Capsule Stiffness Research Articles

Poster 187: Describing the Contribution of the Vacuum Effect and Hip Capsule in Restraint to Axial Traction in Patients Undergoing Hip Arthroscopy

Objectives: In recent investigations, there has been increased focus on hip laxity and hip capsular instability, particularly in the setting of hip arthroscopy. The capsule and its internal negative pressure effects have been shown to be major contributors to hip joint stability, however, the relative contributory role of these elements remains unknown. Intraoperatively, improved understanding of hip capsule biomechanics is imperative for optimization of arthroscopic technique to access the central compartment with minimal soft tissue trauma. In turn, this can help reduce the risk of hip instability and maximize patient outcomes. The purpose of this study was to define the stiffness coefficient of the hip capsule and vacuum phenomenon in response to hip axial traction. Our hypothesis was that the vacuum phenomenon would have a greater relative contribution to axial distraction stiffness at mid-range distraction, and that the hip capsule stiffness coefficient would be greater at terminal distraction. Methods: A review of a prospectively collected database of patients undergoing hip arthroscopy was conducted from 1 July 2021 to 31 June 2022. Patients in this database underwent hip arthroscopy for the treatment of femoroacetabular impingement syndrome (FAIS). Inclusion criteria were 1) completion of the study traction protocol and 2) completion of hip joint venting prior to capsulotomy. Exclusion criteria were 1) previous hip surgery and 2) lack of hip distraction at 50 pounds of axial traction. The study traction protocol involved applying axial traction prior to instrumentation (Native State) of the hip using a post-free distraction system. Hips were then vented using a spinal needle and the traction protocol was repeated (Vented State). Traction intervals were 0, 50, and 100 lbs of force. Fluoroscopic images were taken at each traction interval and standardized to preoperative radiographs, which allowed for a calculation of the lateral joint space width at each interval. Overall distraction distance was calculated as the difference between 0 lbs traction and 50 and 100 lbs traction. The stiffness coefficient was calculated as k = traction force interval/distraction distance in both the Native and Vented States. Comparisons using paired-samples t-tests were conducted between the stiffness coefficients of the Native State and Vented State at 50 lbs and at 100 lbs. A p-value of <0.05 was utilized to indicate statistical significance. Results: Twenty-one patients were identified who met inclusion criteria. Mean age was 34.4 ± 13.4 years with 100% female and a mean BMI of 24.2 ± 4.8 points. Mean stiffness coefficient at 50 lbs in the Native State (10.9 ± 3.3) was significantly higher than the Vented State (4.9 ± 0.7, p < 0.001), with similar findings at 100 lbs in the Native State (10.1 ± 1.7) and Vented State (8.7 ± 1.3, p < 0.001). In the Vented State, the stiffness coefficient was significantly greater at 100 lbs (8.7 ± 1.3) than at 50 lbs (4.9 ± 0.7, p < 0.001). Conclusions: Our results provide an objective characterization of the individual contributions of the hip soft tissue restraints and the vacuum phenomenon to hip resistance to axial traction. At 50 pounds of traction, the vacuum effect contributes to ~55% of the axial distraction stiffness (resistance to axial distraction). At 100 pounds of traction force, the vacuum effect contributes only ~14% of the axial distraction stiffness. The resistance of the hip to axial distraction is of substantial clinical significance as minimization of traction force decreases intraoperative soft tissue trauma. This, however, needs to be balanced with obtaining sufficient working space within the hip joint. There is still substantial controversy regarding the biomechanics of the hip and the optimal methods for minimizing traction force related injury (e.g., post-less traction, minimization of traction time, air arthrogram, and joint venting). These data demonstrate that soft tissues have a proportionally greater effect on restraint of the of the hip at terminal distraction (~1 cm distraction), whereas the vacuum effect has a greater influence on mid-range distraction (~0.5 cm distraction). The proposed model for this phenomenon is that the negative pressure and the soft tissue tension work in parallel to restrain the hip joint. The increased influence of the soft tissue tension at end-range distraction may be due to a check rein effect of the soft tissues; once the iliofemoral ligament has been tensioned to its maximum length its stiffness and capacity for transfer of tensile force increases rapidly. In conclusion, at 50 pounds of traction, the vacuum effect contributes to ~55% of the axial distraction stiffness (resistance to axial distraction). At 100 pounds of traction force, the vacuum effect contributes only ~14% of the axial distraction stiffness. These results demonstrate that the vacuum effect is a significant restraint to axial traction applied across the hip at mid-range distraction. Additionally, the hip capsule has a relatively greater contribution to terminal distraction stiffness.

