Tissue Reparation Research Articles

ADJUVANT TREATMENT WITH BIPHOSPONATES IN COMPLEX THERAPY OF PAPILLARY THYROID CANCER BONE METASTASES

Distant metastasis of thyroid cancer are founded in 10% of all metastases. Bone metastases are founded in 23% of distant metastasis. Complications associated with metastatic skeletal involvement often lead to a deterioration in the overall condition and a decrease in the quality of life of patients. Surgical treatment, chemotherapy are less effective, provide a higher injury rate and toxicity. This is a reason of increasing of cost of treatment. Bisphosphonates are a class of drugs that prevent the loss of bone mass, which can prolong the time to releasing bone complications: bone fracture, spine column fracture with spinal medulla compression, which decrease the QoL. Surgical treatment and chemotherapy have worse outcomes, higher injury rate, toxicity and increase cost of treatment. Bisphosphonates decrease the level of pain syndrome. Bisphosphonates are used in treatment of oncological patients since 1990. First medication was Fosamax (Aledronat). Later more medications with better efficacy and more useful were synthesised. The last one was Zoledronic acid. Rezorba (zoledronic acid) was synthesised in 2006 in Russia. Rezorba has a same efficacy with other bisphosphonates, it was shown in clinical studies with groups of breast cancer and prostatic cancer. Clinical case of 67 y.o. male patient with diagnosis: Thyroid cancer IV c st pT1bN1bM1, right neck, paratraсheal, bone and lung metastasis. Complex treatment (surgery + radioiodine therapy + 5 courses of Rezorba) was presented. After 3 courses the level of pain was decreased from 3 to 1,5. After 5 courses the ECOQ score was decreased from 2 to 1 point. Inclusion of Resorba in complex treatment of patients with bone metastasis after thyroid cancer at all stages of treatment decreases the score of pain syndrome and bone tissue reparation.

Structure of active cerium sites within bioactive glasses

AbstractThe inclusion of small amounts of cerium within the matrix of bioactive glasses, a class of materials used for bone tissue reparation and regeneration, adds a very important antioxidant property. In this work we investigate the local structure around cerium ions in cerium oxide doped bioactive phosphosilicate and silicate glasses, by X‐ray absorption fine structure at the Ce K‐edge, combined with classical molecular dynamics (MD) simulations. The local structure of the active Ce sites results significantly different from the one in bulk cerium oxide phases. A contracted Ce–O first shell distance with respect to bulk oxides is detected, in full agreement with the results of MD simulations. The cerium environment in the glass matrix at different stages of the reaction with H2O2 does not show significant modifications, in spite of the very high catalytic activity. The accurate description of the active Ce sites within bioactive glasses reported in this work is an important step toward an atomic scale understanding of the material functionalities.

Cranioplasty Using Autologous Fasciae Latae Graft for Nasal Bone Fracture Repair in a Dog

