Animal healer for refractory diseases: Myth or reality?

A vast amount of knowledge has been acquired through human activities such as farming, hunting, and fishing. Throughout history, humans have utilized living creatures for disease treatment, relying on the natural world's healing powers. The special "healers" may be able to treat patients via the power of nature. However, there was no systematic introduction or summary of these treatments. Therefore, we conducted a literature review based on PubMed, Google Scholar, Web of Science, Scopus, CNKI and WanFang DATA. Here, we defined this unique method as "animal healer" and six common kinds of animal healers were reviewed. These are fish therapy, pet therapy, worm therapy, leech therapy, maggot therapy, and bee therapy. According to the different characteristics of healers, treatment methods mainly included bite, parasitism, contact and communication. With the advantages of green and effectiveness, animal healers have great therapy potential against a variety of refractory diseases. The main purpose of this review is to draw people's attention to animal healer, promote it to become a possible clinical treatment strategy, and make further exploration in species cultivation, mechanism research, animal welfare, standard setting, safety evaluation and other aspects. In the future, animal healers will play an increasingly important role in medicine and hopefully solve more medical problems and dilemmas.

Architecture of ß-lactoglobulin coating modulates bioinspired alginate dialdehyde-gelatine/polydopamine scaffolds for subchondral bone regeneration.

In this study, we developed polydopamine (PDA)-functionalized alginate dialdehyde-gelatine (ADA-GEL) scaffolds for subchondral bone regeneration. These polymeric scaffolds were then coated with ß-Lactoglobulin (ß-LG) at concentrations of 1 mg/ml and 2 mg/ml. Morphological analysis indicated a homogeneous coating of the ß-LG layer on the surface of network-like scaffolds. The ß-LG-coated scaffolds exhibited improved swelling capacity as a function of the ß-LG concentration. Compared to ADA-GEL/PDA scaffolds, the ß-LG-coated scaffolds demonstrated delayed degradation and enhanced biomineralization. Here, a lower concentration of ß-LG showed long-lasting stability and superior biomimetic hydroxyapatite mineralization. According to the theoretical findings, the single-state, representing the low concentration of ß-LG, exhibited a homogeneous distribution on the surface of the PDA, while the dimer-state (high concentration) displayed a high likelihood of uncontrolled interactions. ß-LG-coated ADA-GEL/PDA scaffolds with a lower concentration of ß-LG provided a biocompatible substrate that supported adhesion, proliferation, and alkaline phosphatase (ALP) secretion of sheep bone marrow mesenchymal stem cells, as well as increased expression of osteopontin (SPP1) and collagen type 1 (COL1A1) in human osteoblasts. These findings indicate the potential of protein-coated scaffolds for subchondral bone tissue regeneration. STATEMENT OF SIGNIFICANCE: This study addresses a crucial aspect of osteochondral defect repair, emphasizing the pivotal role of subchondral bone regeneration. The development of polydopamine-functionalized alginate dialdehyde-gelatine (ADA-GEL) scaffolds, coated with ß-Lactoglobulin (ß-LG), represents a novel approach to potentially enhance subchondral bone repair. ß-LG, a milk protein rich in essential amino acids and bioactive peptides, is investigated for its potential to promote subchondral bone regeneration. This research explores computationally and experimentally the influence of protein concentration on the ordered or irregular deposition, unravelling the interplay between coating structure, scaffold properties, and in-vitro performance. This work contributes to advancing ordered protein coating strategies for subchondral bone regeneration, providing a biocompatible solution with potential implications for supporting subsequent cartilage repair.

Improving platelet function following prophylactic platelet transfusion in patients with hematological malignancies.

