Biomedical Materials

Alveolar bone loss is widespread in all age groups and remains a severe hazard to periodontal health. Horizontal alveolar bone loss is the pattern of bone loss more commonly seen in periodontitis. Until now, limited regenerative procedures have been applied to treating horizontal alveolar bone loss in periodontal clinics, making it the least predictable periodontal defect type. This article reviews the literature on recent advances in horizontal alveolar bone regeneration. The biomaterials and clinical and preclinical approaches tested for the regeneration of the horizontal type of alveolar bone are first discussed. Furthermore, current obstacles for horizontal alveolar bone regeneration and future directions in regenerative therapy are presented to provide new ideas for developing an effective multidisciplinary strategy to address the challenge of horizontal alveolar bone loss.

Advancement in medicine and technology has resulted into prevention of countless deaths and increased life span. However, it is important to note that, the modern lifestyle has altered the food habits, witnessed increased life-style stresses and road accidents leading to several health complications and one of the primary victims is the bone health. More often than ever, healthcare professionals encounter cases of massive bone fracture, bone loss and generation of critical sized bone defects. Surgical interventions, through the use of bone grafting techniques are necessary in such cases. Natural bone grafts (allografts, autografts and xenografts) however, have major drawbacks in terms of delayed rehabilitation, lack of appropriate donors, infection and morbidity that shifted the focus of several investigators to the direction of synthetic bone grafts. By employing biomaterials that are based on bone tissue engineering (BTE), synthetic bone grafts provide a more biologically acceptable approach to establishing the phases of bone healing. In BTE, various materials are utilized to support and enhance bone regeneration. Biodegradable polymers like poly-(lactic acid), poly-(glycolic acid), and poly-(-caprolactone) are commonly used for their customizable mechanical properties and ability to degrade over time, allowing for natural bone growth. PEG is employed in hydrogels to promote cell adhesion and growth. Ceramics, such as hydroxyapatite and beta-tricalcium phosphate (β-TCP) mimic natural bone mineral and support bone cell attachment, with β-TCP gradually resorbing as new bone forms. Composite materials, including polymer-ceramic and polymer-glasses, combine the benefits of both polymers and ceramics/glasses to offer enhanced mechanical and biological properties. Natural biomaterials like collagen, gelatin, and chitosan provide a natural matrix for cell attachment and tissue formation, with chitosan also offering antimicrobial properties. Hybrid materials such as decellularized bone matrix retain natural bone structure and biological factors, while functionalized scaffolds incorporate growth factors or bioactive molecules to further stimulate bone healing and integration. The current review article provides the critical insights on several biomaterials that could yield to revolutionary improvements in orthopedic medical fields. The introduction section of this article focuses on the statistical information on the requirements of various bone scaffolds globally and its impact on economy. In the later section, anatomy of the human bone, defects and diseases pertaining to human bone, and limitations of natural bone scaffolds and synthetic bone scaffolds were detailed. Biopolymers, bioceramics, and biometals-based biomaterials were discussed in further depth in the sections that followed. The article then concludes with a summary addressing the current trends and the future prospects of potential bone transplants.

Bioprinting, an advanced additive manufacturing technology, enables the fabrication of complex, viable three-dimensional (3D) tissues using bioinks composed of biomaterials and cells. This technology has transformative applications in regenerative medicine, drug screening, disease modeling, and biohybrid robotics. In particular, in situ bioprinting has emerged as a promising approach for directly repairing damaged tissues or organs at the defect site. Unlike traditional 3D bioprinting, which is confined to flat surfaces and require complex equipment, in situ techniques accommodate irregular geometries, dynamic environments and simple apparatus, offering greater versatility for clinical applications. In situ bioprinting via hand-held devices prioritize flexibility, portability, and real-time adaptability while allowing clinicians to directly deposit bioinks in anatomically complex areas, making them cost-effective, accessible, and suitable for diverse environments, including field surgeries. This review explores the principles, advancements, and comparative advantages of robotic and hand-held in situ bioprinting, emphasizing their clinical relevance. While robotic systems excel in precision and scalability, hand-held bioprinters offer unparalleled flexibility, affordability, and ease of use, making them a valuable tool for personalized and minimally invasive tissue engineering. Future research should focus on improving biosafety, aseptic properties, and bioink formulations to optimize these technologies for widespread clinical adoption.

