Scaffolds for Tendon and Ligament Repair and Regeneration

Ratcliffe, Anthony; Butler, David L.; Dyment, Nathaniel A.; Cagle, Paul J.; Proctor, Christopher S.; Ratcliffe, Seena S.; Flatow, Evan L.

doi:10.1007/s10439-015-1263-1

Cited by 77 publications

(93 citation statements)

References 82 publications

(100 reference statements)

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“…Second, by simply tuning the rotational speed of the motor one can adjust the diameter of the fiber in wide ranges (from around 300 to <100 µm) . Furthermore, wet‐spun hydrogel fibers are collected onto a rotating drum such that they form densely packed bundles that closely mimic the architecture of actual tendon fascicles (Figure b,c). In addition, fiber production rate is between 10‐ to 100‐fold faster compared to conventional extrusion‐based bioprinting approaches.…”

Section: Resultsmentioning

confidence: 99%

Tendon Tissue Engineering: Effects of Mechanical and Biochemical Stimulation on Stem Cell Alignment on Cell‐Laden Hydrogel Yarns

Rinoldi

Costantini

Kijeńska‐Gawrońska

et al. 2019

Adv Healthcare Materials

108

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Fiber‐based approaches hold great promise for tendon tissue engineering enabling the possibility of manufacturing aligned hydrogel filaments that can guide collagen fiber orientation, thereby providing a biomimetic micro‐environment for cell attachment, orientation, migration, and proliferation. In this study, a 3D system composed of cell‐laden, highly aligned hydrogel yarns is designed and obtained via wet spinning in order to reproduce the morphology and structure of tendon fascicles. A bioink composed of alginate and gelatin methacryloyl (GelMA) is optimized for spinning and loaded with human bone morrow mesenchymal stem cells (hBM‐MSCs). The produced scaffolds are subjected to mechanical stretching to recapitulate the strains occurring in native tendon tissue. Stem cell differentiation is promoted by addition of bone morphogenetic protein 12 (BMP‐12) in the culture medium. The aligned orientation of the fibers combined with mechanical stimulation results in highly preferential longitudinal cell orientation and demonstrates enhanced collagen type I and III expression. Additionally, the combination of biochemical and mechanical stimulations promotes the expression of specific tenogenic markers, signatures of efficient cell differentiation towards tendon. The obtained results suggest that the proposed 3D cell‐laden aligned system can be used for engineering of scaffolds for tendon regeneration.

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Section: Resultsmentioning

confidence: 99%

Tendon Tissue Engineering: Effects of Mechanical and Biochemical Stimulation on Stem Cell Alignment on Cell‐Laden Hydrogel Yarns

Rinoldi

Costantini

Kijeńska‐Gawrońska

et al. 2019

Adv Healthcare Materials

108

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“…One important aspect for tendon tissue engineering is the appropriate design of fibrous scaffolds that mimic the fibrillary architecture and the mechanical and functional characteristics of native tendon extracellular matrix (ECM) [10, 11]. Such fibrous constructs can potentially be engineered and generated using various fiber-forming techniques and textile processes [12, 13].…”

Section: Introductionmentioning

confidence: 99%

Living nanofiber yarn-based woven biotextiles for tendon tissue engineering using cell tri-culture and mechanical stimulation

