Application of a Purified Protein From Natural Latex and the Influence of Suture Type on Achilles Tendon Repair in Rats

2019 ◽  
Vol 47 (4) ◽  
pp. 901-914 ◽  
Author(s):  
Diego Pulzatto Cury ◽  
Bárbara Tavares Schäfer ◽  
Sonia Regina Yokomizo de Almeida ◽  
Marta Maria da Silva Righetti ◽  
Ii-sei Watanabe

Background: The prolonged tendon-healing process, the high costs associated with treatment, the increase in the number of injuries over the past decades, and the lack of consensus on the optimal treatment of tendon injuries are a global problem. Restoring the normal tendon anatomy and decreasing the healing time are key factors for treatment advancement. Hypothesis: Application of a purified protein from natural latex (PPNL) accelerates the healing process, increasing collagen synthesis and decreasing metalloproteinases. PPNL associated with a simpler suture technique should decrease the healing time. Study Design: Controlled laboratory study. Methods: Injury, surgery, and treatment with PPNL were conducted with male Sprague-Dawley rats. Two suture techniques were used: U-suture, a simpler and lesser traumatic technique, and Kessler-Tajima, to avoid strangulation of the microcirculation. Achilles tendons were completely sectioned, and 100 µL of 0.1% PPNL was applied on the tendon during surgery. Tendon morphology, distribution, and quantity of collagen types I and III, as well as expression of TIMP-1, TIMP-2, MMP-2, and MMP-9 and ultrastructural aspects of cells and collagen fibrils, were assessed after 2 and 4 weeks. Results: PPNL treatment improved collagen type I synthesis and reduced MMP-2 expression. All groups showed a 6.8-times increase in tendon weight as compared with the control group after 2 weeks and a 5.2-times increase after 4 weeks. All groups showed an increase in diameter after 4 weeks, except for the ones treated with PPNL, which showed a slight reduction in diameter. The peak of concentration of collagen fibrils with a 80-nm diameter was 27.79% in the control group; all other experimental groups presented fibrils between 50 and 60 nm. However, the best results were observed with Kessler-Tajima suture associated with PPNL. Conclusion/Clinical Relevance: There are no known medicines or substances capable of aiding the tendon healing process besides surgery. The discovery of a substance able to improve this process and decrease its duration represents an important advancement in orthopaedic medicine.

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1411
Author(s):  
Laura de Girolamo ◽  
Luiz Felipe Morlin Ambra ◽  
Carlotta Perucca Orfei ◽  
John P. McQuilling ◽  
Kelly A. Kimmerling ◽  
...  

Treatment of tendon injuries is challenging, with neither conservative nor surgical approaches providing full recovery. Placental-derived tissues represent a promising tool for the treatment of tendon injuries. In this study, human amniotic suspension allograft (ASA) was investigated in a pre-clinical model of Achilles tendinopathy. Collagenase type I was injected in the right hind limb of Sprague Dawley rats to induce disease. Contralateral tendons were either left untreated or injected with saline as controls. Seven days following induction, tendons were injected with saline, ASA, or left untreated. Rats were sacrificed 14 and 28 days post-treatment. Histological and biomechanical analysis of tendons was completed. Fourteen days after ASA injection, improved fiber alignment and reduced cell density demonstrated improvement in degenerated tendons. Twenty-eight days post-treatment, tendons in all treatment groups showed fewer signs of degeneration, which is consistent with normal tendon healing. No statistically significant differences in histological or biomechanical analyses were observed between treatment groups at 28 days independent of the treatment they received. In this study, ASA treatment was safe, well-tolerated, and resulted in a widespread improvement of the tissue. The results of this study provide preliminary insights regarding the potential use of ASA for the treatment of Achilles tendinopathy.


2020 ◽  
Vol 9 (9) ◽  
pp. 613-622
Author(s):  
Carlotta Perucca Orfei ◽  
Arianna Barbara Lovati ◽  
Gaia Lugano ◽  
Marco Viganò ◽  
Marta Bottagisio ◽  
...  

