Biomechanical Characterization Research Articles

Methods for In Vivo Biomechanical Testing on Brachial Plexus in Neonatal Piglets.

Neonatal brachial plexus palsy (NBPP) is a stretch injury that occurs during the birthing process in nerve complexes located in the neck and shoulder regions, collectively referred to as the brachial plexus (BP). Despite recent advances in obstetrical care, the problem of NBPP continues to be a global health burden with an incidence of 1.5 cases per 1,000 live births. More severe types of this injury can cause permanent paralysis of the arm from the shoulder down. Prevention and treatment of NBPP warrants an understanding of the biomechanical and physiological responses of newborn BP nerves when subjected to stretch. Current knowledge of the newborn BP is extrapolated from adult animal or cadaveric BP tissue instead of in vivo neonatal BP tissue. This study describes an in vivo mechanical testing device and procedure to conduct in vivo biomechanical testing in neonatal piglets. The device consists of a clamp, actuator, load cell, and camera system that apply and monitor in vivo strains and loads until failure. The camera system also allows monitoring of the failure location during rupture. Overall, the presented method allows for a detailed biomechanical characterization of neonatal BP when subjected to stretch.

Structural and Biomechanical Characterization of a Scaffold-Free Skin Equivalent Model via Biophysical Methods

Aims: Among in vitro skin models, the scaffold-free skin equivalent (SFSE), without exogenous material, is interesting for pharmacotoxicological studies. Our aim was to adapt in vivo biophysical methods to study the structure, thickness, and extracellular matrix of our in vitro model without any chemical fixation needed as for histology. Methods: We evaluated 3 batches of SFSE and characterized them by histology, transmission electron microscopy (TEM), and immunofluorescence. In parallel, we investigated 3 biophysical methods classically used for in vivo evaluation, optical coherence tomography (OCT), and laser scanning microscopy (LSM) imaging devices as well as the cutometer suction to study the biomechanical properties. Results: OCT allowed the evaluation of SFSE total thickness and its different compartments. LSM has a greater resolution enabling an evaluation at the cell scale and the orientation of collagen fibers. The viscoelasticity measurement by cutometry was possible on our thin skin model and might be linked with mature collagen bundles visible in TEM and LSM and with elastic fibers seen in immunofluorescence. Conclusion: Our data demonstrated the simplicity and sensitivity of these different in vivo biophysical devices on our thin skin model. These noninvasive tools allow to study the morphology and the biomechanics of in vitro models.

Bilaminar Mechanics of the Human Optic Nerve Sheath

ABSTRACT Purpose/Aim The adult human optic nerve (ON) sheath has recently been recognized to be bilaminar, consisting of inner layer (IL) and outer layer (OL). Since the ON and sheath exert tension on the globe in large angle adduction as these structures transmit reaction force of the medial rectus muscle to the globe, this study investigated the laminar biomechanics of the human ON sheath. Materials and Methods Biomechanical characterization was performed in ON sheath specimens from 12 pairs of fresh, post-mortem adult eyes. Some ON sheath specimens were tested completely, while others were separated into IL and OL. Uniaxial tensile loading under physiological temperature and humidity was used to characterize a linear approximation as Young’s modulus, and hyperelastic non-linear behavior using the formulation of Ogden. Micro-indentation was performed by imposing small compressive deformations with small, hard spheres. Specimens of the same sheaths were paraffin embedded, sectioned at 10 micron thickness, and stained with van Gieson’s stain for anatomical correlation. Results Mean (± standard error of the mean, SEM) tensile Young’s modulus of the inner sheath at 19.8 ± 1.6 MPa significantly exceeded that for OL at 9.7 ± 1.2 MPa; the whole sheath showed intermediate modulus of 15.4 ± 1.1 MPa. Under compression, the inner sheath was stiffer (7.9 ± 0.5 vs 5.2 ± 0.5 kPa) and more viscous (150.8 ± 10.6 vs 75.6 ± 6 kPa s) than outer sheath. The inner sheath had denser elastin fibers than outer sheath, correlating with greater stiffness. Conclusions We conclude that maximum tensile stiffness occurs in the elastin-rich ON sheath IL that inserts near the lamina cribrosa where tension in the sheath exerted during adduction tethering may be concentrated adjacent the ON head.

