Restorative Medicine Research Articles

Проблемы внедрения персонализированной медицины во врачебной косметологии в России

At the present time, the 4P concept (predictive, preventive, personalised and participatory) is a prospective trend in development of clinical medicine. The concept is being actively introduced into diff erent medical specialities. However, the development of personalised approach in medical cosmetology as a speciality at the intersection of medical sciences (dermatology, maxillofacial surgery, plastic surgery, restorative medicine, general practice, psychiatry, clinical pharmacology, etc.) is at the stage of discussion. The concept of 4P medicine suggests, among other things, analysis of genetic risks and development of preventive procedures based thereon that would decrease the risk of cosmetological complications development. The review includes analysis of literature dated 2010-2020. The following databases in Russian and foreign languages were searched using the keywords and advanced search builders: E-Library, PubMed, Springer, Clinicalkeys, Google Scholar. In this paper, we introduce a novel compilation of the known gene polymorphisms that may be used for determination of the genetic risks in cosmetological patients.

Synthesis of biocompatible calcium-phosphate compositions in ultrasound field

Introduction reflects the great interest of practical restorative medicine in artificial structures that mimic the structure and properties of natural bone tissue that are made from biocompatible composite materials suitable for restoring the integrity of bone elements of the musculoskeletal system. The Introduction also contains the physicochemical foundations and approaches to a new ultrasonic technologies providing accelerated production of a biocompatible composite material, precisely hydroxyapatite particles in a collagen matrix. Experimental part contains a description of methods and equipmets for accelerated production of a hydroxyapatite suspension in the field of a hydroacoustic emitter, which ensures that the cavitation threshold at room temperature is exceeded, at which intense acoustic vortex microflows provide a decrease in diffusion restrictions, accelerating the interaction between reacting components. The reaction is carried out with the simultaneous supply of an aqueous solution of calcium monophosphate hydrate and a suspension of calcium hydroxide. The resulting finished product is separated using an ultrasonic self-cleaning filter, where the same, by nature, microflows allow the implementation of a continuous accelerated separation of synthesized particles in an ultrasonic self-cleaning filter of the installation, where, after separation, the precipitate is also subjected to cleaning. The resulting particles of hydroxyapatite mixed with the solution collagen and homogenized in an ultrasonic field at frequency of 22 kHz and an energy density in the reaction volume from 1 to 10 W / cm3. Obtained homogenate can be easily used to create various implant designs with predetermined sizes and shapes and after freezedrying was transformed in biocompatible composite with a porous structure. To control biocompatibility, samples of this composite in form of thin plate was sewed under the skin into the scruff of white lab rats. A suspension of hydroxyapatite mechanically combined with the collagen during 30 s homogenization by ultrasound at frequency of 22 kHz and at energy density of 3 W / cm3, form a complex that is freeze-dried, after which it can be used to form the biocomposite body with porous structure and with given dimensions and shapes. Subcutaneous implantation of plates of a calcium-phosphate biocomposite with a biodegradable polymer collagen, into the scruff of a laboratory white mouse showed its good biocompatibility with tissues of a living organism, without causing either immediate or delayed adverse events in them.

Aragonite-Polylysine: Neuro-Regenerative Scaffolds with Diverse Effects on Astrogliosis.

Biomaterials, especially when coated with adhesive polymers, are a key tool for restorative medicine, being biocompatible and supportive for cell adherence, growth, and function. Aragonite skeletons of corals are biomaterials that support survival and growth of a range of cell types, including neurons and glia. However, it is not known if this scaffold affects neural cell migration or elongation of neuronal and astrocytic processes, prerequisites for initiating repair of damage in the nervous system. To address this, hippocampal cells were aggregated into neurospheres and cultivated on aragonite skeleton of the coral Trachyphyllia geoffroyi (Coral Skeleton (CS)), on naturally occurring aragonite (Geological Aragonite (GA)), and on glass, all pre-coated with the oligomer poly-D-lysine (PDL). The two aragonite matrices promoted equally strong cell migration (4.8 and 4.3-fold above glass-PDL, respectively) and axonal sprouting (1.96 and 1.95-fold above glass-PDL, respectively). However, CS-PDL had a stronger effect than GA-PDL on the promotion of astrocytic processes elongation (1.7 vs. 1.2-fold above glass-PDL, respectively) and expression of the glial fibrillary acidic protein (3.8 vs. and 1.8-fold above glass-PDL, respectively). These differences are likely to emerge from a reaction of astrocytes to the degree of roughness of the surface of the scaffold, which is higher on CS than on GA. Hence, CS-PDL and GA-PDL are scaffolds of strong capacity to derive neural cell movements and growth required for regeneration, while controlling the extent of astrocytic involvement. As such, implants of PDL-aragonites have significant potential as tools for damage repair and the reduction of scar formation in the brain following trauma or disease.