INTRODUCTION: Platelet transfusion is a standard treatment to prevent bleeding in patients with hematological malignancies. Although transfusions can improve platelet count, their impact on platelet function remains controversial. METHODS: We conducted flow cytometry to assess platelet function before and after transfusion and performed subgroup analyses to examine differences based on blood type, corrected count increment (CCI), and platelet microparticles. RESULTS: Overall, 50 patients who received prophylactic platelet transfusion were enrolled. CD42b expression increased, whereas CD41 expression decreased after transfusion. Apheresis platelets exhibited the lowest expression of PAC-1 and P-selectin when exposed to agonist stimulations. PAC-1 expression increased under high adenosine diphosphate (ADP) stimulation, while P-selectin expression increased under both high ADP and thrombin receptor-activating peptide stimulation. In the subgroup analysis, patients with a CCI >4500 and those with the same blood types exhibited a more significant increase in PAC-1 and P-selectin expression under agonist stimulation. When comparing apheresis platelets collected on different days, only the percentage of platelet-derived microparticles showed a significant increase. CONCLUSION: Prophylactic transfusion improved platelet function. Platelet function significantly improved in patients with a CCI >4500, those with the same blood types as that of apheresis platelets, or those with platelet-derived microparticle levels <4.7%. No significant improvement in platelet function was noted after the transfusion of different blood types with acceptable compatibility or the transfusion of incompatible blood types. Our results suggest that transfusing platelets with the same blood type remains the optimal choice.

Flexible Multimodal Sensing System Based on a Vertical Stacking Strategy for Efficiently Decoupling Multiple Signals.

Multisensory integration enables the simultaneous perception of multiple environmental stimuli while minimizing size and energy consumption. However, conventional multifunctional integration in flexible electronics typically requires large-scale horizontal sensing arrays (such as flexible printed circuit boards), posing decoupling complexities, tensile strain limitation, and spatial constraints. Herein, a fully flexible multimodal sensing system (FMSS) is developed by coupling biomimetic stretchable conductive films (BSCFs) and strain-insensitive communication interfaces using a vertical stacking integration strategy. The FMSS achieves vertical integration without additional adhesives, and it can incorporate individual sensing layers and stretchable interconnects without any essential constraint on their deformations. Accordingly, the temperature and pressure are precisely decoupled simultaneously, and tensile stress can be accurately discerned in different directions. This vertical stacking integration strategy is expected to offer a new approach to significantly streamline the design and fabrication of multimodal sensing systems and enhance their decoupling capabilities.

Conformationally regulated "nanozyme-like" cerium oxide with multiple free radical scavenging activities for osteoimmunology modulation and vascularized osseointegration.

Given post-operative aseptic loosening in orthopedic disease treatment, osteointegration occurs at the bone-implant interface as a holistic process, including immunoregulation (e.g., macrophage polarization), angiogenesis and osteogenesis in sequence. In order to achieve early rapid and satisfactory osseointegration, different nano-shaped (nanocone, nanopolyhedron and nanoflower abbr. NC, NP & NF) cerium oxide (CeO2-x) coatings, endowed with "nanozyme-like" activities for multiple free radical elimination and osteoimmunology regulation, were hydrothermally synthesized on titanium alloy (TC4). In vitro cell experiments showed that nano-CeO2-x coated TC4 not only induced polarization of RAW264.7 cells toward M2 phenotype, but also promoted angiogenesis and vascularization of endothelial cells along with differentiation and mineralization of osteogenic precursor cells. Improvements in M2-polarized macrophage, angiogenesis, and bone regeneration were further confirmed in a rat femoral condyle model. Among the above three nano-morphologies, NF exhibited the best osseoinetegration. RNA sequencing and mechanism exploration suggested that the inhibition of PI3K-AKT signaling pathway was essential for immunomodulatory capacity of NF. In conclusion, it provided promising insights into the immunomodulatory exploitation of orthopedic implants.

Correction: Shen et al. Platelet Activation and Cytokine Release of Interleukin-8 and Interferon-Gamma-Induced Protein 10 after ChAdOx1 nCoV-19 Coronavirus Vaccine Injection. Vaccines 2023, 11, 456.

The authors wish to make the following corrections to this published paper [...].

Beyond Tissue replacement: The Emerging role of smart implants in healthcare.