Background: In facial reconstruction, several kinds of grafts can be used, like bone grafting, cutaneous grafting, biological membranes, fasciae latae, biomaterials, and others. The advantage of using fasciae latae in the tissue reparation is the need of little blood supply, making it a viable option in the restoration of biological functions. The objective of this study was to describe the case of a female poodle, 12-year-old, and with subcutaneous emphysema due to fracture of the nasal bone, submitted to cranioplasty using fasciae latae.Case: It was attended a 12-year-old female poodle due to a traumatic brain injury. At physical examination, the animal had presented facial swelling and respiratory distress with inspiratory effort. Additionally, were verified subcutaneous emphysema and a depression in the nasal plane region with crepitus on palpation. Radiographic examinations revealed nasal bone and maxilla fractures. The animal was submitted to cranioplasty for nasal bone fracture repair. To access the nasal bone and frontal sinus was performed an incision in the dorsal midline from the level of medial orbital rim to the nasal plane. The subcutaneous tissue was divulsioned to allow the exposure of the nasal bone fracture, whose small fragments prevented the internal fixation. The bone defect was then repaired using free autologous fasciae latae of 2 cm wide x 3 cm long, sutured to the periosteum. Subcutaneous emphysema gradually decreased until its resolution at three days postoperatively. The surgical wound had complete healing at 10 days after surgery without concomitant complications.Discussion: The choice of the reconstructive technique is based on the operative planning and the surgeon’s experience. In the present case we opted for the autologous fasciae latae graft since its ready availability and lesser predisposition to immunogenic sensibilization and rejection. In addition, we opted for the autologous fasciae latae graft because it is an occlusive material that would prevent the air flow through it during the inspiration and expiration, and consequently the aggravation of the subcutaneous emphysema. In fact, the resolution of the subcutaneous emphysema occurred three days after grafting. Furthermore, the resolution of the subcutaneous emphysema was determined by the lower retraction of the autologous fasciae latae graft due to the scar fibrous tissue deposition. The choice of the reconstructive technique is also based on the viability of the recipient bed, which should provide adequate blood supply for the reception of the free graft. In the present case, however, the bone defect did not provide adequate blood supply and structural support. Due to this, the autologous fasciae latae graft was crucial to the verified results, since it requires less blood supply and structural support to remain the graft viable. We concluded that the autologous fasciae latae graft may be a viable option for the anatomical and functional reconstruction of traumatic lesions localized in the skull, particularly the nasal bone, due to the satisfactory follow-up in the present case without the occurrence of complications. A larger sample size, however, it is necessary to evaluate the real effectiveness of the autologous fasciae latae graft in reconstructive skull surgery on small animals.

Diffusion imaging of mild traumatic brain injury in the impact accelerated rodent model: A pilot study

ABSTRACTPrimary Objective: There is a need to understand pathologic processes of the brain following mild traumatic brain injury (mTBI). Previous studies report axonal injury and oedema in the first week after injury in a rodent model. This study aims to investigate the processes occurring 1 week after injury at the time of regeneration and degeneration using diffusion tensor imaging (DTI) in the impact acceleration rat mTBI model.Research Design: Eighteen rats were subjected to impact acceleration injury, and three rats served as sham controls. Seven days post injury, DTI was acquired from fixed rat brains using a 7T scanner. Group comparison of Fractional Anisotropy (FA) values between traumatized and sham animals was performed using Tract-Based Spatial Statistics (TBSS), a method that we adapted for rats.Main Outcomes and Results: TBSS revealed white matter regions of the brain with increased FA values in the traumatized versus sham rats, localized mainly to the contrecoup region. Regions of increased FA included the pyramidal tract, the cerebral peduncle, the superior cerebellar peduncle and to a lesser extent the fibre tracts of the corpus callosum, the anterior commissure, the fimbria of the hippocampus, the fornix, the medial forebrain bundle and the optic chiasm.Conclusion: Seven days post injury, during the period of tissue reparation in the impact acceleration rat model of mTBI, microstructural changes to white matter can be detected using DTI.

Alloplant biomaterials as postburn skin scarring inhibitors

Allotransplants for eyelid frame plasty by Alloplant may facilitate recovery of eyelid anatomical position and function and prevent postburn scar tissue traction. Purpose of the study. To determine the level of fibrogenic factors after skin burn wound treatment with Alloplant biomaterials in experiment. The tissue level of TGF-1 and FGF-1 fibrogenic factors was detected immunohistochemically in 84 Wistar rats treated with Alloplant biomaterials for skin burn wounds. It was established that the tissue level of fibrogenic cytokines reduced significantly after treatment with allogenic biomaterials that leads to inhibition of fibroblast proliferation and prevents excessive collagen synthesis. At tissue reparation, allogenic biomaterials inhibit coarse scar formation.

Experimental Validation of the Efficiency of Gamalant-paste-FORTE Plus, a Russian Osteoinductive Material, in Oral Surgery.

For evaluation of the efficiency of bone substitute, nanostructurized Gamalant-paste-FORTEPlus was placed into a mandibular defect in rats. Bone tissue reparation was evaluated after 30 days by histological methods under a microscope. Use of bone substitute in experimental mandibular defect ensured more complete and rapid restructuring of the bone tissue in comparison with the control (natural healing).