Blood-derived biomaterials with high platelet content have recently emerged as attractive products for tissue engineering and regenerative medicine (TERM). Platelet-derived bioactive molecules have been shown to play a role in wound healing and tissue regeneration processes by promoting collagen synthesis, angiogenesis, cell proliferation, migration, and differentiation. Given their regenerative potential, platelet-rich blood derivatives have become a promising treatment option for use in a variety of conditions. Platelet-Rich Plasma (PRP), one of the platelet-rich blood derivatives, is a platelet concentrate suspended in a small volume of blood plasma obtained from whole blood. Due to its potential clinical benefits, PRP is widely used alone or in combination with various biomaterials/scaffolds in different fields of medicine and has shown promising results in wound healing. The recent growing interest in the development of PRP-based scaffolds also reveals new perspectives on the use of PRP or platelet lysate in TERM. This topical review contains a comprehensive summary of recent trends in the fabrication of PRP-based scaffolds that can deliver growth factors, serve as mechanical support for cells, and have therapeutic or regenerative properties. The article briefly focuses on diverse PRP-based constructs using PRP as a scaffolding material, their current fabrication approaches as well as the challenges encountered and provides a selection of existing strategies and new insights.

Naturally derived materials are often preferred over synthetic materials for biomedical applications due to their innate biological characteristics, relative availability, sustainability, and agreement with conscientious end-users. The chicken eggshell membrane (ESM) is an abundant resource with a defined structural profile, chemical composition, and validated morphological and mechanical characteristics. These unique properties have not only allowed the ESM to be exploited within the food industry but has also led to it be considered for other novel translational applications such as tissue regeneration and replacement, wound healing and drug delivery. However, challenges still exist in order to enhance the native ESM (nESM): the need to improve its mechanical properties, the ability to combine/join fragments of ESM together, and the addition or incorporation of drugs/growth factors to advance its therapeutic capacity. This review article provides a succinct background to the nESM, its extraction, isolation, and consequent physical, mechanical and biological characterisation including possible approaches to enhancement. Moreover, it also highlights current applications of the ESM in regenerative medicine and hints at future novel applications in which this novel biomaterial could be exploited to beneficial use.

Temporary anchorage devices (TADs) have evolved as useful anchorage providers for orthodontic tooth movements. To improve the stability of TADs, a number of modifications on their surface have been developed and investigated. This review comprehensively summarizes recent findings of clinically applied surface modifications of TADs and compared the biological improvement of these modifications. We focused on sandblasting, large-grit, acid etching (SLA), anodic oxidation (AO) and ultraviolet photofunctionalization (UVP). In vitro, in vivo and clinical studies of these surface modifications on TADs with clear explanations, low possibility of bias and published in English were included. Studies demonstrated that SLA, AO and UVP enhance cell attachment, proliferation, and differentiation in vitro. The biocompatibility and osteoconductivity of TAD surface are improved in vivo. However, in clinical studies, the changes are generally not so impressive. Furthermore, this review highlights the promising potential in combinations of different modifications. In addition, some other surface modifications, for instance, the biomimetic calcium phosphate coating, deserve to be proposed as future strategies.

The mechanical properties of soft tissues play a key role in studying human injuries and their mitigation strategies. While such properties are indispensable for computational modelling of biological systems, they serve as important references in loading and failure experiments, and also for the development of tissue simulants. To date, experimental studies have measured the mechanical properties of peripheral tissues (e.g. skin) in-vivo and limited internal tissues ex-vivo in cadavers (e.g. brain and the heart). The lack of knowledge on a majority of human tissues inhibit their study for applications ranging from surgical planning, ballistic testing, implantable medical device development, and the assessment of traumatic injuries. The purpose of this work is to overcome such challenges through an extensive review of the literature reporting the mechanical properties of whole-body soft tissues from head to toe. Specifically, the available linear mechanical properties of all human tissues were compiled. Non-linear biomechanical models were also introduced, and the soft human tissues characterized using such models were summarized. The literature gaps identified from this work will help future biomechanical studies on soft human tissue characterization and the development of accurate medical models for the study and mitigation of injuries.

