Monitoring the hypoxic microenvironment is fundamental due to its implication in tumor aggressiveness and progression. In this work, we propose the fabrication of ratiometric fluorescent fibers via electrospinning of poly(trimethylsylil)propine (PTMSP) polymer, an optically clear and gas permeable polymer, for oxygen (O2) sensing in a melanoma tumor model. The ratiometric sensing configuration was obtained by entrapping tris(4,7-diphenyl-1,10-phenanthroline) ruthenium (II) dichloride, capable of detecting dissolved O2 variations, together with rhodamine B isothiocyanate, serving as a reference dye, within the polymer matrix. The fibers were characterized to point out morphology, porosity, and hydrophilicity. The sensing ability of the fibrous mat was deeply investigated by means of microplate reader and confocal imaging, showing a strict correlation between the fluorescent ratiometric read-out and the increasing concentration of dissolved O2 in aqueous-based media. Moreover, the fibers exhibited high photostability, reversibility and excellent cytocompatibility, allowing monitoring O2 gradients over time and space in vitro melanoma co-cultures. Overall, the optimized micrometric sensing system holds potential for real-time assessments of dissolved O2 levels in vitro complex cell systems and heterogeneous tumour microenvironments, and can open up new engineering possibilities by means of using O2-sensitive dyes in tissue engineering scaffolding strategies.

Valvular heart disease (VHD) poses a thorny problem in cardiovascular diseases. The most effective treatment for VHD is heart valve replacement. Biological heart valve (BHV) is more favored than mechanical heart valve due to the maturity of transcatheter heart valve replacement (THVR) and the absence of the need for lifelong anticoagulant use. However, traditional commercial BHV suffers degeneration within 10-15 years because of calcification caused by the cross-linking reagent, glutaraldehyde. Considering the remarkable properties of POSS, PEG, and the star-like eight-arm structure, we fabricated POSS-PEG-PP, which is a decellularized porcine pericardium (DPP) crosslinked by a star-like eight-arm cross-linker octafunctionalized POSS of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) based on the Schiff's base reaction. POSS-PEG-PP exhibits more intense fiber arrangement and better mechanical properties than GLUT-PP (glutaraldehyde crosslinked DPP). The results also show that the cytocompatibility, endothelialization, and hemocompatibility of POSS-PEG-PP are outstanding in vitro. Subsequently, in vivo assessments demonstrate that POSS-PEG-PP has anti-inflammatory and anti-calcification abilities. Furthermore, RNA sequencing analysis of subcutaneous implants suggests that the intervention of AMPK and IL-17 signaling pathways plays an important role in the inflammatory and immune responses regulation of POSS-PEG-PP. Therefore, POSS-PEG-PP is an excellent substitute material for BHVs and is expected to be clinically transformed.

Dry, transduction biomaterial scaffolds (Drydux) represent a novel platform for enhancing viral transduction, achieving drastic improvements in transduction efficiency (from ∼10% to >80%) while simplifying production of potent genetically engineered cells. This technology addresses a critical bottleneck in cell therapy manufacturing, where conventional methods require complex protocols and often yield suboptimal results. However, the underlying material science driving Drydux-enhanced transduction remains unclear. Here, we comprehensively assess biomaterial properties that influence viral transduction enhancement through systematic testing of polysaccharides, proteins, elastin-like polypeptides (ELPs), and synthetic polymers. Our findings reveal that surface porosity and liquid absorption are primary drivers of transduction enhancement, while polymer charge and flexibility play secondary roles. Negatively charged and flexible materials-particularly gelatin, hyaluronan, and alginate-demonstrated superior performance. Notably, despite promising material characteristics, synthetic polymers failed to enhance transduction, highlighting the unique advantages of specific biomaterial compositions. By elucidating these structure-function relationships, this work establishes design principles for optimizing biomaterial-enhanced transduction and expands the Drydux platform's potential for transforming cell therapy manufacturing, regenerative medicine, and beyond.

Understanding and exploiting bioelectric signaling pathways and physicochemical properties of materials that interface with living tissues is central to advancing tissue regeneration. In particular, the emerging field of bioelectronics leverages these principles to develop personalized, minimally invasive therapeutic strategies tailored to the dynamic demands of individual patients. By integrating sensing and actuation modules into flexible, biocompatible devices, clinicians can continuously monitor and modulate local electrical microenvironments, thereby guiding regenerative processes without extensive surgical interventions. This review provides a critical examination of how fundamental bioelectric cues and physicochemical considerations drive the design and engineering of next-generation bioelectronic platforms. These platforms not only promote the formation and maturation of new tissues across neural, cardiac, musculoskeletal, skin, and gastrointestinal systems but also precisely align therapies with the unique structural, functional, and electrophysiological characteristics of each tissue type. Collectively, these insights and innovations represent a convergence of biology, electronics, and materials science that holds tremendous promise for enhancing the efficacy, specificity, and long-term stability of regenerative treatments, ushering in a new era of advanced tissue engineering and patient-centered regenerative medicine.

Medical implants, being biomaterials with increasing global use, continue to attract researchers focused on enhancing clinical performance. In situations requiring bone substitutes, there is a search for advancements in synthetic graft biomaterials, with polymer-based implants being one of the potential materials. Thus, this study aims to develop versatile nanohydroxyapatite (nHAP) biocomposites that can not only be generalized by resin composite systems but also be applicable for 3D printing, overcoming the limitations associated with traditional implants. Polymeric biocomposites are prepared by incorporating nHAPs and strontium-doped SiO2 glass particles (GPs) into a photocurable methacrylate monomer system, followed by 3 min of cold atmosphere plasma irradiation. In light of our findings, this medical implant possesses strong mechanical strength. Its surface hydrophilicity is enhanced through cold plasma treatment, which involves surface dry etching with nanoscale precision and exposing the embedded nanofillers to the outmost surface. This cold plasma treatment also induces osteogenic activity in vitro and bone integration in vivo. Furthermore, the 3D printability is demonstrated through the fabrication of a gyroid lattice structure. Collectively, this nHAP-biocomposite exhibits promising biomechanical and biological properties, providing potential for revolutionizing future implant applications in dental and maxillofacial reconstruction as well as orthopedic interbody fusion.

