Topical Treatment with Bergamot Flavonoid-Based Gel in Post-Surgical Wounds after Hemorrhoidectomy: Preliminary Results

Background: Haemorrhoidal Disease (HD) is a very diffuse anorectal condition that involves a large part of the population, both male and female of every age. Among the several procedures proposed to treat HD, conventional excisional surgery remains one of the most performed, it is characterized by important post-operative pain whose historical knowledge often scare the patients. The pain is mainly related to the anal wounds and the healing speed surely influence the post-operative course. The aim of this study was to evaluate the effect of using Benebeo Gel® on post-operative wound healing after open haemorrhoidectomy. Methods and Results: This was an observational prospective study conducted in the Proctological and Pelvic Floor Clinical Centre (PPFCC) of the University Hospital of Pisa. From April 2019 to January 2020 all the 175 patients aged between 18 and 75 undergone to open hemorrhoidectomy were enrolled. The post-operative follow-up was scheduled as follows: 7 day, 15 day, 22 days and 30 days after surgery. The primary end point was: time taken to get complete wound healing with a re-epithelized tissue. Secondary endpoints were: evaluate post-operative pain using VAS scale, bleeding, discharge and overall patients satisfaction about the procedure and the topical gel. All the patients were instructed to take topical gel by using the cannula provided with the product put it into the finger phalanx and then upon injured area twice a day (once in the morning after defecation and once before sleeping) for 25 days after. The administration of the product begins in 4th post-operative day. The mean post-operative pain at 7 days was 6±2, at 15 days 4±1 at 22 day 3 and at 30 days was 2±1. The mean time to get complete wound healing was 23±4 days. Conclusions: He present study aimed to evaluate the efficacy of a new topical gel mainly composed by bergamot-derived flavonoids and hyaluronic acid in patients treated with excisional hemorrhoidectomy. The results after 2 weeks of treatment seems to be promising with a very good clinical outcome and patient satisfaction within 1 month.

Biological performance of a bioabsorbable Poly (L-Lactic Acid) produced in polymerization unit: in vivo studies

Background: The biomaterials engineering goal is to manufacture a biocompatible scaffold that adequately supports or improves tissue regeneration after implantation of the biomaterial in the injured area. Many requirements are demanded for a biomaterial, such as biocompatibility, elasticity, degradation time, and a very important factor is its cost of importation or synthesis, making its application inaccessible to some countries. Studies about biomaterials market show that Polylactic acid (PLLA) is one of the most used polymers, but expensive to produce. It becomes important to prove the biocompatibility of the new PLLA and to find strategies to produce biocompatible biopolymers at an acceptable production cost. Methods: In this work, the polylactic acid biomaterial was synthesized by ring-opening polymerization. The polymer was submitted to initial in vivo biocompatibility studies in 12 New Zealand female rabbits, assigned to two groups: (1) Lesion and PLLA group (n = 6), (2) Lesion No PLLA group (n = 6). Each group was divided into two subgroups at six and nine months post-surgical time. Before euthanasia clinical and biochemical studies were performed and after that tomographic (CT), histological (Hematoxylin and Eosin and Masson's trichrome) and histomorphometric analyses were performed to evaluate the injury site and prove biocompatibility. The final cost of this polymer was analyzed. Results: The statistical studies of hemogram and hepatocyte enzymes, showed that there were no significant differences between the groups for any of the times studied, in any of the variables considered and the results of CT and histology showed that there was an important process of neoregeneration. The cost analysis showed the biopolymer synthesis is between R$3,06 - R$5,49 cheaper than the import cost. Conclusions: It was possible to synthesize the PLLA biopolymer by cyclic ring opening, which proved to be biocompatible, potential osteoregenerative and cheaper than other imported biopolymers.

Conditioned Medium From M1 Macrophages Induces the Migration of Neural Stem Cells Through MCP-1/CCR2 and ERK Pathway

After spinal cord injury, grafted neural stem cells (NSCs) can migrate toward injured area, where there are a large number of bone marrow derived macrophage. However, little is known about the effect of M1 macrophage from bone marrow on NSCs migration and the mechanism responsible for migratory responses of grafted NSCs in vitro and in vivo. Migration of NSCs were conducted by using the transwell chamber and SCI model. Conditioned medium from M1 macrophages (M1-CM) can attract NSCs migration in vitro. The number of migrated C-C chemokine receptor 2 (CCR2) -/- NSCs induced by M1-CM were significantly decreased compared with wild type (WT) NSCs (P<0.05). Furthermore, compared with M0 macrophages, the production of MCP-1 by M1 macrophages was significantly increased and M1-CM treated with anti-MCP-1 antibody to neutralize MCP-1 can lead to a significant reduction of NSCs migration (P<0.05). In addition, Western blot showed that ERK1/2 was dramatically activated following the stimuli of M1-CM and then ERK inhibitor can also inhibit M1-CM-mediated MSCs migration. Finally, CCR2 was needed for grafted NSCs migration toward injured area. Bone marrow derived M1 macrophage persisted within the epicenter of injured area and the expression of MCP-1 mRNA was significantly increased 7days after SCI (P<0.05). These results demonstrated the effect of M1 macrophages on NSCs migration and the important role of MCP-1/CCR2 and ERK signal pathway on M1-CM-induced NSCs migration.

