Platelet-Rich Plasma Releasate Promotes Early Healing in Tendon After Acute Injury

Background: Acute tendon injury can limit motion and thereby inhibit tendon healing. Positive results have been found after the use of platelet-rich plasma (PRP) to treat tendon injury; however, the early effects of PRP on tendon regeneration are not known. Purpose/Hypothesis: The purpose of this study was to evaluate the effects of PRP releasate (PRPr) on the early stages of tendon healing in a rat partial tenotomy model. It was hypothesized that PRPr can promote early healing of an Achilles tendon in rats. Study Design: Controlled laboratory study. Methods: PRP was prepared by a 2-step method of manual platelet concentration from 10 rats. PRPr was isolated from the clotted preparation after activation by thrombin and was applied to an Achilles tendon on 1 side of 30 rats on the second day after partial tenotomy, with normal saline used as the control on the other side. Achilles tendon samples were harvested 5 and 10 days after tenotomy. At each time point, 15 Achilles tendon samples were obtained, of which 5 samples were evaluated by Masson trichrome staining, apoptosis, and cell proliferation, while the other 10 samples were tested for tensile strength using a material testing machine. Results: Compared with saline-treated control tendons, the PRPr-treated tendons showed increased collagen synthesis near the cut edge and fewer apoptotic cells ( P = .01). An immunohistochemical analysis revealed more Ki-67–positive cells but fewer cluster of differentiation (CD) 68+ (ED1+) macrophages in PRPr tendons compared with saline-treated tendons ( P < .01). Tendons treated with PRPr also showed higher ultimate tensile strength than those treated with saline ( P = .03). Conclusion: PRPr treatment promotes tissue recovery in the early phase of tendon healing by stimulating tendon cell proliferation and collagen production while inhibiting cell apoptosis and CD68+ (ED1+) macrophage infiltration. Clinical Relevance: These findings suggest that with PRPr treatment, higher loads can be applied to the healing tendon at an earlier time, which can help the patient resume activity earlier.

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Effects of Redox Modulation on Cell Proliferation, Viability, and Migration in Cultured Rat and Human Tendon Progenitor Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/8785042 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Yuk Wa Lee ◽

Sai Chuen Fu ◽

Man Yi Yeung ◽

Chun Man Lawrence Lau ◽

Kai Ming Chan ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Proliferation ◽

Vitamin C ◽

Tendon Healing ◽

In Vitro Study ◽

Tendon Injury ◽

Antioxidant Vitamin ◽

Redox Modulation ◽

And Migration

Tendon healing is slow and usually results in inferior fibrotic tissue formation. Recently, application of tendon derived stem cells (TDSCs) improved tendon healing in animal studies. In a chicken model, local injection of antioxidants reduced tendon adhesion after tendon injury. An in vitro study demonstrated that supplementation of H2O2reduced tenogenic marker expression in TDSCs. These findings suggested that the possibility of TDSCs is involved in tendon healing and the cellular activities of TDSCs might be affected by oxidative stress of the local environment. After tendon injury, oxidative stress is increased. Redox modulation might affect healing outcomes via affecting cellular activities in TDSCs. To study the effect of oxidative stress on TDSCs, the cellular activities of rat/human TDSCs were measured under different dosages of vitamin C or H2O2in this study. Lower dose of vitamin C increased cell proliferation, viability and migration; H2O2affected colony formation and suppressed cell migration, cell viability, apoptosis, and proliferation. Consistent with previous studies, oxidative stresses (H2O2) affect both recruitment and survival of TDSCs, while the antioxidant vitamin C may exert beneficial effects at low doses. In conclusion, redox modulation affected cellular activities of TDSCs and might be a potential strategy for tendon healing treatment.

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Response of the Injured Tendon to Growth Factors in the Presence or Absence of the Paratenon

The American Journal of Sports Medicine ◽

10.1177/0363546518814534 ◽

2018 ◽

Vol 47 (2) ◽

pp. 462-467 ◽

Cited By ~ 2

Author(s):

Sebastian A. Müller ◽

Nicholas P. Quirk ◽

Julia A. Müller-Lebschi ◽

Patricia E. Heisterbach ◽

Lutz Dürselen ◽

...