Aims In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy. Methods A total of 68 Sprague Dawley rats received a single injection of type I collagenase in Achilles tendons to induce the tendinopathy and then were daily exposed to PEMFs (1.5 mT and 75 Hz) for up to 14 days - starting 1, 7, or 15 days after the injection - to identify the best treatment option with respect to the phase of the disease. Then, 7 and 14 days of PEMF exposure were compared to identify the most effective protocol. Results The daily exposure to PEMFs generally provided an improvement in the fibre organization, a decrease in cell density, vascularity, and fat deposition, and a restoration of the physiological cell morphology compared to untreated tendons. These improvements were more evident when the tendons were exposed to PEMFs during the mid-acute phase of the pathology (7 days after induction) rather than during the early (1 day after induction) or the late acute phase (15 days after induction). Moreover, the exposure to PEMFs for 14 days during the mid-acute phase was more effective than for 7 days. Conclusion PEMFs exerted a positive role in the tendon healing process, thus representing a promising conservative treatment for tendinopathy, although further investigations regarding the clinical evaluation are needed. Cite this article: Bone Joint Res 2020;9(9):613–622.


2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Chris Kirchhoff

Abstract Background Tendinopathy accounts for more than half of reported musculoskeletal injuries worldwide. The subsequent healing process results in a disorganised tendon structure secondary to neovascularisation, forming a bulky tendon with overall reduced strength. Current treatment options remain controversial as re-rupture rates following surgical intervention are high. It has been proposed that the use of anti-vascular endothelial growth factors could improve tendon healing. Methods This literature review employed a systematic approach. The search strategy incorporated an adjusted PICO format and PRISMA flow diagram. Search findings were critically appraised using the CASP tool checklist. Identified studies investigated the effect of injectable anti-angiogenic drugs on tendon healing.  Results Three final studies were identified. Tempfer et al. showed a reduction in cross sectional tendon area in the intervention group (5.6mm²+1.8), comparatively to the control group (9.1mm² +2.0), and increased tendon strength in the intervention group (47.7N+6.41) comparatively to the control group(32.41N+9.23). Dallaudiere (2014) et al. showed reduced cross-sectional area in the intervention group (0.95mm²+0.01) compared with the control group (0.75mm²+0.01). Dallaudiere (2013) et al. also showed reduced cross sectional areas in the intervention group (1.10mm²+0.01) compared with the control group (1.11mm²+0.03).  Conclusion All studies supported the use of anti-angiogenic drugs to support tendon healing. The use of injectable anti-angiogenic drugs may potentially serve in conjunction with surgical intervention or as an alternative minimally invasive intervention to improve tendon rehabilitation. This review recommends that further randomised control studies will be needed to strengthen the current evidence. 


Author(s):  
Eliane TAGLIARI ◽  
Leticia Fuganti CAMPOS ◽  
Antonio Carlos CAMPOS ◽  
Thaís Andrade COSTA-CASAGRANDE ◽  
Lúcia de NORONHA

ABSTRACT Background: Manipulating intestinal microbiota with probiotics might stimulate skin response. Understanding all stages of the healing process, as well as the gut-skin-healing response can improve the skin healing process. Aim: To evaluate the effect of perioperative oral administration of probiotics on the healing of skin wounds in rats. Methods: Seventy-two Wistar male adult rats were weighed and divided into two groups with 36 each, one control group (supplemented with oral maltodextrin 250 mg/day) and one probiotic group (supplemented with Lactobacillus paracasei LPC-37, Bifidobacterium lactis HN0019, Lactobacillus rhamnosus HN001, Lactobacillus acidophilus NCFM® at a dose of 250 mg/day), both given orally daily for 15 days. The two groups were subsequently divided into three subgroups according to the moment of euthanasia: in the 3rd, 7th and 10th postoperative days. Results: There were no significant changes in weight in both groups. Wound contraction was faster in probiotic group when compared to the controls, resulting in smaller wound area in the 7th postoperative day. As for histological aspects, the overall H&E score was lower in the probiotic group. The probiotic group showed increased fibrosis from 3rd to the 7th postoperative day. The type I collagen production was higher in the probiotic group at the 10th postoperative day, and the type III collagen increased in the 7th. Conclusion: The perioperative use of orally administrated probiotic was associated with a faster reduction of the wound area in rats probably by reducing the inflammatory phase, accelerating the fibrosis process and the deposition of collagen.