Smart implants are increasingly used to treat various diseases, track patient status, and restore tissue and organ function. These devices support internal organs, actively stimulate nerves, and monitor essential functions. With continuous monitoring or stimulation, patient observation quality and subsequent treatment can be improved. Additionally, using biodegradable and entirely excreted implant materials eliminates the need for surgical removal, providing a patient-friendly solution. In this review, we classify smart implants and discuss the latest prototypes, materials, and technologies employed in their creation. Our focus lies in exploring medical devices beyond replacing an organ or tissue and incorporating new functionality through sensors and electronic circuits. We also examine the advantages, opportunities, and challenges of creating implantable devices that preserve all critical functions. By presenting an in-depth overview of the current state-of-the-art smart implants, we shed light on persistent issues and limitations while discussing potential avenues for future advancements in materials used for these devices.

Theoretical modeling approach for adsorption of fibronectin on the nanotopographical implants.

The success of orthopedic implants depends on the sufficient integration between tissue and implant, which is influenced by the cellular responses to their microenvironment. The conformation of adsorbed extracellular matrix is crucial for cellular behavior instruction via manipulating the physiochemical features of materials. To investigate the electrostatic adsorption mechanism of fibronectin on nanotopographies, a theoretical model was established to determine surface charge density and Coulomb's force of nanotopography - fibronectin interactions using a Laplace equation satisfying the boundary conditions. Surface charge density distribution of nanotopographies with multiple random fibronectin was simulated based on random number and Monte Carlo hypothesis. The surface charge density on the nanotopographies was compared to the experimental measurements, to verify the effectiveness of the theoretical model. The model was implemented to calculate the Coulomb force generated by nanotopographies to compare the fibronectin adsorption. This model has revealed the multiple random quantitative fibronectin electrostatic adsorption to the nanotopographies, which is beneficial for orthopedic implant surface design.Significance: The conformation and distribution of adsorbed extracellular matrix on biomedical implants are crucial for directing cellular behaviors. However, the Ti nanotopography-ECM interaction mechanism remains largely unknown. This is mostly because of the interactions that are driven by electrostatic force, and any experimental probe could interfere with the electric field between the charged protein and Ti surface. A theoretical model is hereby proposed to simulate the adsorption between nanotopographies and fibronectin. Random number and Monte Carlo hypothesis were applied for multiple random fibronectin simulation, and the Coulomb's force between nanoconvex and nanoconcave structures was comparatively analyzed.

Research Progress of Superhydrophobic Materials in the Field of Anti-/De-Icing and Their Preparation: A Review.

Accumulated ice has brought much damage to engineering and people's lives. The accumulation of ice can affect the flight safety of aircraft and lead to the failure of cables and power generation blades; it can even cause damage to human life. Traditional anti-icing and de-icing strategies have many disadvantages such as high energy consumption, low efficiency, or pollution of the environment. Therefore, inspired by animal communities, researchers have developed new passive anti-icing materials such as superhydrophobic material. In this paper, the solid surface wetting phenomenon and superhydrophobic anti-icing and de-icing mechanism were introduced. The methods of fabrication of superhydrophobic surfaces were summarized. The research progress of wear-resistant superhydrophobic coatings, self-healing/self-repairing superhydrophobic coatings, photothermal superhydrophobic coatings, and electrothermal superhydrophobic coatings in the field of anti-icing and de-icing was reviewed. The current problems and challenges were analyzed, and the development trend of superhydrophobic materials was also prospected in the field of anti-icing and de-icing. The practicality of current superhydrophobic materials should continue to be explored in depth.

Magnesium-Rich Calcium Phosphate Derived from Tilapia Bone Has Superior Osteogenic Potential.

We extracted magnesium-rich calcium phosphate bioceramics from tilapia bone using a gradient thermal treatment approach and investigated their chemical and physicochemical properties. X-ray diffraction showed that tilapia fish bone-derived hydroxyapatite (FHA) was generated through the first stage of thermal processing at 600-800 °C. Using FHA as a precursor, fish bone biphasic calcium phosphate (FBCP) was produced after the second stage of thermal processing at 900-1200 °C. The beta-tricalcium phosphate content in the FBCP increased with an increasing calcination temperature. The fact that the lattice spacing of the FHA and FBCP was smaller than that of commercial hydroxyapatite (CHA) suggests that Mg-substituted calcium phosphate was produced via the gradient thermal treatment. Both the FHA and FBCP contained considerable quantities of magnesium, with the FHA having a higher concentration. In addition, the FHA and FBCP, particularly the FBCP, degraded faster than the CHA. After one day of degradation, both the FHA and FBCP released Mg2+, with cumulative amounts of 4.38 mg/L and 0.58 mg/L, respectively. Furthermore, the FHA and FBCP demonstrated superior bone-like apatite formation; they are non-toxic and exhibit better osteoconductive activity than the CHA. In light of our findings, bioceramics originating from tilapia bone appear to be promising in biomedical applications such as fabricating tissue engineering scaffolds.

