Patterning Anisotropic Collagen Scaffolds for Tendon Insertion Regeneration

2012 ◽  
Author(s):  
S. R. Caliari ◽  
D. W. Weisgerber ◽  
R. A. Hortensius ◽  
D. O. Kelkhoff ◽  
M. A. Ramirez ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Structural Complexity ◽  
The Elderly ◽  
Biomechanical Properties ◽  
Clinical Results ◽  
Scar Tissue ◽  
Collagen Scaffolds ◽  
Stress Concentrations ◽  
Connective Tissues ◽  
Tendon Insertion

Tendons are connective tissues that transmit loads between bone and muscle. The biological solution to the problem of connecting relatively compliant tendon to stiffer (∼2 orders of magnitude) bone is a gradient interface zone ∼100μm wide. Over the tendon-bone-junction (TBJ) a linear transition takes place in the ECM inorganic:organic (mineral:collagen) ratio as well as mineral crystallinity from that of tendon to bone. While small TBJ injuries can heal via regeneration, severe defects undergo repair-mediated healing characterized by fibrocartilagenous scar tissue with inferior biomechanical and functional properties. Severe TBJ injuries are common in athletes, the elderly, and following severe craniofacial and extremity trauma. Many tendon injuries (i.e. supraspinatus injuries), particularly those associated with acute trauma, are prone to occur at the TBJ due to high levels of region-specific stress concentrations; rotator cuff tendons injuries, one of the most common TBJ injuries, exhibit re-tears at rates as high as 94%. The scale of such defects and current poor clinical results suggest the need for a biomaterial solution that can mimic the dynamic heterogeneities of the native insertion and tendon body to induce rapid, functional regeneration. Three-dimensional collagen-GAG (CG) scaffolds have been successfully used clinically to regenerate large soft tissue defects (skin, peripheral nerves); they act by mimicking the native extracellular matrix (ECM) of the damaged tissue to prevent wound contraction and scar tissue synthesis. However these scaffolds have not traditionally been used for orthopedics due to an inability to recapitulate two critical features of orthopedic tissues: multiscale structural complexity, biomechanical properties.

Collagen Scaffold-Membrane Composites for Mimicking Orthopedic Interfaces

2011 ◽  
Author(s):  
Brendan A. C. Harley
Keyword(s):  
Three Dimensional ◽  
Structural Complexity ◽  
Collagen Scaffold ◽  
The Elderly ◽  
Biomechanical Properties ◽  
Clinical Results ◽  
Scar Tissue ◽  
Core Shell ◽  
Stress Concentrations ◽  
Scale Properties

Tendons are specialized connective tissues that transmit load between bone and muscle, and whose microstructural and compositional features underlie their function. The biological solution to the problem of connecting relatively compliant tendon to stiffer (∼2 orders of magnitude) bone is a gradient interface zone ∼100μm wide. Over the tendon-bone-junction (TBJ) a linear transition takes place in the ECM inorganic:organic (mineral:collagen) ratio as well as mineral crystallinity from that of tendon to bone. While small TBJ injuries can heal via regeneration, severe defects undergo repair-mediated healing characterized by fibrocartilagenous scar tissue with inferior biomechanical and functional properties. Severe TBJ injuries are common in athletes, the elderly, and following severe craniofacial and extremity trauma. Many tendon injuries (i.e. supraspinatus injuries), particularly those associated with acute trauma, are prone to occur at the TBJ due to high levels of region-specific stress concentrations; rotator cuff tendons injuries, one of the most common TBJ injuries, exhibit re-tears at rates as high as 94%. The scale of such defects and current poor clinical results suggest the need for a biomaterial solution that can mimic the dynamic heterogeneities of the native insertion and tendon body to induce rapid, functional regeneration. Three-dimensional collagen-GAG (CG) scaffolds have been successfully used clinically to regenerate large soft tissue defects (skin, peripheral nerves); they act by mimicking the native extracellular matrix (ECM) of the damaged tissue to prevent wound contraction and scar tissue synthesis. However these scaffolds have not traditionally been used for orthopedics due to an inability to recapitulate two critical features of orthopedic tissues: multiscale structural complexity, biomechanical properties. While the multi-scale properties of tendon itself cannot be currently replicated, nature provides an alternative paradigm: core-shell composites. Plant stems combine a porous core with a dense shell to aid osmotic transport (core) while maintaining sufficient tensile/bending stiffness (shell); many bird beaks use core-shell designs to efficiently enhance compressive strength. Here we describe development of three biomaterial engineering approaches to create the next generation of regeneration templates for tendon insertion injuries: composite, spatially patterned CG biomaterials.

scholarly journals Factors related to large bone defects of bipolar lesions and a high number of instability episodes with anterior glenohumeral instability

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Noboru Matsumura ◽  
Kazuya Kaneda ◽  
Satoshi Oki ◽  
Hiroo Kimura ◽  
Taku Suzuki ◽  
...  
Keyword(s):  
Humeral Head ◽  
Glenohumeral Joint ◽  
Three Dimensional ◽  
Clinical Results ◽  
Bone Defects ◽  
Symptom Duration ◽  
Glenohumeral Instability ◽  
Explanatory Variables ◽  
Large Bone ◽  
Large Bone Defects

