Strong and tough mineralized PLGA nanofibers for tendon-to-bone scaffolds.

Engineering complex tissues such as the tendon-to-bone insertion sites require a strong and tough biomimetic material system that incorporates both mineralized and unmineralized tissues with different strengths and stiffnesses. However, increasing strength without degrading toughness is a fundamental challenge in materials science. Here, we demonstrate a promising nanofibrous polymer-hydroxyapatite system, in which, a continuous fibrous network must function as a scaffold for both mineralized and unmineralized tissues.

Functional attachment of soft tissues to bone: development, healing, and tissue engineering.

Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge.

Muscle loading is necessary for the formation of a functional tendon enthesis.

Muscle forces are essential for skeletal patterning during development. Eliminating muscle forces, e.g.

The effect of unloading on gene expression of healthy and injured rotator cuffs.

Tendon unloading following rupture of one of the rotator cuff tendons can induce alterations in muscle physiology and tendon structure, which can subsequently affect reparability and healing potential. Yet little is known about the effects of muscle and tendon unloading on the molecular response of the rotator cuff. We determined the effect of mechanical unloading on gene expression and morphology of healthy supraspinatus tendons and muscles, and the same muscles after acute injury and repair.

Controlled delivery of mesenchymal stem cells and growth factors using a nanofiber scaffold for tendon repair.

Outcomes after tendon repair are often unsatisfactory, despite improvements in surgical techniques and rehabilitation methods. Recent studies aimed at enhancing repair have targeted the paucicellular nature of tendon for enhancing repair; however, most approaches for delivering growth factors and cells have not been designed for dense connective tissues such as tendon. Therefore, we developed a scaffold capable of delivering growth factors and cells in a surgically manageable form for tendon repair.

Electrospun nanofibers for regenerative medicine.

This Progress Report reviews recent progress in applying electrospun nanofibers to the emerging field of regenerative medicine. It begins with a brief introduction to electrospinning and nanofibers, with a focus on issues related to the selection of materials, incorporation of bioactive molecules, degradation characteristics, control of mechanical properties, and facilitation of cell infiltration. Next, a number of approaches to fabricate scaffolds from electrospun nanofibers are discussed, including techniques for controlling the alignment of nanofibers and for producing scaffolds with complex architectures.

The effect of core and epitendinous suture modifications on repair of intrasynovial flexor tendons in an in vivo canine model.

Purpose: To determine in vivo effects of modifications to core and epitendinous suture techniques in a canine intrasynovial flexor tendon repair model using clinically relevant rehabilitation. Our null hypothesis was that gap formation and rupture rates would remain consistent across repair techniques.

Methods: We evaluated gap formation and rupture in 75 adult mongrel dogs that underwent repair of intrasynovial flexor tendon lacerations followed by standardized postoperative therapy.

Mineral distributions at the developing tendon enthesis.

Tendon attaches to bone across a functionally graded interface, "the enthesis". A gradient of mineral content is believed to play an important role for dissipation of stress concentrations at mature fibrocartilaginous interfaces. Surgical repair of injured tendon to bone often fails, suggesting that the enthesis does not regenerate in a healing setting.

Generation of controllable gradients in cell density.

Making the grad(ient): a gradient in cell density was generated on a substrate that was inserted into a homogeneous suspension of cells at a specific tilt angle by taking advantage of the gradual change in the number of cells available for sedimentation. Reverse gradients were also fabricated on the same substrate using multiple sedimentation procedures.

Effect of bone morphogenetic protein 2 on tendon-to-bone healing in a canine flexor tendon model.

Tendon-to-bone healing is typically poor, with a high rate of repair-site rupture. Bone loss after tendon-to-bone repair may contribute to poor outcomes. Therefore, we hypothesized that the local application of the osteogenic growth factor bone morphogenetic protein 2 (BMP-2) would promote bone formation, leading to improved repair-site mechanical properties.

Intrasynovial flexor tendon repair: a biomechanical study of variations in suture application in human cadavera.

To improve the functional outcomes of intrasynovial tendon suture, prior experiments evaluated individual technical modifications used in the repair process. Few studies, however, have assessed the combinatorial effects of those suture modifications in an integrated biomechanical manner, including a sample size sufficient to make definitive observations on repair technique. Two hundred fifty-six flexor tendon repairs were performed in human cadavera, and biomechanical properties were determined.

The nanometre-scale physiology of bone: steric modelling and scanning transmission electron microscopy of collagen-mineral structure.

The nanometre-scale structure of collagen and bioapatite within bone establishes bone's physical properties, including strength and toughness. However, the nanostructural organization within bone is not well known and is debated. Widely accepted models hypothesize that apatite mineral ('bioapatite') is present predominantly inside collagen fibrils: in 'gap channels' between abutting collagen molecules, and in 'intermolecular spaces' between adjacent collagen molecules.