Keyword(s):

Growth Factors ◽

Achilles Tendon ◽

Platelet Rich Plasma ◽

Tendon Repair ◽

Tendon Healing ◽

Cross Sectional ◽

Autologous Conditioned Serum ◽

Injured Tendon ◽

The Right ◽

Exogenous Growth Factors

Background: The paratenon is important for Achilles tendon healing. There is much interest in the use of exogenous growth factors (GFs) as potential agents for accelerating the healing of damaged Achilles tendons. Purpose/Hypothesis: The present study used a rat model to study the responses of the injured Achilles tendon to GFs in the presence or absence of the paratenon. The hypothesis was that responses of the injured tendon to GFs would be lower in the absence of a paratenon. Study Design: Controlled laboratory study. Methods: A 4-mm defect was created in the right Achilles tendon of 60 skeletally mature rats, which were treated with a validated combination of GFs (bFGF, BMP-12, and TGF-β1). Animals were randomly assigned to the intact paratenon (IP) group or resected paratenon (RP) group. Healing was studied anatomically, mechanically, and histologically after 1, 2, and 4 weeks. Results: IP tendons showed improved healing compared with RP tendons. IP tendons were significantly stronger (32.2 N and 48.9 N, respectively) than RP tendons (20.1 N and 31.1 N, respectively) after 1 and 2 weeks. IP tendons did not elongate as much as RP tendons and had greater cross-sectional areas (18.0 mm2, 14.4 mm2, and 16.4 mm2, respectively) after 1, 2, and 4 weeks compared with RP tendons (10.5 mm2, 8.4 mm2, and 11.9 mm2, respectively). On histology, earlier collagen deposition and parallel orientation of fibrils were found for IP tendons. Conclusion: The paratenon is essential for efficient Achilles tendon healing. Healing with GFs in this Achilles tendon defect model was superior in the presence of the paratenon. Clinical Relevance: Biological approaches to tendon engineering using GFs are in vogue and have been shown to improve healing of the rat Achilles tendon, most likely by inducing progenitor cells located within the paratenon. Clinically, resection or incision of the paratenon has been proposed for wound closure. Our data demonstrate the fundamental importance of the paratenon, which therefore should be preserved during Achilles tendon repair, especially if augmented with products such as platelet-rich plasma or autologous conditioned serum that are rich in GFs.

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Quantitative Assessment of Tendon Healing by Using MR T2 Mapping in a Rabbit Achilles Tendon Transection Model Treated with Platelet-rich Plasma

Radiology ◽

10.1148/radiol.2015141544 ◽

2015 ◽

Vol 276 (3) ◽

pp. 748-755 ◽

Cited By ~ 17

Author(s):

Taisuke Fukawa ◽

Satoshi Yamaguchi ◽

Atsuya Watanabe ◽

Takahisa Sasho ◽

Ryuichiro Akagi ◽

...

Keyword(s):

Achilles Tendon ◽

Quantitative Assessment ◽

Platelet Rich Plasma ◽

T2 Mapping ◽

Tendon Healing

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Pifithrin-α, an inhibitor of p53 transactivation, alters the inflammatory process and delays tendon healing following acute injury

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00411.2005 ◽

2007 ◽

Vol 292 (1) ◽

pp. R321-R327 ◽

Cited By ~ 11

Author(s):

David Marsolais ◽

Claude H. Côté ◽

Jérôme Frenette

Keyword(s):