Glenohumeral internal rotation deficit: insights into pathologic, clinical, diagnostic, and therapeutic characteristics.

Overhead athletes undergo significant biomechanical adaptations due to repetitive overhead movements, primarily affecting the glenohumeral joint. These adaptations can lead to glenohumeral internal rotation deficit (GIRD), which is characterized by posterior capsule stiffness that results in glenohumeral joint translation and a shift in the center of gravity. The severity of GIRD is dependent upon the presence of asymmetry between gained external and lost internal rotation, which is defined clinically as an asymmetry exceeding 20º; this reduces the total range of motion compared to the unaffected limb or baseline measurements. Diagnosis is challenging, as it can be mistaken for chronic scapular adaptations. To mitigate misdiagnosis, a high clinical suspicion is crucial in overhead athletes, especially those who began performing forceful overhead movements before closure of growth plates. Periodic physical examinations should establish baseline values for glenohumeral rotation and track changes in glenohumeral motion to aid in diagnosis. Symptoms of GIRD include shoulder pain, stiffness, and decreased force exertion. Magnetic resonance imaging is the preferred imaging method for evaluating GIRD and assessing concomitant soft tissue pathologies. Untreated GIRD can lead to rotator cuff strength imbalances. Treatment mainly involves conservative measures, such as physical therapy, to improve internal rotation and alleviate posterior tightness. Surgical interventions are considered when symptoms persist despite conservative treatment with physical therapy or in the presence of concomitant pathologies.

Muscle spindles of the multifidus muscle undergo structural change after intervertebral disc degeneration

PurposeProprioceptive deficits are common in low back pain. The multifidus muscle undergoes substantial structural change after back injury, but whether muscle spindles are affected is unclear. This study investigated whether muscle spindles of the multifidus muscle are changed by intervertebral disc (IVD) degeneration in a large animal model.MethodsIVD degeneration was induced by partial thickness annulus fibrosus lesion to the L3-4 IVD in nine sheep. Multifidus muscle tissue at L4 was harvested at six months after lesion, and from six age-/sex-matched naïve control animals. Muscle spindles were identified in Van Gieson’s-stained sections by morphology. The number, location and cross-sectional area (CSA) of spindles, the number, type and CSA of intrafusal fibers, and thickness of the spindle capsule were measured. Immunofluorescence assays examined Collagen I and III expression.ResultsMultifidus muscle spindles were located centrally in the muscle and generally near connective tissue. There were no differences in the number or location of muscle spindles after IVD degeneration and only changes in the CSA of nuclear chain fibers. The thickness of connective tissue surrounding the muscle spindle was increased as was the expression of Collagen I and III.ConclusionChanges to the connective tissue and collagen expression of the muscle spindle capsule are likely to impact their mechanical properties. Changes in capsule stiffness may impact the transmission of length change to muscle spindles and thus transduction of sensory information. This change in muscle spindle structure may explain some of the proprioceptive deficits identified with low back pain.

Impact of Collagen Crosslinking on Dislocated Human Shoulder Capsules-Effect on Structural and Mechanical Properties.

