Biocompatible near-infrared quantum dots delivered to the skin by microneedle patches record vaccination.

Accurate medical recordkeeping is a major challenge in many low-resource settings where well-maintained centralized databases do not exist, contributing to 1.5 million vaccine-preventable deaths annually. Here, we present an approach to encode medical history on a patient using the spatial distribution of biocompatible, near-infrared quantum dots (NIR QDs) in the dermis. QDs are invisible to the naked eye yet detectable when exposed to NIR light. QDs with a copper indium selenide core and aluminum-doped zinc sulfide shell were tuned to emit in the NIR spectrum by controlling stoichiometry and shelling time. The formulation showing the greatest resistance to photobleaching after simulated sunlight exposure (5-year equivalence) through pigmented human skin was encapsulated in microparticles for use in vivo. In parallel, microneedle geometry was optimized in silico and validated ex vivo using porcine and synthetic human skin. QD-containing microparticles were then embedded in dissolvable microneedles and administered to rats with or without a vaccine. Longitudinal in vivo imaging using a smartphone adapted to detect NIR light demonstrated that microneedle-delivered QD patterns remained bright and could be accurately identified using a machine learning algorithm 9 months after application. In addition, codelivery with inactivated poliovirus vaccine produced neutralizing antibody titers above the threshold considered protective. These findings suggest that intradermal QDs can be used to reliably encode information and can be delivered with a vaccine, which may be particularly valuable in the developing world and open up new avenues for decentralized data storage and biosensing.

Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk.

Platelets contract forcefully after their activation, contributing to the strength and stability of platelet aggregates and fibrin clots during blood coagulation. Viscoelastic approaches can be used to assess platelet-induced clot strengthening, but they require thrombin and fibrin generation and are unable to measure platelet forces directly. Here, we report a rapid, microfluidic approach for measuring the contractile force of platelet aggregates for the detection of platelet dysfunction. We find that platelet forces are significantly reduced when blood samples are treated with inhibitors of myosin, GPIb-IX-V, integrin αIIbß3, P2Y12, or thromboxane generation. Clinically, we find that platelet forces are measurably lower in cardiology patients taking aspirin. We also find that measuring platelet forces can identify Emergency Department trauma patients who subsequently require blood transfusions. Together, these findings indicate that microfluidic quantification of platelet forces may be a rapid and useful approach for monitoring both antiplatelet therapy and traumatic bleeding risk.

Amputee socks: how does sock ply relate to sock thickness?

BACKGROUND: The term 'sock ply' may be a source of confusion in prosthetics practice because there may not be a consistent relationship between sock ply and sock thickness. OBJECTIVES: The purpose of this study was to characterize how sock ply related to sock thickness for different sock materials commonly used in limb prosthetics. We also evaluated how sock thickness changed under loading conditions experienced while wearing a lower limb prosthesis compared with unstressed conditions. STUDY DESIGN: Experimental. Mechanical assessment. METHODS: Seven sock materials of varying ply and sheaths were tested using a custom instrument. Sock thickness under eight different compressive stress conditions and two different biaxial in-plane tensile strain conditions were measured. RESULTS: For socks woven from a single material, thickness under walking stance phase conditions averaged 0.7, 1.2 and 1.5 mm for 1, 3 and 5-ply, respectively. For socks woven from several materials, the corresponding results were 0.4, 0.7 and 0.8 mm, respectively. Sock ply did not sum, e.g. a 3-ply sock was not three times the thickness of a 1-ply sock. CONCLUSIONS: Sock thickness and compressive stiffness are strongly dependent upon sock material, interface pressure, and in-plane biaxial strain.

Melt electrospinning of biodegradable polyurethane scaffolds.