Extracellular Matrix ◽

Inflammatory Process ◽

Tendon Repair ◽

Tendon Healing ◽

Tendon Injury ◽

Acute Injury ◽

Inflammatory Phase ◽

Load To Failure ◽

Transcription Factor P53

Transcription factor p53, which was initially associated with cancer, has now emerged as an important regulator of inflammation and extracellular matrix homeostasis, two processes highly relevant to tendon repair. The goal of this study was to evaluate the effect of a p53 transactivation inhibitor, namely, pifithrin-α, on the pathophysiological sequence following collagenase-induced tendon injury. Administration of pifithrin-α during the inflammatory phase reduced the accumulation of neutrophils and macrophages by 30 and 40%, respectively, on day 3 postinjury. Pifithrin-α failed to reduce the percentage of apoptotic cells following collagenase injection but delayed functional recovery. In uninjured Achilles tendons, pifithrin-α increased metalloprotease activity 2.4-fold. Accordingly, pifithrin-α reduced the collagen content in intact tendons as well as in injured tendons 7 days posttrauma compared with placebo. The effect of pifithrin-α on load to failure and stiffness was also evaluated. The administration of pifithrin-α during the inflammatory phase did not significantly decrease the functional deficit 3 days posttrauma. More importantly, load to failure and stiffness were significantly decreased in the pifithrin-α group from day 7 to day 28 compared with placebo. Overall, our results suggest that administration of pifithrin-α alters the inflammatory process and delays tendon healing. The present findings also support the concept that p53 can regulate extracellular matrix homeostasis in vivo.

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Effects of Time to Start Training After Acute Patellar Tendon Enthesis Injuries on Healing of the Injury in a Rabbit Model

The American Journal of Sports Medicine ◽

10.1177/0363546517712223 ◽

2017 ◽

Vol 45 (10) ◽

pp. 2405-2410 ◽

Cited By ~ 1

Author(s):

Lin Wang ◽

Kaiyu Xiong ◽

Bo Wang ◽

Xiaotian Liang ◽

Haiwei Li ◽

...

Keyword(s):

Patellar Tendon ◽

Rabbit Model ◽

Tendon Injury ◽

The Other ◽

Acute Injury ◽

Optimal Time ◽

Control Group ◽

Trabecular Thickness ◽

Training Groups ◽

Low Intensity

Background: A patellar tendon injury is a common injury in sports. The optimal time to start training after an acute, proximal patellar enthesis injury is still unclear. Hypothesis: The time to start training after an acute, proximal patellar enthesis injury significantly affects healing of the patellar tendon 4 weeks after the injury. Study Design: Controlled laboratory study. Methods: The left hindlimbs of 35 mature female rabbits were randomly assigned to 5 injury groups including a 4-week natural healing group (NH4W) and 4 training groups that started low-intensity training at 24 hours (POST24), 48 hours (POST48), 72 hours (POST72), and 96 hours (POST96) after an acute patellar tendon injury, with 7 limbs in each group. The right hindlimbs of the NH4W group were used as a control group (CON). An acute, proximal patellar enthesis injury was created in all injury groups. The training groups underwent low-intensity quadriceps training for 2 hours per day and 3 days per week for 4 weeks. Histological and radiographic data were collected and analyzed. Results: The cell densities of the training groups were significantly lower than those of the NH4W and CON groups ( P = .01). The fibrocartilage zone was significantly thicker in the POST24, POST48, and POST72 groups compared with the CON and NH4W groups and was the thickest in the POST24 group ( P = .01). The bone surface to bone volume ratio was significantly higher in all the injury groups compared with the CON group and in the POST24 group compared with the other groups ( P = .01). Trabecular thickness was significantly lower in all the injury groups compared with the CON group and in the POST24 group compared with the other groups ( P = .01). Conclusion: Resting without training in the first 96 hours after an acute patellar tendon enthesis injury resulted in the best recovery of cell density in the tendon enthesis 4 weeks after the injury. Starting training 96 hours after the injury resulted in the best recovery of fibrocartilage zone thickness. Starting training 48 to 96 hours after the injury resulted in the best healing of the bone component of the attachment site 4 weeks after the injury. The optimal time to start training may be longer than 96 hours after an acute patellar tendon enthesis injury for the best overall healing of the tendon enthesis 4 weeks after the injury. Clinical Relevance: A rest of a minimal 72 hours may be needed for the best healing of a patellar tendon enthesis after an acute injury. Future studies are needed to determine the optimal time to start training after an acute patellar tendon injury.