Biomechanical and microstructural characterisation of the porcine stomach wall: Location- and layer-dependent investigations

The mechanical properties of the stomach wall help to explain its function of storing, mixing, and emptying in health and disease. However, much remains unknown about its mechanical properties, especially regarding regional heterogeneities and wall microstructure. Consequently, the present study aimed to assess regional differences in the mechanical properties and microstructure of the stomach wall. In general, the stomach wall and the different tissue layers exhibited a nonlinear stress-stretch relationship. Regional differences were found in the mechanical response and the microstructure. The highest stresses of the entire stomach wall in longitudinal direction were found in the corpus (201.5 kPa), where food is ground followed by the antrum (73.1 kPa) and the fundus (26.6 kPa). In contrast, the maximum stresses in circumferential direction were 39.7 kPa, 26.2 kPa, and 15.7 kPa for the antrum, fundus, and corpus, respectively. Independent of the fibre orientation and with respect to the biaxial loading direction, partially clear anisotropic responses were detected in the intact wall and the muscular layer. In contrast, the innermost mucosal layer featured isotropic mechanical characteristics. Pronounced layers of circumferential and longitudinal muscle fibres were found in the fundus only, whereas corpus and antrum contained almost exclusively circumferential orientated muscle fibres. This specific stomach structure mirrors functional differences in the fundus as well as corpus and antrum. Within this study, the load transfer mechanisms, connected with these wavy layers but also in total with the stomach wall’s microstructure, are discussed. Statement of significanceThis article examines for the first time the layer-specific mechanical and histological properties of the stomach wall attending to the location of the sample. Moreover, both mechanical behaviour and microstructure were explicitly match identifying the heterogeneous characteristics of the stomach. On the one hand, the results of this study contribute to the understanding of stomach mechanics and thus to their functional understanding of stomach motility. On the other hand, they are relevant to the fields of constitutive formulation of stomach tissue, whole stomach mechanics, and stomach-derived scaffolds i.e., tissue-engineering grafts.

Morphological and biomechanical characterization of immature and mature nasoseptal cartilage

Nasoseptal cartilage has been assumed to be isotropic, unlike the well-defined zonal organization of articular cartilage attributed to postnatal biomechanical loading. We know from clinical experience that malrotation of surgical nasoseptal cartilage grafts can lead to increased graft absorption. Other studies have also suggested directionally dependent compressive stiffness suggesting anisotropy, but morphological investigations are lacking. This study characterizes immature and mature native bovine nasoseptal cartilage using a combination of immunohistochemistry, biomechanical testing and structural imaging. Our findings indicate that there is extensive postnatal synthesis and reorganization of the extracellular matrix in bovine nasoseptal cartilage, independent of joint loading forces responsible for articular cartilage anisotropy. Immature nasoseptal cartilage is more cellular and homogenous compared to the zonal organization of cells and extracellular matrix of mature cartilage. Mature samples also exhibited greater glycosaminoglycan content and type II collagen fibre alignment compared to immature cartilage and this correlates with greater compressive stiffness. Engineered neocartilage often consists of immature, isotropic, homogenous tissue that is unable to meet the functional and mechanical demands when implanted into the native environment. This study demonstrates the importance of anisotropy on biomechanical tissue strength to guide future cartilage tissue engineering strategies for surgical reconstruction.

