[Application of exoskeleton with functional electrostimulation for rebalancing of patients in acute and early recovery periods of ischemic stroke]. / Primenenie ekzoskeleta s funktsional'noi elektrostimulyatsiei v vosstanovlenii ravnovesiya u patsientov v ostrom i rannem vosstanovitel'nom periodakh ishemicheskogo insul'ta.

Static motor disorders are the main cause of falls and decrease of daily activity in patients after previous ischemic stroke. OBJECTIVE: To study impact of robotic mechanotherapy with functional electrostimulation (FES) on rebalancing in patients in acute and early recovery periods of ischemic stroke. MATERIAL AND METHODS: The number of patients equal 60, divided into 2 groups, were examined. Study group included 30 patients, who were treated in an exoskeleton with FES; control group consisted of 30 patients, whose walking and balance recovering was carried out with exercise therapy. RESULTS: The study group showed a more pronounced improvement of balance indicators by Tinetti scale compared to the control group (11 [8; 13] against 8 [6; 12]; p=0.0281) at the end of treatment. Patients of study group demonstrated significantly better results both by Tinetti scale and stabilometrical parameters in acute period of stroke compared to the control group. CONCLUSION: Application of exoskeleton with FES in patients in acute and early periods of ischemic stroke contributes (to a better balance recovery), which may be achieved by long-lasting verticalization and large repetition of the correct walking pattern during rehabilitative trainings.

[Robotic mechanotherapy in a complex of procedures for the functional state recovery of the neuromuscular system and peripheral hemodynamics in track-and-field athletes]. / Robotizirovannaya mekhanoterapiya v komplekse protsedur dlya vosstanovleniya funktsional'nogo sostoyaniya nervno-myshechnogo apparata i perifericheskoi gemodinamiki legkoatletov.

The background of the study is caused by the need to develop methods of drug-free neuromuscular system and peripheral hemodynamics recovery of athletes to optimize their functioning after intense physical activity in current conditions of high sporting competition. OBJECTIVE: To develop a program of comprehensive recovery of neuromuscular apparatus and hemodynamics of the lower limbs of track-and-field athletes during intense physical activity, including mechanotherapy on the robotic biomechanical complex with biological feedback and to evaluate its efficacy, comparing with a standard recovery program. MATERIAL AND METHODS: The study involved 23 track-and-field athletes (the mean age 24.6±3.8 years) with qualification «master of sports¼ and «master of sports of international class¼. The athletes were randomly divided into two groups (study and control). In the study group athletes received hydro-, presso- and magnetotherapy procedures, as well as mechanotherapy procedures on a robotic biomechanical complex with biological feedback. The athletes from control group received only traditional rehabilitation with hydro-, press- and magnetotherapy. The examination of the functional state of the neuromuscular apparatus and peripheral hemodynamics was performed with the use of stimulation electroneuromyography, robotic dynamometry and rheovasography. RESULTS: When registering a motor response from a foot extensor digitorum brevis, innervated by the deep fibular nerve, after conduction of procedures set, a decrease in the residual latency parameters of study group's athletes was found. The dynamometric investigation showed a decrease in the fatigue coefficient of knee joint's flexors and extensors, as well as an increase in the strength of knee joint's extensors in the athletes from the study group. During the rheovasography the decrease of the rheographic index in the «foot¼ and «lower leg¼ segments in the study group was revealed. The decrease of the geographic index in the «lower leg¼ segment and normalization of the rheographic waves distribution time in the «foot¼ segment in control group were identified. CONCLUSION: The study results showed the efficacy of both the standard recovery program for athletes and the program, supplemented by mechanotherapy. It has been found that the use of hydro-, presso- and magnetotherapy is more conductive to the normalization of the blood flow, while the inclusion of mechanotherapy, in addition to the action on peripheral hemodynamics, improves the neuromuscular transmission, reduces fatigue of muscular system and increases its strength indicators.

[Modern view on upper limb physical rehabilitation after stroke. Literature review]. / Sovremennyi podkhod k fizicheskoi reabilitatsii funktsii verkhnei konechnosti posle insul'ta. Obzor literatury.