Polyphenol-Related Epigenetic Modifications in Osteoarthritis: Current Therapeutic Perspectives.

The hyaline cartilage is an avascular, aneural and alymphatic tissue with a limited ability to repair itself. When the cartilage is exposed to some kind of injury, it usually triggers osteoarthritis (OA), a prevalent and degenerative joint disease closely related to aging. OA is both complex and multifactorial, and is the most common form of arthritis, being positioned as a major cause of pain and dysfunction in the world. In addition, high OA prevalence can greatly affect work capacity, making this disease a significant social problem, therefore, its prevention and treatment becomes a priority. At this time, there are numerous therapeutic strategies available to improve hyaline cartilage repair by using chondrocytes or mesenchymal cells, but neither is effective enough to generate functional and durable tissue reparation over time. In OA, chondrocytes have an aberrant gene expression and phenotype, resulting in a loss of balance between anabolic and catabolic processes. Environmental influences such as radiation, infection, smoking, nutrients, toxins and stress can affect gene expression patterns, which may constitute risk factors for various chronic and degenerative diseases, such as OA. In addition, considerable evidence shows that epigenetic mechanisms play an important role in OA chondrogenesis and pathogenesis. Natural plant-derived products such as polyphenols, which are secondary metabolites considered to have potential activity to block inflammation in several degenerative diseases, can stimulate epigenetic modifications, and may provide new therapeutic targets and cost-effective treatments. This review aims to present various polyphenolbased therapies currently used for the treatment of several progressive diseases, including OA.

Changes in serum levels of the key factors of angiogenesis in different outcomes of combined injuries in children

To study the changes in the key angiogenic factors VEGF-A and angiogenin (ANG) in children with different outcomes of combined injuries. Contents of VEGF-A and ANG in blood serum were determined by enzyme immunoassay. The study included 40 patients, 21 boys and 19 girls. Patients were divided into 4 groups according to the outcome of injury: 1 - the recovery or mild residual symptoms; 2 - disabled; 3 - vegetable state; 4 - death. Patients were examined at different times after injury: 1-6 days, 7-11 days, 12-19 and 20-33 days. In the first days after injury, the content of VEGF-A in patients of 1-3 groups was at the level of the reference group, moreover, in patients of the 3rd group it was close to the top edge. In group 4, the content of VEGF-A was maximal in the first days after injury and then gradually decreased to the point of death. In groups 1 and 3, the level of VEGF-A increased significantly starting from the 2nd week while in group 2 this indicator was slightly increased approaching later (up to 33 days of observation) to the upper values in the reference group. In the 3rd group, the content of VEGF-A reached the plateau on the 19th day after injury and was higher than the reference data, but lower than in patients of the 1st group. No correlation between the changes in ANG content at different times after combined injuries and outcome was found. There was a trend towards decreased levels of ANG, especially after 3-4 weeks after injury. The data obtained are important for the control over processes of vascular and tissue reparation after injury and for searching for effective ways of treatment of altered angiogenesis in such patients.

Wound Healing Process, Diabetes and Implications of Dipeptidyl Peptidase IV (DPP IV/CD26)

Dipeptidyl Peptidase IV or molecule CD26 (DPP IV/CD26) is a multifunctional protein, identified as a therapeutic target for type 2 diabetes, due to its ability to degrade incretins, insulin secretagogues. Delayed wound healing is a significant complication in diabetic patients that represents a major socio-economic health problem. It has been proposed that DPP IV/CD26 inhibition accelerates healing of chronic diabetic ulcers in those patients, through the induction of a histological pattern consistent with enhanced angiogenesis. Studies on mice models of diabetesdisturbed wound healing also suggested that the inhibition of DPP IV enzymatic activity may improve tissue regeneration processes. However, further research is needed to elucidate the role of DPP IV/CD26 in diabetic wound healing. The objective of this work was to discuss recent findings on the implications of DPP IV/CD26 in tissue regeneration and reparation in diabetic environment.