Micro-indentation and optical coherence tomography for the mechanical characterization of embryos: Experimental setup and measurements on chicken embryos

The investigation of the mechanical properties of embryos is expected to provide valuable information on the phenomenology of morphogenesis. It is thus believed that, by mapping the viscoelastic features of an embryo at different stages of growth, it may be possible to shed light on the role of mechanics in embryonic development. To contribute to this field, we present a new instrument that can determine spatiotemporal distributions of mechanical properties of embryos over a wide area and with unprecedented accuracy. The method relies on combining ferrule-top micro-indentation, which provides local measurements of viscoelasticity, with Optical Coherence Tomography, which can reveal changes in tissue morphology and help the user identify the indentation point. To prove the working principle, we have collected viscoelasticity maps of fixed and live HH11-HH12 chicken embryos. Our study shows that the instrument can reveal correlations between tissue morphology and mechanical behavior. Statement of SignificanceLocal mechanical properties of soft biological tissue play a crucial role in several biological processes, including cell differentiation, cell migration, and body formation; therefore, measuring tissue properties at high resolution is of great interest in biology and tissue engineering. To provide an efficient method for the biomechanical characterization of soft biological tissues, we introduce a new tool in which the combination of non-invasive Optical Coherence Tomography imaging and depth-controlled indentation measurements allows one to map the viscoelastic properties of biological tissue and investigate correlations between local mechanical features and tissue morphology with unprecedented resolution.

Evaluation of Structural and Biomechanical Characterization of Implant for Cranial Restoration

The objective this research was to investigate the biomechanical properties of various structures and thicknesses of implants for cranial restoration. A three-dimensional (3D) printing (3DP) technique has been applied in factories for several decades, but it was only recently introduced to the dental field less than 10 years ago. The structures of pre-shaped cranial mesh implants are critical factors for clinical applications. Many previous studies used finite element models to investigate for implants, but few examined a 3D model for pre-shaped cranial mesh implants with different structures and thicknesses. 3D cranial models were reconstructed using computer tomography to simulate preshaped cranial mesh implants under physical impacts. Data indicated that the stress significantly decreased when implants with greater thicknesses were used. Moreover, the implant with a circular structure created a relatively smaller stress that was approximately 7% lower compared to the implant with a triangular structure. As described above, the results of the present study demonstrate that 3DP-Ti is a reliable material of implants for cranial restoration.

Mechanical Characterization by Mesoscale Indentation: Advantages and Pitfalls for Tissue and Scaffolds.

Regenerative medicine and tissue engineering are hindered by the lack of consistent measurements and standards for the mechanical characterization of tissue and scaffolds. Indentation methods for soft matter are favored because of their compatibility with small, arbitrarily shaped samples, but contact mechanics models required to interpret data are often inappropriate for soft, viscous materials. In this study, we demonstrate indentation experiments on a variety of human biopsies, animal tissue, and engineered scaffolds, and we explore the complexities of fitting analytical models to these data. Although objections exist to using Hertz contact models for soft, viscoelastic biological materials since soft matter violates their original assumptions, we demonstrate the experimental conditions that enable consistency and comparability (regardless of arguable misappropriation). Appropriate experimental conditions involving sample hydration, the indentation depth, and the ratio of the probe size to sample thickness enable repeatable metrics that are valuable when comparing synthetic scaffolds and host tissue, and bounds on these parameters are carefully described and discussed. We have also identified a reliable quasistatic parameter that can be derived from indentation data to help researchers compare results across materials and experiments. Although Hertz contact mechanics and linear viscoelastic models may constitute oversimplification for biological materials, the reporting of such simple metrics alongside more complex models is expected to support researchers in tissue engineering and regenerative medicine by providing consistency across efforts to characterize soft matter. Impact Statement To engineer replacement tissue requires a deep understanding of its biomechanical properties. Mesoscale indentation (between micron and millimeter length scales) is well-suited to characterize tissue and engineered replacements as it accommodates small, oddly shaped samples. However, it is easy to run afoul of the assumptions for common contact models when working with biological materials. In this study, we describe experimental procedures and modeling approaches that allow researchers to take advantage of indentation for biomechanical characterization while minimizing its weaknesses.