Stroke is the world's second leading cause of death and the first cause of disability among all diseases. The most common complication of a stroke is a violation of the motor function of the limbs, which significantly worsens the quality of life and the level of self-care and independence of patients. Restoring the function of the upper limb is one of the priority tasks of rehabilitation after a stroke. A large number of factors, such as the location and size of the primary brain lesion, the presence of complications in the form of spasticity, impaired skin and proprioceptive sensitivity, and comorbidities, determine the patient's rehabilitation potential and the prognosis of ongoing rehabilitation measures. Of particular note are the timing of the start of rehabilitation measures, the duration and regularity of the treatment methods. A number of authors propose scales for assessing the rehabilitation prognosis, as well as algorithms for compiling rehabilitation programs for restoring the function of the upper limb. A fairly large number of rehabilitation methods and their combinations have been proposed, including special methods of kinesitherapy, robotic mechanotherapy with biofeedback, the use of physiotherapeutic factors, manual and reflex effects, as well as ready-made programs that include sequential and combined use of various methods. Dozens of studies have been devoted to comparative analysis and evaluation of the effectiveness of these methods. The purpose of this work is to review current research on a given topic and draw up our own conclusion on the appropriateness of using and combining these methods at various stages of rehabilitation in stroke patients.

Mechanobiology-based physical therapy and rehabilitation after orthobiologic interventions: a narrative review.

PURPOSE: This review aims to summarize the evidence for the role of mechanotherapies and rehabilitation in supporting the synergy between regeneration and repair after an orthobiologic intervention. METHODS: A selective literature search was performed using Web of Science, OVID, and PubMed to review research articles that discuss the effects of combining mechanotherapy with various forms of regenerative medicine. RESULTS: Various mechanotherapies can encourage the healing process for patients at different stages. Taping, bracing, cold water immersion, and extracorporeal shockwave therapy can be used throughout the duration of acute inflammatory response. The regulation of angiogenesis can be sustained with blood flow restriction and resistance training, whereas heat therapy and tissue loading during exercise are recommended in the remodeling phase. CONCLUSION: Combining mechanotherapy with various forms of regenerative medicine has shown promise for improving treatment outcomes. However, further studies that reveal a greater volume of evidence are needed to support clinical decisions.

[The use of underwater horizontal traction and mechanotherapy in the complex treatment of degenerative spondylolisthesis of the lumbosacral spine: a pilot clinical study]. / Primenenie podvodnogo gorizontal'nogo vytyazheniya i mekhanoterapii v kompleksnom lechenii degenerativnogo spondilolisteza poyasnichno-kresttsovogo otdela pozvonochnika: pilotnoe klinicheskoe issledovanie.

Underwater traction of the spine is a physiotherapeutic method that combines the effects of mechanical traction and fresh water of indifferent temperature and seems promising for the treatment of pain in the lower back, which is due to the physiological basis of the mechanism of action on the spinal motion segment by eliminating muscle spasm and restoring the biomechanics of the spine. OBJECTIVE: To study the effectiveness of underwater horizontal traction in combination with mechanotherapy in patients with non-stenosing unstable degenerative spondylolisthesis of the lumbosacral spine of the 1st degree, accompanied by pain. MATERIAL AND METHODS: The clinical study included 14 patients (mean age 50.21 years). Patients underwent underwater horizontal traction of the spine according to the modified Pushkareva-Vozdvizhenskaya method in a variable mode, the procedures were performed every other day, for a course of 6 procedures. After completion of the traction procedure, patients were recommended to put on a fixing lumbosacral corset, in which they rested for 30 minutes in the supine position. At the end of the rest period, the patients performed training of the back muscles with biofeedback on the mechanotherapeutic complex of simulators for 30 minutes daily, except for weekends, for a course of 10 procedures. RESULTS: All patients completed the course of treatment, during the procedures no side effects or deterioration were noted. During the treatment, motor and daily activity significantly improved according to the Oswestry scale (p=0.002), the severity of the pain syndrome and its effect on the patient's activity decreased, according to the Roland-Morris questionnaire (p=0.003). According to an objective assessment of the muscle strength of the lumbosacral spine at the initial level, no deviations from the normative parameters were revealed, however, during the treatment, a significant increase in strength was noted in all muscle groups. CONCLUSION: Underwater horizontal traction of the spine in variable mode according to Pushkareva-Vozdvizhenskaya is an effective and safe method of conservative treatment of unstable non-stenosing degenerative spondylolisthesis of the 1st degree, accompanied by back pain, which helps to reduce the intensity of the pain syndrome and improve the daily motor and social activity of patients. The traction method should be supplemented with therapeutic exercises using mechanotherapeutic simulators to achieve a clinical result.