2018 ◽  
Author(s):  
Yasuhiko Kaita ◽  
Takehiko Tarui ◽  
Hideaki Yoshino ◽  
Takeaki Matsuda ◽  
Yoshihiro Yamaguchi ◽  
...  

AbstractThe purpose of this study was to evaluate whether cryopreserved (frozen) adipose-derived regenerative cells (ADRCs) have a therapeutic effect on burn wound healing as well as freshly isolated (fresh) ADRCs.Full thickness burns were created on dorsum of nude mice and burn wound was excised. The wound was covered by artificial dermis with; (i) fresh ADRCs, (ii) frozen ADRCs, and (iii) PBS (control). The assessment for wound healing was performed by morphological, histopathological and immunohistochemical analyses.In vivo analyses exhibited the significant therapeutic effect of frozen ADRCs on burn wound healing up to the similar or higher level of fresh ADRCs. There were significant differences of wound closure, epithelized tissue thickness, and neovascularization between the treatment groups and control group. Although there was no significant difference of therapeutic efficacy between fresh ADRC group and frozen ADRC group, frozen ADRCs improved burn wound healing process in dermal regeneration with increased great type I collagen synthesis compared with fresh ADRCs.These findings indicate that frozen ADRCs allow us to apply not only quickly but also for multiple times, and the cryopreserved ADRCs could therefore be useful for the treatment of burn wounds in clinical settings.


2021 ◽  
Vol 33 (2) ◽  
pp. 145
Author(s):  
Hendry Rusdy ◽  
Astri Suryani Pasaribu Saruksuk ◽  
Rahmi Syaflida Dalimunte ◽  
Gostry Aldica Dohude

