engineers and biomaterials scientists have explored relationships between stent design and stent performance and work continues to optimize stent design and biocompatibility of stent biomaterials. Pharmaceutical scientists are continually expanding the range of candidate drugs for pharmacological intervention, and improving the technology using novel coatings to modulate drug release. Clinical scientists are investigating issues such as long-term safety and efficacy, new applications of drug-eluting stents and optimal deployment techniques.

The characterization of novel polymeric paste formulations for intratumoral delivery.

The objective of this work was to characterize a polymeric paste formulation of the anticancer drug paclitaxel that was injectable through a narrow gauge needle at room temperature and set to a solid implant in vivo for the intratumoral treatment of localized cancer. Pastes were manufactured from a triblock copolymer composed of poly(D,L-lactide-co-caprolactone)-block-polyethylene glycol-block-poly(D,L-lactide-co-caprolactone) (PLC-PEG-PLC) or triblock blended with a low molecular weight polymer methoxypolyethylene glycol (MePEG). Characterization of pastes was performed using differential scanning calorimetry (DSC), gel permeation chromatography (GPC) and drug release studies. Paste integrity in water was measured by determining the degree of fragmentation under initial agitation. MePEG was found to be miscible with the triblock polymer and paclitaxel dissolved in various blends of these polymers up to 15% drug loading. Pastes composed of 40:60 triblock:MePEG blends and 10% paclitaxel were found to inject through a 23-gauge needle and set to a solid pellet in phosphate-buffered saline at 37 degrees C. Such pellets released paclitaxel in a controlled manner over 7 weeks. Pastes composed of 40:60 triblock:MePEG blends containing 10% paclitaxel are proposed as suitable injectable formulations of the drug for intratumoral therapy.

Characterization of perivascular poly(lactic-co-glycolic acid) films containing paclitaxel.

The objectives of this study were to investigate the use of poly(lactic-co-glycolic acid) (PLGA) for the formulation of paclitaxel loaded films and to characterize these films for potential application as perivascular "wraps" to prevent restenosis. Films were manufactured from PLGA blended with either methoxypolyethylene glycol (MePEG) or a diblock copolymer composed of poly(D,L-lactic acid)-block-methoxypolyethylene glycol, PDLLA-MePEG (diblock) by solvent evaporation on teflon discs. Elasticity was determined by gravimetric stress/strain analysis. Thermal analysis was determined using differential scanning calorimetry (DSC). Changes in film composition and degradation in aqueous media were determined using gel permeation chromatography (GPC). Paclitaxel release from films was measured by incubation of the films in phosphate buffered saline (PBS) with drug analysis by HPLC methods. The addition of MePEG or diblock to PLGA caused a concentration dependent increase in the elasticity of films, due to plasticizing effects. DSC analysis showed that MePEG and diblock caused a concentration dependent decrease in the glass transition temperature (Tg) of PLGA indicating miscibility of the polymers. When placed in aqueous media, more than 75% of MePEG dissolved out of the PLGA films within 2 days, whereas diblock partitioned slowly and in a controlled manner out of the films. Paclitaxel release from PLGA/MePEG films was very slow with less than 5% of the encapsulated drug being released over 2 weeks. The addition of 30% diblock to paclitaxel loaded PLGA films caused a substantial increase (five- to eight-fold) in the release rate of paclitaxel. PLGA films containing 30% diblock and either 1% or 5% paclitaxel were partially or completely degraded following perivascular implantation in rats.

The encapsulation of ribozymes in biodegradable polymeric matrices.

Ribozymes are catalytic RNA that bind and cleave specific regions of target RNA. Therefore, protein synthesis by the target RNA may be specifically inhibited by ribozymes. However, ribozymes are rapidly cleared from plasma so effective treatment of proliferative diseases may rely on the repeated administration of these agents to maintain therapeutic ribozyme concentrations. Therefore, the objective of this study was to encapsulate ribozymes in injectable polymeric paste and microsphere formulations to allow for the controlled release of these agents over extended periods of time. Ribozymes were effectively encapsulated in poly(L-lactic acid) (PLLA) and poly(lactic-co-glycolic) (PLGA) microspheres in various size ranges using a modified water-in-oil-in-water emulsion system and in poly(epsilon-caprolactone) (PCL) pastes by physical blending. These formulations released non-degraded ribozymes, in vitro, in a controlled manner. PLLA microspheres released the ribozymes rapidly whereas PLGA released drugs more slowly. The release rate of ribozymes from PCL pastes could be effectively controlled by altering the loading concentration of ribozymes in the paste. These polymeric injectable formulations of ribozymes may allow for the extended treatment of localized disease sites, such as cancer and arthritis, without the need for repeated dosing.

Paclitaxel-loaded crosslinked hyaluronic acid films for the prevention of postsurgical adhesions.

PURPOSE: Post surgical adhesion formation results in significant morbidity for surgical patients. The purpose of this study was to investigate the use of paclitaxel (PTX) as an inhibitor of adhesion formation in rats and to design and characterize a controlled release film formulation of the drug for application to exposed surgical sites. METHODS: The rat cecal side wall abrasion model was used to investigate the anti-adhesion properties of PTX. The drug was administered by either intraperitoneal injection (i.p.), as the cremophor formulation (Taxol) or by application of carbodiimide crosslinked hyaluronic acid (HA) films containing PTX. The HA films were also characterized by measurements of elasticity, degree of swelling in water and drug release rates. RESULTS: Taxol administered by i.p. injection at 4 mg/kg on a daily basis for between 3 and 5 days resulted in a significant reduction in adhesion formation. All animals in the control group (n = 10) had some form of adhesion following abrasion whereas the percent of animals without adhesions significantly increased and the mean incidence of adhesion formation decreased in the three Taxol treated groups. The application of 5% PTX loaded HA films had a similar significant effect in increasing both the % of animals without adhesions and in reducing the mean incidence of adhesions. CONCLUSIONS: Paclitaxel is an effective inhibitor of adhesion formation in rats. HA crosslinked with 2 mM water soluble carbodiimide and containing 10% glycerol and 5% PTX are flexible, mucoadhesive, biocompatible controlled release films suitable for application to surgical sites for the prevention of adhesion formation.

Insect attack and wounding induce traumatic resin duct development and gene expression of (-)-pinene synthase in Sitka spruce.

Conifers possess inducible terpenoid defense systems. These systems are associated with the formation of traumatic resin ducts (TRD) and are underpinned by enhanced gene expression and activity of terpene synthases (TPS), enzymes responsible for oleoresin formation. We first determined that Sitka spruce (Picea sitchensis [Bong.] Carriere) had the capacity for TRD formation by mechanically wounding representative trees. We then proceeded to investigate whether the white pine weevil (Pissodes strobi Peck.), a stem-boring insect, can influence the expression of genes encoding monoterpene synthases (mono-tps) in Sitka spruce. We went on to compare this response with the effects of a simulated insect attack by drill wounding. A significant increase in mono-tps transcript level was observed in the leaders of lateral branches of weevil-attacked and mechanically wounded trees. In this study, weevils induced a more rapid enhancement of mono-tps gene expression. A full-length Sitka spruce mono-tps cDNA (PsTPS2) was isolated, expressed in Escherichia coli, and functionally identified as (-)-pinene synthase. The recombinant (-)-pinene synthase catalyzes the formation of (-)-alpha-pinene and (-)-beta-pinene, both of which are known constituents of stem oleoresin in Sitka spruce and increase in abundance after weevil attack. These data suggest that increased (-)-pinene synthase gene expression is an important element of the direct defense system deployed in Sitka spruce after insect attack.