[The rehabilitation, health path, mechanotherapy in recuperation of functional reserves of organism].

The article presents historical essays concerning each method of rehabilitation, period of its revision depending on time and pathological etiology of each disease, application of rehabilitation (health path, mechanotherapy), different modes of choosing each method of rehabilitation. The term "rehabilitation" became widespread after adoption of the Federal Law No. 181 of November 24, 1995 "On social protection of disabled people in the Russian Federation". This is the set of measures targeted to recuperation of functional reserves of organism, improving quality of life, maintaining working capacity of patient, one's integration into society, reducing incapacitating states impact to support people with impaired functions to adapt to new conditions of life in society. The rehabilitation and habilitation are processes targeting to ensure that the disabled could be able to achieve and maintain optimal levels of physical, sensory, intellectual, psychological and/or social functioning. The rehabilitation covers wide range of activities, including rehabilitative medical care, physiotherapy, psychotherapy, logopedics and ergotherapy and supportive services too. The disabled are to have access to both general medical services and appropriate rehabilitation services.

[The application of the David back concept mechanotherapy in patients survived after myocardium infarction].

The medical rehabilitation in all areas of medicine is developing actively and rapidly. In cardiology, medical rehabilitation contributes to prevention of recurrent myocardial infarction and other complications in patients with myocardial infarction. The study evaluated impact of anaerobic exercise and strength rehabilitation program on hemodynamics in patients with myocardial infarction using the David back concept mechanotherapy method.

[Methods to restore fine motor skills in stroke patients]. / Metody vosstanovleniya tonkoi motoriki u patsientov, perenesshikh insul't.

The review article considers the problem of nonmedical post-stroke rehabilitation, in particular the restoration of fine motor skills in patients in the early period of the disease. A review and analysis of various randomized controlled trials concerning the use of various rehabilitation methods both in monotherapy and in their combined application is carried out, and modern technical devices, with the use of computer technology and biofeedback, are reviewed. Proceeding from the presented literature data and their analysis, there are certain grounds for introducing modern apparatus complexes and robotized devices for fine motor skills restoration in post-stroke patients, especially in the early period, into the multimodal rehabilitation system. However, further research in this direction is needed to achieve a sustained positive result.

[Implementation of robotic mechanotherapy for movement recovery in patients after stroke]. / Primenenie robotizirovannoi mekhanoterapii dlya vosstanovleniya dvizheniya u patsientov posle insul'ta.

Lower extremity dysfunction after a stroke can vary from mild to extremely severe and significantly reduce the functional independence of patients. The restoration of walking is one of the key components of rehabilitation, it requires a balanced approach and the participation of a multidisciplinary team. In the last decade, new rehabilitation methods have appeared that meet high safety standards and have a minimum set of contraindications. One of the promising methods is robotic mechanotherapy. The article presents an overview of modern technologies of robotic mechanotherapy, its types and recommendations for use in medical rehabilitation.

[Topical issues of rehabilitation of patients with osteoporotic vertebral fractures]. / Aktual'nye voprosy reabilitatsii patsientov s perelomami pozvonkov na fone osteoporoza.

The literature review analyzed 20 Russian and 69 foreign publications on the rehabilitation of elderly patients with osteoporotic vertebral fractures. The article deals in detail with the prevalence, medical and social significance of pathological osteoporotic fractures, including vertebral deformities. The data confirming the importance of osteoporosis for physical and rehabilitation medicine specialists are presented. Changes in the quality of life, functional and gate disorders associated with osteoporotic vertebral fractures are described. Based on the available literature data, the principles of rehabilitation of patients with osteoporotic vertebral compression fractures are formulated, including the effectiveness of various methods of physical therapy, mechanotherapy and apparatus physiotherapy. From the standpoint of evidence-based medicine, the role of orthotics in the complex rehabilitation of such patients is described. Based on the analysis of literature data, it was concluded that the problem of osteoporosis is relevant for physicians working in the field of rehabilitation medicine; osteoporotic vertebral fractures are characterized by a high prevalence over the age of 50 years and are associated with a decrease in the quality of life, motor and functional limitations, and an increased risk of death, and well-planned medical rehabilitation programs including physical exercises, physiotherapy and orthotics can significantly improve patient functionality.

[Effectiveness of medical rehabilitation of elderly patients who have suffered a myocardial infarction.]