Pendahuluan: Pencabutan gigi merupakan prosedur yang sering dilakukan di kedokteran gigi. Setelah pencabutan gigi akan dihasilkan suatu perlukaan. Proses penyembuhan luka dapat dipercepat pada kondisi tertentu. Salah satu bahan alami yang dapat membantu proses penyembuhan luka adalah getah tanaman betadine (Jatropha multifida L.). Penelitian bertujuan untuk menganalisis efektivitas getah tanaman betadine terhadap penyembuhan luka dan terhadap tanda-tanda infeksi pasca pencabutan gigi Metode: Desain penelitian studi eksperimental laboratorium dengan rancangan penelitian post-test only control group design menggunakan 30 ekor tikus Sprague-Dawley. Teknik pengambilan sampel yaitu convenience sampling. Sampel dibagi menjadi 2 kelompok yaitu kelompok perlakuan dan kelompok kontrol. Kelompok perlakuan diberikan getah tanaman betadine dan kelompok kontrol diberikan asam traneksamat secara oral menggunakan sonde lambung. Tunggu selama 4 jam setelah pemberian getah tanaman betadine dan asam traneksamat. Anestesi pada tikus menggunakan ketamin 50 mg/kg berat badan secara intramuskular kemudian dilakukan pencabutan pada gigi tikus. Pengamatan dilakukan dengan melihat kriteria klinis pada hari 1,3,7 dan diperhatikan sampai luka sembuh serta lihat tanda-tanda infeksi. Analisis data dilakukan dengan uji normalitasShapiro Wilik. Hasil penelitian menunjukkan bahwa data berdistribusi tidak normal. Analisis data dilanjutkan menggunakan uji statistik mann whitney. Hasil: Terdapat perbedaan signifikan penyembuhan luka soket pasca pencabutan gigi setelah diberikan getah betadine dan asam traneksamat dengan nilai p=0,037 (p<0,005). Simpulan: Pemberian getah tanaman betadine terbukti lebih efektif terhadap proses penyembuhan luka soket pasca pencabutan gigi dibandingkan dengan pemberian asam traneksamat. Kata kunci: tikus Sprague-Dawley; penyembuhan luka; pencabutan gigi; getah batang betadine ABSTRACTIntroduction: Tooth extraction is a procedure often performed in dentistry. Tooth extraction will always cause injuries. However, the wound healing process can be accelerated under certain conditions. One of the natural ingredients that can accelerate the wound healing process is betadine (Jatropha multifida L.) plant sap. The study was aimed to analyzed the effect of betadine plant sap on wound healing and signs of infection after tooth extraction. Methods: Experimental laboratory study design with post-test only control group design was conducted towards 30 Sprague-Dawley rats. The sampling technique was convenience sampling. The sample was divided into two groups, the treatment group and the control group. The treatment group was administered with betadine plant sap, and the control group was administered with tranexamic acid orally using a gastric probe, then waited 4 hours after. The anaesthesia was then performed using 50 mg/kg body weight of ketamine intramuscularly. The extraction was performed after. Observations was conducted at the clinical criteria on days 1, 3, and 7 and continue to be monitored until the wound heals. Then, the signs of infection were observed. Data analysis was carried out using the Shapiro Wilk normality test. The results showed that the data was not normally distributed. Thus, data analysis was continued using the Mann Whitney statistical test. Results: The results showed a significant difference in the healing of socket wounds after tooth extraction after being administered with betadine sap and tranexamic acid with a value of p=0.037 (p<0.005). Conclusions: Administration of betadine plant sap is proven to be more effective in accelerating the healing process of socket wounds after tooth extraction than tranexamic acid. Keywords: Sprague-Dawley rats; wound healing; pencabutan gigi; getah batang betadine 


2021 ◽  
Vol 3 (2) ◽  
pp. 192-206
Author(s):  
Sergey G. Sсherbak ◽  
Stanislav V. Makarenko ◽  
Olga V. Shneider ◽  
Tatyana A. Kamilova ◽  
Alexander S. Golota

The mechanical properties of tendons are thought to be affected by different loading levels. Changes in the mechanical properties of tendons, such as stiffness, have been reported to influence the risk of tendon injuries chiefly in athletes and the elderly, thereby affecting motor function execution. Unloading resulted in reduced tendons stiffness, and resistance exercise exercise counteracts this. Transforming growth factor-1 is a potent inducer of type I collagen and mechanosensitive genes encoding tenogenic differentiation markers expression which play critical roles in tendon tissue formation, tendon healing and their adaptation during exercise. In recent years, our understanding of the molecular biology of tendons growth and repair has expanded. It is probable that the next advance in the treatment of tendon injuries will result from the application of this basic science knowledge and the clinical solution will encompass not only the the best postoperative rehabilitation protocols, but also the optimal biological modulation of the healing process.


2013 ◽  
Vol 4 (4) ◽  
pp. 259-259
Author(s):  
L. Ferhatovic ◽  
A. Jelicic ◽  
M. Boric ◽  
A. Banozic ◽  
D. Sapunar ◽  
...  