et al. 2017

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Non-woven nanofibrous scaffolds have been developed for tendon graft application by using electrospinning strategies. However, electrospun nanofibrous scaffolds face some obstacles and limitations, including suboptimal scaffold structure, weak tensile and suture-retention strengths, and compact structure for cell infiltration. In this work, a novel nanofibrous, woven biotextile, fabricated based on electrospun nanofiber yarns, was implemented as a tissue engineered tendon scaffold. Based on our modified electrospinning setup, polycaprolactone (PCL) nanofiber yarns were fabricated with reproducible quality, and were further processed into plain-weaving fabrics interlaced with polylactic acid (PLA) multifilaments. Nonwoven nanofibrous PCL meshes with random or aligned fiber structures were generated using typical electrospinning as comparative counterparts. The woven fabrics contained 3D aligned microstructures with significantly larger pore size and obviously enhanced tensile mechanical properties than their nonwoven counterparts. The biological results revealed that cell proliferation and infiltration, along with the expression of tendon-specific genes by human adipose derived mesenchymal stem cells (HADMSC) and human tenocytes (HT), were significantly enhanced on the woven fabrics compared with those on randomly-oriented or aligned nanofiber meshes. Co-cultures of HADMSC with HT or human umbilical vein endothelial cells (HUVEC) on woven fabrics significantly upregulated the functional expression of most tenogenic markers. HADMSC/HT/HUVEC tri-culture on woven fabrics showed the highest upregulation of most tendon-associated markers than all the other mono- and co-culture groups. Furthermore, we conditioned the tri-cultured constructs with dynamic conditioning and demonstrated that dynamic stretch promoted total collagen secretion and tenogenic differentiation. Our nanofiber yarn-based biotextiles have significant potential to be used as engineered scaffolds to synergize the multiple cell interaction and mechanical stimulation for promoting tendon regeneration.

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“…To address these limitations, tissue engineering and biologic augmentations to improve rotator cuff healing have gained much interest [1,7,8]. It is generally thought the key to success of these tissue engineering strategies lies in utilizing and/or stimulating the appropriate target population of cells.…”

Section: Introductionmentioning

confidence: 99%

Murine supraspinatus tendon injury model to identify the cellular origins of rotator cuff healing

Yoshida

Alaee

Dyrna

et al. 2016

Connective Tissue Research

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Purpose of this study To elucidate the origin of cell populations that contribute to rotator cuff healing, we developed a mouse surgical model where a full-thickness, central detachment is created in the supraspinatus. Materials and Methods Three different inducible Cre transgenic mice with Ai9-tdTomato reporter expression (PRG4-9, αSMA-9, and AGC-9) were used to label different cell populations in the shoulder. The defect was created surgically in the supraspinatus. The mice were injected with tamoxifen at surgery to label the cells and sacrificed at 1, 2, and 5 weeks post-operatively. Frozen sections were fluorescently imaged then stained with Toluidine Blue and re-imaged. Results Three notable changes were apparent post-operatively. 1) A long thin layer of tissue formed on the bursal side overlying the supraspinatus tendon. 2) The tendon proximal to the defect initially became hypercellular and disorganized. 3) The distal stump at the insertion underwent minimal remodeling. In the uninjured shoulder, tdTomato expression was seen in the tendon midsubstance and paratenon cell on the bursal side in PRG4-9, in paratenon, blood vessels, and periosteum of acromion in SMA-9, and in articular cartilage, unmineralized fibrocartilage of supraspinatus enthesis, and acromioclavicular joint in AGC-9 mice. In the injured PRG4-9 and SMA-9 mice, the healing tissues contained an abundant number of tdTomato+ cells, while minimal contribution of tdTomato+ cells was seen in AGC-9 mice. Conclusions The study supports the importance of the bursal side of the tendon to rotator cuff healing and PRG4 and αSMA may be markers for these progenitor cells.

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Scaffolds for Tendon and Ligament Repair and Regeneration

Cited by 77 publications

References 82 publications

Tendon Tissue Engineering: Effects of Mechanical and Biochemical Stimulation on Stem Cell Alignment on Cell‐Laden Hydrogel Yarns

Tendon Tissue Engineering: Effects of Mechanical and Biochemical Stimulation on Stem Cell Alignment on Cell‐Laden Hydrogel Yarns

Living nanofiber yarn-based woven biotextiles for tendon tissue engineering using cell tri-culture and mechanical stimulation

Murine supraspinatus tendon injury model to identify the cellular origins of rotator cuff healing

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