Hydrogels for Oral Tissue Engineering: Challenges and Opportunities.

Oral health is crucial to daily life, yet many people worldwide suffer from oral diseases. With the development of oral tissue engineering, there is a growing demand for dental biomaterials. Addressing oral diseases often requires a two-fold approach: fighting bacterial infections and promoting tissue growth. Hydrogels are promising tissue engineering biomaterials that show great potential for oral tissue regeneration and drug delivery. In this review, we present a classification of hydrogels commonly used in dental research, including natural and synthetic hydrogels. Furthermore, recent applications of these hydrogels in endodontic restorations, periodontal tissues, mandibular and oral soft tissue restorations, and related clinical studies are also discussed, including various antimicrobial and tissue growth promotion strategies used in the dental applications of hydrogels. While hydrogels have been increasingly studied in oral tissue engineering, there are still some challenges that need to be addressed for satisfactory clinical outcomes. This paper summarizes the current issues in the abovementioned application areas and discusses possible future developments.

3D printing method for bone tissue engineering scaffold.

3D printing technology is an emerging technology. It constructs solid bodies by stacking materials layer by layer, and can quickly and accurately prepare bone tissue engineering scaffolds with specific shapes and structures to meet the needs of different patients. The field of life sciences has received a great deal of attention. However, different 3D printing technologies and materials have their advantages and disadvantages, and there are limitations in clinical application. In this paper, the technology, materials and clinical applications of 3D printed bone tissue engineering scaffolds are reviewed, and the future development trends and challenges in this field are prospected.

Advances in Peptide-Based Hydrogel for Tissue Engineering.

The development of peptide-based materials has emerged as one of the most challenging aspects of biomaterials in recent years. It has been widely acknowledged that peptide-based materials can be used in a broad range of biomedical applications, particularly in tissue engineering. Among them, hydrogels have been attracting considerable interest in tissue engineering because they mimic tissue formation conditions by providing a three-dimensional environment and a high water content. It has been found that peptide-based hydrogels have received more attention due to mimicking proteins, particularly extracellular matrix proteins, as well as the wide variety of applications they are capable of serving. It is without a doubt that peptide-based hydrogels have become the leading biomaterials of today owing to their tunable mechanical stability, high water content, and high biocompatibility. Here, we discuss in detail various types of peptide-based materials, emphasizing peptide-based hydrogels, and then we examine in detail how hydrogels are formed, paying particular attention to the peptide structures that are incorporated into the final structure. Following that, we discuss the self-assembly and formation of hydrogels under various conditions, as well as the parameters to be considered as critical factors, which include pH, amino acid composi- tion within the sequence, and cross-linking techniques. Further, recent studies on the development of peptide-based hydrogels and their applications in tissue engineering are reviewed.

Electrosprayed Particles Loaded with Kartogenin as a Potential Osteochondral Repair Implant.

The restoration of cartilage damage is a slow and not always successful process. Kartogenin (KGN) has significant potential in this space-it is able to induce the chondrogenic differentiation of stem cells and protect articular chondrocytes. In this work, a series of poly(lactic-co-glycolic acid) (PLGA)-based particles loaded with KGN were successfully electrosprayed. In this family of materials, PLGA was blended with a hydrophilic polymer (either polyethyleneglycol (PEG) or polyvinylpyrrolidone (PVP)) to control the release rate. Spherical particles with sizes in the range of 2.4-4.1 µm were fabricated. They were found to comprise amorphous solid dispersions, with high entrapment efficiencies of >93%. The various blends of polymers had a range of release profiles. The PLGA-KGN particles displayed the slowest release rate, and blending with PVP or PEG led to faster release profiles, with most systems giving a high burst release in the first 24 h. The range of release profiles observed offers the potential to provide a precisely tailored profile via preparing physical mixtures of the materials. The formulations are highly cytocompatible with primary human osteoblasts.