One of the greatest obstacles to achieving implantable electronics with long-term functionality and minimized inflammatory reactions is the immune-mediated foreign-body response (FBR). Recently, semiconducting polymers with mixed electron-ion conductivity have been demonstrated as promising candidates to achieve direct electrical interfacing on bio-tissues. However, there is limited understanding of their immune compatibility in vivo, and strategies for minimizing the FBR through molecular design remain underexplored. Here we introduce a set of molecular design strategies for enhancing the immune compatibility of semiconducting polymers. Specifically, we show that selenophene, when incorporated in the backbone, can mitigate the FBR by suppressing macrophage activation. In addition, side-chain functionalization with immunomodulatory groups decreases the FBR further by downregulating the expression of inflammatory biomarkers. Together, our synthesized polymers achieve suppression of the FBR by as much as 68% (as indicated by the collagen density). In the meantime, these immune-compatible designs still provide a high charge-carrier mobility of around 1 cm2 V-1 s-1. We anticipate that such immune-compatible design principles can be translated to a variety of conjugated polymers to suppress the FBR for implantable applications.

Wound healing for various diseases and wounds such as diabetes and burns remains a major biomedical challenge. Conventional monotherapy is ineffective, and the efficacy of drug delivery is limited by the depth of drug penetration. In this study, we develop a novel, multifunctional, dissolvable hyaluronic acid (HA) microneedle patch (MN-LTT). Microneedling is biocompatible and delivers the drug in a painless and non-invasive manner. Lidocaine and thrombin are mixed with HA hydrogel and loaded onto the needle tips of the MN-LTT, which facilitates wound repair by continuously delivering the drug deep into the dermis for rapid analgesia and hemostasis. In addition, the backing layer of the MN-LTT is composed of tetracycline hydrochloride and HA hydrogel, and its excellent antimicrobial properties further accelerate wound healing. In a mouse full-thickness skin wound model, MN-LTT accelerated cell proliferation and granulation tissue growth, reduced inflammatory-factor levels, and restored collagen deposition, resulting in complete wound healing within seven days. Thus, the proposed microneedle delivery system achieved rapid hemostatic, analgesic, and bactericidal effects, providing a safer and more effective strategy for wound healing. These features make the multifunctional HA microneedle patch potentially valuable for clinical applications.

Biomaterials play a crucial role in modern medicine through their use as medical implants and devices. However, they can support biofilm formation and infection, and lack integration with the surrounding human tissue at the implant site. This work reports the development of novel poly(ethyl acrylate) (PEA) based copolymers that address both issues. These PEA materials were molecularly designed polymeric surfactants (surfmers) synthesised via controlled radical polymerisations to achieve different polymeric architectures, (i.e., statistical and block copolymers). These were both deposited as structured 2D films on glass coverslips and used to manufacture monodisperse 3D micro-particles with functional surfaces (via microfluidics). ToF-SIMS was used to analyse these 2D and 3D surfaces to understand: (a) the surface arrangement of the monomer sequences exhibited by the different polymer structures and (b) how this surface monomer arrangement influenced mammalian fibroblast cell and/or Staphylococcus aureus behaviour at these film/particle surfaces. In addition, the form of the fibronectin (FN) network assembly's importance in promoting growth factor (GF) binding was probed using atomic force microscopy (AFM) on the 2D films. This confirmed that specific surfmer molecular surface organisations were achieved during film/micro-particle fabrication, which presented exterior functionalities that either prevent biofilm attachment or promote the formation of structured FN networks for GF binding.

Surface coverage is an important parameter in describing the kinetics of adsorption in interface science, the adsorption theory of macromolecules (e.g., proteins, DNA) on biomaterial surface, the stability of colloids with surface modifications and the application of surfactants at interfaces. In this work, we focus on nanoparticles (NPs) with polymer coatings and, with a mean-field approach, propose a universal theoretical model for calculating the coverage of polymers on planar or spherical substrates at different solvent qualities. Validated by molecular dynamics simulations, our model is applicable to a wide range of polymer morphologies - from partially occluded to completely covered NPs - and provides a novel quantitative approach to characterize this type of polymer patchy particles.

A bone scaffold with well-designed porous structure and material composition is essential for bone regeneration as it supports various biological functions. In this study, a dual-scale porous polylactic acid-pearl/chitosan (PLA-P/CS) scaffold was developed by integrating 3D printing and conventional techniques. An interconnected macroporous PLA-P scaffold with pore sizes ranging from 680-800 μm was fabricated using FDM 3D printing. Additionally, a microporous CS foam with pore sizes of 10-200 μm was prepared via freeze-drying within the macropores of the 3D-printed scaffold. The microporous CS foam enhanced the scaffold's hydrophilicity while preserving its favorable mechanical properties. Moreover, the dual-scale porous structure demonstrated improved biomineralization, due to its larger specific surface area and increased nucleation sites, along with the electrostatic adsorption provided by the amino and hydroxyl functional groups of chitosan. Furthermore, cell culture experiments revealed the dual-scale porous structure, and the effects of CS enhanced the cellular response of BMSCs. More importantly, a 12-week in vivo study on rat skull defect repair demonstrated that the dual-scale porous PLA-P/CS scaffold exhibited enhanced bone formation. These findings suggest that designing a graded porous structure and optimizing material composition can effectively enhance biological responses, thereby facilitating bone regeneration.