Abstract Aim The aim of this study was to compare expression of total calcium/calmodulin-dependent protein kinase II (tCaMKII) and its α, β, γ and δ isoforms in dorsal root ganglion (DRG) in rat models of diabetes mellitus type I (DM1), 6 months and 1 year after diabetes induction. Methods A total of 45 male Sprague-Dawley rats weighing 160-200 g were assigned into four experimental groups: 6-months DM1 and its control group, 1-year and its control group. For the induction of DM1, after overnight fasting animals were injected intraperitonealy with 55 mg/kg of the streptozotocine (STZ). Rats were sacrificed 6 months and 1 year after the diabetes induction. The L4 and L5 ganglions were removed, fixed, embedded in freezing medium and sectioned on a cryostat. Immunofluorescence analysis was performed for detection of tCaMKII and its α, β, γ and δ isoforms. Image J software was used for analysis of immunofluorescence. Results The diabetes was successfully induced as confirmed by measurement of glucose levels and weight increase. Analysis of tCaMKII expression in DRGs revealed no differences between DM1 and control animals after 6 and 12 months. In diabetic animals, the expression of α and β isoforms decreased significantly after 6 months, compared to the controls, while decrease of γ and δ was observed after one year of diabetes in diabetic animals. Conclusions The observed changes in the expression of CaMKII isoforms reveal plastic changes of this enzyme during the chronic diabetic state and may be involved in the chronic neuropathic pain development.


2006 ◽  
Vol 21 (suppl 4) ◽  
pp. 13-17 ◽  
Author(s):  
Paulo de Tarso Camillo de Carvalho ◽  
Iandara Schettert Silva ◽  
Filipe Abdalla dos Reis ◽  
Ana Carulina Guimarães Belchior ◽  
Ricardo Dutra Aydos ◽  
...  

PURPOSE: To investigate the effects of therapeutic ultrasound on the healing of tendon injuries in malnourished rats. METHODS: After the intended nutritional states had been attained, the animals (N=36) were distributed into three groups, named: G1(N=12), control group; G2(N=12), malnourished rats treated with 3 MHz ultrasound at an intensity of 0.5 W/cm²; and G3 (N=12), normal animals treated with 3 MHz at 0.5 W/cm². The injuries were induced by means of an operation to expose the heel tendon and crush it using Allis forceps. RESULTS: The data obtained relating to leukocyte counts, fibroblasts, vessel neoformation, fibrosis and collagen were subjected to statistical treatment using analysis of variance (ANOVA) and Student's t test. Results of p < 0.05 were obtained for fibrosis and collagen. CONCLUSION: The ultrasound was shown to be effective in repairing the tendon, even in malnourished animals whose healing process was retarded.


2021 ◽  
Author(s):  
Jessica E Ackerman ◽  
Katherine T Best ◽  
Samantha N Muscat ◽  
Chia-Lung Wu ◽  
Alayna E Loiselle

The tendon healing process is regulated by the coordinated interaction of multiple cell types and molecular processes. However, these processes are not well-defined leading to a paucity of therapeutic approaches to enhance tendon healing. Scleraxis-lineage (ScxLin) cells are the major cellular component of adult tendon and make time-dependent contributions to the healing process. Prior work from our lab and others suggests heterogeneity within the broader ScxLin population over the course of tendon healing; therefore delineating the temporal and spatial contributions of these cells is critical to understanding and improving the healing process. In the present study we utilize lineage tracing of the adult ScxLin population to determine whether these cells undergo cellular activation and subsequent myofibroblast differentiation, which is associated with both proper healing and fibrotic progression in many tissues. We show that adult ScxLin cells undergo transient activation in the organized cellular bridge at the tendon repair site, contribute to the formation of an organized neo-tendon, and contribute to a persistent myofibroblast population in the native tendon stubs. The mechanisms dictating this highly specialized spatial response are unknown. We therefore utilized spatial transcriptomics to better define the spatio-molecular program of tendon healing. Integrated transcriptomic analyses across the healing time-course identifies five distinct molecular regions, including key interactions between the inflammatory bridging tissue and highly reactive tendon tissue at the repair site, with adult ScxLin cells being a central player in the transition from native tendon to reactive, remodeling tendon. Collectively, these data provide important insights into both the role of adult ScxLin cells during healing as well as the molecular mechanisms that underpin and coordinate the temporal and spatial healing phenotype, which can be leveraged to enhance the healing process.


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