Identification of copper death-associated molecular clusters and immunological profiles in rheumatoid arthritis.

Objective: An analysis of the relationship between rheumatoid arthritis (RA) and copper death-related genes (CRG) was explored based on the GEO dataset. Methods: Based on the differential gene expression profiles in the GSE93272 dataset, their relationship to CRG and immune signature were analysed. Using 232 RA samples, molecular clusters with CRG were delineated and analysed for expression and immune infiltration. Genes specific to the CRGcluster were identified by the WGCNA algorithm. Four machine learning models were then built and validated after selecting the optimal model to obtain the significant predicted genes, and validated by constructing RA rat models. Results: The location of the 13 CRGs on the chromosome was determined and, except for GCSH. LIPT1, FDX1, DLD, DBT, LIAS and ATP7A were expressed at significantly higher levels in RA samples than in non-RA, and DLST was significantly lower. RA samples were significantly expressed in immune cells such as B cells memory and differentially expressed genes such as LIPT1 were also strongly associated with the presence of immune infiltration. Two copper death-related molecular clusters were identified in RA samples. A higher level of immune infiltration and expression of CRGcluster C2 was found in the RA population. There were 314 crossover genes between the 2 molecular clusters, which were further divided into two molecular clusters. A significant difference in immune infiltration and expression levels was found between the two. Based on the five genes obtained from the RF model (AUC = 0.843), the Nomogram model, calibration curve and DCA also demonstrated their accuracy in predicting RA subtypes. The expression levels of the five genes were significantly higher in RA samples than in non-RA, and the ROC curves demonstrated their better predictive effect. Identification of predictive genes by RA animal model experiments was also confirmed. Conclusion: This study provides some insight into the correlation between rheumatoid arthritis and copper mortality, as well as a predictive model that is expected to support the development of targeted treatment options in the future.

Platelet Activation and Cytokine Release of Interleukin-8 and Interferon-Gamma-Induced Protein 10 after ChAdOx1 nCoV-19 Coronavirus Vaccine Injection.

Coronavirus disease 2019 (COVID-19) vaccines are associated with serious thromboembolic or thrombocytopenic events including vaccine-induced immune thrombocytopenia and thrombosis and immune thrombocytopenia, particularly AZD1222/ChAdOx1. According to the proposed mechanism, COVID-19 vaccines stimulate inflammation and platelet activation. In this study, we analyzed the role of AZD1222/ChAdOx1 vaccines in the activation of platelets and the release of anti-PF4 antibodies and inflammatory cytokines in a cohort of healthy donors without vaccine-induced immune thrombotic thrombocytopenia (VITT). Forty-eight healthy volunteers were enrolled in this study. Blood samples were collected from peripheral blood at three time points: before vaccination and 1 and 7 days after vaccination. Compared with the prevaccination data, a decrease in the leukocyte and platelet counts was observed 1 day after vaccination, which recovered 7 days after injection. The percentage of activated GPIIb/IIIa complex (PAC-1) under high ADP or thrombin receptor-activating peptide stimulation increased 1 day after vaccination. Furthermore, interluekin-8 (IL-8) and interferon-gamma-induced protein 10 (IP-10) increased significantly. Additionally, platelet activation and inflammation, with the release of cytokines, were observed; however, none of the individuals developed VITT. Mild thrombocytopenia with platelet activation and inflammation with an elevation of IL-8 and IP-10 were observed after AZ vaccination.

A novel hybrid design and modelling of a customised graded Ti-6Al-4V porous hip implant to reduce stress-shielding: An experimental and numerical analysis.