Biomechanical characterization of human small bowel wall under inflation conditions

Biomechanical characterization of human small bowel wall under inflation conditions

Biomechanical and geometric characterization of peroneus longus allografts with respect to age

BackgroundAnterior cruciate ligament injuries are among the most common injuries in high impact sports, and reconstruction is the standard surgical procedure for these ruptures. Reconstructions are often performed using allografts rather than autografts on a case-by-case basis. Controversy exists as to whether or not age of donor tissue plays a factor in the mechanical properties of allografts. Methods38 peroneus longus (PL) tendons were prepared using the two-strand graft technique and then subjected to a cyclic loading test regimen of 1000 cycles to determine material properties. Specimens were grouped based on age to ascertain whether donor age affects the material properties of PL tendons. FindingsSecant modulus of the first cycle was determined to be 150.43 (SD 40.24) MPa. The average magnitude of the dynamic modulus was determined to be 82.81 (SD 24.65) MPa. Specimens were grouped into three distinct groups for analysis (x < 40 yo, 40 yo ≤ x < 60 yo, 60 yo < x). InterpretationThe need for using intrinsic material properties is highlighted. There is no significant difference in any intrinsic material property with respect to age or the fatigue of the tendon as the cycle count increases. Conversely, the measured stiffness of a tendon decreased as function of age with a large effect size. Based on analysis of graft geometries, it was determined that PL tendons become significantly more slender with increased age which result in the observed decrease in stiffness.

Force-Regulated Refolding of the Mechanosensory Domain in the Platelet Glycoprotein Ib-IX Complex

In platelets, the glycoprotein (GP) Ib-IX receptor complex senses blood shear flow and transmits the mechanical signals into platelets. Recently, we have discovered a juxtamembrane mechanosensory domain (MSD) within the GPIbα subunit of GPIb-IX. Mechanical unfolding of the MSD activates GPIb-IX signaling into platelets, leading to their activation and clearance. Using optical tweezer-based single-molecule force measurement, we herein report a systematic biomechanical characterization of the MSD in its native, full-length receptor complex and a recombinant, unglycosylated MSD in isolation. The native MSD unfolds at a resting rate of 9 × 10−3 s−1. Upon exposure to pulling forces, MSD unfolding accelerates exponentially over a force scale of 2.0 pN. Importantly, the unfolded MSD can refold with or without applied forces. The unstressed refolding rate of MSD is ∼17 s−1 and slows exponentially over a force scale of 3.7 pN. Our measurements confirm that the MSD is relatively unstable, with a folding free energy of 7.5 kBT. Because MSD refolding may turn off GPIb-IX’s mechanosensory signals, our results provide a mechanism for the requirement of a continuous pulling force of >15 pN to fully activate GPIb-IX.

Decellularization as a method to reduce calcification in bovine pericardium bioprosthetic valves.

Decellularization is an alternative method for processing biological tissues with decreased antigenicity and resistance to calcification. The aim of this study was to characterize the properties of decellularized (dCell) bovine pericardium fixed with 0.1% glutaraldehyde (GA) and to evaluate outcomes of bioprosthetic valves constructed with this tissue when implanted in the mitral position of juvenile sheep. Bioprosthetic mitral valves were constructed with fresh bovine pericardium fixed in 0.5% GA (control group) or dCell bovine pericardium fixed in 0.1% GA (study group). Before implantation, samples were submitted to histological (haematoxylin-eosin, Movat and 4',6-diamidino-2-phenylindole), biochemical (residual deoxyribonucleic acid and α-gal epitopes) and biomechanical characterization. Valves were implanted (n = 8 in each group) as a mitral valve replacement for 180 days in sheep and explants were re-evaluated histologically and for calcification with radiological studies and calcium content determination. Unimplanted dCell pericardia exhibited a well-preserved extracellular matrix with absence of cells, a 77% reduction in deoxyribonucleic acid levels and with no detectable α-gal epitopes. When compared to controls, they had lower ultimate tensile strength (7.3 ± 5.4 vs 10.2 ± 3.0 mPa, P = 0.04) and greater percentage elongation in the longitudinal direction (29 ± 6.5% vs 23.8 ± 5.1%, P = 0.02). After 180 days in mitral position, dCell valves showed pliable leaflets without macroscopic signs of calcification. Histologically, dCell leaflets had intact collagen fibres, better tissue remodelling and a significant 89% reduction in calcium content. This study demonstrates that bioprosthetic valves constructed with dCell bovine pericardium fixed in low GA concentration were resistant to calcification and may thereby improve long-term durability of the tissue.

