The Use of Electrospun Scaffolds in Musculoskeletal Tissue Engineering: A Focus on Tendon and the Rotator Cuff

Stace, Edward T.; Nagra, Navraj S.; Tiberwel, Saket; Khan, Wasim; Carr, Andrew

doi:10.2174/1574888x13666180129105707

Cited by 10 publications

(4 citation statements)

References 67 publications

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“…While natural extracellular matrix (ECM)-derived scaffolds, such as collagen patches, provide strong cues for cell infiltration, their degradation rate is rapid and the mechanical support they offer is therefore limited [3,5]. On the other hand, biodegradable synthetic polymers offer tunable degradation characteristics to provide initial mechanical support during the critical tissue regeneration phase [2,6]. In particular, electrospun fiber scaffolds can be designed to resemble native tissue ECM, for instance mimicking the highly aligned collagen fiber matrix that characterizes healthy tendon [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Macromechanics and polycaprolactone fiber organization drive macrophage polarization and regulate inflammatory activation of tendon in vitro and in vivo

et al. 2020

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Appropriate macrophage response to an implanted biomaterial is crucial for successful tissue healing outcomes. In this work we investigated how intrinsic topological cues from electrospun biomaterials and extrinsic mechanical loads cooperate to guide macrophage activation and macrophage-tendon fibroblast cross-talk. We performed a series of in vitro and in vivo experiments using aligned or randomly oriented polycaprolactone nanofiber substrates in both mechanically loaded and unloaded conditions. Across all experiments a disorganized biomaterial fiber topography was alone sufficient to promote a pro-inflammatory signature in macrophages, tendon fibroblasts, and tendon tissue. Extrinsic mechanical loading was found to strongly regulate the character of this signature by reducing pro-inflammatory markers both in vitro and in vivo. We observed that macrophages generally displayed a stronger response to biophysical cues than tendon fibroblasts, with dominant effects of cross-talk between these cell types observed in mechanical co-culture models. Collectively our data suggest that macrophages play a potentially important role as mechanosensory cells in tendon repair, and provide insight into how biological response might be therapeutically modulated by rational biomaterial designs that address the biomechanical niche of recruited cells.

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Section: Introductionmentioning

confidence: 99%

Macromechanics and polycaprolactone fiber organization drive macrophage polarization and regulate inflammatory activation of tendon in vitro and in vivo

et al. 2020

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“…Advanced manufacturing technologies have been developed to fabricate this class of scaffolds for rotator cuff repair applications, including electrowriting and electrospinning approaches. 11 , 13 , 18 , 19 , 31 , 34 , 35 , 44 , 45 , 51 , 55 , 56 , 60 , 61 Furthermore, the capacity of manufacturing synthetic polymers of various components—or blending with collagen or other materials—allows for an unlimited number of scaffold variations. However, the complexity of the manufacturing, the ability to scale the production of the scaffold, and the ability to achieve cost-effective pricing for these devices will restrict most experimental or investigational scaffolds from widespread human use.…”

Section: Discussionmentioning

confidence: 99%

Rotator cuff repair using a bioresorbable nanofiber interposition scaffold: a biomechanical and histologic analysis in sheep