Stress shielding secondary to bone resorption is one of the main causes of aseptic loosening, which limits the lifespan of hip prostheses and exacerbates revision surgery rates. In order to minimise post-hip replacement stress variations, this investigation proposes a low-stiffness, porous Ti6Al4V hip prosthesis, developed through selective laser melting (SLM). The stress shielding effect and potential bone resorption properties of the porous hip implant were investigated through both in vitro quasi-physiological experimental assays, together with finite element analysis. A solid hip implant was incorporated in this investigation for contrast, as a control group. The stiffness and fatigue properties of both the solid and the porous hip implants were measured through compression tests. The safety factor of the porous hip stem under both static and dynamic loading patterns was obtained through simulation. The porous hip implant was inserted into Sawbone/PMMA cement and was loaded to 2,300 N (compression). The proposed porous hip implant demonstrated a more natural stress distribution, with reduced stress shielding (by 70%) and loss in bone mass (by 60%), when compared to a fully solid hip implant. Solid and porous hip stems had a stiffness of 2.76 kN/mm and 2.15 kN/mm respectively. Considering all daily activities, the porous hip stem had a factor of safety greater than 2. At the 2,300 N load, maximum von Mises stresses on the hip stem were observed as 112 MPa on the medial neck and 290 MPa on the distal restriction point, whereby such values remained below the endurance limit of 3D printed Ti6Al4V (375 MPa). Overall, through the strut thickness optimisation process for a Ti6Al4V porous hip stem, stress shielding and bone resorption can be reduced, therefore proposing a potential replacement for the generic solid implant.

Advanced Bionic Attachment Equipment Inspired by the Attachment Performance of Aquatic Organisms: A Review.

In nature, aquatic organisms have evolved various attachment systems, and their attachment ability has become a specific and mysterious survival skill for them. Therefore, it is significant to study and use their unique attachment surfaces and outstanding attachment characteristics for reference and develop new attachment equipment with excellent performance. Based on this, in this review, the unique non-smooth surface morphologies of their suction cups are classified and the key roles of these special surface morphologies in the attachment process are introduced in detail. The recent research on the attachment capacity of aquatic suction cups and other related attachment studies are described. Emphatically, the research progress of advanced bionic attachment equipment and technology in recent years, including attachment robots, flexible grasping manipulators, suction cup accessories, micro-suction cup patches, etc., is summarized. Finally, the existing problems and challenges in the field of biomimetic attachment are analyzed, and the focus and direction of biomimetic attachment research in the future are pointed out.

Stress-dependent design and optimization methodology of gradient porous implant and application in femoral stem.

Gradient porous structure made by additive manufacturing (AM) technology is potential to improve the long-term stability of orthopaedic implants through bone ingrowth while maintaining mechanical safety. In this study, a parametrical optimization methodology for the customized gradient porous implants was developed based on a stress-dependent design algorithm. Clinical requirements and manufacturing capabilities of AM were considered in the design procedure. A femoral stem with a minimum bone loss proportion of 2.4% by optimizing the control parameters. This study provided a feasible and flexible design approach for the customized implant with gradient porous structure or material components.

A critical review on polydopamine surface-modified scaffolds in musculoskeletal regeneration.

Increasing concern about age-related diseases, particularly musculoskeletal injuries and orthopedic conditions, highlights the need for strategies such as tissue engineering to address them. Surface modification has been developed to create pro-healing interfaces, personalize scaffolds and provide novel medicines. Polydopamine, a mussel-inspired adhesive polymer with highly reactive functional groups that adhere to nearly all substrates, has gained attention in surface modification strategies for biomaterials. Polydopamine was primarily developed to modify surfaces, but its effectiveness has opened up promising approaches for further applications in bioengineering as carriers and nanoparticles. This review focuses on the recent discoveries of the role of polydopamine as a surface coating material, with focus on the properties that make it suitable for tackling musculoskeletal disorders. We report the evolution of using it in research, and discuss papers involving the progress of this field. The current research on the role of polydopamine in bone, cartilage, muscle, nerve, and tendon regeneration is discussed, thus giving comprehensive overview about the function of polydopamine both in-vitro and in-vivo. Finally, the report concludes presenting the critical challenges that must be addressed for the clinical translation of this biomaterial while exploring future perspectives and research opportunities in this area.