Application of Targeting-Optimized Chronos for Stimulation of the Auditory Pathway.

In the last 15years, optogenetics has revolutionized the life sciences and enabled studies of complex biological systems such as the brain. Applying optogenetics also has great potential for restorative medicine, such as hearing restoration, by stimulating genetically modified spiral ganglion neurons of the cochlea with light. To this end, opsins with short closing kinetics are required, given the high firing rates and utmost temporal precision of spiking in these neurons. Chronos is the fastest native blue channelrhodopsin (ChR) reported so far with a closing kinetics bellow 1ms at body temperature and an interesting candidate for the development of the future optogenetic cochlear implants. This book chapter explains in more details the development and application of Chronos with optimized membrane targeting for temporally precise optical stimulation of spiral ganglion neurons. In addition, the generation of adeno-associated virus (AAV) and AAV delivery to the cochlea of postnatal mice and the procedure to record optically evoked auditory brainstem responses are described.

Preliminary Quality Control of Magnetic Materials for applications in Restorative Medicine - Quantitative Analysis of Structural Homogeneity of RE-M-B /Polymer Composites

The properties of bonded magnetic materials (RE-M-B /polymer magnetic composites) depend not only on the magnetic properties of powder, but also on the parameters of the consolidation process and the type of binder. Increasing the binder content in RE-M-B /polymer composites could be very beneficial from the cor-rosion resistance point of view, which, unfortunately, is not conducive to the magnetic properties improve-ment. Therefore, a compromise between both trends is necessary to obtain a material with adequate corro-sion resistance with an acceptable decrease in magnetic properties. In the paper the results of research un-der Nd12Fe77Co5B / biotolerant-polymer composites with different binder content have been presented. The research has been carried out on Nd12Fe77Co5B / biotolerant-polymer composites with 20 and 10 wt. % of binder. Due to the possibility of using the magnetic material in restorative medicine, as a binder the bio-tolerable polymeric material has been used (acrylate). All results has been compared to previously deter-mined measurements for composite with a binder content about 3 % wt.. It has been found that the content of 10 % wt. bio-tolerable polymeric material in the magnetic composite is the most favorable (optimal) - the binder material is evenly distributed throughout the composite volume.

Genetically Modified Mesenchymal Stem Cells: The Next Generation of Stem Cell-Based Therapy for TBI.

Mesenchymal stem cells (MSCs) are emerging as an attractive approach for restorative medicine in central nervous system (CNS) diseases and injuries, such as traumatic brain injury (TBI), due to their relatively easy derivation and therapeutic effect following transplantation. However, the long-term survival of the grafted cells and therapeutic efficacy need improvement. Here, we review the recent application of MSCs in TBI treatment in preclinical models. We discuss the genetic modification approaches designed to enhance the therapeutic potency of MSCs for TBI treatment by improving their survival after transplantation, enhancing their homing abilities and overexpressing neuroprotective and neuroregenerative factors. We highlight the latest preclinical studies that have used genetically modified MSCs for TBI treatment. The recent developments in MSCs’ biology and potential TBI therapeutic targets may sufficiently improve the genetic modification strategies for MSCs, potentially bringing effective MSC-based therapies for TBI treatment in humans.