Cell membrane-derived nanovesicles (NVs) have emerged as promising alternatives to extracellular vesicles (EVs) for wound healing applications, addressing the limitations of traditional EVs, which include insufficient targeting capability, low production yield, and limited drug-loading capacity. Through mechanical cell extrusion methods, NVs exhibit superior characteristics, demonstrating enhanced yield, stability, and purity compared to natural EVs. These NVs can be derived from various membrane sources, including single cell types (stem cells, blood cells, immune cells, and bacterial membranes), hybrid cell membranes and cell membranes mixed with liposomes, with each offering unique therapeutic properties. The integration of genetic engineering and surface modifications has further enhanced NV functionality, enabling precise targeting and improved drug delivery capabilities. Recent advances in NV-based therapies have demonstrated their potential across multiple biomedical applications. Although challenges persist in terms of standardization, storage stability, and clinical translation, the combination of natural cell-derived functions with artificial modification potential positions NVs as a promising platform for next-generation therapeutic delivery systems, thereby offering new possibilities in wound healing applications. Finally, we explore the challenges and future prospects of translating NV-based therapeutics into clinical practice, providing insights into the future development of this innovative approach in wound healing and tissue repair.

The musculoskeletal system relies on critical tissue interfaces for its function; however, these interfaces are often compromised by injuries and diseases. Restoration of these interfaces is complex by nature which renders traditional treatments inadequate. An emerging solution is three-dimensional printing, which allows for precise fabrication of biomimetic scaffolds to enhance tissue regeneration. This review summarizes the use of 3D printing in creating scaffolds for musculoskeletal interfaces, mainly focusing on advanced techniques such as multi-material printing, bioprinting, and 4D printing. We emphasize the significance of mimicking natural tissue gradients and the selection of appropriate biomaterials to ensure scaffold success. The review outlines state-of-the-art 3D printing technologies, varying from extrusion, inkjet and laser-assisted bioprinting, which are crucial for producing scaffolds with tailored mechanical and biological properties. Applications in cartilage-bone, intervertebral disc, tendon/ligament-bone, and muscle-tendon junction engineering are discussed, highlighting the potential for improved integration and functionality. Furthermore, we address challenges in material development, printing resolution, and the in vivo performance of scaffolds, as well as the prospects for clinical translation. The review concludes by underscoring the transformative potential of 3D printing to advance orthopedic medicine, offering a roadmap for future research at the intersection of biomaterials, drug delivery, and tissue engineering.

This study explores the synergistic effects of combining titania nanotubes (TiNTs) with the biopolymer Tanfloc (TAN) to enhance the surface properties of TiNTs for biomedical applications. We investigated the interactions of blood components and human adipose-derived stem cells (ADSCs) with TiNT surfaces covalently functionalized with Tanfloc (TAN), an aminolyzed polyphenolic tannin derivative. The functionalized surfaces (TiNT-TAN) have great potential to control protein adsorption and platelet adhesion and activation. Fluorescence and scanning electron microscopy (SEM) were used to analyze platelet adherence and activation. The amphoteric nature and multiple functional groups on TAN can control blood protein adsorption, platelet adhesion, and activation. Further, the modified surface supports adipose-derived stem cell (ADSC) viability, attachment, and growth without any cytotoxic effect. The TAN conjugation significantly (****p < 0.0001) increased the proliferation rate of ADSCs compared to the TiNT surfaces.

Bone defects, whether caused by trauma, cancer, infectious diseases, or surgery, can significantly impair people's quality of life. Although autografts are the gold standard for treating bone defects, they often fall short in adequately forming bone tissue. The field of bone tissue engineering has made strides in using scaffolds with various biomaterials, stem cells, and growth factors to enhance bone healing. However, some biological structures do not yield satisfactory therapeutic outcomes for new bone formation. Recent studies have shed light on the crucial role of immunomodulation, specifically the interaction between the implanted scaffold and host immune systems, in bone regeneration. Immune cells, particularly macrophages, are pivotal in the inflammatory response, angiogenesis, and osteogenesis. This review delves into the immune system's mechanism toward foreign bodies and the recent advancements in scaffolds' physical and biological properties that foster bone regeneration by modulating macrophage polarization to an anti-inflammatory phenotype and enhancing the osteoimmune microenvironment.

Poly(vinylidene fluoride) (PVDF)/hydroxyapatite (HAP) nanocomposite films, incorporating HAP nanoparticles as filler within a PVDF matrix, were successfully synthesized by solution casting method. Increasing the HAP concentration in the nanocomposite significantly enhances its electroactive properties, with synergistic effects on surface, electrical and biological characteristics are investigated comprehensively. Improvements in topographical and mechanical parameters reveal the nanocomposite films for biomimetic suitability. Notably, the impact of dielectric and ferroelectric properties on biological studies is well established. With increasing the HAP concentration, we observed significant improvements in remnant polarization from 0.28 to 1.87 µC cm-2, saturation polarization from 1.1 to 2.10 µC cm-2, and coercive field from 88.55 to 243.65 kV cm-1. Inin-vitroexperiments with osteosarcoma cells, the nanocomposite films with 40% HAP showed higher cell proliferation and viability. Present finding indicated 60PVDF/40HAP nanocomposite films as a biomimicry candidate for bone regeneration applications.

Periodontitis and bone loss in the maxillofacial and dental areas pose considerable challenges for both functional and aesthetic outcomes. To date, implantable dental barrier membranes, designed to prevent epithelial migration into defects and create a favorable environment for targeted cells, have garnered significant interest from researchers. Consequently, a variety of materials and fabrication methods have been explored in extensive research on regenerative dental barrier membranes.

This review focuses on dental barrier membranes, summarizing the various biomaterials used in membrane manufacturing, fabrication methods, and state-of-the-art applications for dental tissue regeneration. Based on a discussion of the pros and cons of current membrane strategies, future research directions for improved membrane designs are proposed.

To endow dental membranes with various biological properties that accommodate different clinical situations, numerous biomaterials and manufacturing methods have been proposed. These approaches provide theoretical support and hold promise for advancements in dental tissue regeneration.