Electrospinning from a melt, in contrast to from a solution, is an attractive tissue engineering scaffold manufacturing process as it allows for the formation of small diameter fibers while eliminating potentially cytotoxic solvents. Despite this, there is a dearth of literature on scaffold formation via melt electrospinning. This is likely due to the technical challenges related to the need for a well-controlled high-temperature setup and the difficulty in developing an appropriate polymer. In this paper, a biodegradable and thermally stable polyurethane (PU) is described specifically for use in melt electrospinning. Polymer formulations of aliphatic PUs based on (CH(2))(4)-content diisocyanates, polycaprolactone (PCL), 1,4-butanediamine and 1,4-butanediol (BD) were evaluated for utility in the melt electrospinning process. The final polymer formulation, a catalyst-purified PU based on 1,4-butane diisocyanate, PCL and BD in a 4/1/3M ratio with a weight-average molecular weight of about 40kDa, yielded a nontoxic polymer that could be readily electrospun from the melt. Scaffolds electrospun from this polymer contained point bonds between fibers and mechanical properties analogous to many in vivo soft tissues.

A noncontact sensor for measurement of distal residual-limb position during walking.

A simple noncontact device was implemented for measuring the position of the distal residual limb relative to the prosthetic socket during ambulation. The device was a small and lightweight photoelectric sensor positioned within a frame mounted immediately beneath the socket. Calibration tests showed that the sensor had a displacement range of 60.0 mm. The root-mean-square error for all sources of error considered (different reflective surfaces, peak-to-peak signal noise, drift, nonlinearity, different surface tilt angles, surface curvature, and wetness [simulating sweating]) was <1.95% full-scale output. We used the sensor in a preliminary study on a unilateral, transtibial amputee with diabetes to assess pistoning during ambulation. Results showed an average 41.7 mm proximal displacement during swing phase relative to stance phase. When the subject was walking on a flat surface, pistoning was significantly less (p = 0.000) with a supracondylar strap compared with no supracondylar strap, although the difference was not substantial (0.8 mm). A 5 min rest period caused the limb to displace proximally in the socket approximately 4.8 mm during subsequent walking trials, possibly reflecting limb enlargement and thus a more proximal position in the socket after the rest period. The device can potentially be used in prosthetics research for evaluating clinical features that may affect limb position and pistoning and thus fit.

Matricellular hevin regulates decorin production and collagen assembly.

Matricellular proteins such as SPARC, thrombospondin 1 and 2, and tenascin C and X subserve important functions in extracellular matrix synthesis and cellular adhesion to extracellular matrix. By virtue of its reported interaction with collagen I and deadhesive activity on cells, we hypothesized that hevin, a member of the SPARC gene family, regulates dermal extracellular matrix and collagen fibril formation. We present evidence for an altered collagen matrix and levels of the proteoglycan decorin in the normal dermis and dermal wound bed of hevin-null mice. The dermal elastic modulus was also enhanced in hevin-null animals. The levels of decorin protein secreted by hevin-null dermal fibroblasts were increased by exogenous hevin in vitro, data indicating that hevin might regulate both decorin and collagen fibrillogenesis. We also report a decorin-independent function for hevin in collagen fibrillogenesis. In vitro fibrillogenesis assays indicated that hevin enhanced fibril formation kinetics. Furthermore, cell adhesion assays indicated that cells adhered differently to collagen fibrils formed in the presence of hevin. Our observations support the capacity of hevin to modulate the structure of dermal extracellular matrix, specifically by its regulation of decorin levels and collagen fibril assembly.

Fibro-porous meshes made from polyurethane micro-fibers: effects of surface charge on tissue response.

The purpose of this research was to evaluate the influence of surface charge on fibrous encapsulation, cell nuclei density, and vessel ingrowth into small-fiber, fibro-porous, biomaterial meshes. Meshes electrospun from polyurethane with mean fiber diameters of 5.8 microm and mean fiber spacing of 64.9 microm were plasma coated with films of different relative surface charge: Hexafluoropropylene (HF) (neutral), N,N-dimethylaminoethyl methacrylate (NN) (positive charge), and methacrylic acid (MA) (negative charge). Samples were implanted in rat subcutaneous dorsum for 5 weeks then fibrous capsule presence around the implants, cell nuclei density, and vessel number were assessed. Results showed that within the resolution of the histological analysis methods used, no implant experienced fibrous encapsulation. There was no significant difference between cell nuclei density and coating for the four groups: uncoated, HF-coated, NN-coated, and MA-coated. HF-coated and NN-coated samples had lower vessel numbers than uncoated samples (p = 0.055 and 0.032, respectively). MA-coated samples had vessel numbers not significantly different from uncoated polyurethane (slightly negatively charged) samples (p = 0.879). The results suggest that negatively charged surfaces may facilitate vessel ingrowth into fibro-porous mesh biomaterials.