Classical treatments of shoulder instability are associated with recurrence. To determine whether the modification of the capsule properties may be an alternative procedure, the effect of crosslinking treatment on the structure and mechanical properties of diseased human shoulder capsules was investigated. Joint capsules harvested from patients during shoulder surgery (n = 5) were treated or not with UV and/or riboflavin (0.1%, 1.0% and 2.5%). The structure and the mechanical properties of the capsules were determined by atomic force microscopy. The effect of treatments on cell death was investigated. Collagen fibrils were well-aligned and adjacent to each other with a D-periodicity of 66.9 ± 3.2 nm and a diameter of 71.8 ± 15.4 nm in control untreated capsules. No effect of treatments was observed on the organization of the collagen fibrils nor on their intrinsic characteristics, including D-periodicity or their mean diameter. The treatments also did not induce cell death. In contrast, UV + 2.5% riboflavin induced capsule stiffness, as revealed by the increased Young’s modulus values (p < 0.0001 for each patient). Our results showed that the crosslinking procedure changed the biomechanics of diseased capsules, while keeping their structural organisation unchanged at the single fibril level. The UV/riboflavin crosslinking procedure may be a promising way to preserve the functions of collagen-based tissues and tune their elasticity for clinically relevant treatments.

Comparison of HPMC Inhalation-Grade Capsules and Their Effect on Aerosol Performance Using Budesonide and Rifampicin DPI Formulations.

Despite the fact that capsules play an important role in many dry powder inhalation (DPI) systems, few studies have been conducted to investigate the capsules’ interactions with respirable powders. The effect of four commercially available hydroxypropyl methylcellulose (HPMC)inhalation-grade capsule types on the aerosol performance of two model DPI formulations (lactose carrier and a carrier-free formulation) at two different pressure drops was investigated in this study. There were no statistically significant differences in performance between capsules by using the carrier-based formulation. However, there were some differences between the capsules used for the carrier-free rifampicin formulation. At 2-kPa pressure drop conditions, Embocaps® VG capsules had a higher mean emitted fraction (EF) (89.86%) and a lower mean mass median aerodynamic diameter (MMAD) (4.19 µm) than Vcaps® (Capsugel) (85.54%, 5.10 µm) and Quali-V® I (Qualicaps) (85.01%, 5.09 µm), but no significant performance differences between Embocaps® and ACGcaps™ HI. Moreover, Embocaps® VG capsules exhibited a higher mean respirable fraction (RF)/fine particle fraction (FPF) with a 3-µm–sized cutoff (RF/FPF< 3 µm) (33.05%/35.36%) against Quali-V® I (28.16%/31.75%) (P < 0.05), and a higher RF/FPF with a 5-µm–sized cutoff (RF/FPF< 5 µm) (49.15%/52.57%) versus ACGcaps™ HI (38.88%/41.99%) (P < 0.01) at 4-kPa pressure drop condition. Aerosol performance variability, pierced-flap detachment, as well as capsule hardness and stiffness, may all influence capsule type selection in a carrier-based formulation. The capsule type influenced EF, RF, FPF, and MMAD in the carrier-free formulation.

The effects of vıtal dyes on mechanıcal propertıes of the human anterıor lens capsule.

Purpose:The purpose of this study was to evaluate the mechanical effects of vital dyes on the anterior lens capsule via the nanoindentation method.Methods:Twenty anterior lens capsules of 20 different patients were dissected into four equal fragments. Each fragment was stained separately with dyes for intraocular surgeries, such as trypan blue 0.06% (TB), brilliant blue 0.025% (BB), and indocyanine green 0.05% (ICG), for 1 min. The remaining fragment was assessed as an untreated control group. The alterations on the mechanical characteristics of the anterior lens capsule were evaluated using a nanoindentation testing device with Oliver–Pharr and Martens hardness methods.Results:The mean values of elasticity were 7.842 ± 0.55 GPa for capsules fragments stained with TB (P < 0.05), 8.407 ± 0.82 GPa for capsules fragments stained with BB (P < 0.05), 8.557 ± 0.60 GPa for ICG (P < 0.05), and 6.09 ± 0.57 GPa for the untreated control group. The mean values of stiffness were 299.7 ± 47 MPa for TB (P < 0.05), 317.9 ± 34 MPa for BB (P < 0.05), 331.8 ± 48 MPa for ICG (P < 0.05), and 229.85 ± 44 MPa for the untreated control group. The elasticity of the capsules statistically decreased in comparison to the control group, and the capsule stiffness showed a statistically significant increase in comparison to the untreated controls.Conclusion:The mechanical characteristics of the human anterior lens capsule were affected in association with the alterations in the elasticity and stiffness properties of the capsule as a result of exposure to three different dyes.