Robotization in healthcare: legal perspective

Introduction. The development and application of medical robotics, medical robotic devices, automated technical systems in the field of health care are already quite successful and have great potential. Such large-scale technological changes inevitably actualize the social roles of law, that should properly settle, protect and guide the development of nascent social relations, which until recently occurred everywhere in a kind of regulatory vacuum. Material and methods. The methodological basis of the study included general scientific methods (dialectical, logical, systemic, historical, sociological, statistical) and private scientific methods of legal science (formal-legal, historical-legal and comparative-legal). The empirical basis of the study was Russian and foreign regulatory legal acts and law enforcement practice, as well as legal doctrine. Results. Based on the comparative legal study a legal definition of the medical robots and various options for their classification, among them a special one, including surgical robots, robots used in restorative medicine, rehabilitation of immobilized patients, nursing and care robots, have been developed. Cyborgs are biological organisms containing mechanical or electronic components are allocated to a special group. Legal mechanisms for ensuring security and cybersecurity in this area are highlighted. The necessity of more flexible legal regulation of personal data concerning the health of citizens and medical confidentiality under new technological conditions is justified. Discussion. Legal regulation of the medical robots should be of a staged nature. General norms of sectoral significance can be formulated at later stages. At the moment, it is more rational to direct efforts to determine the legal regime of certain types of created artificial intelligence systems in the healthcare sector. Conclusion. The legal concept of robotics in healthcare should take a significant place in a wide range of scientific studies of the development of new technologies for the benefit, not to the detriment, of a person.

The role of generalized muscule hyperfacilitation in pathogenesis and clinical picture of myofascial pain syndrome. Possible option of its correction

Introduction. Psychoemotional stress contributes to the increase of the muscle tone and the development of general muscle hyperfacilitation. This in turn makes the diagnostics by manual muscle testing impossible and complicates the course of myofascial pain syndrome, which explains the interest of practitioners in methods of its correction. However, possible methods of correction described in literature do not always lead to the desired result, which is the cause of the further search for solutions to this problem. The goal of research — was to determine the clinical effi cacy of Bach remedies selected with the help of vegetative resonance testing and manual muscle testing in treatment of patients with myofascial pain syndrome against the background of generalized hyperfacilitation.Materials and methods. A prospective, controlled, randomized trial was conducted in the period from January to December 2018 at the Department of Restorative Medicine, Rehabilitation and Balneology at the Sechenov First Moscow State Medical University. The work is based on the results of observation and treatment of 60 patients aged 21 to 65 years. Before and after the treatment practitioners performed osteopathic diagnostics, manual muscle testing according to the methodology, used in applied kinesiology. Assessment of psychological status was carried out using the Spielberger–Khanin test and Well-being-activity-mood questionnaire (WAM questionnaire). The level of pain manifestation was assessed with the use of the visual analogue scale (VAS). All patients were divided into two statistically comparable groups of 30 people using the method of simple randomization. Patients of both groups underwent osteopathic correction of dysfunctions with a frequency of one time per week, only 3–5 sessions. Patients of the 1st group, in addition to osteopathic treatment, underwent therapy with individually selected Bach remedies.Results. In all patients of the 1st group, generalized muscle hyperfacilitation regressed already by the 2nd–3rd procedure, while in the 2nd group it was eliminated only by the 4th procedure in 12 (40%) patients, and in the remaining patients it stopped only by the end of the course. The study of the regression of myofascial pain syndrome showed a difference in the rate of occurrence of the analgesic effect in the groups. So, patients of the 1st group experienced a persistent antinociceptive effect after the 2nd procedure, and in the 2nd group a similar effect was noted only by the 4th–5th session. In patients of the 1st group, the severity of pain after treatment averaged 10,4±4,5 points according to VAS, in patients of the 2nd group it averaged 20,3±4,3 points (p<0,01). The results of psychological testing according to the Spielberger–Khanin questionnaire also revealed a positive dynamics in the psychoemotional state of patients of both groups. After treatment, in 27 (90 %) patients of the 1st group, the results of the test showed the norm (<30 points), while in the 2nd group the test showed the norm only in 19 (63,3 %) patients. A comparative analysis of the results of psychological testing by the WAM method, performed at the end of the treatment, showed a positive dynamics in the psychoemotional state (categories of well-being, activity, mood) in patients of both groups, but in the 1st group the changes were more pronounced (p=0,05). It should be noted that only in patients of the 1st group this indicator was in the range of 5–5,5 points after the treatment, which corresponds to the norm criteria for this questionnaire.Conclusion. The use of Bach remedies individually selected with the help of manual muscle testing and the vegetative resonance testing helps to increase the effectiveness of the treatment of myofascial pain syndrome in patients with generalized muscle hyperfacilitation formed against the background of the chronic stress.