Romeo

Easley

Regan

et al. 2022

Journal of Shoulder and Elbow Surgery

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Background: The purpose of this study was to evaluate the mechanical, structural, and histologic quality of rotator cuff repairs augmented with an interposition electrospun nanofiber scaffold composed of polyglycolic acid (PGA) and poly-L-lactide-co-ε-caprolactone (PLCL) in an acute sheep model. Methods: Forty acute infraspinatus tendon detachment and repair procedures were performed in a sheep infraspinatus model using a double-row transosseous-equivalent anchor technique either with an interposition nanofiber scaffold composed of polyglycolic acid-poly-L-lactide-co-ε-caprolactone or with no scaffold. Animals were euthanized at the 6-week (20 samples) and 12-week (20 samples) postoperative time points to assess the biomechanical and histologic properties of the repairs and to compare differences within each group. Results: Within the scaffold-treated group, there was a significant increase in ultimate failure force (in newtons) from 6 to 12 weeks (P < .01), a significant increase in ultimate failure load from 6 to 12 weeks (P < .01), and a significant increase in ultimate failure stress (in megapascals) from 6 to 12 weeks (P < .01). At 6 weeks, the tendon-bone attachment was most consistent with an ''indirect'' type of insertion, whereas at 12 weeks, a visible difference in the progression and re-formation of the enthesis was observed. Compared with controls, animals in the scaffold-treated group displayed an insertion of the fibrous tendon with the humeral footprint that was beginning to be organized in a manner similar to the ''native'' direct/fibrocartilaginous insertion of the ovine infraspinatus tendon. In the majority of these animals treated with the scaffold, prominent perforating collagen fibers, similar to Sharpey fibers, were present and extending through a region of calcified fibrocartilage and attaching to the humeral footprint. No surgical complications occurred in any of the 40 sheep, including delayed wound healing or infection. Conclusions: In a sheep acute rotator cuff repair model, securing a nanofiber scaffold between the tendon and the bone using a doublerow transosseous-equivalent anchor fixation technique resulted in greater failure strength. Additionally, at the enthesis, Sharpey fiber-like attachments (ie, collagen fibers extending from the tendon into the calcified fibrocartilage of the humerus) were observed, which were not seen in the control group.Institutional review board approval was not required for this basic science study. This study was conducted under Institutional Animal Care and Use Committee approval by board-certified veterinary surgeons (Colorado State University no. 17-7154).

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“…The advantage of combining active biologics with scaffolds to promote tendon-tobone healing is illustrated by localized recombinant human parathyroid hormone (rhPTH) delivery on a scaffold for targeted and controlled hormone release with a scaffold template to introduce fibrocartilage tissue ingrowth along the fibers [74][75][76]. There is less drug use, fewer off-target risks, and lower costs associated with this localized and targeted approach.…”

Section: Composite Scaffoldsmentioning

confidence: 99%

“…The systemic effects of rhPTH coupled with bioengineered scaffolds to augment tendon repairs in an animal model demonstrate improved short-term integrity of a tendon repair and promote the formation of a more organized tendon-to-bone interface [74,75]. Interest in PTH as a targeted adjunct therapy to improve healing at the tendon-bone interface continues to develop, initiated with the introduction of biointegrative scaffolds to enhance rotator cuff repair healing [74,76]. PTH activates chondrogenesis and angiogenesis, in addition to preventing fatty infiltration within the rotator cuff.…”

Section: Composite Scaffoldsmentioning

confidence: 99%

Treatment of Tendon Injuries in the Servicemember Population across the Spectrum of Pathology: From Exosomes to Bioinductive Scaffolds

DeFoor,

Cognetti,

Yuan

et al. 2024

Bioengineering

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Tendon injuries in military servicemembers are one of the most commonly treated nonbattle musculoskeletal injuries (NBMSKIs). Commonly the result of demanding physical training, repetitive loading, and frequent exposures to austere conditions, tendon injuries represent a conspicuous threat to operational readiness. Tendon healing involves a complex sequence between stages of inflammation, proliferation, and remodeling cycles, but the regenerated tissue can be biomechanically inferior to the native tendon. Chemical and mechanical signaling pathways aid tendon healing by employing growth factors, cytokines, and inflammatory responses. Exosome-based therapy, particularly using adipose-derived stem cells (ASCs), offers a prominent cell-free treatment, promoting tendon repair and altering mRNA expression. However, each of these approaches is not without limitations. Future advances in tendon tissue engineering involving magnetic stimulation and gene therapy offer non-invasive, targeted approaches for improved tissue engineering. Ongoing research aims to translate these therapies into effective clinical solutions capable of maximizing operational readiness and warfighter lethality.

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The Use of Electrospun Scaffolds in Musculoskeletal Tissue Engineering: A Focus on Tendon and the Rotator Cuff

Cited by 10 publications

References 67 publications

Macromechanics and polycaprolactone fiber organization drive macrophage polarization and regulate inflammatory activation of tendon in vitro and in vivo

Macromechanics and polycaprolactone fiber organization drive macrophage polarization and regulate inflammatory activation of tendon in vitro and in vivo

Rotator cuff repair using a bioresorbable nanofiber interposition scaffold: a biomechanical and histologic analysis in sheep

Treatment of Tendon Injuries in the Servicemember Population across the Spectrum of Pathology: From Exosomes to Bioinductive Scaffolds

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