Injuries of the Wrist

Schoen, Delores C.

doi:10.1097/00006416-200507000-00015

Cited by 9 publications

(6 citation statements)

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“…Tendons can be injured through a variety of acute and chronic modes [1][2][3][4] with some 35 million injuries occurring annually in the United States. 5 Of these injuries, severe tendon traumas account for more than 1 million physician visits and 250,000 surgical procedures annually in the United States. 6 While tendon homeostasis is maintained by fibroblast-like cells called tenocytes interspersed within collagen fibrils, these cells have limited intrinsic regenerative capacity.…”

Section: Introductionmentioning

confidence: 99%

Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds

Caliari

Harley

2013

Tissue Engineering Part A

103

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Biomolecular environments encountered in vivo are complex and dynamic, with combinations of biomolecules presented in both freely diffusible (liquid-phase) and sequestered (bound to the extracellular matrix) states. Strategies for integrating multiple biomolecular signals into a biomimetic scaffold provide a platform to simultaneously control multiple cell activities, such as motility, proliferation, phenotype, and regenerative potential. Here we describe an investigation elucidating the influence of the dose and mode of presentation (soluble, sequestered) of five biomolecules (stromal cell-derived factor 1a , platelet-derived growth factor BB [PDGF-BB], insulin-like growth factor 1 [IGF-1], basic fibroblast growth factor [bFGF], and growth/ differentiation factor 5 [GDF-5]) on the recruitment, proliferation, collagen synthesis, and genomic stability of equine tenocytes within an anisotropic collagen-GAG scaffold for tendon regeneration applications. Critically, we found that single factors led to a dose-dependent trade-off between driving tenocyte proliferation (PDGF-BB, IGF-1) versus maintenance of a tenocyte phenotype (GDF-5, bFGF). We identified supplementation schemes using factor pairs (IGF-1, GDF-5) to rescue the tenocyte phenotype and gene expression profiles while simultaneously driving proliferation. These results suggest coincident application of multi-biomolecule cocktails has a significant value in regenerative medicine applications where control of cell proliferation and phenotype are required. Finally, we demonstrated an immobilization strategy that allows efficient sequestration of bioactive levels of these factors within the scaffold network. We showed sequestration can lead to a greater sustained bioactivity than soluble supplementation, making this approach particularly amenable to in vivo translation where diffusive loss is a concern and continuous biomolecule supplementation is not feasible.

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Section: Introductionmentioning

confidence: 99%

Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds

Caliari

Harley

2013

Tissue Engineering Part A

103

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“…The ability to make tendons in vitro from bone marrow-derived cells or stem cells would be expected to have a major impact on the treatment of musculoskeletal injuries. As summarized by Butler et al (2008), more than 32 million traumatic and repetitive motion injuries to tendons and ligaments occur annually in the USA (Schoen, 2005) with rotator cuff and iatrogenic tendon injuries of the anterior cruciate ligament being among the most common. Tendons are rich in extracellular matrix (ECM) and have relatively few cells, which helps to explain why tendons heal slowly and why re-establishment of normal function after surgery remains challenging.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor β3

Kapacee

Yeung

et al. 2010

Matrix Biology

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Tendon-like tissue generated from stem cells in vitro has the potential to replace tendons and ligaments lost through injury and disease. However, thus far, no information has been available on the mechanism of tendon formation in vitro and how to accelerate the process. We show here that human mesenchymal stem cells (MSCs) and bone marrow-derived mononuclear cells (BM-MNCs) can generate tendon-like tissue in 7 days mediated by transforming growth factor (TGF) β3. MSCs cultured in fixed-length fibrin gels spontaneously synthesized narrow-diameter collagen fibrils and exhibited fibripositors (actin-rich, collagen fibril-containing plasma membrane protrusions) identical to those that occur in embryonic tendon. In contrast, BM-MNCs did not synthesize tendon-like tissue under these conditions. We performed real-time PCR analysis of MSCs and BM-MNCs. MSCs upregulated genes encoding type I collagen, TGFβ3, and Smad2 at the time of maximum contraction of the tendon-like tissue (7 days). Western blot analysis showed phosphorylation of Smad2 at maximum contraction. The TGFβ inhibitor SB-431542, blocked the phosphorylation of Smad2 and stopped the formation of tendon-like tissue. Quantitative PCR showed that BM-MNCs expressed very low levels of TGFβ3 compared to MSCs. Therefore we added exogenous TGFβ3 protein to BM-MNCs in fibrin gels, which resulted in phosphorylation of Smad2, synthesis of collagen fibrils, the appearance of fibripositors at the plasma membrane, and the formation of tendon-like tissue. In conclusion, MSCs that self-generate TGFβ signaling or the addition of TGFβ3 protein to BM-MNCs in fixed-length fibrin gels spontaneously make embryonic tendon-like tissue in vitro within 7 days.

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“…An artificial tendon could provide a quick, easy linkage for reattachment to revision, allowing better rehabilitation. Patients sustain >32 million traumatic and repetitive motion injuries to tendons and ligaments [18], costing$30 billion per year in the U.S. alone [19]. Tendon injuries can dramatically affect quality of life and are expected to increase in number and severity in our aging and active population.…”

Section: Introductionmentioning

confidence: 99%

An artificial tendon to connect the quadriceps muscle to the Tibia

Melvin¹,

Litsky²,

Mayerson³

et al. 2011

Journal Orthopaedic Research

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No permanent, reliable artificial tendon exists clinically. Our group developed the OrthoCoupler™ device as a versatile connector, fixed at one end to a muscle, and adaptable at the other end to inert implants such as prosthetic bones or to bone anchors. The objective of this study was to evaluate four configurations of the device to replace the extensor mechanism of the knee in goats. Within muscle, the four groups had: (A) needle-drawn uncoated bundles, (B) needle-drawn coated bundles, (C) barbed uncoated bundles, and (D) barbed coated bundles. The quadriceps tendon, patella, and patellar tendon were removed from the right hind limb in 24 goats. The four groups (n=6 for each) were randomly assigned to connect the quadriceps muscle to the tibia (with a bone plate). Specimens were collected from each operated leg and contralateral unoperated controls both for mechanical testing and histology at 90 days post-surgery. In strength testing, maximum forces in the operated leg (vs. unoperated control) were 1288±123 N (vs. 1387±118 N) for group A, 1323±144 N (vs. 1396±779 N) for group B, 930±125 N (vs. 1337±126 N) for group C, and 968±109 N (vs. 1528±146 N) for group D (mean ± SEM). The strengths of the OrthoCoupler™ legs in the needled device groups were equivalent to unoperated controls (p=0.6), while both barbed device groups had maximum forces significantly lower than their controls (p=0.001). We believe this technology will yield improved procedures for clinical challenges in orthopaedic oncology, revision arthroplasty, tendon transfer, and tendon injury reconstruction.

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Injuries of the Wrist

Cited by 9 publications

References 0 publications

Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds

Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds

Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor β3

An artificial tendon to connect the quadriceps muscle to the Tibia

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