Pathophysiological mechanisms caused by adverse influence of climatic and geographical factors of the Arctic on human health and technologies of rehabilitation medicine

Adverse conditions in the Arctic North provoke the development of various diseases, primarily cardiovascular and respiratory systems, metabolism. The main etiological factors are hypoxia, low temperatures, geomagnetic storms, desynchronosis, stress, impaired microcirculation, pathogenetic changes in hormonal regulation of metabolic reactions. To develop effective methods of treating diseases provoked by adverse environmental conditions and activities in the Arctic North, as well as their prevention, it is necessary to develop a new strategy for medical support of this problem. As an alternative, it is proposed to use methods of restorative medicine, based on the use of non-drug factors (natural origin and physiotherapy), which have a systemic effect on various functional systems of the body. In this regard, of particular interest are mineral waters used internally, in the form of baths and inhalations, controlled hypoxia, physical activity, reflexology.

YOGA as a Potential Mind-Body Medicine for Circadian Rhythm Restoration for Cancer Patients

YOGA as a Potential Mind-Body Medicine for Circadian Rhythm Restoration for Cancer Patients

Quantum Functional Energy Medicine: The Next Frontier of Restorative Medicine

Living systems may be thought of as complex, nonlinear, dynamic, self-organizing energetic and field phenomena with negative entropy. At the highest level of organization, each life form may possess an innate biologic field, or biofield. This energy field maintains the integrity of the whole organism; regulates its physiologic and biochemical responses; and is integral to development, healing, and regeneration. Energy medicine refers to several systems that work with energy fields of the body to help restore health. Many energy-related therapies challenge the current biomedical paradigm because they cannot be explained by conventional biochemical or physiological mechanisms. Quantum physics is a better paradigm with which to understand these therapies.

Analysis of regeneration mechanisms in auto ransplantation

Search for effective and available methods of stimulation of regenerative processes is a priority task of restorative medicine. Of high interest is a kind of biostimulation that induces activation of metabolic and reparative processes in the whole organism.
 Aim. Generalization of the relevant literature data concerning possible mechanisms of biostimulation in transplantation of self tissues of an organism. The results of literature survey showed that there still remain many debatable questions concerning cellular and molecular mechanisms that underlie intermolecular interactions in the stage of regeneration. Stimulating effects of an autotransplant both in the zone of the transplant or in an organism in whole may be caused by mediators and signal molecules released in destruction of the autotransplant tissues and of its perifocal region, and also by bioactive substances produced by immune-competent and stem cells.
 Conclusion. Tissue transplants may be used as inductors of production of biologically active substances and activators of immune and/or stromal cells. The latter, in turn, are producers of a number of chemical mediators required for large-scale regeneration. Therefore, a promising method of stimulation of regenerative processes is transplantation of self tissue. This method is characterized by simplicity, effectiveness and availability which evokes special interest and requires further study.

Small Intestinal Bacterial Overgrowth (SIBO): An Interview with Preet Khangura, ND

Liz Sutherland, ND, Editor-in-Chief of the Journalof Restorative Medicine, recently spoke with PreetKhangura, ND, who practices in Victoria, BC,Canada. Dr. Khangura is an expert in the diagnosisand treatment of small intestinal bacterial overgrowth(SIBO). He has developed treatment and preventionprotocols for this condition, and offers consultationsand educational seminars on the topic to healthcareproviders.

USE OF PLATELETS RICH PLASMA AS A FACTOR OF THE REDUCTION OF THE RISK OF EARLY POSTOPERATIVE COMPLICATIONS IN PATIENTS WITH POSTOPERATIVE VENTRAL HERNIAS