Dynamic optical coherence elastography: Emerging tool for noninvasive quantification of mechanical properties of ocular tissues

Optical coherence elastography (OCE) is an emerging method for noninvasive quantification of tissue viscoelastic properties. The underlying technology is based on Optical Coherence Tomography (OCT) imaging and analysis of external (or internal) force-induced mechanical waves propagating through the tissue. In this presentation, I will overview recent progress made in my lab on quantification of mechanical properties of ocular tissues (such as cornea and the lens of the eye) using OCE and their alternations during diseases progression. In particular, I will demonstrate that it is possible to quantify mechanical properties of the cornea and lens as a function of Intra-Ocular Pressure (IOP) and during controlled tissue modifications and treatments, such as corneal cross-linking. These results indicate that OCE is a powerful new technology that can be utilized for the nondestructive biomechanical characterization of ocular tissues in normal and pathological states and could not only assist in basic biomechanical studies but also lead to a new class of optical sensors for diagnosis of diseases. [Work supported, in part, by the U.S. National Institutes of Health (NIH) under Grant Nos. 2R01EY022362 and 1R01HL120140 and U.S. Department of Defense (DOD) Congressionally Directed Medical Research Programs (CDMRP) under Grant No. PR150338.]

Biomechanical characterization of a novel collagen-hyaluronan infused 3D-printed polymeric device for partial meniscus replacement.

The menisci transmit load by increasing the contact area and decreasing peak contact stresses on the articular surfaces. Meniscal lesions are among the most common orthopedic injuries, and resulting meniscectomies are associated with adverse polycaprolactone contact mechanics changes and, ultimately, an increased likelihood of osteoarthritis. Meniscus scaffolds were fabricated by 3D-printing a network of circumferential and radial filaments of resorbable polymer (poly(desaminotyrosyl-tyrosine dodecyl ester dodecanoate)) and infused with collagen-hyaluronan. The scaffold demonstrated an instantaneous compressive modulus (1.66 ± 0.44 MPa) comparable to native meniscus (1.52 ± 0.59 MPa). The scaffold aggregate modulus (1.33 ± 0.51 MPa) was within 2% of the native value (1.31 ± 0.36 MPa). In tension, the scaffold displayed a comparable stiffness to native tissue (127.6-97.1 N/mm) and an ultimate load of 33% of the native value. Suture pull-out load of scaffolds (83.1 ± 10.0 N) was within 10% of native values (91.5 ± 15.4 N). Contact stress analysis demonstrated the scaffold reduced peak contact stress by 60-67% and increased contact area by 38%, relative to partial meniscectomy. This is the first meniscal scaffold to match both the axial compressive properties and the circumferential tensile stiffness of the native meniscus. The improvement of joint contact mechanics, relative to partial meniscectomy alone, motivates further investigation using a large animal model. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2457-2465, 2019.