Intercellular adhesion is accompanied by several physical quantities and actions. In this review, we tried to collect information about the influence of surface energy and its impact on cell-cell adhesion. It still undergoes development for cancer treatment. Data on receptor-ligand interactions that occur on circulating tumor cells (CTCs) are described, and adhesion receptors as therapeutic targets are collected. Additionally, the impact of surface roughness on the interactions between CTC cells and the surface was monitored. The effects of different cell adhesion molecules (CAMs) on cell adhesion, growth, and proliferation were investigated. This review offers general principles of cell adhesion, through the blockade of adhesion with blocking drugs and inhibitors like computational models that describe the process of adhesion. Some theoretical models based on the minimum of the total free energy of interaction between CAMs and selected organic molecules have been presented. The final aim was to find information on how modulation of the surface of CTCs (by medicals or physically) inhibits cancer metastases formation.

Peripheral arterial disease (PAD) poses a global health challenge, particularly in its advanced stages known as critical limb ischemia (CLI). Conventional treatments often fail to achieve satisfactory outcomes. Patients with CLI face high rates of morbidity and mortality, underscoring the urgent need for innovative therapeutic strategies. Recent advancements in biomaterials and biotechnology have positioned biomaterial-based vascularization strategies as promising approaches to improve blood perfusion and ameliorate ischemic conditions in affected tissues. These materials have shown potential to enhance therapeutic outcomes while mitigating toxicity concerns. This work summarizes the current status of PAD and highlights emerging biomaterial-based strategies for its treatment, focusing on functional genes, cells, proteins, and metal ions, as well as their delivery and controlled release systems. Additionally, the limitations associated with these approaches are discussed. This review provides a framework for designing therapeutic biomaterials and offers insights into their potential for clinical translation, contributing to the advancement of PAD treatments.

An ideal drug carrier system should demonstrate optimal payload and release characteristics, thereby ensuring prolonged therapeutic index while minimizing adverse effects. The field of drug delivery has undergone significant advancements, particularly within the last two decades, owing to the revolutionary impact of biomaterials. The use of biomaterials presents significant due to their biocompatibility and biodegradability, which must be addressed in order to achieve effective drug delivery. The properties of the biomaterial and its interface are primarily influenced by their physicochemical attributes, physiological barriers, cellular trafficking, and immunomodulatory effects. By attuning these barriers, regulating the physicochemical properties, and masking the immune system's response, the bio interface can be effectively modulated, leading to the development of innovative supramolecular structures with enhanced effectiveness. With a comprehensive understanding of these technologies, there is a growing demand for repurposing existing drugs for new therapeutic indications within this space. This review aims to provide a substantial body of evidence showcasing the productiveness of biomaterials and their interface in drug delivery, as well as methods for mitigating and modulating barriers and physicochemical properties along with an examination of future prospects in this field.

Skin aging is the phenomenon of degenerative changes in the structure and function of skin tissues over time and is manifested by a gradual loss of skin elasticity and firmness, an increased number of wrinkles, and hyperpigmentation. Skin anti-aging refers to a reduction in the skin aging phenomenon through medical cosmetic technologies. In recent years, new biomaterials have been continuously developed for improving the appearance of the skin through mechanical tissue filling, regulating collagen synthesis and degradation, inhibiting pigmentation, and repairing the skin barrier. This review summarizes the mechanisms associated with skin aging, describes the biomaterials that are commonly used in medical aesthetics and their possible modes of action, and discusses the application strategies of biomaterials in this area. Moreover, the synergistic effects of such biomaterials and other active ingredients, such as stem cells, exosomes, growth factors, and antioxidants, on tissue regeneration and anti-aging are evaluated. Finally, the possible challenges and development prospects of biomaterials in the field of anti-aging are discussed, and novel ideas for future innovations in this area are summarized.

Biomaterials often have subtle properties that ultimately drive their bespoke performance. Given this nuanced structure-function behavior, the standard scientific approach of one experiment at a time or design of experiment methods is largely inefficient for the discovery of complex biomaterials. More recently, high-throughput experimentation coupled with machine learning methods has matured beyond expert users allowing scientists and engineers from diverse backgrounds to access these powerful data science tools. As a result, we now have the opportunity to strategically utilize all available data from high-throughput experiments to train efficacious models and map the structure-function behavior of biomaterials for their discovery. Herein, we discuss this necessary shift to data-driven determination of structure-function properties of biomaterials as we highlight how machine learning is leveraged in identifying physicochemical cues for biomaterials in tissue engineering, gene delivery, drug delivery, protein stabilization, and antifouling materials. We also discuss data-mining approaches that are coupled with machine learning to map biomaterial functions that reduce the load on experimental approaches for faster biomaterial discovery. Ultimately, harnessing the prowess of machine learning will lead to accelerated discovery and development of optimal biomaterial designs.

Guided bone regeneration (GBR) technology has been demonstrated to be an effective method for reconstructing bone defects. A membrane is used to cover the bone defect to stop soft tissue from growing into it. The biosurface design of the barrier membrane is key to the technology. In this work, an asymmetric functional gradient Janus membrane was designed to address the bidirectional environment of the bone and soft tissue during bone reconstruction. The Janus membrane was simply and efficiently prepared by the multilayer self-assembly technique, and it was divided into the polycaprolactone isolation layer (PCL layer, GBR-A) and the nanohydroxyapatite/polycaprolactone/polyethylene glycol osteogenic layer (HAn/PCL/PEG layer, GBR-B). The morphology, composition, roughness, hydrophilicity, biocompatibility, cell attachment, and osteogenic mineralization ability of the double surfaces of the Janus membrane were systematically evaluated. The GBR-A layer was smooth, dense, and hydrophobic, which could inhibit cell adhesion and resist soft tissue invasion. The GBR-B layer was rough, porous, hydrophilic, and bioactive, promoting cell adhesion, proliferation, matrix mineralization, and expression of alkaline phosphatase and RUNX2. In vitro and in vivo results showed that the membrane could bind tightly to bone, maintain long-term space stability, and significantly promote new bone formation. Moreover, the membrane could fix the bone filling material in the defect for a better healing effect. This work presents a straightforward and viable methodology for the fabrication of GBR membranes with Janus-based bioactive surfaces. This work may provide insights for the design of biomaterial surfaces and treatment of bone defects.