Abstract Background Significant bone defects are associated with poor clinical results after surgical stabilization in cases of glenohumeral instability. Although multiple factors are thought to adversely affect enlargement of bipolar bone loss and increased shoulder instability, these factors have not been sufficiently evaluated. The purpose of this study was to identify the factors related to greater bone defects and a higher number of instability episodes in patients with glenohumeral instability. Methods A total of 120 consecutive patients with symptomatic unilateral instability of the glenohumeral joint were retrospectively reviewed. Three-dimensional surface-rendered/registered models of bilateral glenoids and proximal humeri from computed tomography data were matched by software, and the volumes of bone defects identified in the glenoid and humeral head were assessed. After relationships between objective variables and explanatory variables were evaluated using bivariate analyses, factors related to large bone defects in the glenoid and humeral head and a high number of total instability episodes and self-irreducible dislocations greater than the respective 75th percentiles were evaluated using logistic regression analyses with significant variables on bivariate analyses. Results Larger humeral head defects (P < .001) and a higher number of total instability episodes (P = .032) were found to be factors related to large glenoid defects. On the other hand, male sex (P = .014), larger glenoid defects (P = .015), and larger number of self-irreducible dislocations (P = .027) were related to large humeral head bone defects. An increased number of total instability episodes was related to longer symptom duration (P = .001) and larger glenoid defects (P = .002), and an increased number of self-irreducible dislocations was related to larger humeral head defects (P = .007). Conclusions Whereas this study showed that bipolar lesions affect the amount of bone defects reciprocally, factors related to greater bone defects differed between the glenoid and the humeral head. Glenoid defects were related to the number of total instability episodes, whereas humeral head defects were related to the number of self-irreducible dislocations.

Effective Convergence Checks for Verifying Finite Element Stresses at Three-Dimensional Stress Concentrations

2018 ◽  
Vol 3 (3) ◽  
Author(s):  
J. R. Beisheim ◽  
G. B. Sinclair ◽  
P. J. Roache
Keyword(s):  
Finite Element ◽  
Error Estimation ◽  
A Posteriori Error Estimates ◽  
Three Dimensional ◽  
Posteriori Error ◽  
Test Problems ◽  
A Posteriori ◽  
Stress Concentrations ◽  
Element Analysis ◽  
A Posteriori Error

Current computational capabilities facilitate the application of finite element analysis (FEA) to three-dimensional geometries to determine peak stresses. The three-dimensional stress concentrations so quantified are useful in practice provided the discretization error attending their determination with finite elements has been sufficiently controlled. Here, we provide some convergence checks and companion a posteriori error estimates that can be used to verify such three-dimensional FEA, and thus enable engineers to control discretization errors. These checks are designed to promote conservative error estimation. They are applied to twelve three-dimensional test problems that have exact solutions for their peak stresses. Error levels in the FEA of these peak stresses are classified in accordance with: 1–5%, satisfactory; 1/5–1%, good; and <1/5%, excellent. The present convergence checks result in 111 error assessments for the test problems. For these 111, errors are assessed as being at the same level as true exact errors on 99 occasions, one level worse for the other 12. Hence, stress error estimation that is largely reasonably accurate (89%), and otherwise modestly conservative (11%).

scholarly journals Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery

2021 ◽  
Vol 22 (3) ◽  
pp. 1203
Author(s):  
Lu Qian ◽  
Julia TCW
Keyword(s):  
Drug Discovery ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Structural Complexity ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Central Nerve System ◽  
Human Ipscs ◽  
Nerve System

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients’ CNS and serve as a platform for therapeutic development and personalized precision medicine.

scholarly journals Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D Collagen Scaffolds

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Gayathri Subramanian ◽  
Alexander Stasuk ◽  
Mostafa Elsaadany ◽  
Eda Yildirim-Ayan
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Expression Profiles ◽  
Three Dimensional ◽  
Uniaxial Tensile ◽  
Adipose Derived Stem Cells ◽  
Collagen Scaffolds ◽  
Differentiation Potential ◽  
Tenogenic Differentiation ◽  
Matrix Organization

Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.

Optimisation of the drill-in behaviour of the EcoFit® SC threaded cup

2020 ◽  
Vol 65 (4) ◽  
pp. 477-484
Author(s):  
Christoph Thorwächter ◽  
Matthias Woiczinski ◽  
Inês Santos ◽  
Florian Schmidutz ◽  
Alexander Paulus ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Primary Stability ◽  
Clinical Results ◽  
Clinical Applications ◽  
Testing System ◽  
Clinical Use ◽  
Maximum Torque ◽  
3D Images ◽  
Universal Testing ◽  
Biomechanical Investigation