Optimization of tissue reparation at treatment by Remaxol

Studying influence of remaxol on reparative process of tissue reparation in a laparotomy wound. 90 patients with the acute appendicitis complicated by local peritonitis in the early postoperative period are examined. 50 patients received traditional therapy. Therapy of other 40 patients included Remaxol (intravenous introduction, daily within 5 days, of 400 ml). It is established that Remaxol optimizes the course of reparative process in laparotomy wound that was confirmed with data of tenziomety and wound exudate cytological research. Efficiency of a Remaxol is based on its capability to improve microcirculation, antiedematous action and its capability to reduce excessive intensity peroxide oxidation of membrane lipids, phospholipase activity and the phenomena of a hypoxia.

The catalytic microwave synthesis of biodegradable polyester polyols based on castor oil and l-lactide

Various strategies for achieving a functional poly(lactic acid) (PLA) have been developed such as ring-opening copolymerization with a functional monomer, the use of functional initiator and various post polymerization modifications. It is possible to obtain the star shaped polymer using natural oil with at least three OH groups as an initiator. It was estimated that despite of low-molecular mass of star-shaped PLA, the hydrophobic castor oil central core influenced the slow degradation rate in the case of injectable biomedical application. The star-shaped polymers with low-molecular-mass have a lower melt viscosity correlated with linear counterparts. In soft tissue reparation the polymer viscosity increases with fluid body contact and the solid implant can be formed. To ensure liquid state at injection temperature the low molar mass polymer is favorable. There is a particular size for each macromolecular chains at which chain entanglement occurs. In this work the influence of the l-lactide (LA) and the castor oil (CO) contents on the size of biodegradable branched polyester polyols was studied. The average molecular masses of synthesized polymers were estimated by GPC procedure. In sample formulations the [LA]/[CO] ratios were from to 113 to 533. Mn values for obtained polymers were from 5000 to 20000 Da. The molecular mass distribution for the resulting polymers was between 1.09 and 1.37.

Identification of DNA methylation changes associated with disease progression in subchondral bone with site-matched cartilage in knee osteoarthritis.

Subchondral bone plays a key role in the development of osteoarthritis, however, epigenetics of subchondral bone has not been extensively studied. In this study, we examined the genome-wide DNA methylation profiles of subchondral bone from three regions on tibial plateau representing disease progression using HumanMethylation450 BeadChip to identify progression associated DNA methylation alterations. Significant differential methylated probes (DMPs) and differential methylated genes (DMGs) were identified in the intermediate and late stages and during the transition from intermediate to late stage of OA in the subchondral bone. Over half of the DMPs were hyper-methylated. Genes associated with OA and bone remodeling were identified. DMGs were enriched in morphogenesis and development of skeletal system, and HOX transcription factors. Comparison of DMGs identified in subchondral bone and site-matched cartilage indicated that DNA methylation changes occurred earlier in subchondral bone and identified different methylation patterns at the late stage of OA. However, shared DMPs, DMGs and common pathways that implicated the tissue reparation were also identified. Methylation is one key mechanism to regulate the crosstalk between cartilage and subchondral bone.

Stem cell procedures in arthroscopic surgery.

The stem cell as the building block necessary for tissue reparation and homeostasis plays a major role in regenerative medicine. Their unique property of being pluripotent, able to control immune process and even secrete a whole army of anabolic mediators, draws interest. While new arthroscopic procedures and techniques involving stem cells have been established over the last decade with improved outcomes, failures and dissatisfaction still occur. Therefore, there is increasing interest in ways to improve the healing response. MSCs are particularly promising for this task given their regenerative potential. While methods of isolating those cells are no longer poses a challenge, the best way of application is not clear. Several experiments in the realm of basic science and animal models have recently been published, addressing this issue, yet the application in clinical practice has lagged. This review provides an overview addressing the current standing of MSCs in the field of arthroscopic surgery.Level of evidence IV.