Xenografts are commonly used for bone regeneration in dental and orthopaedic domains to repair bone voids and other defects. The first-generation xenografts were made through sintering, which deproteinizes them and alters their crystallinity, while later xenografts are produced using cold-temperature chemical treatments to maintain the structural collagen phase. However, the impact of collagen and the crystalline phase on physicochemical properties have not been elucidated. We hypothesized that understanding these factors could explain why the latter provides improved bone regeneration clinically. In this study, we compared two types of xenografts, one prepared through a low-temperature chemical process (Treated) and another subsequently sintered at 1100°C (Sintered) using advanced microscopy, spectroscopy, X-ray analysis and compressive testing. Our investigation showed that the Treated bone graft was free of residual blood, lipids or cell debris, mitigating the risk of pathogen transmission. Meanwhile, the sintering process removed collagen and the carbonate phase of the Sintered graft, leaving only calcium phosphate and increased mineral crystallinity. Microcomputed tomography revealed that the Treated graft exhibited an increased high porosity (81%) and pore size compared to untreated bone, whereas the Sintered graft exhibited shrinkage, which reduced the porosity (72%), pore size and strut size. Additionally, scanning electron microscopy displayed crack formation around the pores of the Sintered graft. The Treated graft displayed median mechanical properties comparable to native cancellous bone and clinically available solutions, with an apparent modulus of 166 MPa, yield stress of 5.5 MPa and yield strain of 4.9%. In contrast, the Sintered graft exhibited a lower median apparent modulus of 57 MPa. It failed in a brittle manner at a median stress of 1.7 MPa and strain level of 2.9%, demonstrating the structural importance of the collagen phase. This indicates why bone grafts prepared through cold-temperature processes are clinically favourable.

The ability of thermoelectric materials to generate electricity in response to local temperature gradients makes them a potentially promising solution for the regulation of cellular functions and reconstruction of tissues. Biocompatibility of implants is a crucial attribute for the successful integration of thermoelectric techniques in biomedical applications. This work focuses on the in vitro and in vivo evaluation of biocompatibility for 12 typical chalcogenide thermoelectrics, which are composed of biocompatible elements. Ag2Se, SnSe, Bi2Se3, Bi2Te2.88Se0.12 and Bi2Te3, each with a released ion concentration lower than 10 ppm in extracts, exhibited favorable biocompatibility, including cell viability, adhesion, and hemocompatibility, as observed in initial in vitro assessments. Moreover, in vivo biocompatibility assessment, achieved by hematological and histopathological analyses in the rat subcutaneous model, further substantiated the biocompatibility of Ag2Se, Bi2Se3, and Bi2Te3, with each possessing superior thermoelectric performance at room temperature. This work offers robust evidence to promote Ag2Se, Bi2Se3, and Bi2Te3 as potential thermoelectric biomaterials, establishing a foundation for their future applications in biomedicine.

The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 μm). It was found that scaffolds with a mesh size of 500 μm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration.

Calcium phosphate-based biomaterials (CaP) are the most widely used biomaterials to enhance bone regeneration in the treatment of alveolar bone deficiencies, cranio-maxillofacial and periodontal infrabony defects, with positive preclinical and clinical results reported. This systematic review aimed to assess the influence of the physicochemical properties of CaP biomaterials on the performance of bone regeneration in preclinical animal models.

The PubMed, EMBASE and Web of Science databases were searched to retrieve the preclinical studies investigating physicochemical characteristics of CaP biomaterials. The studies were screened for inclusion based on intervention (physicochemical characterization and in vivo evaluation) and reported measurable outcomes.

A total of 1532 articles were retrieved and 58 studies were ultimately included in the systematic review. A wide range of physicochemical characteristics of CaP biomaterials was found to be assessed in the included studies. Despite a high degree of heterogeneity, the meta-analysis was performed on 39 studies and evidenced significant effects of biomaterial characteristics on their bone regeneration outcomes. The study specifically showed that macropore size, Ca/P ratio, and compressive strength exerted significant influence on the formation of newly regenerated bone. Moreover, factors such as particle size, Ca/P ratio, and surface area were found to impact bone-to-material contact during the regeneration process. In terms of biodegradability, the amount of residual graft was determined by macropore size, particle size, and compressive strength.

The systematic review showed that the physicochemical characteristics of CaP biomaterials are highly determining for scaffold's performance, emphasizing its usefulness in designing the next generation of bone scaffolds to target higher rates of regeneration.

The ideal implant surface plays a substantial role in maintaining bone homeostasis by simultaneously promoting osteoblast differentiation and limiting overactive osteoclast activity to a certain extent, which leads to satisfactory dynamic osseointegration. However, the rational search for implant materials with an ideal surface structure is challenging and a hot research topic in the field of tissue engineering. In this study, we constructed titanium dioxide titanium nanotubes (TNTs) by anodic oxidation and found that this structure significantly promoted osteoblast differentiation and inhibited osteoclast formation and function while simultaneously inhibiting the total protein levels of proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK). Knockdown of the PYK2 gene by siRNA significantly suppressed the number and osteoclastic differentiation activity of mouse bone marrow mononuclear cells (BMMs), while overexpression of PYK2 inhibited osteogenesis and increased osteoclastic activity. Surprisingly, we found for the first time that neither knockdown nor overexpression of the FAK gene alone caused changes in osteogenesis or osteoclastic function. More importantly, compared with deletion or overexpression of PYK2/FAK alone, coexpression or cosilencing of the two kinases accelerated the effects of TNTs on osteoclastic and osteogenic differentiation on the surface of cells. Furthermore, in vivo experiments revealed a significant increase in positiveexpression-PYK2 cells on the surface of TNTs, but no significant change in positiveexpression -FAK cells was observed. In summary, PYK2 is a key effector molecule by which osteoblasts sense nanotopological mechanical signals and maintain bone homeostasis around implants. These results provide a referable molecular mechanism for the future development and design of homeostasis-based regulatory implant biomaterials.