NanoMIPs are nanoscale molecularly imprinted polymers (MIPs) ranging in size between 30 to 300 nm offering a high affinity binding reagent as an alternative to antibodies. They are being extensively researched for applications in biological extraction, disease diagnostics and biosensors. Various methodologies for nanoMIP production have been reported demonstrating variable timescales required, sustainability, ease of synthesis and final yields. We report herein a fast (<2 h) method for one pot aqueous phase synthesis of nanoMIPs using an acrylamide-based monomer and N,N'-methylenebisacrylamide crosslinker. NanoMIPs were produced for a model protein template namely haemoglobin from bovine species. We demonstrate that nanoMIPs can be produced within 15 min. We investigated reaction quenching times between 5 and 20 min. Dynamic light scattering results demonstrate a distribution of particle sizes (30–900 nm) depending on reaction termination time, with hydrodynamic particle diameter increasing with increasing reaction time. We attribute this to not only particle growth due to polymer chain growth but based on AFM analysis, also a tendency (after reaction termination) for particles to agglomerate at longer reaction times. Batches of nanoMIPs ranging 400–800 nm, 200–400 nm and 100–200 nm were isolated using membrane filtration. The batches were captured serially on decreasing pore size microporous polycarbonate membranes (800–100 nm) and then released with sonication to isolate nanoMIP batches in the aforementioned ranges. Rebinding affinities of each batch were determined using electrochemical impedance spectroscopy, by first trapping nanoMIP particles within an electropolymerized thin layer. Binding constants determined for NanoMIPs using the E-MIP sensor approach are in good agreement with surface plasmon resonance results. We offer a rapid (<2 h) and scalable method for the mass production (40–80 mg per batch) of high affinity nanoMIPs.

Healthy synovium is critical for joint homeostasis. Synovial inflammation (synovitis) is implicated in the onset, progression and symptomatic presentation of arthritic joint diseases such as rheumatoid arthritis and osteoarthritis. Thus, the synovium is a promising target for the development of novel, disease-modifying therapeutics. However, target exploration is hampered by a lack of good pre-clinical models that accurately replicate human physiology and that are developed in a way that allows for widespread uptake. The current study presents a multi-channel, microfluidic, organ-on-a-chip (OOAC) model, comprising a 3D configuration of the human synovium and its associated vasculature, with biomechanical and inflammatory stimulation, built upon a commercially available OOAC platform. Healthy human fibroblast-like synoviocytes (hFLS) were co-cultured with human umbilical vein endothelial cells (HUVECs) with appropriate matrix proteins, separated by a flexible, porous membrane. The model was developed within the Emulate organ-chip platform enabling the application of physiological biomechanical stimulation in the form of fluid shear and cyclic tensile strain. The hFLS exhibited characteristic morphology, cytoskeletal architecture and matrix protein deposition. Synovial inflammation was initiated through the addition of interleukin−1β (IL−1β) into the synovium channel resulting in the increased secretion of inflammatory and catabolic mediators, interleukin-6 (IL−6), prostaglandin E2 (PGE₂), matrix metalloproteinase 1 (MMP−1), as well as the synovial fluid constituent protein, hyaluronan. Enhanced expression of the inflammatory marker, intercellular adhesion molecule-1 (ICAM-1), was observed in HUVECs in the vascular channel, accompanied by increased attachment of circulating monocytes. This vascularised human synovium-on-a-chip model recapitulates a number of the functional characteristics of both healthy and inflamed human synovium. Thus, this model offers the first human synovium organ-chip suitable for widespread adoption to understand synovial joint disease mechanisms, permit the identification of novel therapeutic targets and support pre-clinical testing of therapies.

Diabetes, a chronic metabolic disease, causes complications such as chronic wounds, which are difficult to cure. New treatments have been investigated to accelerate wound healing. In this study, a novel wound dressing from fibroblast-laden atelocollagen-based hydrogel with Cotinus coggygria extract was developed for diabetic wound healing. The antimicrobial activity of C. coggygria hexane (H), dichloromethane (DCM), dichloromethane:methanol (DCM-M), methanol (M), distilled water (DW) and traditional (T) extracts against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis and Candida albicans, as well as their cytotoxic effects on fibroblasts were determined. While fibroblast growth was significantly (p< 0.05) promoted with DCM (121.41 ± 1.04%), M (109.40 ± 5.89%) and DW (121.83 ± 6.37%) extracts at their lowest concentrations, 2000 μg ml⁻¹ DCM and 7.8 μg ml⁻¹ T extracts had both non-cytotoxic and antifungal effects. An atelocollagen-based hydrogel was produced by thermal crosslinking, and its pore size (38.75 ± 7.67 μm), water content (96.63 ± 0.24%) and swelling ratio (27.21 ± 4.08%) were found to be suitable for wound dressings. A significant increase in the deoxyribonucleic acid amount (28.27 ± 1.41%) was observed in the plain hydrogel loaded with fibroblasts after 9 d of incubation, and the hydrogel had an extensively interconnected cellular network. The hydrogels containing DW and T extracts were applied to wounds generated in an in vitro 3D type-2-diabetic human skin model. Although the incubation period was not sufficient for closure of the wounds in either of the treatments, the hydrogel with T extract stimulated more fibroblast migration. In the fibroblast-laden version of the hydrogel with T extract, no wound closure was observed but more keratinocytes migrated to the wound region. These positive outcomes underline the potential of the developed wound dressing as a powerful alternative to improve diabetic wound healing in clinical practice.

