Cellular and Molecular Bioengineering: A Tipping Point.

In January of 2011, the Biomedical Engineering Society (BMES) and the Society for Physical Regulation in Biology and Medicine (SPRBM) held its inaugural Cellular and Molecular Bioengineering (CMBE) conference. The CMBE conference assembled worldwide leaders in the field of CMBE and held a very successful Round Table discussion among leaders. One of the action items was to collectively construct a white paper regarding the future of CMBE.

A hydrogel-mineral composite scaffold for osteochondral interface tissue engineering.

Osteoarthritis is the leading cause of physical disability among Americans, and tissue engineered cartilage grafts have emerged as a promising treatment option for this debilitating condition. Currently, the formation of a stable interface between the cartilage graft and subchondral bone remains a significant challenge. This study evaluates the potential of a hybrid scaffold of hydroxyapatite (HA) and alginate hydrogel for the regeneration of the osteochondral interface.

Matrix deposition modulates the viscoelastic shear properties of hydrogel-based cartilage grafts.

Hydrogel-based scaffolds such as alginate have been extensively investigated for cartilage tissue engineering, largely due to their biocompatibility, ambient gelling conditions, and the ability to support chondrocyte phenotype. While it is well established that the viscoelastic response of articular cartilage is essential for articulation and load bearing, the time-dependent mechanical properties of hydrogel-based cartilage scaffolds have not been extensively studied. Therefore, the objective of this study was to characterize the intrinsic viscoelastic shear properties of chondrocyte-laden alginate scaffolds and determine the effects of seeding density and culturing time on these properties.

Geometric control of human stem cell morphology and differentiation.

During tissue morphogenesis, stem cells and progenitor cells migrate, proliferate, and differentiate, with striking changes in cell shape, size, and acting mechanical stresses. The local cellular function depends on the spatial distribution of cytokines as well as local mechanical microenvironments in which the cells reside. In this study, we controlled the organization of human adipose derived stem cells using micro-patterning technologies, to investigate the influence of multi-cellular form on spatial distribution of cellular function at an early stage of cell differentiation.

A triphasic orthotropic laminate model for cartilage curling behavior: fixed charge density versus mechanical properties inhomogeneity.

Osmotic pressure and associated residual stresses play important roles in cartilage development and biomechanical function. The curling behavior of articular cartilage was believed to be the combination of results from the osmotic pressure derived from fixed negative charges on proteoglycans and the structural and compositional and material property inhomogeneities within the tissue. In the present study, the in vitro swelling and curling behaviors of thin strips of cartilage were analyzed with a new structural model using the triphasic mixture theory with a collagen-proteoglycan solid matrix composed of a three-layered laminate with each layer possessing a distinct set of orthotropic properties.

A linearized formulation of triphasic mixture theory for articular cartilage, and its application to indentation analysis.

The negative charges on proteoglycans significantly affect the mechanical behaviors of articular cartilage. Mixture theories, such as the triphasic theory, can describe quantitatively how this charged nature contributes to the mechano-electrochemical behaviors of such tissue. However, the mathematical complexity of the theory has hindered its application to complicated loading profiles, e.

The impact of biomechanics in tissue engineering and regenerative medicine.

Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues.

Temperature-dependent viscoelastic properties of the human supraspinatus tendon.

Temperature effects on the viscoelastic properties of the human supraspinatus tendon were investigated using static stress-relaxation experiments and the quasi-linear viscoelastic (QLV) theory. Twelve supraspinatus tendons were randomly assigned to one of two test groups for tensile testing using the following sequence of temperatures: (1) 37, 27, and 17 degrees C (Group I, n=6), or (2) 42, 32, and 22 degrees C (Group II, n=6). QLV parameter C was found to increase at elevated temperatures, suggesting greater viscous mechanical behavior at higher temperatures.

Calcium Concentration Effects on the Mechanical and Biochemical Properties of Chondrocyte-Alginate Constructs.

