Mechanisms of lamellar collagen formation in connective tissues

The objective of tissue engineering is to regenerate functional tissues. Engineering functional tissues requires an understanding of the mechanisms that guide the formation and evolution of structure in the extracellular matrix (ECM). In particular, the three-dimensional (3D) collagen fiber arrangement is important as it is the key structural determinant that provides mechanical integrity and biological function. In this review, we survey the current knowledge on collagen organization mechanisms that can be applied to create well-structured functional lamellar tissues and in particular intervertebral disc and cornea. Thus far, the mechanisms behind the formation of cross-aligned collagen fibers in the lamellar structures is not fully understood. We start with cell-induced collagen alignment and strain-stabilization behavior mechanisms which can explain a single anisotropically aligned collagen fiber layer. These mechanisms may explain why there is anisotropy in a single layer in the first place. However, they cannot explain why a consecutive collagen layer is laid down with an alternating alignment. Therefore, we explored another mechanism, called liquid crystal phasing. While dense concentrations of collagen show such behavior, there is little evidence that the conditions for liquid crystal phasing are actually met in vivo. Instead, lysyl aldehyde-derived collagen cross-links have been found essential for correct lamellar matrix deposition. Furthermore, we suggest that supra-cellular (tissue-level) shear stress may be instrumental in the alignment of collagen fibers. Understanding the potential mechanisms behind the lamellar collagen structure in connective tissues will lead to further improvement of the regeneration strategies of functional complex lamellar tissues

Restrained Differential Growth: The Initiating Event of Adolescent Idiopathic Scoliosis?

An experimental model study and a short review of literature. The purpose of this study was to explore a new hypothesis suggesting that the curvatures seen in adolescent idiopathic scoliosis (AIS) originate from restrained differential growth between the vertebral column and the surrounding musculo-ligamentary structures. Despite decades of research, there is no generally accepted theory on the physical origin of the severe spinal deformations seen in AIS. The prevailing theories tend to focus on left-right asymmetry, rotational instability, or the sagittal spinal profile in idiopathic scoliosis. We test our hypothesis with a physical model of the spine that simulates growth, counteracted by ligaments and muscles, modeled by tethers and springs. Growth of the spine is further restrained by an anterior band representing the thorax, the linea alba, and abdominal musculature. We also explore literature in search of molecular mechanisms that may induce differential growth. Differential growth in the restrained spine model first induces hypokyphosis and mild lateral bending of the thoracic spine, but then suddenly escalates into a scoliotic deformity, consistent with clinical observations of AIS. The band simulating the ventral structures of the body had a pivotal effect on sagittal curvature and the initiation of lateral bending and rotation. In literature, several molecular mechanisms were found that may explain the occurrence of differential growth between the spine and the musculo-ligamentary structures. While AIS is a three-dimensional deformation of the spine, it appears that restrained differential growth in the sagittal plane can result in lateral bending and rotation without a pre-existing left-right asymmetry. This supports the concept that AIS may result from a growth imbalance rather than a local anatomical defect. N/

Electrospun Matrices for Pelvic Floor Repair: Effect of Fiber Diameter on Mechanical Properties and Cell Behavior

Electrospun matrices are proposed as an alternative for polypropylene meshes in reconstructive pelvic surgery. Here, we investigated the effect of fiber diameter on (1) the mechanical properties of electrospun poly (lactic-co-glycolic acid)-blended-poly(caprolactone) (PLGA/PCL) matrices; (2) cellular infiltration; and (3) the newly formed extracellular matrix (ECM) in vitro. We compared electrospun matrices with 1- and 8 μm fiber diameter and used nonporous PLGA/PCL films as controls. The 8-μm matrices were almost twice as stiff as the 1-μm matrices with 1.38 and 0.66 MPa, respectively. Matrices had the same ultimate tensile strength, but with 80% the 1-μm matrices were much more ductile than the 8-μm ones (18%). Cells infiltrated deeper into the matrices with larger pores, but cellular activity was comparable on both substrates. New ECM was deposited faster on the electrospun samples, but after 2 and 4 weeks the amount of collagen was comparable with that on nonporous films. The ECM deposited on the 1-μm matrices, and the nonporous film was about three times stiffer than the ECM found on the 8-μm matrices. Cell behavior in terms of myofibroblastic differentiation and remodeling was similar on the 1-μm matrices and nonporous films, in comparison to that on the 8-μm matrices. We conclude that electrospinning enhances the integration of host cells as compared with a nonporous film of the same material. The 1-μm matrices result in better mechanical behavior and qualitatively better matrix production than the 8-μm matrices, but with limited cellular infiltration. These data are useful for designing electrospun matrices for the pelvic floo

Biomechanical evaluation of a novel nucleus pulposus prosthesis in canine cadaveric spines

Partial disc replacement is a new surgical technique aimed at restoring functionality to degenerated intervertebral discs (IVDs). The aim of the present study was to assess biomechanically the behaviour of a novel nucleus pulposus prosthesis (NPP) in situ and its ability to restore functionality to the canine IVD after nuclectomy alone or after combined dorsal laminectomy and nuclectomy. Nine canine T13-L5 specimens (L2L3 group) and 10 L5-Cd1 specimens (LS group) were tested biomechanically in the native state, after nuclectomy (L2L3 group) or after combined dorsal laminectomy and nuclectomy (LS group), and after insertion of the NPP. Range of motion (ROM), neutral zone (NZ), and neutral zone stiffness (NZS) were determined in flexion/extension, lateral bending, and axial rotation. Nuclectomy alone and combined dorsal laminectomy and nuclectomy caused significant instability in all motion directions. Implantation of the NPP resulted in significant restoration of the parameters (ROM, NZ, and NZS) towards the native state; however, fragmentation/herniation of the NPP occurred in 47% of the cases. In conclusion, the NPP has the ability to improve functionality of the nuclectomized canine IVD. The high rate of NPP failure requires modifications directed at the integrity of the NPP and its confinement to the nuclear cavit