DESIGN OF SPECIALIZED SURGICAL SCREW INSERTED IN PLATE TYPE CERVICAL IMPLANT

In the field of Implantology the screws are an important part because they transfer the loads that occur in the bones. Surgical screws are similar to those in Mechanical Engineering, but the materials should have specific characteristics like biocompatibility, strength, corrosion resistance and fatigue strength. The main function of the surgical screw is to create pressure between two bones which is necessary in order to heal the injured bones. The surgical screw transforms all forces of the movements to pressure and distributes the pressure on the bone’s surfaces. Surgical screws can help in the setting of implants into an injured area. It also ensures static position of the injured bones. The research aims to analyse how the surgical screw type affects the bone of the patient with the help of the Finite Elements Method (FEM). Based on the results from the analysis of the surgical screw a new specialized surgical screw was designed with complex geometry to withstand the occurring loads and also be able to transfer them to the bone tissue. In additional, a comparison analysis between two different types of surgical screws was conducted. This paper shows how a surgical screw could be optimized in order to improve its function with the help of virtual tools. Finally, the materials used are biocompatible and often used for such screws and surgical implant analysis, the challenge was to recreate the bone tissue properties and to used them in the FEM analysis.

A Dual-Factor Releasing Hydrogel for Rotator Cuff Injury Repair

Rotator cuff injury causes pain in the shoulder and is a challenge to be repaired even after surgical reconstruction. Here, we developed a dual-factor releasing hydrogel based on sulfhydrylated chitosan to deliver KGN and FGF-2 to the injured area to enable fast healing of the tendon–bone interface, which is essential for the repair of rotator cuff injury. We found that the two factors could be easily loaded into the hydrogel, which could in turn continuously release the factors in physiological conditions. The hydrogel was found to be a porous structure through a scanning electron microscope (SEM). The micropores in the hydrogel structure enable the loading and releasing of these molecules. This study showed that KGN and FGF-2 could play a synergistic effect by recruiting and promoting stem cell proliferation and chondrogenesis, thus accelerating the healing of the tendon–bone interface. An in vivo study based on a rabbit rotator cuff injury model demonstrated that the dual-factor releasing hydrogel possesses superior repair capacity than a single-factor releasing hydrogel and the untreated groups. In conclusion, the KGN and FGF-2 dual-factor releasing hydrogel could be a promising biomaterial for the regeneration of the tendon–bone interface and rotator cuff injury repair.

Rat Bone Mesenchymal Stem Cell-Derived Exosomes Loaded with miR-494 Promoting Neurofilament Regeneration and Behavioral Function Recovery after Spinal Cord Injury

Exosomes (Exo) exhibit numerous advantages (e.g., good encapsulation, high targeting efficiency, and easy to penetrate the blood-brain barrier to the central nervous system). Exosomes are recognized as prominent carriers of mRNAs, siRNAs, miRNAs, proteins, and other bioactive molecules. As confirmed by existing studies, miR-494 is important to regulate the occurrence, progression, and repair of spinal cord injury (SCI). We constructed miR-494-modified exosomes (Exo-miR-494). As indicated from related research in vitro and vivo, Exo-miR-494 is capable of effectively inhibiting the inflammatory response and neuronal apoptosis in the injured area, as well as upregulating various anti-inflammatory factors and miR-494 to protect neurons. Moreover, it can promote the regeneration of the neurofilament and improve the recovery of behavioral function of SCI rats.

Heat flow, heat capacity and thermal resistance of localized surfaces of the human body using a new calorimetric sensor

A non-invasive sensor equipped with a programmable thermostat has been developed to assess in vivo the heat flow transmitted by conduction from human skin to the sensor thermostat. This device enables the assessment of the thermal properties of a 2 × 2 cm2 skin surface with a thermal penetration depth of 3–4 mm. In this work, we report the thermal magnitudes recorded with this sensor in 6 different areas (temple, hand, abdomen, thigh, wrist and heel) of 6 healthy subjects of different genders and ages, which were measured under resting conditions. Heat flow and equivalent thermal resistance are proportionally related to each other and are highly variable in magnitude and different for each zone. The heat capacity is also different for each zone. The heat flow values varied from 362 ± 17 mW at the temple to 36 ± 12 mW at the heel for the same subject, when the sensor thermostat was set at 26 °C. The equivalent thermal resistance ranged from 23 ± 2 K W−1 in the volar area of the wrist to 52 ± 4 KW−1 in the inner thigh area. The heat capacity varies from 4.8 ± 0.4 J K−1 in the heel to 6.4 ± 0.2 J K−1 in the abdomen. These magnitudes were also assessed over a 2 × 1 cm2 second-degree burn scar in the volar area of the wrist. The scar area had 27.6 and 11.6% lower heat capacity and equivalent thermal resistance, respectively, allowing an increased heat flow in the injured area. This work is a preliminary study of the measurement capacity of this new instrument.