The improvement of the capability of poly(N-isopropylacrylamide) (PNIPAAm) hydrogel coating in cell adhesion and detachment is critical to efficiently prepare cell sheets applied in cellular therapies and tissue engineering. To enhance cell response on the surface, the amine group-modified PNIPAAm (PNIPAAm-APTES) nanohydrogels were synthesized and deposited spontaneously on tannic acid (TA)-modified polyethylene (PE) plates. Subsequently, TA was introduced onto PNIPAAm-APTES nanohydrogels to fabricate coatings composed of TA-modified PNIPAAm-APTES (PNIPAAm-APTES-TA). Characterization techniques, including TEM, SEM, XPS, and UV-Vis spectroscopy, confirmed the effective deposition of hydrogels of PNIPAAm as well as the morphologies, content of chemical bonding-TA, and stability of various coatings. Importantly, the porous hydrogel coatings exhibited superhydrophilicity at 20 °C and thermo-responsive behavior. The fluorescence measurement demonstrated that the coating's stability effectively regulated protein behavior, influencing cell response. Notably, cell response tests revealed that even without precise control over the chain length/thickness of PNIPAAm during synthesis, the coatings enhanced cell adhesion and detachment, facilitating efficient cell culture. This work represented a novel and facile approach to preparing bioactive PNIPAAm for cell culture.

The sprayable hydrogel coatings that can establish robust adhesion onto diverse materials and devices hold enormous potential; however, a significant challenge persists due to monomer hydration, which impedes even coverage during spraying and induces inadequate adhesion post-gelation. Herein, a polycation-reinforced (PCR) surface bridging strategy is presented to achieve tough and sprayable hydrogel coatings onto diverse materials. The polycations offer superior wettability and instant electrostatic interactions with plasma-treated substrates, facilitating an effective spraying application. This PCR-based hydrogel coatings demonstrate tough adhesion performance to inert PTFE and silicone, including remarkable shear strength (161 ± 49 kPa for PTFE), interfacial toughness (198 ± 27 J m-2 for PTFE), and notable tolerance to cyclic tension (10 000 cycles, 200% strain, silicone). Meanwhile, this method can be applied to various hydrogel formulations, offering diverse functionalities, including underwater adhesion, lubrication, and drug delivery. Furthermore, the PCR concept enables the conformal construction of durable hydrogel coatings onto sophisticated medical devices like cardiovascular stents. Given its simplicity and adaptability, this approach paves an avenue for incorporating hydrogels onto solid surfaces and potentially promotes untapped applications.

Cellular response to the topography of their environment, known as contact guidance, is a crucial aspect to many biological processes yet remains poorly understood. A prevailing model to describe cellular contact guidance involves the lateral confinement of focal adhesions (FA) by topography as an underlying mechanism governing how cells can respond to topographical cues. However, it is not clear how this model is consistent with the well-documented depth-dependent contact guidance responses in the literature. To investigate this model, we fabricated a set of contact guidance chips with lateral dimensions capable of confining focal adhesions and relaxing that confinement at various depths. We find at the shallowest depth of 330 nm, the model of focal adhesion confinement is consistent with our observations. However, the cellular response at depths of 725 and 1000 nm is inadequately explained by this model. Instead, we observe a distinct reorganization of F-actin at greater depths in which topographically induced cell membrane deformation alters the structure of the cytoskeleton. These results are consistent with an alternative curvature-hypothesis to explain cellular response to topographical cues. Together, these results indicate a confluence of two molecular mechanisms operating at increased induced membrane curvature that govern how cells sense and respond to topography.

The surge in 'Big data' has significantly influenced biomaterials research and development, with vast data volumes emerging from clinical trials, scientific literature, electronic health records, and other sources. Biocompatibility is essential in developing safe medical devices and biomaterials to perform as intended without provoking adverse reactions. Therefore, establishing an artificial intelligence (AI)-driven biocompatibility definition has become decisive for automating data extraction and profiling safety effectiveness. This definition should both reflect the attributes related to biocompatibility and be compatible with computational data-mining methods. Here, we discuss the need for a comprehensive and contemporary definition of biocompatibility and the challenges in developing one. We also identify the key elements that comprise biocompatibility, and propose an integrated biocompatibility definition that enables data-mining approaches.

Dysfunction of the mucosal barrier as well as local inflammation are major challenges in the treatment of ulcerative colitis (UC). Mag, a natural compound derived from traditional Chinese medicine, has been shown to have anti-inflammatory and mucosal protection properties. However, its poor gastrointestinal stability as well as its insufficient accumulation in inflamed colonic lesions limit its potential use as an alternative therapeutic drug in UC. The present research involved the design and preparation of a hybrid nanoparticle system (LPNs) specifically targeting macrophages at the colonic site. This was achieved by electrostatically adsorbing HA onto positively charged lipid-polymer hybrid nanoparticles (HA-LPNs). The prepared HA-LPNs exhibited a rounded morphology and a narrow size distribution. In vitro, the anti-inflammatory efficacy of Mag-HA-LPNs (which control levels of the pro-inflammatory cytokines NO, IL-6 and TNF-α) was assessed in RAW 264.7 cells. Analysis by flow cytometry and fluorescence microscopy demonstrated increased cellular uptake through HA/CD44 interaction. As expected, Mag-HA-LPNs was found to effectively increased colon length and reduced DAI scores in DSS-treated mice. This effect was achieved by regulating the inflammatory cytokines level and promoting the restoration of the colonic mucosal barrier through increased expression of Claudin-1, ZO-1 and Occludin. In this study, we developed an efficient and user-friendly delivery method for the preparation of HA-functionalized PLGA nanoparticles, which are intended for oral delivery of Mag. The findings suggest that these HA-LPNs possess the potential to serve as a promising approach for direct drug delivery to the colon for effective treatment of UC.