In vivo biomechanical measurement and haptic simulation of portal placement procedure in shoulder arthroscopic surgery

A survey of 67 experienced orthopedic surgeons indicated that precise portal placement was the most important skill in arthroscopic surgery. However, none of the currently available virtual reality simulators include simulation / training in portal placement, including haptic feedback of the necessary puncture force. This study aimed to: (1) measure the in vivo force and stiffness during a portal placement procedure in an actual operating room and (2) implement active haptic simulation of a portal placement procedure using the measured in vivo data. We measured the force required for port placement and the stiffness of the joint capsule during portal placement procedures performed by an experienced arthroscopic surgeon. Based on the acquired mechanical property values, we developed a cable-driven active haptic simulator designed to train the portal placement skill and evaluated the validity of the simulated haptics. Ten patients diagnosed with rotator cuff tears were enrolled in this experiment. The maximum peak force and joint capsule stiffness during posterior portal placement procedures were 66.46 (±10.76N) and 2560.82(±252.92) N/m, respectively. We then designed an active haptic simulator using the acquired data. Our cable-driven mechanism structure had a friction force of 3.763 ± 0.341 N, less than 6% of the mean puncture force. Simulator performance was evaluated by comparing the target stiffness and force with the stiffness and force reproduced by the device. R-squared values were 0.998 for puncture force replication and 0.902 for stiffness replication, indicating that the in vivo data can be used to implement a realistic haptic simulator.

Comparison of the mechanical properties of the anterior lens capsule in senile cataract, senile cataract with trypan blue application, and pseudoexfoliation syndrome

To evaluate the elastic modulus, hardness, and mechanicalproperties of the anterior lens capsule in different typesof cataract and to assess the correlation with age. Baskent University Hospital, Department of Ophthalmology, Ankara, Turkey. Prospective comparative study. Patients were divided into 3 groups. Group 1 comprised patients with senile cataract, Group 2 patients had pseudoexfoliation (PXF) syndrome, and Group 3 patients had dye-enhanced cataract surgery. The capsules were analyzed using a nanoindentation device. Young's modulus of elasticity was measured by the Oliver-Pharr method and capsule hardness by the Martens method. The study comprised 72 patients, 24 per group. The mean Young's modulus was 7.53GPa±1.07 (SD) in Group 1, 6.01±1.25GPa in Group 2, and 8.12±0.98GPa in Group3.The capsules in Group 2 were more elastic than in Group 1 and Group 3 (P<.001). The capsules in Group 3 had lower elasticity than in Group 1, although the difference was not significant (P=.94). The mean capsule stiffness was 326.41±98.40MPa in Group 1, 210.5±52.32MPa in Group 2, and 315.54±163.15MPa in Group 3. The lens capsules in Group 2 were less stiff than those in Group 1 and Group 3 (P<.001). Capsule thickness was positively correlated with increasing age in all groups. The anterior lens capsules of patients with PXF had more elasticity and less stiffness than the other groups. Intracameral trypan blue application had no effect on capsule elasticity and stiffness.

Capsule stiffness regulates the efficiency of pancreatic differentiation of human embryonic stem cells

