Potential targets and applications of nanodrug targeting myeloid cells in osteosarcoma for the enhancement of immunotherapy.

Targeted immunotherapies have emerged as a transformative approach in cancer treatment, offering enhanced specificity to tumor cells, and minimizing damage to healthy tissues. The targeted treatment of the tumor immune system has become clinically applicable, demonstrating significant anti-tumor activity in both early and late-stage malignancies, subsequently enhancing long-term survival rates. The most frequent and significant targeted therapies for the tumor immune system are executed through the utilization of checkpoint inhibitor antibodies and chimeric antigen receptor T cell treatment. However, when using immunotherapeutic drugs or combined treatments for solid tumors like osteosarcoma, challenges arise due to limited efficacy or the induction of severe cytotoxicity. Utilizing nanoparticle drug delivery systems to target tumor-associated macrophages and bone marrow-derived suppressor cells is a promising and attractive immunotherapeutic approach. This is because these bone marrow cells often exert immunosuppressive effects in the tumor microenvironment, promoting tumor progression, metastasis, and the development of drug resistance. Moreover, given the propensity of myeloid cells to engulf nanoparticles and microparticles, they are logical therapeutic targets. Therefore, we have discussed the mechanisms of nanomedicine-based enhancement of immune therapy through targeting myeloid cells in osteosarcoma, and how the related therapeutic strategies well adapt to immunotherapy from perspectives such as promoting immunogenic cell death with nanoparticles, regulating the proportion of various cellular subgroups in tumor-associated macrophages, interaction with myeloid cell receptor ligands, activating immunostimulatory signaling pathways, altering myeloid cell epigenetics, and modulating the intensity of immunostimulation. We also explored the clinical implementations of immunotherapy grounded on nanomedicine.

RCS reduction of composite transparent flexible coding metasurface combined phase cancellation and absorption.

A wideband low-scattering metasurface with optical transparency and flexibility is proposed by using the combination of phase cancellation and absorption mechanisms. Electromagnetic (EM) diffusion is achieved through the random phase distribution design of the two coding elements. The enhanced energy absorption can be obtained in a wide spectrum by using indium tin oxide (ITO) with suitable sheet resistance in the supercells. The experimental results show that the radar cross section (RCS) reductions of less than -10 dB under the planar and conformal cases are in 6.65-19.40 GHz and 6.11-17.37 GHz, corresponding relative bandwidth are 97.89% and 95.91%, respectively. Both theoretical analysis and simulated results are good accordance with the experiment. Furthermore, the analyses of the surface current, EM field distribution and power loss density are given to explain the hybrid RCS reduction mechanism. The proposed composite transparent flexible coding metasurface (CTFCM) maintains good angular stability within 0°-60° oblique incidence and has polarization insensitivity. The CTFCM has excellent flexibility and high optical transparency, which provides a way to reduce RCS in a wider band and has important application potential for stealth aircraft cockpit and transparent radome.

Potential therapeutic targets of macrophages in inhibiting immune damage and fibrotic processes in musculoskeletal diseases.

Macrophages are a heterogeneous cell type with high plasticity, exhibiting unique activation characteristics that modulate the progression and resolution of diseases, serving as a key mediator in maintaining tissue homeostasis. Macrophages display a variety of activation states in response to stimuli in the local environment, with their subpopulations and biological functions being dependent on the local microenvironment. Resident tissue macrophages exhibit distinct transcriptional profiles and functions, all of which are essential for maintaining internal homeostasis. Dysfunctional macrophage subpopulations, or an imbalance in the M1/M2 subpopulation ratio, contribute to the pathogenesis of diseases. In skeletal muscle disorders, immune and inflammatory damage, as well as fibrosis induced by macrophages, are prominent pathological features. Therefore, targeting macrophages is of great significance for maintaining tissue homeostasis and treating skeletal muscle disorders. In this review, we discuss the receptor-ligand interactions regulating macrophages and identify potential targets for inhibiting collateral damage and fibrosis in skeletal muscle disorders. Furthermore, we explore strategies for modulating macrophages to maintain tissue homeostasis.

Application of platelet-rich plasma in spinal surgery.