Metallic materials are an important class of biomaterials used in various medical devices, owing to a suitable combination of their mechanical properties. The (bio)-functionalization of their surfaces is frequently performed for biocompatibility requirements, as it offers a powerful way to control their interaction with biological systems. This is particularly important when physicochemical processes and biological events, mainly involving proteins and cells, are initiated at the host-material interface. This review addresses the state of "real interfaces" in the context of (bio)-functionalization of metallic materials, and the necessity to cope with it to avoid frequent improper evaluation of the procedure used. This issue is, indeed, well-recognized but often neglected and emerges from three main issues: (i) ubiquity of surface contamination with organic compounds, (ii) reactivity of metallic surfaces in biological medium, and (iii) discrepancy in (bio)-functionalization procedures between expectations and reality. These disturb the assessment of the strategies adopted for surface modifications and limit the possibilities to provide guidelines for their improvements. For this purpose, X-ray photoelectrons spectroscopy (XPS) comes to the rescue. Based on significant progresses made in methodological developments, and through a large amount of data compiled to generate statistically meaningful information, and to insure selectivity, precision and accuracy, the state of "real interfaces" is explored in depth, while looking after the two main constituents: (i) the bio-organic adlayer, in which the discrimination between the compounds of interest (anchoring molecules, coupling agents, proteins, etc) and organic contaminants can be made, and (ii) the metallic surface, which undergoes dynamic processes due to their reactivity. Moreover, through one of the widespread (bio)-functionalization strategy, given as a case study, a particular attention is devoted to describe the state of the interface at different stages (composition, depth distribution of contaminants and (bio)compounds of interest) and the mode of protein retention. It is highlighted, in particular, that the occurrence or improvement of bioactivity does not demonstrate that the chemical schemes worked in reality. These aspects are particularly essential to make progress on the way to choose the suitable (bio)-functionalization strategy and to provide guidelines to improve its efficiency.

The lubrication modification of biomedical devices significantly enhances the functionality of implanted interventional medical devices, thereby providing additional benefits for patients. Polymer brush coating provides a convenient and efficient method for surface modification while ensuring the preservation of the substrate's original properties. The current research has focused on a "trial and error" method to finding polymer brushes with superior lubricity qualities, which is time-consuming and expensive, as obtaining effective and long-lasting lubricity properties for polymer brushes is difficult. This review summarizes recent research advances in the biomedical field in the design, material selection, preparation, and characterization of lubricating and antifouling polymer brushes, which follow the polymer brush development process. This review begins by examining various approaches to polymer brush design, including molecular dynamics simulation and machine learning, from the fundamentals of polymer brush lubrication. Recent advancements in polymer brush design are then synthesized and potential avenues for future research are explored. Emphasis is placed on the burgeoning field of zwitterionic polymer brushes, and highlighting the broad prospects of supramolecular polymer brushes based on host-guest interactions in the field of self-repairing polymer brush applications. The review culminates by providing a summary of methodologies for characterizing the structural and functional attributes of polymer brushes. It is believed that a development approach for polymer brushes based on "design-material selection-preparation-characterization" can be created, easing the challenge of creating polymer brushes with high-performance lubricating qualities and enabling the on-demand creation of coatings. STATEMENT OF SIGNIFICANCE: Biomedical devices have severe lubrication modification needs, and surface lubrication modification by polymer brush coating is currently the most promising means. However, the design and preparation of polymer brushes often involves "iterative testing" to find polymer brushes with excellent lubrication properties, which is both time-consuming and expensive. This review proposes a polymer brush development process based on the "design-material selection-preparation-characterization" strategy and summarizes recent research advances and trends in the design, material selection, preparation, and characterization of polymer brushes. This review will help polymer brush researchers by alleviating the challenges of creating polymer brushes with high-performance lubricity and promises to enable the on-demand construction of polymer brush lubrication coatings.

In recent years, rapid advancements in multidisciplinary fields (materials, biology, chemical physics, etc [...].

Spiders, assigned to macroconcentrators of heavy metals, are particularly threatened by the toxic effects of these chemicals. Until now, it has not been specified to what extent metals alter the processes proceeding in silk glands and if such changes could consequently influence the chemical and structural properties of the spun web threads. In the present study selected biological properties of Steatoda grossa (Theridiidae) silk yarn after nutritional exposure to copper at sublethal doses (0.234 mM CuSO4) were assessed. It was determined both changes in ultrastructure of ampullate glands and hunting web's architecture as well the cytotoxic effect in model cells (fibroblasts: line ATCC® CCL-1 NCTC clone 929), that were in contact with the analyzed biomaterial. The exposure of spiders to copper caused the occurrence of apoptotic cells in the ampullate glands as well as a significant reduction in the diameter of single fibers in double and multiple connection complexes as compared with control. At both 24 and 72 h of incubation, intensification of apoptotic and necrotic processes was observed in the fibroblast cultures that were remaining in indirect contact with the webs produced by copper-contaminated individuals. In the case of fibroblasts in direct contact with silk from the copper group, a clear cytotoxic effect resulting in an increased frequency of necrosis was observed after 72 h of incubation. The results indicated that copper may change the biological properties of spider silk and compromise its biomaterial properties.

Tendon/ligament (T/L) injuries are a worldwide health problem that affects millions of people annually. Due to the characteristics of tendons, the natural rehabilitation of their injuries is a very complex and lengthy process. Surgical treatment of a T/L injury frequently necessitates using autologous or allogeneic grafts or synthetic materials. Nonetheless, these alternatives have limitations in terms of mechanical properties and histocompatibility, and they do not permit the restoration of the original biological function of the tissue, which can negatively impact the patient's quality of life. It is crucial to find biological materials that possess the necessary properties for the successful surgical treatment of tissues and organs. In recent years, the in vitro regeneration of tissues and organs from stem cells has emerged as a promising approach for preparing autologous tissue and organs, and cell culture scaffolds play a critical role in this process. However, the biological traits and serviceability of different materials used for cell culture scaffolds vary significantly, which can impact the properties of the cultured tissues. Therefore, this review aims to analyze the differences in the biological properties and suitability of various materials based on scaffold characteristics such as cell compatibility, degradability, textile technologies, fiber arrangement, pore size, and porosity. This comprehensive analysis provides valuable insights to aid in the selection of appropriate scaffolds for in vitro tissue and organ culture.