Encapsulation of donor islets using a hydrogel material is a well-studied strategy for islet transplantation, which protects donor islets from the host immune response. Replacement of donor islets by human embryonic stem cell (hESC) derived islets will also require a means of immune-isolating hESCs by encapsulation. However, a critical consideration of hESC differentiation is the effect of surrounding biophysical environment, in this case capsule biophysical properties, on differentiation. The objective of this study, thus, was to evaluate the effect of capsule properties on growth, viability, and differentiation of encapsulated hESCs throughout pancreatic induction. It was observed that even in the presence of soluble chemical cues for pancreatic induction, substrate properties can significantly modulate pancreatic differentiation, hence necessitating careful tuning of capsule properties. Capsules in the range of 4–7kPa supported cell growth and viability, whereas capsules of higher stiffness suppressed cell growth. While an increase in capsule stiffness enhanced differentiation at the intermediate definitive endoderm (DE) stage, increased stiffness strongly suppressed pancreatic progenitor (PP) induction. Signaling pathway analysis indicated an increase in pSMAD/pAKT levels with substrate stiffness likely the cause of enhancement of DE differentiation. In contrast, sonic hedgehog inhibition was more efficient under softer gel conditions, which is necessary for successful PP differentiation. Statement of SignificanceCell replacement therapy for type 1 diabetes (T1D), affecting millions of people worldwide, requires the immunoisolation of insulin-producing islets by encapsulation with a semi-impermeable material. Due to the shortage of donor islets, human pluripotent stem cell (hPSC) derived islets are an attractive alternative. However, properties of the encapsulating substrate are known to influence hPSC cell fate. In this work, we determine the effect of substrate stiffness on growth and pancreatic fate of encapsulated hPSCs. We precisely identify the range of substrate properties conducive for pancreatic cell fate, and also the mechanism by which substrate properties modify the cell signaling pathways and hence cell fate. Such information will be critical in driving regenerative cell therapy for long term treatment of T1D.

The role of capsule stiffness on cellular processing.

Particle stiffness is emerging as an important parameter in determining the cell uptake dynamics of particles. Understanding the effects of capsule stiffness on their biological behavior is essential for the development of polymer capsules as therapeutic carriers. Herein, we report the preparation of polysaccharide capsules via atom transfer radical polymerization-mediated continuous assembly of polymers (CAPATRP) on silica templates using methacrylated hyaluronic acid (HA) as the macrocrosslinker. This approach affords HA capsules with controllable wall thickness and tunable stiffness. The influence of capsule stiffness on cellular interaction and intracellular distribution is systematically investigated using flow cytometry, imaging flow cytometry, and deconvolution microscopy. The softest HA capsules with a stiffness (γ) of 7.5 mN m-1 possess higher cell surface binding and cellular association when compared to stiffer capsules with γ of 17.6-28.9 mN m-1. Furthermore, the uptake of HA capsules is a stiffness-dependent process, with slower and less cellular internalization observed with increasing capsule stiffness. Nevertheless, regardless of the stiffness, all internalized capsules are deformed and located in the lysosomes. These findings offer insights into the influence of capsule stiffness on cellular interaction as well as intracellular fate, providing information for the design of rational polymer capsules for biomedical applications.

Biocompatible Shaped Particles from Dried Multilayer Polymer Capsules

We demonstrated a simple and facile approach to fabricate biocompatible monodisperse hollow microparticles of controlled geometry. The hemispherical, spherical, and cubical microparticles are obtained by drying multilayer capsules of hydrogen-bonded poly(N-vinylpyrrolidone)/tannic acid (PVPON/TA)n. Drying spherical capsules results in hemispherical particles if 15 < n < 20. This shape transformation is controlled by capsule stiffness, which is regulated by the layer number, capsule diameter, and PVPON molecular weight. Cubical and spherical hollow particles maintaining their three-dimensional shapes in the dry state are obtained if n ≥ 25.5. A 17-fold stiffness increase is required to lead from totally collapsed (PVPON/TA)5.5 to dried self-supporting (PVPON/TA)25.5 particles of 2 μm in dimensions. All hollow particles could be further resuspended in aqueous solutions while retaining their shapes upon rehydration. The cell growth and viability studies using human cancer cells revealed noncytotoxic properties of the (PVPON/TA) multilayer particles. Both spherical and hemispherical capsules were internalized by macrophages with the uptake of the hemispherical particles per cell two times more efficient. The method presented here allows for a robust preparation of biocompatible shaped particles whose shape and dimensions can be easily tuned by controlling capsule size and wall thickness. The reported structures can be potentially useful for biomedical applications such as shape-controlled cellular uptake and flow dynamics.