With the aging of the population and changes in lifestyle, the incidence of spine-related diseases is increasing, which has become a major global public health problem; this results in a huge economic burden on the family and society. Spinal diseases and complications can lead to loss of motor, sensory, and autonomic functions. Therefore, it is necessary to identify effective treatment strategies. Currently, the treatment of spine-related diseases includes conservative, surgical, and minimally invasive interventional therapies. However, these treatment methods have several drawbacks such as drug tolerance and dependence, adjacent spondylosis, secondary surgery, infection, nerve injury, dural rupture, nonunion, and pseudoarthrosis. Further, it is more challenging to promote the regeneration of the interstitial disc and restore its biomechanical properties. Therefore, clinicians urgently need to identify methods that can limit disease progression or cure diseases at the etiological level. Platelet-rich plasma (PRP), a platelet-rich form of plasma extracted from venous blood, is a blood-derived product. Alpha granules contain a large number of cytokines, such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), epidermal growth factor, platelet factor 4 (PF-4), insulin-like growth factor-1 (IGF-1), and transforming growth factor-ß (TGF-ß). These growth factors allow stem cell proliferation and angiogenesis, promote bone regeneration, improve the local microenvironment, and enhance tissue regeneration capacity and functional recovery. This review describes the application of PRP in the treatment of spine-related diseases and discusses the clinical application of PRP in spinal surgery.

Natural products can modulate inflammation in intervertebral disc degeneration.

Intervertebral discs (IVDs) play a crucial role in maintaining normal vertebral anatomy as well as mobile function. Intervertebral disc degeneration (IDD) is a common clinical symptom and is an important cause of low back pain (LBP). IDD is initially considered to be associated with aging and abnormal mechanical loads. However, over recent years, researchers have discovered that IDD is caused by a variety of mechanisms, including persistent inflammation, functional cell loss, accelerated extracellular matrix decomposition, the imbalance of functional components, and genetic metabolic disorders. Of these, inflammation is thought to interact with other mechanisms and is closely associated with the production of pain. Considering the key role of inflammation in IDD, the modulation of inflammation provides us with new options for mitigating the progression of degeneration and may even cause reversal. Many natural substances possess anti-inflammatory functions. Due to the wide availability of such substances, it is important that we screen and identify natural agents that are capable of regulating IVD inflammation. In fact, many studies have demonstrated the potential clinical application of natural substances for the regulation of inflammation in IDD; some of these have been proven to have excellent biosafety. In this review, we summarize the mechanisms and interactions that are responsible for inflammation in IDD and review the application of natural products for the modulation of degenerative disc inflammation.

Mesenchymal stem cells in the treatment of spinal cord injury: Mechanisms, current advances and future challenges.

Spinal cord injury (SCI) has considerable impact on patient physical, mental, and financial health. Secondary SCI is associated with inflammation, vascular destruction, and subsequent permanent damage to the nervous system. Mesenchymal stem cells (MSCs) have anti-inflammatory properties, promoting vascular regeneration and the release neuro-nutrients, and are a promising strategy for the treatment of SCI. Preclinical studies have shown that MSCs promote sensory and motor function recovery in rats. In clinical trials, MSCs have been reported to improve the American Spinal Injury Association (ASIA) sensory and motor scores. However, the effectiveness of MSCs in treating patients with SCI remains controversial. MSCs promote tumorigenesis and ensuring the survival of MSCs in the hostile environment of SCI is challenging. In this article we examine the evidence on the pathophysiological changes occurring after SCI. We then review the underlying mechanisms of MSCs in the treatment of SCI and summarize the potential application of MSCs in clinical practice. Finally, we highlight the challenges surrounding the use of MSCs in the treatment of SCI and discuss future applications.

Biomaterial scaffolds regulate macrophage activity to accelerate bone regeneration.

Bones are important for maintaining motor function and providing support for internal organs. Bone diseases can impose a heavy burden on individuals and society. Although bone has a certain ability to repair itself, it is often difficult to repair itself alone when faced with critical-sized defects, such as severe trauma, surgery, or tumors. There is still a heavy reliance on metal implants and autologous or allogeneic bone grafts for bone defects that are difficult to self-heal. However, these grafts still have problems that are difficult to circumvent, such as metal implants that may require secondary surgical removal, lack of bone graft donors, and immune rejection. The rapid advance in tissue engineering and a better comprehension of the physiological mechanisms of bone regeneration have led to a new focus on promoting endogenous bone self-regeneration through the use of biomaterials as the medium. Although bone regeneration involves a variety of cells and signaling factors, and these complex signaling pathways and mechanisms of interaction have not been fully understood, macrophages undoubtedly play an essential role in bone regeneration. This review summarizes the design strategies that need to be considered for biomaterials to regulate macrophage function in bone regeneration. Subsequently, this review provides an overview of therapeutic strategies for biomaterials to intervene in all stages of bone regeneration by regulating macrophages.