Cellular Traction Forces and Locations of Adhesion Site Regulate Cell Functions

Biomechanical characterization of cells is becoming one of the non-invasive techniques to monitor the different physical phenomenon of cells including cell growth, proliferation, migration and adhesion on micropatterned substrates. The present study demonstrates micropillars patterned-Polydimethylsiloxane (PDMS) substrate to investigate the biophysico-mechanical properties of normal, cancer and drug-treated cancer cells. The compositions of PDMS were varied to explore the effect of substrate rigidity providing important signals to change in cell-cell and cell-substrate interactions on micropillar substrates. Further, micropillars of different PDMS compositions were fabricated through lithography followed by softlithography technique. Subsequently, normal HaCaT cells, untreated and doxorubicin-treated MDA-MB 231 & MCF-7 breast cancer cells were cultured on without any protein coated micropillar substrates for 24 h that individually act as a force sensor. Deflection of pillar allows the direct visualization and quantification of cell traction forces applied to the pillar using python image processing algorithm developed by us. Results revealed cell focal adhesion site on micropillar varied among HaCaT, untreated and treated MDA-MB 231 & MCF-7 cancerous cells. It was observed HaCaT cells were adhered at (20-26)% of pillars height, however, both untreated cancer cells adhered above 68% but after drug treatment cancer cells adhesion site shifted at (35-55)% of pillar height from bottom. Therefore, changes in the deflection magnitude and traction force with cell types are attributed to the alterations in their different location of cell adhesion site that constitute different mechanical properties of cells. Thus, traction force exerted by various cell lines due to their different biophysico-mechanical properties exploring new insights and advances in cell mechanics and differentiation of normal and cancer cells as well as drug effect on cancer cells and in cancer therapeutics.

Use of flexible sensor to characterize biomechanics of canine skin

BackgroundSuture materials and techniques are frequently evaluated in ex vivo studies by comparing tensile strengths. However, the direct measurement techniques to obtain the tensile forces in canine skin are not available, and, therefore, the conditions suture lines undergo is unknown. A soft elastomeric capacitor is used to monitor deformation in the skin over time by sensing strain. This sensor was applied to a sample of canine skin to evaluate its capacity to sense strain in the sample while loaded in a dynamic material testing machine. The measured strain of the sensor was compared with the strain measured by the dynamic testing machine. The sample of skin was evaluated with and without the sensor adhered.ResultsIn this study, the soft elastomeric capacitor was able to measure strain and a correlation was made to stress using a modified Kelvin-Voigt model for the canine skin sample. The sensor significantly increases the stiffness of canine skin when applied which required the derivation of mechanical models for interpretation of the results.ConclusionsFlexible sensors can be applied to canine skin to investigate the inherent biomechanical properties. These sensors need to be lightweight and highly elastic to avoid interference with the stress across a suture line. The sensor studied here serves as a prototype for future sensor development and has demonstrated that a lightweight highly elastic sensor is needed to decrease the effect on the sensor/skin construct. Further studies are required for biomechanical characterization of canine skin.

Biomechanical characterization of TIM protein\u2013mediated Ebola virus\u2013host cell adhesion

Since the most recent outbreak, the Ebola virus (EBOV) epidemic remains one of the world’s public health and safety concerns. EBOV is a negative-sense RNA virus that can infect humans and non-human primates, and causes hemorrhagic fever. It has been proposed that the T-cell immunoglobulin and mucin domain (TIM) family proteins act as cell surface receptors for EBOV, and that the interaction between TIM and phosphatidylserine (PS) on the surface of EBOV mediates the EBOV–host cell attachment. Despite these initial findings, the biophysical properties of the TIM-EBOV interaction, such as the mechanical strength of the TIM-PS bond that allows the virus-cell interaction to resist external mechanical perturbations, have not yet been characterized. This study utilizes single-molecule force spectroscopy to quantify the specific interaction forces between TIM-1 or TIM-4 and the following binding partners: PS, EBOV virus-like particle, and EBOV glycoprotein/vesicular stomatitis virus pseudovirion. Depending on the loading rates, the unbinding forces between TIM and ligands ranged from 40 to 100 pN, suggesting that TIM-EBOV interactions are mechanically comparable to previously reported adhesion molecule–ligand interactions. The TIM-4–PS interaction is more resistant to mechanical force than the TIM-1–PS interaction. We have developed a simple model for virus–host cell interaction that is driven by its adhesion to cell surface receptors and resisted by membrane bending (or tension). Our model identifies critical dimensionless parameters representing the ratio of deformation and adhesion energies, showing how single-molecule adhesion measurements relate quantitatively to the mechanics of virus adhesion to the cell.