Quantum dots (QDs) are luminescent semiconductor nanoparticles with unique optical properties that facilitate their use in sensing, biological labeling, optical imaging, and diagnostics. Wider band gap materials, such as Zinc sulfide, are extensively employed as QD nanoprobes since they offer higher photostability, higher quantum yield, larger molar extinction coefficients, and longer fluorescence lifetimes than conventional organic fluorescent dyes used in bioassays. Tunable multiphoton emission in QDs is accomplished by doping with transition metals, of which, copper is the most beneficial owing to its comparable ionic radius, intense emission, and composition-variable spectral broadening. However, an overdose of Cu is toxic to the cells, leading to apoptosis. This cytotoxicity impedes the utilization of Cu-doped ZnS QDs for biolabeling. The present work deals with the diminution of copper cytotoxicity in Cu-doped ZnS Q-dots by means of silica entrapment, equipping them for in vitro and in vivo bioassays in the future. Cu-doped ZnS Q-dots were synthesized by chemical precipitation method and overlaid with silica by sol–gel method. Cytotoxicity investigation was performed on L929 Mouse fibroblast cells. X-ray diffraction studies confirmed that the prepared Q-dots were approximately 2 nm in size and were in the cubic phase. High resolution transmission electron microscopy revealed the spherical morphology of Q-dots. Micro-Raman Analysis was used to determine the Raman modes of the samples. Band gap energy was computed using UV–Visible Spectroscopy. Photoluminescence (PL) Spectroscopy demonstrated two emission peaks around 418 nm and 455 nm due to sulfur vacancy and copper trap levels, respectively, for Cu:ZnS Q-dots with hiked PL intensity on silica coating. In vitro cell toxicity studies performed on the as-prepared Q-dots by microscopic observation of treated cells, as well as by MTT colorimetric assay, manifested the attenuation of cytotoxicity in silica overspread copper-doped Q-dots. Silica entrapment subsided the copper-induced cytotoxicity by minimizing the photochemical oxidation of the Q-dots surface together with making them hydrophilic. Furthermore, silica coating boosted the PL intensity of the Q-dots. Such Q-dots could be a potent alternative to fluorescent organic pigments for biolabeling.

Portable biosensing is crucial for rapid detection and continuous monitoring of bone diseases such as osteoporosis and bone cancer. It is well established that such bone disorders or diseases trigger release of inflammatory cytokines including interleukin-6 (IL6), detectable in sweat by electrochemical immunosensors. To this end, this study presents a novel hydrogel nanocomposite based immunosensor with highly conductive dual-layer of thermally exfoliated graphene oxide, toward precise detection and determination of loading level of IL-6 biomarker, and in turn, developing a label-free flexible bone biosensing platform. The immunosensor employed antibody immobilization process, which was further facilitated by the modification of the dual-layer by using 1-pyrenebutyric acid N-hydroxy succinimide ester. A thorough analysis of the effects of surface modification was conducted utilizing spectroscopic, electrochemical, and morphological methods. The biosensor's response was assessed through the utilization of the cyclic voltammetry measurement, which exhibited remarkable selectivity, achieving a low limit of detection of 15.4 pg ml⁻¹ across a wide linear range. Additionally, field emission scanning electron microscopy, Fourier transform infrared spectroscopy and Raman spectroscopy were successfully used to validate the sensing substrate in bio-fluidic samples and to understand the structure–property correlation. This innovative portable and flexible biosensor thus offers a practical and effective tool for potential application in continuous monitoring of bone health.