Tension in a double loop tendon anterior cruciate graft during a simulated open chain knee extension exercise.

Concerns exist regarding the tension developed in a reconstructed anterior cruciate ligament (ACL) during open chain knee extension exercises used to rehabilitate the knee. Therefore, the primary objective was to measure tension in an ACL graft during a simulated open chain knee extension exercise as a function of ankle weight. A secondary objective was to determine whether the graft tension was reduced with relatively high stiffness fixation. The open chain exercise was simulated in seven cadaveric specimens in which the ACL had been reconstructed with double loop tendon grafts. Graft tension was measured at 15 degrees of flexion as the effective ankle weight was increased from 22.5 to 67.5 and then to 112.5 N for three different fixation stiffnesses (25, 125, and 225 N/mm). The initial tension was set to restore the 225 N anterior limit of motion to that of the intact knee at 30 degrees of flexion. Increasing the ankle weight caused the graft tension to increase significantly (p<0.0001), but the increase with the highest ankle weight was only 62 N on average. Increasing the fixation stiffness caused the graft tension to decrease significantly (p<0.0001) because the initial tension decreased by 107 N as the fixation stiffness increased. Because the graft tension with the highest ankle weight was limited to 112 N on average, high stiffness fixation methods, which are also resistant to lengthening in the region of the fixation, may reduce the risk of graft construct lengthening during open chain knee extension exercises.

Testing of elastomeric liners used in limb prosthetics: classification of 15 products by mechanical performance.

The mechanical properties of 15 elastomeric liner products used in limb prosthetics were evaluated under compressive, frictional, shear, and tensile loading conditions. All testing was conducted at load levels comparable to interface stress measurements reported on transtibial amputee subjects. For each test configuration, materials were classified into four groups based on the shapes of their response curves. For the 15 liners tested, there were 10 unique classification sets, indicating a wide range of unique materials. In general, silicone gel liners classified within the same groups thus were quite similar to each other. They were of lower compressive, shear, and tensile stiffness than the silicone elastomer products, consistent with their lightly cross-linked, high-fluid content structures. Silicone elastomer products better spanned the response groups than the gel liners, demonstrating a wide range of compressive, shear, and tensile stiffness values. Against a skin-like material, a urethane liner had the highest coefficient of friction of any liner tested, although coefficients of friction values for most of the materials were higher than interface shear:pressure ratios measured on amputee subjects using Pelite liners. The elastomeric liner material property data and response groupings provided here can potentially be useful to prosthetic fitting by providing quantitative information on similarities and differences among products.

Initial tension and anterior load-displacement behavior of high-stiffness anterior cruciate ligament graft constructs.

BACKGROUND: Because the tension that exists in an anterior cruciate ligament graft when the knee is unloaded (the initial tension) affects the surgical outcome and because high initial tension has a number of adverse consequences, the primary purpose of this study was to determine quantitatively how much less initial tension was required for a high-stiffness construct than for a low-stiffness construct. A secondary purpose was to determine how the stiffness of the graft construct affects the anterior load-displacement behavior of the knee from 0 degrees to 90 degrees of flexion. METHODS: Anterior-posterior load-displacement was measured in each of ten intact cadaveric knee specimens, the anterior cruciate ligament was excised, and the anterior cruciate ligament was reconstructed with a double-loop bovine tendon graft. Graft constructs of different stiffness were created with use of six springs, ranging in stiffness from 25 to 275 N/mm to simulate the fixation stiffness. After adjusting the initial tension of the graft so that the anterior-posterior laxity of the reconstructed knee matched that of the intact knee, the 0-N posterior limit and the 225-N anterior limit were measured at 0 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion. RESULTS: The highest stiffness fixation (275 N/mm) required an average of 73 N of initial tension, which was more than three times less than the average of 242 N of initial tension required by the lowest stiffness fixation (25 N/mm). The 225-N anterior limit was overconstrained an average of 1.0 mm with the highest stiffness fixation (275 N/mm), which was 3.6 mm less than the overconstraint with the lowest stiffness fixation (25 N/mm). Likewise, the posterior limit was overconstrained an average of 2.6 mm with the highest stiffness fixation (275 N/mm), which was 3.8 mm less than the overconstraint with the lowest stiffness fixation (25 N/mm). CONCLUSIONS: The initial tension for a high-stiffness graft construct is more than three times less than that for a low-stiffness construct. The initial tension for a high-stiffness graft construct better restores both the 225-N anterior limit and the 0-N posterior limit to normal than the initial tension for a low-stiffness graft construct over the range of flexion from 0 degrees to 90 degrees.