At all stages of recovery after myocardial infarction (MI), the expansion of physical activity of elderly patients is one of the most important components. Of course, certain restrictions can reduce the load on the myocardium, reduce its oxygen needs and create conditions for early healing. Subsequently, depending on the dynamics and indicators of the cardiovascular system, the elderly patient is transferred from one stage of activity to another, the level of blood pressure, the number of heartbeats, the presence of arrhythmia, electrocardiogram data, EchoCG data, as well as individual load tolerance are evaluated. To date, there is a huge selection of optimal options for selecting methods of medical rehabilitation for elderly patients who have suffered a MI, and one of them is mechanotherapy. The mechanical therapy program of the David Back Concept complex - strength training is a set of simulators for working on the back muscles. The medical and diagnostic complex is designed for the diagnosis, treatment and prevention of pathologies of the musculoskeletal system, as well as for the rehabilitation of patients after surgical interventions and spinal injuries. Medical rehabilitation of elderly patients with coronary heart disease and after a MI through mechanotherapy, the program of the David Back Concept complex, provides for the restoration of their physical and social status to an optimally achievable level, determined by the capabilities of adaptive mechanisms.

Biologic-free mechanically induced muscle regeneration.

Severe skeletal muscle injuries are common and can lead to extensive fibrosis, scarring, and loss of function. Clinically, no therapeutic intervention exists that allows for a full functional restoration. As a result, both drug and cellular therapies are being widely investigated for treatment of muscle injury. Because muscle is known to respond to mechanical loading, we investigated instead whether a material system capable of massage-like compressions could promote regeneration. Magnetic actuation of biphasic ferrogel scaffolds implanted at the site of muscle injury resulted in uniform cyclic compressions that led to reduced fibrous capsule formation around the implant, as well as reduced fibrosis and inflammation in the injured muscle. In contrast, no significant effect of ferrogel actuation on muscle vascularization or perfusion was found. Strikingly, ferrogel-driven mechanical compressions led to enhanced muscle regeneration and a ∼threefold increase in maximum contractile force of the treated muscle at 2 wk compared with no-treatment controls. Although this study focuses on the repair of severely injured skeletal muscle, magnetically stimulated bioagent-free ferrogels may find broad utility in the field of regenerative medicine.

[Steel or titanium for osteosynthesis : A mechanobiological perspective]. / Stahl oder Titan bei der Osteosynthese : Eine mechanobiologische Perspektive.

BACKGROUND: An implant used for stabilizing a fracture creates a mechanical construct, which directly determines the biology of bone healing. The stabilization of fractures places high mechanical demands on implants and therefore steel and titanium are currently almost exclusively used as the materials of choice. OBJECTIVES: The possible range of attainable mechanobiological stimulation for mechanotherapy as a function of plate stiffness depending on the selection of the plate material and the physical and mechanical properties of the material options are discussed. MATERIAL AND METHODS: An overview of the material properties of steel and titanium is given. For dynamically fixed long bone fractures as examples, various finite element models of plate osteosynthesis (steel/titanium) are created and the plate working length (PWL, screw configuration close to fracture) is varied. The interfragmentary movement (IFM) as a measure of mechanobiological stimulation is evaluated. RESULTS: Stimulation in the form of IFM varies across the fracture and also as a function of the osteosynthesis material and the configuration. The influence of the material appears to be notably smaller than the influence of PWL but both lose their influence largely over a bridged fracture situation (contact). With a flexible titanium plate and large PSS, a greater mechanobiological stimulation is produced. CONCLUSION: An essential prerequisite for the secondary fracture healing is an appropriate mechanobiological environment, which can be controlled by the osteosynthesis material and the configuration and is also affected by the type of fracture and load.

Emerging Strategies for Immunotherapy of Solid Tumors Using Lipid-Based Nanoparticles.

The application of lipid-based nanoparticles for COVID-19 vaccines and transthyretin-mediated amyloidosis treatment have highlighted their potential for translation to cancer therapy. However, their use in delivering drugs to solid tumors is limited by ineffective targeting, heterogeneous organ distribution, systemic inflammatory responses, and insufficient drug accumulation at the tumor. Instead, the use of lipid-based nanoparticles to remotely activate immune system responses is an emerging effective strategy. Despite this approach showing potential for treating hematological cancers, its application to treat solid tumors is hampered by the selection of eligible targets, tumor heterogeneity, and ineffective penetration of activated T cells within the tumor. Notwithstanding, the use of lipid-based nanoparticles for immunotherapy is projected to revolutionize cancer therapy, with the ultimate goal of rendering cancer a chronic disease. However, the translational success is likely to depend on the use of predictive tumor models in preclinical studies, simulating the complexity of the tumor microenvironment (e.g., the fibrotic extracellular matrix that impairs therapeutic outcomes) and stimulating tumor progression. This review compiles recent advances in the field of antitumor lipid-based nanoparticles and highlights emerging therapeutic approaches (e.g., mechanotherapy) to modulate tumor stiffness and improve T cell infiltration, and the use of organoids to better guide therapeutic outcomes.