Enhanced In Situ Availability of Aphanizomenon Flos-Aquae Constituents Entrapped in Buccal Films for the Treatment of Oxidative Stress-Related Oral Diseases: Biomechanical Characterization and In Vitro/Ex Vivo Evaluation

In recent years, the key role of oxidative stress in pathogenesis of oral diseases has been emphasized and the use of antioxidant agents has been encouraged. Aphanizomenon flos-aquae (AFA) is a unicellular blue-green alga with antioxidant and anti-inflammatory properties. The aim of this study was the formulation and characterization of mucoadhesive thin layer films loaded with AFA, finalized to the treatment of oxidative stress (OS)-related oral diseases. First, to enhance the bioavailability of AFA constituents, the raw food grade material was appropriately treated by a high frequency homogenization able to disrupt cell walls. Thus, Eudragit® E100-based buccal films were produced by the solvent casting method, containing 7% and 18% of AFA. The films, characterized by uniformity in thickness, weight, and drug content, showed low swelling degree, good muco-adhesiveness and controlled drug release. The mechanical tests showed elastic moduli of films of almost 5 MPa that is well-suitable for human buccal applications without discomfort, besides biaxial tests highlighted a marked material isotropy. Permeation studies through porcine mucosae demonstrated the ability of films to promote AFA penetration in the tissues, and when sublingually administered, they produced a drug flux up to six-fold higher than an AFA solution. The new formulations represent an interesting alternative for the development of cosmetics and nutraceuticals with a functional appeal containing plant extracts.

Biomechanical Characterization of Mouse Sclera in Myopia

Biomechanical Characterization of Mouse Sclera in Myopia

Live human assessment of depth-dependent corneal displacements with swept-source optical coherence elastography.

PurposeTo assess depth-dependent corneal displacements in live normal subjects using optical coherence elastography (OCE).MethodsA corneal elastography method based on swept-source optical coherence tomography (OCT) was implemented in a clinical prototype. Low amplitude corneal deformation was produced during OCT imaging with a linear actuator-driven lens coupled to force transducers. A cross-correlation algorithm was applied to track frame-by-frame speckle displacement across horizontal meridian scans. Intra-measurement force and displacement data series were plotted against each other to produce local axial stiffness approximations, k, defined by the slope of a linear fit to the force/displacement data (ignoring non-axial contributions from corneal bending). Elastographic maps displaying local k values across the cornea were generated, and the ratio of mean axial stiffness approximations for adjacent anterior and posterior stromal regions, ka/kp, was calculated. Intraclass correlation coefficients (ICC) were used to estimate repeatability.ResultsSeventeen eyes (ten subjects) were included in this prospective first-in-humans translational study. The ICC was 0.84. Graphs of force vs. displacement demonstrated that, for simultaneously acquired measurements involving the same applied force, anterior stromal displacements were lower (suggesting stiffer behavior) than posterior stromal displacements. Mean ka was 0.016±0.004 g/mm and mean kp was 0.014±0.004 g/mm, giving a mean ka/kp ratio of 1.123±0.062.ConclusionOCE is a clinically feasible, non-invasive corneal biomechanical characterization method capable of resolving depth-dependent differences in corneal deformation behavior. The anterior stroma demonstrated responses consistent with stiffer properties in compression than the posterior stroma, but to a degree that varied across normal eyes. The clinical capability to measure these differences has implications for assessing the biomechanical impact of corneal refractive surgeries and for ectasia risk screening applications.