Critical-sized bone defects resulting from severe trauma and open fractures cannot spontaneously heal and require surgical intervention. Limitations of traditional bone grafting include immune rejection and demand-over-supply issues leading to the development of novel tissue-engineered scaffolds. Nuciferine (NF), a plant-derived alkaloid, has excellent therapeutic properties, but its osteogenic potential is yet to be reported. Furthermore, the bioavailability of NF is obstructed due to its hydrophobicity, requiring an efficient drug delivery system, such as chitosan (CS) hydrogel. We designed and fabricated polylactic acid (PLA) scaffolds via 3D printing and integrated them with NF-containing CS hydrogel to obtain the porous biocomposite scaffolds (PLA/CS-NF). The fabricated scaffolds were subjected to in vitro physicochemical characterization, cytotoxicity assays, and osteogenic evaluation studies. Scanning electron microscopic studies revealed uniform pore size distribution on PLA/CS-NF scaffolds. An in vitro drug release study showed a sustained and prolonged release of NF. The cyto-friendly nature of NF in PLA/CS-NF scaffolds towards mouse mesenchymal stem cells (mMSCs) was observed. Also, cellular and molecular level studies signified the osteogenic potential of NF in PLA/CS-NF scaffolds on mMSCs. These results indicate that the PLA/CS-NF scaffolds could promote new bone formation and have potential applications in bone tissue engineering.

Bovine pericardium (BP) has been used as a biomaterial for several decades in many medical applications particularly due to its mechanical properties and the high collagen content. In the acellular form it favors faster tissue repair, providing a three-dimensional support for cellular and vascular events observed during tissue repair and due, to a low elastin content, may favor its use as a breast implant cover, resulting in a low possibility of contracture of the biomaterial, preventing the appearance of irregularities during the reconstruction process. Thus, the aim of this study was to evaluate, histomorphologically, the behavior of acellularized bovine pericardium (ABP) as a mammary implant cover in rats. For this purpose, 16 animals were divided into two groups, with eight animals at each biological point: 7 and 15 days after surgery. Of the 16 animals, 32 specimens were obtained: 16 in the experimental group (EG) and 16 in the control group (CG). Throughout this study, none of the studied groups had postoperative complications. Results: The histomorphological results showed, in the two biological points, both in the EG and in the CG, chronic inflammatory infiltrate, leukocyte fibrin exudate, formation of granulation tissue and deposition of collagen fibers, more evident in the EG, regressive along the biological points. At 15 days, the implanted ABP showed initial biointegration with the fibrous capsule and surrounding tissues of the recipient bed. Conclusion: These results indicate that the due to the observed favorable tissue response ABP may be of potential use as a breast implant cover.

Bioceramics, while offering excellent biocompatibility, are often compromised by their fragility and brittleness, especially under wet conditions. Even though recent hybrid processes combining biocompatible polymers and bioceramics have shown promise, complete mitigation of these challenges remains elusive. In this research, a biomimetic process was employed to mimic the structure of biological bone tissue. This led to the development of block materials composed of octacalcium phosphate (OCP) and sodium polyacrylic acid (PAA-Na) that display flexibility and resilience in wet conditions. Adjusting the PAA-Na concentration enabled the OCP-PAA-Na blocks to demonstrate superior mechanical strength when dry and increased flexibility when wet. Notably, these blocks expanded in aqueous solutions while preserving their structure, making them ideal for oral surgeries by preventing issues like blood flooding from implanted areas.

Bacterial infectious diseases are one of the leading causes of death worldwide. Even with the use of multiple antibiotic treatment strategies, 4.95 million people died from drug-resistant bacterial infections in 2019. By 2050, the number of deaths will reach 10 million annually. The increasing mortality may be partly due to bacterial heterogeneity in the infection microenvironment, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants. In addition, the complexity of the immune microenvironment at different stages of infection makes biomaterials with direct antimicrobial activity unsatisfactory for the long-term treatment of chronic bacterial infections. The increasing mortality may be partly attributed to the biomaterials failing to modulate the active antimicrobial action of immune cells. Therefore, there is an urgent need for effective alternatives to treat bacterial infections. Accordingly, the development of immunomodulatory antimicrobial biomaterials has recently received considerable interest; however, a comprehensive review of their research progress is lacking. In this review, we focus mainly on the research progress and future perspectives of immunomodulatory antimicrobial biomaterials used at different stages of infection. First, we describe the characteristics of the immune microenvironment in the acute and chronic phases of bacterial infections. Then, we highlight the immunomodulatory strategies for antimicrobial biomaterials at different stages of infection and their corresponding advantages and disadvantages. Moreover, we discuss biomaterial-mediated bacterial vaccines' potential applications and challenges for activating innate and adaptive immune memory. This review will serve as a reference for future studies to develop next-generation immunomodulatory biomaterials and accelerate their translation into clinical practice.

In vitro human skin models are evolving into versatile platforms for the study of skin biology and disorders. These models have many potential applications in the fields of drug testing and safety assessment, as well as cosmetic and new treatment development. The development of in vitro skin models that accurately mimic native human skin can reduce reliance on animal models and also allow for more precise, clinically relevant testing. Recent advances in biofabrication techniques and biomaterials have led to the creation of increasingly complex, multilayered skin models that incorporate important functional components of skin, such as the skin barrier, mechanical properties, pigmentation, vasculature, hair follicles, glands, and subcutaneous layer. This improved ability to recapitulate the functional aspects of native skin enhances the ability to model the behavior and response of native human skin, as the complex interplay of cell-to-cell and cell-to-material interactions are incorporated. In this review, we summarize the recent developments in in vitro skin models, with a focus on their applications, limitations, and future directions.