Biomaterials delivery strategies to repair degenerated intervertebral discs by regulating the inflammatory microenvironment.

Intervertebral disc degeneration (IVDD) is one of the leading causes of lower back pain. Although IVDD cannot directly cause death, it can cause pain, psychological burdens, and economic burdens to patients. Current conservative treatments for IVDD can relieve pain but cannot reverse the disease. Patients who cannot tolerate pain usually resort to a strategy of surgical resection of the degenerated disc. However, the surgical removal of IVDD can affect the stability of adjacent discs. Furthermore, the probability of the reherniation of the intervertebral disc (IVD) after surgery is as high as 21.2%. Strategies based on tissue engineering to deliver stem cells for the regeneration of nucleus purposes (NP) and annulus fibrosus (AF) have been extensively studied. The developed biomaterials not only locally withstand the pressure of the IVD but also lay the foundation for the survival of stem cells. However, the structure of IVDs does not provide sufficient nutrients for delivered stem cells. The role of immune mechanisms in IVDD has recently become clear. In IVDD, the IVD that was originally in immune privilege prevents the attack of immune cells (mainly effector T cells and macrophages) and aggravates the disease. Immune regulatory and inflammatory factors released by effector T cells, macrophages, and the IVD further aggravate IVDD. Reversing IVDD by regulating the inflammatory microenvironment is a potential approach for the treatment of the disease. However, the biological factors modulating the inflammatory microenvironment easily degrade in vivo. It makes it possible for different biomaterials to modulate the inflammatory microenvironment to repair IVDD. In this review, we have discussed the structures of IVDs and the immune mechanisms underlying IVDD. We have described the immune mechanisms elicited by different biological factors, including tumor necrosis factors, interleukins, transforming growth factors, hypoxia-inducible factors, and reactive oxygen species in IVDs. Finally, we have discussed the biomaterials used to modulate the inflammatory microenvironment to repair IVDD and their development.

Osteoimmunity-regulating biomaterials promote bone regeneration.

Image, graphical abstract.

Application of stem cells combined with biomaterial in the treatment of intervertebral disc degeneration.

As the world population is aging, intervertebral disc degeneration (IDD) is becoming a global health issue of increasing concern. A variety of disc degeneration diseases (DDDs) have been proven to be associated with IDD, and these illnesses have significant adverse effects on both individuals and society. The application of stem cells in regenerative medicine, such as blood and circulation, has been demonstrated by numerous studies. Similarly, stem cells have made exciting progress in the treatment of IDD. However, due to complex anatomical structures and functional requirements, traditional stem cell injection makes it difficult to meet people's expectations. With the continuous development of tissue engineering and biomaterials, stem cell combined with biomaterials has far more prospects than before. This review aims to objectively and comprehensively summarize the development of stem cells combined with contemporary biomaterials and the difficulties that need to be overcome.

Application of single and cooperative different delivery systems for the treatment of intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration (IDD) is the most universal pathogenesis of low back pain (LBP), a prevalent and costly medical problem across the world. Persistent low back pain can seriously affect a patient's quality of life and even lead to disability. Furthermore, the corresponding medical expenses create a serious economic burden to both individuals and society. Intervertebral disc degeneration is commonly thought to be related to age, injury, obesity, genetic susceptibility, and other risk factors. Nonetheless, its specific pathological process has not been completely elucidated; the current mainstream view considers that this condition arises from the interaction of multiple mechanisms. With the development of medical concepts and technology, clinicians and scientists tend to intervene in the early or middle stages of intervertebral disc degeneration to avoid further aggravation. However, with the aid of modern delivery systems, it is now possible to intervene in the process of intervertebral disc at the cellular and molecular levels. This review aims to provide an overview of the main mechanisms associated with intervertebral disc degeneration and the delivery systems that can help us to improve the efficacy of intervertebral disc degeneration treatment.

Engineered nanomaterials trigger abscopal effect in immunotherapy of metastatic cancers.

Despite advances in cancer treatment, metastatic cancer is still the main cause of death in cancer patients. At present, the treatment of metastatic cancer is limited to palliative care. The abscopal effect is a rare phenomenon in which shrinkage of metastatic tumors occurs simultaneously with the shrinkage of a tumor receiving localized treatment, such as local radiotherapy or immunotherapy. Immunotherapy shows promise for cancer treatment, but it also leads to consequences such as low responsiveness and immune-related adverse events. As a promising target-based approach, intravenous or intratumoral injection of nanomaterials provides new opportunities for improving cancer immunotherapy. Chemically modified nanomaterials may be able to trigger the abscopal effect by regulating immune cells. This review discusses the use of nanomaterials in killing metastatic tumor cells through the regulation of immune cells and the prospects of such nanomaterials for clinical use.

Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is a main cause of lower back pain, leading to psychological and economic burdens to patients. Physical therapy only delays pain in patients but cannot eliminate the cause of IVDD. Surgery is required when the patient cannot tolerate pain or has severe neurological symptoms. Although surgical resection of IVD or decompression of the laminae eliminates the diseased segment, it damages adjacent normal IVD. There is also a risk of re-protrusion after IVD removal. Cell therapy has played a crucial role in the development of regenerative medicine. Cell transplantation promotes regeneration of degenerative tissue. However, owing to the lack of vascular structure in IVD, sufficient nutrients cannot be provided for transplanted mesenchymal stem cells (MSCs). In addition, dead cells release harmful substances that aggravate IVDD. Extracellular vesicles (EVs) have been extensively studied as an emerging therapeutic approach. EVs generated by paracrine MSCs retain the potential of MSCs and serve as carriers to deliver their contents to target cells to regulate target cell activity. Owing to their double-layered membrane structure, EVs have a low immunogenicity and no immune rejection. Therefore, EVs are considered an emerging therapeutic modality in IVDD. However, they are limited by mass production and low loading rates. In this review, the structure of IVD and advantages of EVs are introduced, and the application of MSC-EVs in IVDD is discussed. The current limitations of EVs and future applications are described.

Quantifying the effects of submerged aquatic vegetation on internal loading in lake: A modeling study of the largest shallow lake in North China.

Shallow lakes are greatly influenced by submerged aquatic vegetation (SAV), which affects hydraulic and water quality during their entire life cycle. An integrated model was developed based on the Environmental Fluid Dynamics Code (EFDC), which considers the dynamic bottom roughness and sediment release flux related to SAV growth and decomposition. Model results of hydrodynamics, water quality, and sediment-P release in Baiyangdian Lake (BL) were analyzed with and without the SAV module. The results showed that SAV played a critical and alterable role in regulating the internal loading in lakes. During the period of exponential growth, SAV reduced the velocity and sediment-P release in Zaozhadian by 20 % and 12 %, respectively. During the period of senescence, SAV reduced the velocity by 19 % and increased sediment-P release by 49 %, which was mainly attributed to dissolved oxygen (DO) consumption during residue decomposition. To mitigate the adverse effects of SAV on internal loading, measures should be taken to control the growth of SAV and ensure timely salvage before decomposition.

Reverse Adverse Immune Microenvironments by Biomaterials Enhance the Repair of Spinal Cord Injury.

Spinal cord injury (SCI) is a severe and traumatic disorder that ultimately results in the loss of motor, sensory, and autonomic nervous function. After SCI, local immune inflammatory response persists and does not weaken or disappear. The interference of local adverse immune factors after SCI brings great challenges to the repair of SCI. Among them, microglia, macrophages, neutrophils, lymphocytes, astrocytes, and the release of various cytokines, as well as the destruction of the extracellular matrix are mainly involved in the imbalance of the immune microenvironment. Studies have shown that immune remodeling after SCI significantly affects the survival and differentiation of stem cells after transplantation and the prognosis of SCI. Recently, immunological reconstruction strategies based on biomaterials have been widely explored and achieved good results. In this review, we discuss the important factors leading to immune dysfunction after SCI, such as immune cells, cytokines, and the destruction of the extracellular matrix. Additionally, the immunomodulatory strategies based on biomaterials are summarized, and the clinical application prospects of these immune reconstructs are evaluated.

Biomaterials delivery strategies to repair spinal cord injury by modulating macrophage phenotypes.

Spinal cord injury (SCI) causes tremendous harm to a patient's physical, mental, and financial health. Moreover, recovery of SCI is affected by many factors, inflammation is one of the most important as it engulfs necrotic tissue and cells during the early stages of injury. However, excessive inflammation is not conducive to damage repair. Macrophages are classified into either blood-derived macrophages or resident microglia based on their origin, their effects on SCI being two-sided. Microglia first activate and recruit blood-derived macrophages at the site of injury-blood-borne macrophages being divided into pro-inflammatory M1 phenotypes and anti-inflammatory M2 phenotypes. Among them, M1 macrophages secrete inflammatory factors such as interleukin-ß (IL-ß), tumor necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ) at the injury site, which aggravates SCIs. M2 macrophages secrete IL-4, IL-10, IL-13, and neurotrophic factors to inhibit the inflammatory response and inhibit neuronal apoptosis. Consequently, modulating phenotypic differentiation of macrophages appears to be a meaningful therapeutic target for the treatment of SCI. Biomaterials are widely used in regenerative medicine and tissue engineering due to their targeting and bio-histocompatibility. In this review, we describe the effects of biomaterials applied to modulate macrophage phenotypes on SCI recovery and provide an outlook.