Non-tensioned allohernioplasty with a polypropylene mesh implant has several disadvantages associated with the local occurrence of non-specific long-lasting inflammatory reactions in response to a foreign body. Excessive exudation in the implantation zone leads to the formation of seromas, requiring puncture aspiration, which significantly increases the treatment time. In the long-term, chronic prolonged inflammatory process leads to the formation of coarse connective tissue, which explains the development of biomechanical complications. Growth factors, introduced by platelet rich plasma (PRP), stimulate the release of regenerative cytokines, reduce local inflammatory manifestations in the integration of homoplastic grafts and reduce the incidence of postoperative complications. Aim: through the use of plasma enriched with platelets reduce the severity of early postoperative complications in patients with postoperative ventral hernias. Materials and methods. A clinical study was performed in the surgical department of the center for reconstructive and restorative medicine (university clinic) of the Odessa National Medical University (ONMedU) in the period from 2013 to 2019: 84 patients were operated because of postoperative ventral hernia. The average age of patients was 60.1±7.6 years. The size of hernial defects was on average 8.2 cm. The average BMI was 31.8 kg/m2. According to indications, patients underwent a standard surgical extent of intervention: hernia repair, allohernioplasty of the anterior abdominal wall with a lightweight (80 g/m2) polypropylene implant. After the plastics of the main group, a prosthesis implantation zone was infiltrated with activated autologous PRP, which was prepared by double centrifugation, in a volume of 14–38 ml. There was a control group in which PRP infiltration was not performed. The cavity above the mesh implant was actively drained by Redon for 2–4 days. An ultrasound examination was performed and, if necessary, fine needle aspiration of serous fluid over the mesh was done. Results. The evaluation of the postoperative period (up to 28 days) in patients of both groups. In none of the cases were manifestations of allergic, pyrogenic, local inflammatory or infectious complications. According to the quantitative assessment of early postoperative complications as well as the assessment of the degree of pain syndrome subjectively, according to VAS, the postoperative period in the main and control study groups was almost identical. The need for puncture aspirations and the total volume of discharge was significantly less in the main study group. The dependence of the severity of the effect of the proposed technology on such factors as the size of the hernial defect, the nature of plastics, and body mass index was noted. The greatest efficacy was demonstrated in the group of patients undergoing plastic surgery with the placement of a mesh implant in direct contact with subcutaneous fatty tissue for large-sized hernias (W2+) in the presence of concomitant obesity. Conclusions: the risk of development and the severity of fluid accumulations in the area of allohernioplasty can be predicted taking into account such risk factors as the size of the hernial defect, the nature of plastics, the presence of concomitant pathology, overweight. The technique of soft tissue infiltration in contact with a polypropylene prosthesis is safe, without significantly increasing the risk of local or systemic complications. The proposed method significantly reduces the risk of development and the severity of fluid accumulations in the area of implantation of the prosthesis. The effectiveness of technology is significantly higher compared to groups of patients with a high risk of seromas formation.

Glycosaminoglycan functionalization of electrospun scaffolds enhances Schwann cell activity

Nerve fibers of the peripheral nervous system (PNS) have a remarkable ability to regenerate up to an almost complete recovery of normal function following a crush or a Sunderland Type II injury. This process is governed by glial cells, known as Schwann cells, through their unique capacity to dedifferentiate into cells that drive the healing process. Despite that many progresses have occurred in restorative medicine and microsurgery, the regenerative process after a severe lesion of a major nerve trunk (e.g., Sunderland Types III-V) is often incomplete and functional recovery is unsatisfactory. In this aspect, it is known that glycosaminoglycans (GAGs) of the extracellular matrix are involved in proliferation, synaptogenesis, neural plasticity, and regeneration of the PNS. Here, we developed poly(caprolactone) (PCL) fibrous scaffolds functionalized with GAGs, which allowed us to assess their influence on the adhesion, proliferation, and differentiation of Schwann cells. We found that both aligned and random fiber scaffolds functionalized with GAGs resulted in increased cell proliferation on day 1. In addition, aligned functionalized scaffolds also resulted in increased GAG presence on day 1, probably because of cell extracellular matrix (ECM) formation and an increased syndecan-4 expression on day 7. A different modification and activation of Schwann cells in the presence of GAG versus no-GAG scaffolds was underlined by proteomic comparative analysis, where a general downregulation of the expression of intracellular/structural and synthetic proteins was shown on day 7 for GAG-functionalized scaffolds with regard to the nonfunctionalized ones. In conclusion, we have shown that GAG-functionalized scaffolds are effective in modulating Schwann cell behavior in terms of adhesion, proliferation, and differentiation and should be considered in strategies to improve PNS repair. Statement of SignificanceNerve fibers functional recovery following a severe trauma of the Peripheral Nervous System (PNS) still represents a huge challenge for neurosurgery nowadays. In this respect, tissue engineering is committed to develop new constructs able to guide Schwann cells by mimicking the natural extracellular matrix environment. To this purpose, we successfully fabricated polycaprolactone (PCL) scaffolds with two well-defined fiber deposition patterns, functionalized with glycosaminoglycans (GAGs) and assessed for their potential as support for Schwann cells adhesion, growth and differentiation, by both classical biochemistry and LC-MS-based proteomic profiling. By this way, we showed that PCL–GAGs scaffolds could represent a promising artificial substrate that closely mimics the recently established pattern of Schwann cells migration into the regenerating nerve and, therefore, it should be considered in strategies to improve PNS repair.