992 Infrared Thermal Imaging in The Diagnosis and Management of Upper Limb Trauma

Aim Trauma can affect perfusion and thereby the temperature of the injured area. Infrared thermal imaging (IRT) has been used as a non-invasive, non-ionising means of diagnosing and monitoring various pathologies. We aim to evaluate the role of IRT in upper limb trauma. Method A review of all literature from the Cochrane Database, PubMed, Medline and EMBASE was performed. All papers evaluating infrared thermal imaging in trauma of the upper limb were included. Exclusion criteria included animal or cadaveric studies, and studies not measuring outcomes related to thermal imaging. Results Six papers were included from a total of 149 papers. There were five observational studies (with limited population numbers) and one case report. Four studies (N = 217) identified significantly higher skin temperatures in fractured limbs compared to non-injured side (p ≤ 0.05). Two studies included follow-ups with skin temperature differences between injured and non-injured sides decreasing over time, consistent with fracture healing times (approximately 3-4 weeks for paediatrics and 6 weeks for adults). One study (N = 9) identified that the presence of activity-related chronic pain in the hand was consistent with higher mean skin temperatures, even at baseline (p = 0.00000795). Conclusions IRT has been successfully used as a means of diagnosis and monitoring fracture healing in the upper limb. It also shows potential for use in detecting fractures that may not be initially evident on x-ray in the acute setting e.g., scaphoid fractures. Further robust and higher quality studies with larger patient populations are required.

Effects of hyperoxia and hypoxia on the proliferation of C2C12 myoblasts

Hyperoxic conditions are known to accelerate skeletal muscle regeneration after injuries. In the early phase of regeneration, macrophages invade the injured area and subsequently secrete various growth factors, which regulate myoblast proliferation and differentiation. Although hyperoxic conditions accelerate muscle regeneration, it is unknown whether this effect is indirectly mediated by macrophages. Here, using C2C12 cells, we show that not only hyperoxia but also hypoxia enhance myoblast proliferation directly, without accelerating differentiation into myotubes. Under hyperoxic conditions (95% O2 + 5% CO2), the cell membrane was damaged because of lipid oxidization, and a disrupted cytoskeletal structure, resulting in suppressed cell proliferation. However, a culture medium containing vitamin C (VC), an antioxidant, prevented this lipid oxidization and cytoskeletal disruption, resulting in enhanced proliferation in response to hyperoxia exposure of ≤4 h/day. In contrast, exposure to hypoxic conditions (95% N2 + 5% CO2) for ≤8 h/day enhanced cell proliferation. Hyperoxia did not promote cell differentiation into myotubes, regardless of whether the culture medium contained VC. Similarly, hypoxia did not accelerate cell differentiation. These results suggest that regardless of hyperoxia or hypoxia, changes in oxygen tension can enhance cell proliferation directly, but do not influence differentiation efficiency in C2C12 cells. Moreover, excess oxidative stress abrogated the enhancement of myoblast proliferation induced by hyperoxia. The present research will contribute to basic data for applying the effects of hyperoxia or hypoxia to muscle regeneration therapy.

Chronic Sequelae After Muscle Strain Injuries: Influence of Heavy Resistance Training on Functional and Structural Characteristics in a Randomized Controlled Trial

Background: Muscle strain injury leads to a high risk of recurrent injury in sports and can cause long-term symptoms such as weakness and pain. Scar tissue formation after strain injuries has been described, yet what ultrastructural changes might occur in the chronic phase of this injury have not. It is also unknown if persistent symptoms and morphological abnormalities of the tissue can be mitigated by strength training. Purpose: To investigate if heavy resistance training improves symptoms and structural abnormalities after strain injuries. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 30 participants with long-term weakness and/or pain after a strain injury of the thigh or calf muscles were randomized to eccentric heavy resistance training of the injured region or control exercises of the back and abdominal muscle. Isokinetic (hamstring) or isometric (calf) muscle strength was determined, muscle cross-sectional area measured, and pain and function evaluated. Scar tissue ultrastructure was determined from biopsy specimens taken from the injured area before and after the training intervention. Results: Heavy resistance training over 3 months improved pain and function, normalized muscle strength deficits, and increased muscle cross-sectional area in the previously injured region. No systematic effect of training was found upon pathologic infiltration of fat and blood vessels into the previously injured area. Control exercises had no effect on strength, cross-sectional area, or scar tissue but a positive effect on patient-related outcome measures, such as pain and functional scores. Conclusion: Short-term strength training can improve sequelae symptoms and optimize muscle function even many years after a strain injury, but it does not seem to influence the overall structural abnormalities of the area with scar tissue. Registration: NCT02152098 (ClinicalTrials.gov identifier).