Physical Cues of Matrices Reeducate Nerve Cells.

The behavior of nerve cells plays a crucial role in nerve regeneration. The mechanical, topographical, and electrical microenvironment surrounding nerve cells can activate cellular signaling pathways of mechanical transduction to affect the behavior of nerve cells. Recently, biological scaffolds with various physical properties have been developed as extracellular matrix to regulate the behavior conversion of nerve cell, such as neuronal neurite growth and directional differentiation of neural stem cells, providing a robust driving force for nerve regeneration. This review mainly focused on the biological basis of nerve cells in mechanical transduction. In addition, we also highlighted the effect of the physical cues, including stiffness, mechanical tension, two-dimensional terrain, and electrical conductivity, on neurite outgrowth and differentiation of neural stem cells and predicted their potential application in clinical nerve tissue engineering.

Thermo-sensitive electroactive hydrogel combined with electrical stimulation for repair of spinal cord injury.

The strategy of using a combination of scaffold-based physical and biochemical cues to repair spinal cord injury (SCI) has shown promising results. However, integrating conductivity and neurotrophins into a scaffold that recreates the electrophysiologic and nutritional microenvironment of the spinal cord (SC) remains challenging. In this study we investigated the therapeutic potential of a soft thermo-sensitive polymer electroactive hydrogel (TPEH) loaded with nerve growth factor (NGF) combined with functional electrical stimulation (ES) for the treatment of SCI. The developed hydrogel exhibits outstanding electrical conductance upon ES, with continuous release of NGF for at least 24 days. In cultured nerve cells, TPEH loaded with NGF promoted the neuronal differentiation of neural stem cells and axonal growth, an effect that was potentiated by ES. In a rat model of SCI, TPEH combined with NGF and ES stimulated endogenous neurogenesis and improved motor function. These results indicate that the TPEH scaffold that combines ES and biochemical cues can effectively promote SC tissue repair.

Clinical Therapy of Metastatic Spinal Tumors.

Metastatic spinal tumors (MST) have high rates of morbidity and mortality. MST can destroy the vertebral body or compress the nerve roots, resulting in an increased risk of pathological fractures and intractable pain. Here, we elaborately reviewed the currently available therapeutic options for MST according to the following four aspects: surgical management, minimally invasive therapy (MIT), radiation therapy, and systemic therapy. In particular, these aspects were classified and introduced to show their developmental process, clinical effects, advantages, and current limitations. Furthermore, with the improvement of treatment concepts and techniques, we discovered the prevalent trend toward the use of radiation therapy and MIT in clinic therapies. Finally, the future directions of these treatment options were discussed. We hoped that along with future advances and study will lead to the improvement of living standard and present status of treatment in patients with MST.

Postoperative discal pseudocyst and its similarities to discal cyst: A case report.

BACKGROUND: Postoperative discal pseudocyst (PDP) is a rare condition that presents after surgery for lumbar disc herniation. Due to the lack of information, the diagnosis and treatment of PDP remain controversial. Herein, we report a PDP case that occurred following percutaneous endoscopic lumbar discectomy and received conservative treatment. Additionally, we review all the published literature regarding PDP and propose our hypothesis regarding PDP pathology. CASE SUMMARY: A 23-year-old man presented with a relapse of low back pain and numbness in his left lower extremity after undergoing percutaneous endoscopic lumbar discectomy for lumbar disc herniation. Repeat magnetic resonance imaging demonstrated a cystic lesion at the surgical site with communication with the inner disc. The patient was diagnosed as having PDP. The patient received conservative treatment, which resulted in rapid improvement and spontaneous regression of the lesion, and had a favorable outcome in follow-up. CONCLUSION: PDP and discal cyst (DC) exhibit similarities in both histological and epidemiological characteristics, which indicates the same pathological origin of PDP and DC. The iatrogenic annular injury during discectomy might accelerate the pathological progression of DC. For patients with mild to moderate symptoms, conservative treatment can lead to great improvement, even inducing spontaneous regression. However, surgical cystectomy is necessary in patients with neurological deficits and where conservative treatment is ineffective.