Microwell chip culture is a promising technique for controlling spheroid size and producing a large number of homogeneous spheroids. In this study, we focused on the relationship between chip material and the properties of hepatocyte spheroids. The basic chip design was 397 circular microwells, each 400 µm in diameter. Two types of microwell chips were fabricated, coating the bottom surface either with polyethylene glycol (PEG chip) or polyimide (PI chip). Hepatocytes gradually aggregated and formed floating spheroids within each microwell in the PEG chip but formed adherent spheroids within each microwell of the PI chip. Such floating and adherent spheroid morphologies were maintained for at least one month of culture. An explanation for the spheroid formation mechanism is that the plasminogen activator (PA) /plasmin and matrix degradation/remodeling systems were activated in the formation of adherent spheroids. Furthermore, in adherent spheroid cultures, the formation of cell–matrix junctions was promoted, in addition to the development of intercellular junctions. The albumin secretion and drug metabolism activities of the hepatocyte spheroids were higher than those of traditional monolayer hepatocytes, and the adherent spheroids in the PI chip maintained a higher functional expression than the floating spheroids in the PEG chip. Further to this, functional properties of hepatocytes, the expressions of key metabolic enzymes, glucose 6-phosphatase (sugar metabolism), tryptophan 2, 3-dioxygenase (amino acid metabolism), arginase 1 (urea cycle), cytochrome P450 7a1 (lipid metabolism), and cytochrome P450 families (drug metabolism) were evaluated by gene expression analysis. The expression of these key enzymes in hepatocytes was higher in spheroid culture than in general monolayer culture, and the functions of adherent spheroids were superior to those of floating spheroids. These results indicate that the material properties of the microwell chips are important factors that regulate the morphological and functional characteristics of hepatocyte spheroids.

This study aimed to investigate the osteogenic function of polyetheretherketone (PEEK) scaffolds modified with bone morphogenetic protein 2 (BMP2) and its possibility for orbital fracture repair. The 3D-printed PEEK sheets were combined with BMP2-loaded hyaluronic acid hydrogel (HAH) to fabricate PEEK-BMP2-HAH composite scaffolds. Bone marrow mesenchymal stem cells (BMSCs) were seeded onto PEEK or PEEK-BMP2-HAH scaffolds. Cell adhesion and cell proliferation were measured by transmission electron microscopy and CCK-8 assay. Alkaline phosphatase (ALP) chromogenic, alizarine red S staining, and PCR analysis of Runt-related transcription factor 2 (Runx2), collagen-I (Col-I), Osterix, and osteopontin (OPN) were performed to assess osteogenic activity. The rat orbital fracture defect model is proposed for evaluating the biocompatibility, osteogenic integration, and functional recovery of PEEK orbital implants. Compared with PEEK, cell adhesion and cell proliferation were increased in PEEK-BMP2-HAH scaffolds. ALP activity and mineralized nodule formation were increased in PEEK-BMP2-HAH scaffolds than that in PEEK the mRNA expression of Runx2, Osterix, Col-I and OPN was increased on PEEK-BMP2-HAH scaffolds than that on PEEK at 14 d of osteogenic induction. Besides, a bone defect animal model revealed that BMP2-HAH-modified PEEK scaffolds could effectively facilitate the repair of the orbital bone defect, with increased expression of OPN and Runx2. BMP2-loaded HAH effectively increased adhesion, proliferation, and osteogenic differentiation of BMSCs on PEEK. PEEK-BMP2-HAH scaffolds are expected to become new materials for orbital fracture repair.

Intervention without implantation has become a requirement for developing percutaneous coronary intervention for coronary heart disease. In this paper, the recent advances of three representative types of bioresorbable metal coronary drug-eluting stents (DESs) are reviewed, and the material composition, structural design, mechanical properties and degradability of iron-based, magnesium-based and zinc-based bioresorbable metal coronary DES are analyzed. The methods of regulating the radial strength and degradation rate of the coronary stents are summarized, and the in vivo/in vitro performance evaluation methods and ideal testing systems of the bioresorbable metal coronary DES are analyzed. Advances made in bioresorbable metal coronary DES, the existing shortcomings and optimization methods are proposed, and the future development direction is prospected.