Alginate gel crosslinked by calcium ions (Ca(2+)) has been widely used in cartilage tissue engineering. However, most studies have been largely performed in vitro in medium with a calcium concentration ([Ca(2+)]) of 1.8mM, while the calcium level in the synovial fluid of the human knee joints, for example, has been reported to be 4mM or even higher.

Biomechanics of articular cartilage and determination of material properties.

Descriptions of the mechanical behaviors of articular cartilage and their correlations with collagen, proteoglycan, water, and ions are summarized, with particular emphasis on understanding the osmotic effect inside the tissue. First, a descriptive explanation is presented of the biphasic theory required to understand how interstitial water contributes toward the viscoelastic behavior of any hydrated soft tissue. Then, the famous osmotic effect in charged, hydrated soft tissue is interpreted in light of the triphasic mixture theory framework.

Tissue engineering and developmental biology: going biomimetic.

This article contains the collective views expressed at the first session of the workshop "Tissue Engineering--The Next Generation," which was devoted to the interactions between developmental biology and tissue engineering. Donald Ingber discussed the chasms between developmental biology and tissue engineering from the perspective of a cell biologist who has had interest in tissue engineering since its early days. Van C.

The generalized triphasic correspondence principle for simultaneous determination of the mechanical properties and proteoglycan content of articular cartilage by indentation.

The triphasic mixture theory has been used to describe the mechanical and physicochemical behaviors of articular cartilage under some specialized loading conditions. However, the mathematical complexities of this theory have limited its applications for theoretical analyses of experimental studies and models for predicting cartilage and other biological tissues' deformational behaviors. A generalized correspondence principle has been established in the present study, and this principle shows that the equilibrium deformational behavior of a charged-hydrated material under loading is identical to that of an elastic medium without charge.

The inferior glenohumeral ligament: a correlative investigation.

The inferior glenohumeral ligament (IGHL) was investigated by correlating the biomechanical properties, biochemical composition, and histologic morphology of its 3 anatomic regions (superior band, anterior axillary pouch, and posterior axillary pouch) in 8 human cadaveric shoulders. The overall biochemical composition of the IGHL appeared similar to other ligaments, with average water content of 80.9 +/- 2.

Fixed electrical charges and mobile ions affect the measurable mechano-electrochemical properties of charged-hydrated biological tissues: the articular cartilage paradigm.

The triphasic constitutive law [Lai, Hou and Mow (1991)] has been shown in some special 1D cases to successfully model the deformational and transport behaviors of charged-hydrated, porous-permeable, soft biological tissues, as typified by articular cartilage. Due to nonlinearities and other mathematical complexities of these equations, few problems for the deformation of such materials have ever been solved analytically. Using a perturbation procedure, we have linearized the triphasic equations with respect to a small imposed axial compressive strain, and obtained an equilibrium solution, as well as a short-time boundary layer solution for the mechano-electrochemical (MEC) fields for such a material under a 2D unconfined compression test.

The effect of matrix tension-compression nonlinearity and fixed negative charges on chondrocyte responses in cartilage.

Thorough analyses of the mechano-electrochemical interaction between articular cartilage matrix and the chondrocytes are crucial to understanding of the signal transduction mechanisms that modulate the cell metabolic activities and biosynthesis. Attempts have been made to model the chondrocytes embedded in the collagen-proteoglycan extracellular matrix to determine the distribution of local stress-strain field, fluid pressure and the time-dependent deformation of the cell. To date, these models still have not taken into account a remarkable characteristic of the cartilage extracellular matrix given rise from organization of the collagen fiber architecture, now known as the tension-compression nonlinearity (TCN) of the tissue, as well as the effect of negative charges attached to the proteoglycan molecules, and the cell cytoskeleton that interacts with mobile ions in the interstitial fluid to create osmotic and electro-kinetic events in and around the cells.

An in vitro analysis of ligament reconstruction or extension osteotomy on trapeziometacarpal joint stability and contact area.