Personalized Vascularized Models of Breast Cancer Desmoplasia Reveal Biomechanical Determinants of Drug Delivery to the Tumor.

Desmoplasia in breast cancer leads to heterogeneity in physical properties of the tissue, resulting in disparities in drug delivery and treatment efficacy among patients, thus contributing to high disease mortality. Personalized in vitro breast cancer models hold great promise for high-throughput testing of therapeutic strategies to normalize the aberrant microenvironment in a patient-specific manner. Here, tumoroids assembled from breast cancer cell lines (MCF7, SKBR3, and MDA-MB-468) and patient-derived breast tumor cells (TCs) cultured in microphysiological systems including perfusable microvasculature reproduce key aspects of stromal and vascular dysfunction causing impaired drug delivery. Models containing SKBR3 and MDA-MB-468 tumoroids show higher stromal hyaluronic acid (HA) deposition, vascular permeability, interstitial fluid pressure (IFP), and degradation of vascular HA relative to models containing MCF7 tumoroids or models without tumoroids. Interleukin 8 (IL8) secretion is found responsible for vascular dysfunction and loss of vascular HA. Interventions targeting IL8 or stromal HA normalize vascular permeability, perfusion, and IFP, and ultimately enhance drug delivery and TC death in response to perfusion with trastuzumab and cetuximab. Similar responses are observed in patient-derived models. These microphysiological systems can thus be personalized by using patient-derived cells and can be applied to discover new molecular therapies for the normalization of the tumor microenvironment.

A Hierarchical Mechanotransduction System: From Macro to Micro.

Mechanotransduction is a strictly regulated process whereby mechanical stimuli, including mechanical forces and properties, are sensed and translated into biochemical signals. Increasing data demonstrate that mechanotransduction is crucial for regulating macroscopic and microscopic dynamics and functionalities. However, the actions and mechanisms of mechanotransduction across multiple hierarchies, from molecules, subcellular structures, cells, tissues/organs, to the whole-body level, have not been yet comprehensively documented. Herein, the biological roles and operational mechanisms of mechanotransduction from macro to micro are revisited, with a focus on the orchestrations across diverse hierarchies. The implications, applications, and challenges of mechanotransduction in human diseases are also summarized and discussed. Together, this knowledge from a hierarchical perspective has the potential to refresh insights into mechanotransduction regulation and disease pathogenesis and therapy, and ultimately revolutionize the prevention, diagnosis, and treatment of human diseases.

Emerging role of extracellular vesicles and exogenous stimuli in molecular mechanisms of peripheral nerve regeneration.

Peripheral nerve injuries lead to significant morbidity and adversely affect quality of life. The peripheral nervous system harbors the unique trait of autonomous regeneration; however, achieving successful regeneration remains uncertain. Research continues to augment and expedite successful peripheral nerve recovery, offering promising strategies for promoting peripheral nerve regeneration (PNR). These include leveraging extracellular vesicle (EV) communication and harnessing cellular activation through electrical and mechanical stimulation. Small extracellular vesicles (sEVs), 30-150 nm in diameter, play a pivotal role in regulating intercellular communication within the regenerative cascade, specifically among nerve cells, Schwann cells, macrophages, and fibroblasts. Furthermore, the utilization of exogenous stimuli, including electrical stimulation (ES), ultrasound stimulation (US), and extracorporeal shock wave therapy (ESWT), offers remarkable advantages in accelerating and augmenting PNR. Moreover, the application of mechanical and electrical stimuli can potentially affect the biogenesis and secretion of sEVs, consequently leading to potential improvements in PNR. In this review article, we comprehensively delve into the intricacies of cell-to-cell communication facilitated by sEVs and the key regulatory signaling pathways governing PNR. Additionally, we investigated the broad-ranging impacts of ES, US, and ESWT on PNR.

Macrophage Mechano-Responsiveness Within Three-Dimensional Tissue Matrix upon Mechanotherapy-Associated Strains.