AbstractThreaded cups show good clinical results when implanted correctly. In clinical use, multiple cases with an incomplete placement of the EcoFit threaded cup (implantcast) were observed. This behaviour could not be explained intra- and postoperatively. The aim of this study was to compare and optimise the drill-in-behaviour of the EcoFit cup in a biomechanical investigation. EcoFit cup sizes 46, 50 and 54 mm were compared with the SC cup (Aesculap) size 50 mm. Foam blocks (Sawbones) of density 0.16 g/ml (pcf 10), 0.32 g/ml (pcf 20) and 0.48 g/ml (pcf 30) were used. After standardised placement using a universal testing system (n = 8 per group), the primary stability, the overhang of the cups and the drill-in behaviour were measured. Overreamings of 1 and 2 mm were performed (pcf 20, n = 8) for the EcoFit cup size 50 and the primary stability as well as the overhang measurements were examined. Measurements of the cup diameter, thread depth and thread pitch were performed on three-dimensional (3D) images of the cup size 50 mm. The drill-in behaviour was different between the EcoFit and the SC cups. Even with maximum torque, the EcoFit cup could not be positioned as deep as the SC cup in standard reaming conditions (overhang of 1.1 ± 0.4 mm for the EcoFit size 50 in pcf 20 and of −0.01 ± 0.2 mm for the SC cup). The primary stability was lower for the EcoFit cup in comparison to the SC cup (128.8 ± 3.2 Nm vs. 138.6 ± 9.1 Nm, p = 0.0291). With overreaming to 51 mm, a deeper positioning of the EcoFit was possible (overlap of −0.3 ± 0.1, comparable to the SC cup). The overreaming of the cavity also led to a significantly higher primary stability of 143.4 ± 3.7 Nm (p < 0.001) comparable to the unaltered condition (128.8 ± 3.2 Nm). Overreaming to 52 mm had no further advantage in terms of primary stability or overhang. The geometric measurements showed significant differences as well. The previously clinically observed difficulties in inserting the cup were confirmed by this study. By overreaming to 51 mm, the drill-in behaviour, the primary stability and the measured overhang were comparable to the reference cup. The obtained results suggest that the extension of the acetabulum cavity to 51 mm while using the implantcast EcoFit size 50 should be implemented in clinical applications.

390 Characterisation of a Platelet Rich Fibrin Membrane and Formation of an Autologous Fibrin Mesh

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
Joshua Burke ◽  
Jack Helliwell ◽  
Mikolaj Kowal ◽  
David Jayne
Keyword(s):  
Three Dimensional ◽  
Clinical Results ◽  
Vascular Endothelial ◽  
Blood Draw ◽  
Platelet Rich Fibrin ◽  
Fibrin Scaffold ◽  
Surgical Sutures ◽  
Endothelial Growth Factor ◽  
Range Of Values ◽  
Fibrin Membrane

Abstract Aim Platelet-rich fibrin (PRF) is a three-dimensional fibrin scaffold with associated platelets and leukocytes which releases high quantities of growth factors over a sustained period of time. PRF has shown promising clinical results in promoting wound healing and tissue regeneration. The aims of this feasibility study were to establish optimal spinning methods for production of PRF, to quantify the production of vascular endothelial growth factor (VEGF) by PRF and to explore new vehicles of clinical PRF delivery. Method Assessment of optimal production involved comparisons between Protocol 1 (EDTA bottle) and Protocol 2 (no additive) at three different centrifugation forces: 400g, 1000g and 1700g. VEGF production was analysed using ELISA with varied incubation periods and PRF plug segments. Novel methods for PRF delivery were explored using surgical sutures and a Zimmer® Skin Graft Mesher. Results Protocol 2 demonstrated shorter average time to blood draw (9.8s compared to 13.6s) and to centrifuge (25.5s compared to 33.1s) with a decreased range of values. All PRF segments exhibited a positive correlation between incubation time and amount of VEGF produced with the bottom segments producing on average more VEGF. A segment of the fibrin plug was successfully secured on a suture and meshed in a 1:1.5 ratio. Conclusions PRF production can be optimised using blood bottles with no additive and high centrifugation forces. VEGF production by PRF peaks at 120 hours with the bottom PRF segment exhibiting the highest rate of production. The first description of a PRF mesh enables new clinical applications.

Stress Concentrations in Three-Dimensional Electrostriction

1967 ◽  
Vol 34 (2) ◽  
pp. 431-436 ◽  
Author(s):  
T. E. Smith
Keyword(s):  
Displacement Vector ◽  
Spherical Inclusion ◽  
Crack Problem ◽  
Three Dimensional ◽  
Theory Of Elasticity ◽  
Uniform Electric Field ◽  
Inclusion Problem ◽  
Stress Concentrations ◽  
Displacement Potential ◽  
Penny Shaped Crack

Using the techniques employed in developing a Papkovich-Neuber representation for the displacement vector in classical elasticity, a particular integral of the kinematical equations of equilibrium for the uncoupled theory of electrostriction is developed. The particular integral is utilized in conjunction with the displacement potential function approach to problems of the theory of elasticity to obtain closed-form solutions of several stress concentration problems for elastic dielectrics. Under a prescribed uniform electric field at infinity, the problems of an infinite elastic dielectric having first a spherical cavity and then a rigid spherical inclusion are solved. The rigid spheroidal inclusion problem and the penny-shaped crack problem are also solved for the case where the prescribed field is parallel to their axes of revolution.

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