Automated chemiluminescent analysis of the antioxidant and prooxidant activity of natural and synthetic substrates having perspective for bioengineering

Automated CL-control has a lot of advantages, such as rapidity, information value, objectivity, reproducibility, low-price. As a rule, the method is used for detecting antioxidant capacity of natural substrates. The results described in the paper show that this method has wide opportunities for deciding actual tasks in nutritional industry, preventive and restorative medicine, bioengineering in future. First, the results demonstrated that the method allows to determine optimal extraction conditions to obtain phytopreparates which include nonstability antioxidant and (or) prooxidant compounds. This is shown using phytopreparates (leuzea, rhodiola, rheum, plantago) obtained using local plant materials. Second, results are obtained to determine the presence of real, non-virtual antioxidant or prooxidant properties of commercial micronutrients complexes. In addition, the method allows to provide an individual selection of nutrients in accordance with the characteristics of the ROS balance of the internal environment of the consumer’s body. This way allows to get the reproducible results within a relevant experimental model in short time, which is very important looking for dynamic development of the functional nutrients market. Finally, using this method one get more effective and economic navigation of chemical synthesis. As a result, the efficiency of the subsequent functionalization of synthetic compounds is increased.

Complex spa treatment of patients after removal of the gallbladder (medical technology)*

Medical technology consists in the complex application of natural (drinking mineral water and mineral baths) and preformed (magnetotherapy to the liver and right hypochondrium) physical factors in the rehabilitation treatment of patients in the early stages after removal of the gallbladder. The technology improves the efficiency of treatment by correcting impaired digestion and energy metabolism in patients with a removed gallbladder in the new anatomical and physiological conditions that have developed after the operation. The technology is intended for physicians of restorative medicine, gastroenterologists, balneologists and physiotherapists of health resorts and other medical institutions.

HEMATOPOIETIC STEM CELL GENE THERAPY FOR INHERITED MONOGENIC DISEASES AND ITS IMPLICATIONS FOR FUTURE GENE THERAPY TRIALS IN TURKEY

Stem cell therapy offers a great advantage for the development of new treatments in the field of regenerative and restorative medicine. However, the use of stem cell therapies and their clinical indications can even be further improved using genetic modification of the cells. Due to the high level of consanguineous marriages in Turkey, the country suffers from an increased frequency of inborn genetically inherited diseases. Treatment of these diseases is difficult, since 1) diagnosis is often delayed in rural areas, 2) distance to specialized centers may be considerable, 3) treatment may require frequent hospital visits and 4) treatment procedures are often both invasive and expensive. Here, we discuss the current status of gene therapy of hematopoietic stem cells (HSCs) for rare, inherited monogenic diseases and the advantages to use these cells as an alternative treatment option for patients in Turkey. We discuss results of clinical trials using retroviral and lentiviral gene therapy for the treatment of immune deficiencies, hemoglobinopathies and several enzyme deficiencies, new developments in the field of the HSC gene therapy to improve safety and efficacy and recommendations for the future.

Poster Abstracts from the 16th Annual International Restorative Medicine Conference

Poster Abstracts from the 16th Annual International Restorative Medicine Conference

Projects of distant rehabilitation in neurology. The website of in-home rehabilitation in the territory of Krasnoyarsk Region

At the present time, distant rehabilitation is a relevant direction in restorative medicine. The article considers existing projects in remote rehabilitation, including a self-rehabilitation method developed by academician K.V. Lyadov, the Guided Self-Rehabilitation Contracts system (GSC) etc. The authors present an original project of a remote rehabilitation website 'NeuroHouse' designed for the restoration of balance and gait functions, wrist fine motor skills and speech, spasticity management in patients with neurological diseases. The project combines proprietary rehabilitation methods and classical exercise therapy. This website will make it possible to implement the third ambulatory stage of medical rehabilitation at home.