Increase in lens capsule stiffness caused by vital dyes

To assess potential changes in lens capsule mechanical properties after staining with brilliant blue, indocyanine green (ICG), and trypan blue. Department of Ophthalmology and Applied Physics and Center for NanoScience, Ludwig-Maximilians-University, Munich, Germany. Experimental study. Fifteen unstained lens capsules were dissected into 7 wedge-shaped parts. Three fragments were stained with brilliant blue 0.025%, ICG 0.05%, and trypan blue 0.06%, respectively, for 1 minute. Another 3 specimens were additionally illuminated using a standard light source. The seventh part served as an untreated control. All specimens were analyzed using atomic force microscopy (AFM) in contact mode with a scan rate of 0.6 Hz. Two scan regions of 10 μm × 10 μm were chosen, and stiffness was determined using AFM in a force spectroscopy mode. The force curves were performed with a data rate of 5000 Hz. Staining of the samples resulted in an increase in tissue stiffness (brilliant blue: P<.001; ICG: P<.01; trypan blue: P<.05). Additional illumination after staining further increased tissue stiffness, but not significantly. Mean increase in the relative elasticity values were 1.61 ± 0.15 (SD) for brilliant blue, 2.04 ± 0.21 for brilliant blue with illumination, 1.63 ± 0.22 for ICG, 2.01 ± 0.22 for ICG with illumination, 1.23 ± 0.11 for trypan blue, and 1.39 ± 0.11 for trypan blue with illumination. In relation to unstained tissue, the relative elasticity of the stained tissue increased 1.2-fold after illumination. Staining significantly increased the mechanical properties of the human lens capsule. No author has a financial or proprietary interest in any material or method mentioned.

Systematic study of alginate-based microcapsules by micropipette aspiration and confocal fluorescence microscopy

Micropipette aspiration and confocal fluorescence microscopy were used to study the structure and mechanical properties of calcium alginate hydrogel beads (A beads), as well as A beads that were additionally coated with poly-l-lysine (P) and sodium alginate (A) to form, respectively, AP and APA hydrogels. A beads were found to continue curing for up to 500h during storage in saline, due to residual calcium chloride carried over from the gelling bath. In subsequent saline washes, micropipette aspiration proved to be a sensitive indicator of gel weakening and calcium loss. Aspiration tests were used to compare capsule stiffness before and after citrate extraction of calcium. They showed that the initial gel strength is largely due to the calcium alginate gel cores, while the long term strength is solely due to the poly-l-lysine–alginate polyelectrolyte complex (PEC) shells. Confocal fluorescence microscopy showed that calcium chloride exposure after PLL deposition led to PLL redistribution into the hydrogel bead, resulting in thicker but more diffuse and weaker PEC shells. Adding a final alginate coating to form APA capsules did not significantly change the PEC membrane thickness and stiffness, but did speed the loss of calcium from the bead core.

Antibody Binding to Cryptococcus neoformans Impairs Budding by Altering Capsular Mechanical Properties

Abs to microbial capsules are critical for host defense against encapsulated pathogens, but very little is known about the effects of Ab binding on the capsule, apart from producing qualitative capsular reactions ("quellung" effects). A problem in studying Ab-capsule interactions is the lack of experimental methodology, given that capsules are fragile, highly hydrated structures. In this study, we pioneered the use of optical tweezers microscopy to study Ab-capsule interactions. Binding of protective mAbs to the capsule of the fungal pathogen Cryptococcus neoformans impaired yeast budding by trapping newly emerging buds inside the parental capsule. This effect is due to profound mAb-mediated changes in capsular mechanical properties, demonstrated by a concentration-dependent increase in capsule stiffness. This increase involved mAb-mediated cross-linking of capsular polysaccharide molecules. These results provide new insights into Ab-mediated immunity, while suggesting a new nonclassical mechanism of Ab function, which may apply to other encapsulated pathogens. Our findings add to the growing body of evidence that Abs have direct antimicrobial functions independent of other components of the immune system.