Boosting Angiogenesis in Skin Mechanical Trauma Area by means of Neoskin Skin-Substitute Preparation

Various skin-replacements nowadays are widely used alongside other up-to-date methods for treatment of skin wounds for using this technique decreases the need for wound vascularization, increases the wound’s skin component, decreases or completely removes inhibitory factors, decreases inflammatory process thus contributing to quick and safe wound’s covering up ensuring tissue reparation flexibility. The goal of the study was to assess the influence of Neoskin skin-replacement upon angiogenesis and wound reparation intensity in experiment involving white rats. Skin wound was modeled by removing a 4,9 square mm skin flap by means of incision under general narcosis (Zoletil). The treatment of the wound included the application of innovation preparation Neoskin produced by “Trans-Technologies”, Russia upon the skin wound for 14 days. The preparation Neoskin is a three-layer matrix consisting of extracellular matrix proteins and mesenchimal cells. Angiogenesis markers concentrations were determined in blood plasma by means of immune-enzyme assay (VEGF, NO, tPA and PAI-1). Vascular network density in the wound surface zone was determined by means of histological method in slides stained with hemotoxillin-eosine with the aid of light-microscopy in 50 fields of vision. Skin mechanical trauma model not involving subjacent organs and tissues was accompanied by angiogenesis changes characteristic of wound healing process. Transitory reduction of microcirculatory network density in the area of the wound and increasing activity of basic proangiogenic factors necessary for reparation took place. The use of Neoskin in the therapy of skin lesions in rats has contributed to fast activation of angiogenesis and wound healing.

Overview and perspectives of mesenchymal stem cell therapy in intensive care medicine

Development of innovative therapies in intensive care medicine is particularly important since diseases as sepsis, acute respiratory distress syndrome (ARDS) and acute renal injury (AKI) have an elevated morbidity and mortality in spite of current gold-standard approaches. Mesenchymal stem cells (MSC) may have a promising role due to their properties in immunomodulation, tissue reparation and microbial clearance. Preclinical data and results of a systematic review of PubMed, PMC and ClinicalTrials.gov have been included to review the role of MSC therapy in sepsis, ARDS and AKI. A description of MSC biology, sources and benefits in preclinical models was included. A phase I/II clinical trial (RCT) is recruiting neutropenic patients with septic shock. In ARDS, the START trial (Stem cells in ARDS Treatment) is a phase I/II study of bone marrow-derived human MSC (hMSC) that is currently recruiting patients. In AKI, a phase I study has demonstrated the safety of hMSCs infusion in patients undergoing cardiac surgery with high risk to develop AKI. A phase II study is still active. The results of these studies will determine the real feasibility of MSC therapy in critically ill patients.

Combined application of polyacrylate scaffold and lipoic acid treatment promotes neural tissue reparation after brain injury

Primary objective: The aim of this study was to investigate the reparative potential of a polymeric scaffold designed for brain tissue repair in combination with lipoic acid.Research design: Histological, cytological and structural analysis of a combined treatment after a brain cryo-injury model in rats.Methods and procedures: Adult Wistar rats were subjected to cryogenic brain injury. A channelled-porous scaffold of ethyl acrylate and hydroxyethylacrylate, p(EA-co-HEA) was grafted into cerebral penumbra alone or combined with intraperitoneal LA administration. Histological and cytological evaluation was performed after 15 and 60 days and structural magnetic resonance (MRI) assessment was performed at 2 and 6 months after the surgery.Main outcomes and results: The scaffold was suitable for the establishment of different cellular types. The results obtained suggest that this strategy promotes blood vessels formation, decreased microglial response and neuron migration, particularly when LA was administrated.Conclusions: These evidences demonstrated that the combination of a channelled polymer scaffold with LA administration may represent a potential treatment for neural tissue repair after brain injury.

INTEGUMENTARY REHABILITATION- AN IGNORED AREA IN PHYSICAL THERAPY

Besides many other health related fields, Physical therapy is expected to grow with an average rate of 40% in 20171. New generation entering in the field of physiotherapy are experiencing revolutionary changes. Integumentary rehabilitation is one of undergoing radical changes as the research work is revealing the anonymities of complex manners of the wound healing, tissue reparation, deprivation and revival of tissues.Evidence-based practices bring innovation and new technologies helping in the wound healing, but it is an ignored field in Pakistan, where physiotherapists lack in knowledge of Integumentary rehabilitation. Rehabilitationteams are working for about five decades on the dynamic changes occurring in wound careconcept2.