Mechano-rehabilitation, also known as mechanotherapy, represents the forefront of noninvasive treatment for musculoskeletal (MSK) tissue disorders, encompassing conditions affecting tendons, cartilage, ligaments, and muscles. Recent emphasis has underscored the significance of macrophage presence in the healing of MSK tissues. However, a considerable gap still exists in comprehending how mechanical strains associated with mechanotherapy impact both the naïve and pro-inflammatory macrophage phenotypes within the three-dimensional (3D) tissue matrix, as well as whether the shift in macrophage phenotype is contingent on the mechanical strains inherent to mechanotherapy. In this study, we delineated alterations in mechano-adaptation and polarization of both naive and M1 macrophages within 3D matrices, elucidating their response to varying degrees of mechanical strain exposure (3%, 6%, and 12%). To evaluate macrophage mechano-adaptation and mechano-sensitivity within 3D collagen matrices under mechanical loading, we employed structural techniques (scanning electron microscopy, histology), quantitative morphological measures for phenotypic assessment, and genotypic methods such as quantitative real-time polymerase chain reaction. Our data reveal that the response of macrophages to mechanical loading is not only contingent on their specific sub-phenotype but also varies with the amplitude of mechanical strain. Notably, although supra-mechanical loading (12% strain) was requisite to induce a phenotypic shift in naive (M0) macrophages, as little as 3% mechanical strain proved sufficient to prompt phenotypic alterations in pro-inflammatory (M1) macrophages. These findings pave the way for leveraging the macrophage mechanome in customized and targeted applications of mechanical strain within the mechano-therapeutic framework. Considering the prevalence of MSK tissue injuries and their profound societal and economic implications, the development of well-informed and effective clinical mechanotherapy modalities for MSK tissue healing becomes an imperative endeavor. Impact statement Mechanotherapy is a primary noninvasive treatment for musculoskeletal (MSK) tissue injuries, but the effect of mechanical strain on macrophage phenotypes is not fully understood. A recent study found that macrophage response to mechanical loading is both sub-phenotype specific and amplitude-dependent, with even small strains enough to induce phenotypic changes in pro-inflammatory macrophages. These findings could pave the way for using macrophage mechanome in targeted mechanotherapy applications for better MSK tissue healing.

Contactless mechanical stimulation of the skin using shear waves.

The skin, the outermost organ of the human body, is vital for sensing and responding to stimuli through mechanotransduction. It is constantly exposed to mechanical stress. Consequently, various mechanical therapies, including compression, massage, and microneedling, have become routine practices for skin healing and regeneration. However, these traditional methods require direct skin contact, restricting their applicability. To address this constraint, we developed shear wave stimulation (SWS), a contactless mechanical stimulation technique. The effectiveness of SWS was compared with that of a commercial compression bioreactor used on reconstructed skin at various stages of maturity. Despite the distinct stimulus conditions applied by the two methods, SWS yielded remarkable outcomes, similar to the effects of the compression bioreactor. It significantly increased the shear modulus of tissue-engineered skin, heightened the density of collagen and elastin fibers, and resulted in an augmentation of fibroblasts in terms of their number and length. Notably, SWS exhibited diverse effects in the low- and high-frequency modes, highlighting the importance of fine-tuning the stimulus intensity. These results unequivocally demonstrated the capability of SWS to enhance the mechanical functions of the skin in vitro, making it a promising option for addressing wound healing and stretch mark recovery.

Wireless Magnetic Robot for Precise Hierarchical Control of Tissue Deformation.

Mechanotherapy has emerged as a promising treatment for tissue injury. However, existing robots for mechanotherapy are often designed on intuition, lack remote and wireless control, and have limited motion modes. Herein, through topology optimization and hybrid fabrication, wireless magneto-active soft robots are created that can achieve various modes of programmatic deformations under remote magnetic actuation and apply mechanical forces to tissues in a precise and predictable manner. These soft robots can quickly and wirelessly deform under magnetic actuation and are able to deliver compressing, stretching, shearing, and multimodal forces to the surrounding tissues. The design framework considers the hierarchical tissue-robot interaction and, therefore, can design customized soft robots for different types of tissues with varied mechanical properties. It is shown that these customized robots with different programmable motions can induce precise deformations of porcine muscle, liver, and heart tissues with excellent durability. The soft robots, the underlying design principles, and the fabrication approach provide a new avenue for developing next-generation mechanotherapy.