The Effect of Silicone Gel Bleed on Capsular Contracture

Capsular contracture has multiple causes, all of which lead to increased inflammation and scarring. There have been five generations of silicone breast implants; the most recent are filled with a highly cohesive gel thought to reduce capsular contracture. No independent data exist to support this claim. Eight Göttingen swine were each implanted with eight 50-cc custom gel implants. In phase 1 of the study, the implant shells were photochemically altered to produce a low-bleed shell or a high-bleed shell to simulate a second-generation implant. In phase 2, both the third/fourth generation and the newest, fifth generation (highly cohesive gel) devices were implanted. Half the implants were punctured with a 3-ml punch biopsy to simulate a ruptured implant. Capsule and implant specimens were harvested at 1 and 3 months and analyzed with a Bose strain gauge. Intracapsular fluid was tested for silicon levels with atomic emission spectrometry. Histologic analysis was prepared with hematoxylin and eosin, Masson trichrome, and α-smooth muscle actin immunohistochemistry stains. Gel bleed correlated with capsule stiffness in a dose-dependent manner (p < 0.05). High-bleed second-generation implants had the stiffest capsules, and nonruptured third- and fourth-generation implants had the softest. Histologic examination revealed an intermediate layer of spindle-like cells staining positive for α-smooth actin in the most contracted capsules. There is a dose-dependant relationship between silicone gel bleed and capsule compliance that is independent of the cohesivity of the silicone. Capsule thickness and a fibrotic, α-smooth muscle actin-positive layer are present within the most contracted capsules.

Formation and Mechanical Characterization of Aminoplast Core/Shell Microcapsules

This work aims at establishing a link between process conditions and resulting micromechanical properties for aminoplast core/shell microcapsules. The investigated capsules were produced by the in situ polymerization of melamine formaldehyde resins, which represents a widely used and industrially relevant approach in the field of microencapsulation. Within our study, we present a quantitative morphological analysis of the capsules' size and shell thickness. The diameter of the investigated capsules ranged from 10 to 50 μm and the shell thickness was found in a range between 50 and 200 nm. As key parameter for the control of the shell thickness, we identified the amount of amino resin per total surface area of the dispersed phase. Mechanical properties were investigated using small deformations on the order of the shell thickness by atomic force microscopy with a colloidal probe setup. The obtained capsule stiffness increased with an increasing shell thickness from 2 to 30 N/m and thus showed the same trend on the process parameters as the shell thickness. A simple analytical model was adopted to explain the relation between capsules' geometry and mechanics and to estimate the elastic modulus of the shell about 1.7 GPa. Thus, this work provides strategies for a rational design of microcapsule mechanics.

Primate lens capsule elasticity assessed using Atomic Force Microscopy

The purpose of this project is to measure the elasticity of the human and non-human primate lens capsule at the microscopic scale using Atomic Force Microscopy (AFM). Elasticity measurements were performed using AFM on the excised anterior lens capsule from 9 cynomolgus monkey (5.9–8.0 years), 8 hamadryas baboon (2.8–10.1 years), and 18 human lenses (33–79 years). Anterior capsule specimens were obtained by performing a 5 mm continuous curvilinear capsulorhexis and collecting the resulting disk of capsular tissue. To remove the lens epithelial cells the specimen was soaked in 0.1% trypsin and 0.02% EDTA for 5 min, washed, and placed on a Petri dish and immersed in DMEM. Elasticity measurements of the capsule were performed with a laboratory-built AFM system custom designed for force measurements of ophthalmic tissues. The capsular specimens were probed with an AFM cantilever tip to produce force–indentation curves for each specimen. Young’s modulus was calculated from the force–indentation curves using the model of Sneddon for a conical indenter. Young’s modulus of elasticity was 20.1–131 kPa for the human lens capsule, 9.19–117 kPa for the cynomolgus lens capsule, and 13.1–62.4 kPa for the baboon lens capsule. Young’s modulus increased significantly with age in humans ( p = 0.03). The age range of the monkey and baboon samples was not sufficient to justify an analysis of age dependence. The capsule elasticity of young humans (<45 years) was not statistically different from that of the monkey and baboon. In humans, there is an increase in lens capsule stiffness at the microscale that could be responsible for an increase in lens capsule bulk stiffness.