Epigenetically Modified Endothelial Progenitor Cells in Heart Failure

Heart failure is a global health and medical problem that increases burden of cardiovascular (CV) disease. By now, there is not completely recognition regarding the reasons of various phenotypes of HF development, distinguish in CV risk, clinical outcomes and prognosis. It has suggested that epigenetic modification of several cell components of endogenous repair system might determine phenotypical response of the failing heart and contributes to nature evolution of HF. Moreover, epigenetically modified endothelial progenitor cells playing a central role in the tissue reparation and angiogenesis may link aging, genetic predisposition, co-morbidities, traditional CV risk factor and HF progression. The editorial comment devotes the consideration of the role of epigenetic in manifestation of progenitor endothelial cell dysfunction and perspectives to restore its reparative ability in HF individuals.

Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues

Composite biomaterials comprising nanostructured hydroxyapatite (HAp) have an enormous potential for natural bone tissue reparation, filling and augmentation. Chitosan (Ch) as a naturally derived polymer has many physicochemical and biological properties that make it an attractive material for use in bone tissue engineering. On the other hand, poly-D,L-lactide-co-glycolide (PLGA) is a synthetic polymer with a long history of use in sustained drug delivery and tissue engineering. However, while chitosan can disrupt the cell membrane integrity and may induce blood thrombosis, PLGA releases acidic byproducts that may cause tissue inflammation and interfere with the healing process. One of the strategies to improve the biocompatibility of Ch and PLGA is to combine them with compounds that exhibit complementary properties. In this study we present the synthesis and characterization, as well as in vitro and in vivo analyses of a nanoparticulate form of HAp coated with two different polymeric systems: (a) Ch and (b) a Ch-PLGA polymer blend. Solvent/non-solvent precipitation and freeze-drying were used for synthesis and processing, respectively, whereas thermogravimetry coupled with mass spectrometry was used for phase identification purposes in the coating process. HAp/Ch composite particles exhibited the highest antimicrobial activity against all four microbial strains tested in this work, but after the reconstruction of the bone defect they also caused inflammatory reactions in the newly formed tissue where the defect had lain. Coating HAp with a polymeric blend composed of Ch and PLGA led to a decrease in the reactivity and antimicrobial activity of the composite particles, but also to an increase in the quality of the newly formed bone tissue in the reconstructed defect area.

Adjuvant Therapy With Sodium Alendronate for the Treatment of Experimental Periodontitis in Rats.

This study assesses the effects of topical sodium alendronate (SA) as an adjuvant to the mechanical treatment of ligature-induced periodontitis in rats. Ninety animals were subjected to the induction of periodontitis via the installation of a ligature around the mandibular left first molar. After 7 days, the ligature was removed, and the animals were distributed into the following groups: 1) NT group (n = 30), no treatment; 2) SRP group (n = 30), scaling and root planing (SRP) and local irrigation with physiologic saline solution; and 3) SRP/SA group (n = 30), SRP and local irrigation with SA (10(-5) M). Ten animals from each group were euthanized at 7, 15, and 30 days after treatment. Histologic and histometric analyses were performed in the furcation region. The percentage of bone in the furcation (PBF) was measured. Immunohistochemical analyses for detecting the receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRAP), and activated caspase-3 were performed at the furcation region. Compared with the other groups, the SRP/SA group showed less local inflammation and better tissue reparation during the entire experiment. There was more PBF in the SRP/SA group than in the other groups at days 7 and 15. Stronger OPG immunolabeling and weaker RANKL immunolabeling were observed in the SRP/SA group at 15 and 30 days. There were fewer TRAP-positive cells in the SRP/SA group than in the NT group at all of the time points. There was no difference in the number of activated caspase-3-positive osteocytes among groups and time points. It can be concluded that topical use of SA as an adjuvant to SRP is effective in the treatment of experimental periodontitis.