Cricoid ring integrity: implications for cricothyrotomy.

STUDY OBJECTIVES: The rapid 4-step technique for cricothyrotomy was originally described as making use of a single traction hook on the cricoid ring. However, it is possible that such hook placement could lead to damage of the cricoid ring. As an alternative, a double-hook device was developed to augment the rapid 4-step technique by dispersing forces applied to the cricoid ring. The objectives of this study were to compare the requisite forces for intubation and the structural tolerances of the cricoid ring between the single- and double-hook techniques. METHODS: We randomized 56 human cadaver specimens to undergo either cricothyrotomy with intubation followed by cricoid ring breakage or cricoid ring breakage alone. We randomized those cadaver specimens undergoing cricothyrotomy with intubation with respect to the initial hook technique used and then crossed over to the alternate technique for repeat intubation and subsequent cricoid ring breakage. We performed all cricothyrotomies in a similar manner with a consistent technique. We measured the intubation and breakage forces for the single- and double-hook techniques and calculated 95% confidence intervals (CIs). RESULTS: The mean force to intubate with the single-hook technique was 18 N (95% CI 14 to 22 N), and the mean force to intubate with the double-hook technique was 23 N (95% CI 17 to 29 N). There was a significant difference between the mean forces required to break the cricoid ring with the single-hook technique (54 N; 95% CI 47 to 62 N) versus with the double-hook technique (101 N; 95% CI 89 to 113 N; difference in means 47 [95% CI 34 to 60 N]). CONCLUSION: When applying the rapid 4-step technique for cricothyrotomy, the force required to intubate with either the single- or double-hook technique is small. The cricoid ring, however, tolerates significantly more force without breakage when the double-hook technique is used.

Experimental optimization of pivot point height for swing-arm type rear suspensions in off-road bicycles.

Towards the ultimate goal of designing dual suspension off-road bicycles which decouple the suspension motion from the pedaling action, this study focused on determining experimentally the optimum pivot point height for a swing-arm type rear suspension such that the suspension motion was minimized. Specific objectives were (1) to determine the effect of interaction between the front and rear suspensions on the optimal pivot point height, (2) to investigate the sensitivity of the optimal height to the pedaling mechanics of the rider in both the seated and standing postures, (3) to determine the dependence of the optimal height on the rider posture. Eleven experienced subjects rode a custom-built adjustable dual suspension off-road bicycle, [Needle, S., and Hull, M. L., 1997, "An Off-Road Bicycle With Adjustable Suspension Kinematics," Journal of Mechanical Design 119, pp. 370-375], on an inclined treadmill. The treadmill was set to a constant 6 percent grade at a constant velocity of 24.8 km/hr. With the bicycle in a fixed gear combination of 38 x 14, the corresponding cadence was 84 rpm. For each subject, the pivot point height was varied randomly while the motions across both the front and rear suspension elements were measured. Subjects rode in both the seated and standing postures and with the front suspension active and inactive. It was found that the power loss from the rear suspension at the optimal pivot point height was not significantly dependent on the interaction between the front and rear suspensions. In the seated posture, the optimal pivot point height was 9.8 cm on average and had a range of 8.0-12.3 cm. The average optimal pivot point height for the seated posture corresponded to an average power loss for the rear suspension that was within 10 percent of the minimum power loss for each subject for 8 of the 11 subjects. In the standing posture, the average height was 5.9 cm and ranged from 5.1-7.2 cm. The average heightfor the standing posture was within 10 percent of the minimum power loss for each subject for 9 of the 11 subjects. While the optimum height was relatively insensitive to pedaling mechanics in both the seated and standing postures, the choice of the optimal pivot point height in production bicycles necessitates some compromise in performance given the disparity in the averages between the seated and standing postures.