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The Effect of Platelet-Rich Plasma on Achilles Tendon Healing in a Rabbit Model

Acta Orthopaedica et Traumatologica Turcica ◽

10.3944/aott.2016.16.0045 ◽

2016 ◽

Cited By ~ 1

Author(s):

Masaki Takamura

Keyword(s):

Achilles Tendon ◽

Platelet Rich Plasma ◽

Rabbit Model ◽

Tendon Healing

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BMP-14 Gene Therapy Increases Tendon Tensile Strength in a Rat Model of Achilles Tendon Injury

The Journal of Bone and Joint Surgery (American) ◽

10.2106/00004623-200706000-00021 ◽

2007 ◽

Vol 89 (6) ◽

pp. 1315-1320 ◽

Cited By ~ 39

Author(s):

Patrick Bolt ◽

Avnish Neil Clerk ◽

Hue H. Luu ◽

Quan Kang ◽

Jennifer L. Kummer ◽

...

Keyword(s):

Gene Therapy ◽

Tensile Strength ◽

Achilles Tendon ◽

Rat Model ◽

Tendon Injury

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Polydeoxyribonucleotide improves tendon healing following achilles tendon injury in rats

Journal of Orthopaedic Research® ◽

10.1002/jor.23796 ◽

2017 ◽

Vol 36 (6) ◽

pp. 1767-1776 ◽

Cited By ~ 6

Author(s):

Shin Hyuk Kang ◽

Min Seok Choi ◽

Han Koo Kim ◽

Woo Seob Kim ◽

Tae Hui Bae ◽

...

Keyword(s):

Achilles Tendon ◽

Tendon Healing ◽

Tendon Injury

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Real-time sonoelastography evaluation of the Achilles tendon following ultrasound-guided platelet-rich plasma injection and eccentric exercise for the treatment of refractory Achilles tendinopathy

Ultrasound ◽

10.1177/1742271x18818608 ◽

2018 ◽

Vol 27 (3) ◽

pp. 138-147

Author(s):

Chin Chin Ooi ◽

Michal Schneider ◽

Peter Malliaras ◽

Meng Ai Png ◽

Martine Chadwick ◽

...

Keyword(s):

Achilles Tendon ◽

Eccentric Exercise ◽

Platelet Rich Plasma ◽

Tendon Healing ◽

Inverse Correlation ◽

Strain Ratio ◽

Achilles Tendinopathy ◽

Post Treatment ◽

Tendon Stiffness ◽

Plasma Injection

The objective of this study was to investigate the feasibility of using sonoelastography to depict Achilles tendon stiffness after platelet-rich plasma injection and eccentric exercise for chronic Achilles tendinopathy, and to correlate sonoelastography findings with clinical outcome up to 12 months after treatment. Forty-five Achilles tendons from 45 patients (33 males, 12 females; mean age 51 years) were examined using sonoelastography and ultrasound at baseline, 4–6 weeks, 6 months and 12 months post-treatment. The strain ratio (between Achilles tendon and Kager's fat) during sonoelastography was obtained. The proportion of tendons with hypoechogenicity and neovascularity were documented. Clinical outcomes were assessed by the Victorian Institute of Sport Assessment-Achilles questionnaire and correlated with sonographic findings. The Victorian Institute of Sport Assessment-Achilles improved significantly from 38.4 (±14.1) at baseline, 77.2 (±12.5) at 6 months ( p < 0.001) to 81.2 (±10.8) at 12 months ( p < 0.001). The strain ratio values were 2.16 (±1.02) at baseline, 2.03 (±0.67) at 4–6 weeks, 1.81 (±0.62) at 6 months and 1.19 (±0.34) at 12 months with a significant reduction observed at 6 months (p = 0.006) and 12 months ( p < 0.001). At 12-month evaluation, none of the tendons regained a normal echotexture. Strain ratio demonstrated a moderately good inverse correlation with Victorian Institute of Sport Assessment-Achilles (r = −0.610, p<0.001) while B-mode and Doppler ultrasound did not show a significant correlation (r = −0.041, p = 0.817, and r = −0.116, p = 0.514). Achilles tendon stiffness shows moderately good correlation with clinical symptom at 12-month post-treatment. Sonoelastography using strain ratio could be a promising ancillary tool for monitoring Achilles tendon healing after treatment.

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