Compromised Neurotrophic and Angiogenic Regenerative Capability during Tendon Healing in a Rat Model of Type-II Diabetes

Ahmed, Aisha Siddiqah; Li, Jian; Alim, Abdul; Ahmed, Mahmood; Östenson, Claes‐Göran; Salo, Paul; Hewitt, Carolyn; Hart, David A.; Ackermann, Paul W.

doi:10.1371/journal.pone.0170748

Cited by 19 publications

(18 citation statements)

References 35 publications

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“…Hypovascularity and hypocellularity characteristics of native tendon tissues are crucial issues that hinder the clinical healing of tendon-related diseases or injuries [68, 69]. Accumulating evidence suggests that tendon tissues generally possess more vessels than commonly believed, although they are recognized as a poorly vascularized tissue type [70].…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Recent literature advocates that DM exhibits an essential role in tendon metabolism and healing. In fact, diabetes has been shown to cause non-enzymatic cross-linking [31] and disorganization of collagen fibers [32], promote inflammatory cell invasion and delayed angiogenesis [33], disrupt neurotrophic and angiotrophic factors [5] as well as matrix protein synthesis and degradation [9], and lead to poor biomechanical properties [9,34,35]. Thus, different strategies have been placed to enhance rehabilitation of tendon disorders in patients with DM [36].…”

Section: Discussionmentioning

confidence: 99%

“…In the last years, a growing body of evidence has demonstrated the association between DM and tendinopathy [2,3]. Indeed, this painful connective tissue disorder can affect up to 60% of diabetic patients [4] and cause considerable disability, possibly due to compromised regenerative and healing capability [5].…”

Section: Introductionmentioning

confidence: 99%

Effect of photobiomodulation and exercise on early remodeling of the Achilles tendon in streptozotocin-induced diabetic rats

et al. 2019

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The aim of this study was to compare the treatment effects of laser photobiomodulation (LPBM) therapy and aerobic exercise on the biomechanical properties, tissue morphology and the expression of tendon matrix molecules during early remodeling of Achilles tendon (AT) injury in diabetic rats. Animals were randomly assigned to five groups: injured non diabetic (I, n = 15), injured diabetic (ID, n = 15), injured diabetic plus LPBM (IDL, n = 16), injured diabetic plus aerobic exercise (IDE, n = 16) and injured diabetic plus aerobic exercise and LPBM (IDEAL, n = 17). Type 1 diabetes was induced via a single intravenous injection of Streptozotocin at a dose of 40 mg/kg. A partial tenotomy was performed in the right AT. LPBM was performed with an indium-gallium-aluminum-phosphide 660 nm 10 mW laser device (spot size 0.04 cm2, power density 250 mW/cm2, irradiation duration 16 s, energy 0.16 J, energy density 4 J/cm2) on alternate days for a total of 9 sessions over 3 weeks (total energy 1.44 J), using a stationary contact technique to a single point over the dorsal aspect of the AT. Moderate aerobic exercise was performed on a motorized treadmill (velocity 9 m/min for 60 minutes). At 3 weeks post-injury, biomechanical analyzes as well as assessment of fibroblast number and orientation were performed. Collagen 1 (Col1) and 3 (Col3) and matrix metalloproteinases (MMPs) -3 and 13 protein distributions were studied by immunohistochemistry; while Col1 and Col3 and MMP-2 and 9 gene expression were assessed by quantitative RT-PCR (qRT-PCR). IDEAL exhibited significant increases in several biomechanical parameters in comparison to the other groups. Moreover, IDEAL presented stronger Col1 immunoreactivity when compared to ID, and weaker Col3 immunoreactivity than IDE. Both IDL and IDEAL demonstrated weaker expression of MMP-3 in comparison to I, while IDL presented no expression of MMP-13 when compared to ID. ID, IDL and IDE showed an increased number of fibroblasts in comparison to I, while IDEAL decreased the number of these cells in comparison to ID and IDE. IDL and IDEAL groups exhibited decreased angular dispersion among the fibroblasts when compared to I. The gene expression results showed that IDE demonstrated a downregulation in Col1 mRNA expression in comparison to I and ID. IDEAL demonstrated upregulation of Col1 mRNA expression when compared to IDL or IDE alone and increased MMP-2 expression when compared to IDL and IDE. MMP-9 expression was upregulated in IDEAL when compared to I, IDL and IDE. Our results suggest a beneficial interaction of combining both treatment strategies i.e., aerobic exercise and LPBM, on the biomechanical properties, tissue morphology and the expression of matrix molecules in diabetic tendons.

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“…Ahmed et al hypothesized that impaired healing in DM may be due to abnormal expression of neurotrophic and angiotrophic factors, as neurotrophins play a prominent role in angiogenesis and re‐innervation within connective tissue, which is crucial for regeneration and homeostasis. Indeed, in a study on rats with injured Achilles tendons, the authors observed significantly lower levels of nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) in rats with induced DM vs healthy controls.…”

Section: Ligament and Tendon Injuries In Patients With Dmmentioning

confidence: 99%

Influence of diabetes on tissue healing in orthopaedic injuries

Stolarczyk

Sarzyńska

Gondek

et al. 2018

Clin Exp Pharma Physio

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Diabetes is a group of metabolic diseases characterized by hyperglycaemia resulting from the defective action or secretion of insulin. Chronic hyperglycaemia can lead to the damage, dysfunction and failure of various organs. In the context of complications of healing and orthopaedic rehabilitation, vascular (microangiopathy) and nerve (neuropathy) disorders deserve particular attention. About 12% of the patients admitted to orthopaedic departments have diabetes. Studies indicate that there is an indisputable link between diabetes and: an increased risk of fractures, the difficult healing of injuries of bones, ligaments and musculotendinous. It appears that one of the main reasons for this is non-enzymatic glycosylation (glycation) of collagen molecules, a phenomenon observed in the elderly and diabetic populations, as it leads to the formation of advanced glycation end products (AGEs). Collagen is one of the major connective tissue components, and is therefore part of ligaments, tendons and bones. AGEs affect the weakening of its structure and biomechanical properties, and thus also affects the weakening of the structure and properties of the above-mentioned tissues. The aim of the study is to undertake an overview of the current knowledge of the impact of diabetes on the risk of some injuries and subsequent healing and rehabilitation of patients following orthopaedic injuries.

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Compromised Neurotrophic and Angiogenic Regenerative Capability during Tendon Healing in a Rat Model of Type-II Diabetes

Cited by 19 publications

References 35 publications

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

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

Effect of photobiomodulation and exercise on early remodeling of the Achilles tendon in streptozotocin-induced diabetic rats

Influence of diabetes on tissue healing in orthopaedic injuries

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