EFFECTS OF DIABETES AND EXERCISE ON SOFT CONNECTIVE TISSUE PROPERTIES AT THE KNEE IN THE RAT

The primary diabetes-related health concerns are neuropathy and cardiovascular changes. Connective tissue changes can also affect quality of life by increasing ligament and joint capsule stiffness, impairing proprioception, limiting function, and leading to greater risk of falling. Our objectives were to evaluate effects of Type I diabetes and exercise on medial collateral ligament properties and overall knee-joint stiffness and stress relaxation. Thirty-four male Sprague–Dawley rats, approximately two months old, were divided into three groups—sedentary controls (n=10), sedentary diabetics (n=10) and exercised diabetics (n=14). Diabetes was induced by streptozotocin injection. Exercised rats ran 5 days/week, 1 hr/day, at 20 m/min. All animals were sacrificed seven weeks after induction of diabetes. Stiffness and stress relaxation of the whole knee joint was tested in distraction and anterior–posterior tibial displacement. The joint capsule and knee ligaments were then sectioned, preserving the medial collateral ligament (MCL). The MCL structural properties were tested by knee distraction at a flexion angle of 40°. Whole joint stiffness was 23% higher for anterior tibial displacement in the exercised diabetic group, and 31% higher for posterior tibial displacement, compared to controls. Whole joint stress relaxation in distraction was 25% lower for the exercised diabetic group. No differences were found for MCL properties. Diabetes and exercise clearly increased joint stiffness. The effects may be due to tissue adaptation, but appear more likely to be due to increased blood flow that promotes increased tissue glycation in the joint capsule.

Effect of trypan blue staining on the elastic modulus of anterior lens capsules of diabetic and nondiabetic patients

To determine whether trypan blue causes a significant difference in the biomechanical properties (stiffness) of diabetic and nondiabetic anterior lens capsules and to determine whether diabetes significantly alters the stiffness of anterior lens capsules. Veterans Administration Boston Healthcare Center System, Jamaica Plain, Massachusetts, USA. In this unmasked prospective randomized controlled experimental study, anterior lens capsules were obtained from diabetic and nondiabetic patients approved for cataract surgery. Four treatment groups were created: (1) capsules of nondiabetic patients without trypan blue; capsules of nondiabetic patients with trypan blue; (3) capsules of diabetic patients without trypan blue; (4) capsules of diabetic patients with trypan blue. Anterior lens capsule stiffness as a function of elastic (Young's) modulus (kilopascals) was measured with the Hysitron TriboIndenter. The use of trypan blue led to significantly stiffer anterior lens capsules (P= .036). Trypan blue had the greatest effect on the stiffness of diabetic lens capsules (P= .046). Trypan blue contributed to increased capsule stiffness during capsulorhexis, especially in diabetic patients.

Modeling the interactions between compliant microcapsules and pillars in microchannels

Using a computational model, we investigate the motion of microcapsules inside a microchannel that encompasses a narrow constriction. The microcapsules are composed of a compliant, elastic shell and an encapsulated fluid; these fluid-filled shells model synthetic polymeric microcapsules or biological cells (e.g., leukocytes). Driven by an imposed flow, the capsules are propelled along the microchannel and through the constricted region, which is formed by two pillars that lie in registry, extending from the top and bottom walls of the channels. The tops of these pillars (facing into the microchannel) are modified to exhibit either a neutral or an attractive interaction with the microcapsules. The pillars (and constriction) model topological features that can be introduced into microfluidic devices or the physical and chemical heterogeneities that are inherently present in biological vessels. To simulate the behavior of this complex system, we employ a hybrid method that integrates the lattice Boltzmann model (LBM) for fluid dynamics and the lattice spring model (LSM) for the micromechanics of elastic solids. Through this LBM/LSM technique, we probe how the capsule's stiffness and interaction with the pillars affect its passage through the chambers. The results yield guidelines for regulating the movement of microcarriers in microfluidic systems and provide insight into the flow properties of biological cells in capillaries.