Purpose: Painful instability of the minimally osteoarthritic thumb carpometacarpal (CMC) joint can be treated successfully by either ligament reconstruction or metacarpal extension osteotomy. The purpose of this study was to measure the laxity of cadaveric thumb CMC joints and to determine the influence of ligament reconstruction and metacarpal osteotomy on joint laxity and contact area.

Methods: The baseline laxity of CMC joints from 25 fresh-frozen human cadaveric specimens (average age, 42 y; range, 18-55 y) was measured in the position of lateral pinch on a custom-designed CMC joint laxity tester.

Inhomogeneous mechanical behavior of the human supraspinatus tendon under uniaxial loading.

Disorders of the rotator cuff, particularly tears of the rotator cuff tendons, cause significant shoulder disability. Among numerous factors thought to be responsible for the initiation and progression of supraspinatus tears are those related to the tendon's biomechanical properties. We hypothesized that in supraspinatus tendons subjected to tensile loading a strain gradient (difference) exists between the articular and bursal tendon surfaces, that regional strain differences exist on each of these two tendon surfaces, and that tendon surface strains vary with glenohumeral abduction.

Comparison of glenohumeral mechanics following a capsular shift and anterior tightening.

Background: Numerous surgical techniques have been developed to treat glenohumeral instability. Anterior tightening procedures have been associated with secondary glenohumeral osteoarthritis, unlike the anterior-inferior capsular shift procedure, which has been widely advocated as a more anatomical repair. The objective of the present study was to quantify glenohumeral joint translations, articular contact, and resultant forces in cadaveric specimens in order to compare the effects of unidirectional anterior tightening with those of the anterior-inferior capsular shift.

Anisotropy, inhomogeneity, and tension-compression nonlinearity of human glenohumeral cartilage in finite deformation.

The tensile and compressive properties of human glenohumeral cartilage were determined by testing 120 rectangular strips in uniaxial tension and 70 cylindrical plugs in confined compression, obtained from five human glenohumeral joints. Specimens were harvested from five regions across the articular surface of the humeral head and two regions on the glenoid. Tensile strips were obtained along two orientations, parallel and perpendicular to the split-line directions.

Indentation determined mechanoelectrochemical properties and fixed charge density of articular cartilage.

As a nondestructive technique, the indentation test has been used, both in vitro and in vivo, to determine the in situ apparent mechanical properties of cartilage. In this study, a simple new algorithm was developed using the indentation creep test, combined with both biphasic and triphasic analyses to calculate simultaneously the apparent and intrinsic mechanical (aggregate modulus and Poisson's ratio) and an electrochemical properties, i.e.

Radiography and visual pathology of the osteoarthritic scaphotrapezio-trapezoidal joint, and its relationship to trapeziometacarpal osteoarthritis.

Purpose: To determine and quantify the relationship of osteoarthritis (OA) in the trapeziometacarpal, scaphotrapezial, and scaphotrapezoidal joints; to ascertain the dependability of radiographic assessment of trapeziometacarpal, scaphotrapezial, and scaphotrapezoidal OA; to determine the articular topography of the scaphotrapezio-trapezoidal (STT) joint (composed of the scaphotrapezial and scaphotrapezoidal articulations) using stereophotogrammetry; and to characterize the articular wear patterns of STT OA.

Methods: Sixty-nine fresh-frozen human cadaveric hands were staged radiographically and by gross visual examination for the presence of OA in the trapeziometacarpal and STT joints. Twenty randomly selected joints also were evaluated to determine the topography of the STT joint using stereophotogrammetry.

Simulated extension osteotomy of the thumb metacarpal reduces carpometacarpal joint laxity in lateral pinch.

Purpose: To assess the effect of an extension osteotomy of the thumb metacarpal on thumb carpometacarpal (CMC) joint laxity with respect to the lateral pinch position.

Methods: Seven fresh-frozen specimens were dissected. The metacarpal, trapezium, and trapezoid were removed en bloc and rigidly fixed proximally and distally.