Bi-material attachment through a compliant interfacial system at the tendon-to-bone insertion site.

The attachment of tendon to bone, one of the greatest interfacial material mismatches in nature, presents an anomaly from the perspective of interfacial engineering. Deleterious stress concentrations arising at bi-material interfaces can be reduced in engineering practice by smooth interpolation of composition, microstructure, and mechanical properties. However, following normal development, the rotator cuff tendon-to-bone "insertion site" presents an interfacial zone that is more compliant than either tendon or bone.

Tissue-engineering strategies for the tendon/ligament-to-bone insertion.

Injuries to connective tissues are painful and disabling and result in costly medical expenses. These injuries often require reattachment of an unmineralized connective tissue to bone. The uninjured tendon/ligament-to-bone insertion (enthesis) is a functionally graded material that exhibits a gradual transition from soft tissue (i.

The effect of tear size and nerve injury on rotator cuff muscle fatty degeneration in a rodent animal model.

Background: Irreversible muscle changes after rotator cuff tears is a well-known negative prognostic factor after shoulder surgery. Currently, little is known about the pathomechanism of fatty degeneration of the rotator cuff muscles after chronic cuff tears. The purposes of this study were to (1) develop a rodent animal model of chronic rotator cuff tears that can reproduce fatty degeneration of the cuff muscles seen clinically, (2) describe the effects of tear size and concomitant nerve injury on muscle degeneration, and (3) evaluate the changes in gene expression of relevant myogenic and adipogenic factors after rotator cuff tears using the animal model.

Mechanisms of Bimaterial Attachment at the Interface of Tendon to Bone.

The material mismatch at the attachment of tendon to bone is amongst the most severe for any tensile connection in nature. Attaching dissimilar materials is a major challenge in engineering, and has proven to be a challenge in surgical practice as well. Here, we examine the material attachment schemes employed at this connection through the lens of solid mechanics.

Enhancing the stiffness of electrospun nanofiber scaffolds with a controlled surface coating and mineralization.

A new method was developed to coat hydroxyapatite (HAp) onto electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers for tendon-to-bone insertion site repair applications. Prior to mineralization, chitosan and heparin were covalently immobilized onto the surface of the fibers to accelerate the nucleation of bone-like HAp crystals. Uniform coatings of HAp were obtained by immersing the nanofiber scaffolds into a modified, 10-fold-concentrated simulated body fluid (m10SBF) for different periods of time.

Sustained delivery of transforming growth factor beta three enhances tendon-to-bone healing in a rat model.

Despite advances in surgical technique, rotator cuff repairs are plagued by a high rate of failure. This failure rate is in part due to poor tendon-to-bone healing; rather than regeneration of a fibrocartilaginous attachment, the repair is filled with disorganized fibrovascular (scar) tissue. Transforming growth factor beta 3 (TGF-β3) has been implicated in fetal development and scarless fetal healing and, thus, exogenous addition of TGF-β3 may enhance tendon-to-bone healing.

Fibrocartilage tissue engineering: the role of the stress environment on cell morphology and matrix expression.

Although much is known about the effects of uniaxial mechanical loading on fibrocartilage development, the stress fields to which fibrocartilaginous regions are subjected to during development are mutiaxial. That fibrocartilage develops at tendon-to-bone attachments and in compressive regions of tendons is well established. However, the three-dimensional (3D) nature of the stresses needed for the development of fibrocartilage is not known.

The effects of exogenous basic fibroblast growth factor on intrasynovial flexor tendon healing in a canine model.

Background: Studies have demonstrated that flexor tendon repair strength fails to increase in the first three weeks following suturing of the tendon, a finding that correlates closely with the timing of many clinical failures. The application of growth factors holds promise for improving the tendon-repair response and obviating failure in the initial three weeks.

Methods: The effects of basic fibroblast growth factor on flexor tendon healing were evaluated with use of a canine model.

Effects of botulinum toxin-induced paralysis on postnatal development of the supraspinatus muscle.

The mechanical environment plays an important role in musculoskeletal tissue development. The present study characterized changes in supraspinatus muscle due to removal of mechanical cues during postnatal development. An intramuscular injection of botulinum toxin type A (BTX) was used to induce and maintain paralysis in the left shoulders of mice since birth while the right shoulders received saline and served as contralateral controls.

"Aligned-to-random" nanofiber scaffolds for mimicking the structure of the tendon-to-bone insertion site.

We have demonstrated the fabrication of "aligned-to-random" electrospun nanofiber scaffolds that mimic the structural organization of collagen fibers at the tendon-to-bone insertion site. Tendon fibroblasts cultured on such a scaffold exhibited highly organized and haphazardly oriented morphologies, respectively, on the aligned and random portions.