Intervention without implantation has become a requirement for developing percutaneous coronary intervention for coronary heart disease. In this paper, the recent advances of three representative types of bioresorbable metal coronary drug-eluting stents (DESs) are reviewed, and the material composition, structural design, mechanical properties and degradability of iron-based, magnesium-based and zinc-based bioresorbable metal coronary DES are analyzed. The methods of regulating the radial strength and degradation rate of the coronary stents are summarized, and the in vivo/in vitro performance evaluation methods and ideal testing systems of the bioresorbable metal coronary DES are analyzed. Advances made in bioresorbable metal coronary DES, the existing shortcomings and optimization methods are proposed, and the future development direction is prospected.

Temporary anchorage devices (TADs) have evolved as useful anchorage providers for orthodontic tooth movements. To improve the stability of TADs, a number of modifications on their surface have been developed and investigated. This review comprehensively summarizes recent findings of clinically applied surface modifications of TADs and compared the biological improvement of these modifications. We focused on sandblasting, large-grit, acid etching (SLA), anodic oxidation (AO) and ultraviolet photofunctionalization (UVP). In vitro, in vivo and clinical studies of these surface modifications on TADs with clear explanations, low possibility of bias and published in English were included. Studies demonstrated that SLA, AO and UVP enhance cell attachment, proliferation, and differentiation in vitro. The biocompatibility and osteoconductivity of TAD surface are improved in vivo. However, in clinical studies, the changes are generally not so impressive. Furthermore, this review highlights the promising potential in combinations of different modifications. In addition, some other surface modifications, for instance, the biomimetic calcium phosphate coating, deserve to be proposed as future strategies.

Bioprinting, an advanced additive manufacturing technology, enables the fabrication of complex, viable three-dimensional (3D) tissues using bioinks composed of biomaterials and cells. This technology has transformative applications in regenerative medicine, drug screening, disease modeling, and biohybrid robotics. In particular, in situ bioprinting has emerged as a promising approach for directly repairing damaged tissues or organs at the defect site. Unlike traditional 3D bioprinting, which is confined to flat surfaces and require complex equipment, in situ techniques accommodate irregular geometries, dynamic environments and simple apparatus, offering greater versatility for clinical applications. In situ bioprinting via hand-held devices prioritize flexibility, portability, and real-time adaptability while allowing clinicians to directly deposit bioinks in anatomically complex areas, making them cost-effective, accessible, and suitable for diverse environments, including field surgeries. This review explores the principles, advancements, and comparative advantages of robotic and hand-held in situ bioprinting, emphasizing their clinical relevance. While robotic systems excel in precision and scalability, hand-held bioprinters offer unparalleled flexibility, affordability, and ease of use, making them a valuable tool for personalized and minimally invasive tissue engineering. Future research should focus on improving biosafety, aseptic properties, and bioink formulations to optimize these technologies for widespread clinical adoption.

Natural polymer-based hydrogels, generally composed of hydrophilic polymers capable of absorbing large amounts of water, have garnered attention for biomedical applications because of their biocompatibility, biodegradability, and eco-friendliness. Natural polymer-based hydrogels derived from alginate, starch, cellulose, and chitosan are particularly valuable in fields such as drug delivery, wound dressing, and tissue engineering. However, compared with synthetic hydrogels, their poor mechanical properties limit their use in load-bearing applications. This review explores recent advancements in the enhancement of the mechanical strength of natural hydrogels while maintaining their biocompatibility for biomedical applications. Strategies such as chemical modification, blending with stronger materials, and optimized cross-linking are discussed. By improving their mechanical resilience, natural hydrogels can become more suitable for demanding biomedical applications, like tissue scaffolding and cartilage repair. Additionally, this review identifies the ongoing challenges and future directions for maximizing the potential of natural polymer-based hydrogels in advanced medical therapies.

Bone defects, resulting from trauma, tumor removal, infection, or congenital anomalies, are increasingly prevalent in clinical practice. Progress in bone tissue engineering has significantly advanced bone regeneration techniques. Chitosan-based nanoparticles (ChNPs) have emerged as a promising drug delivery system due to their inherent ability to enhance bone regeneration. These nanoparticles can extend the activity of osteogenic factors while ensuring their controlled release. Common synthesis methods for ChNPs include ionic gelation, complex coacervation, and polyelectrolyte complexation. ChNPs have demonstrated effectiveness in bone regeneration by delivering osteogenic agents, including DNA/RNA, proteins, and therapeutics. This review provides a comprehensive analysis of recent studies on ChNPs in bone regeneration, sourced from the PubMed database. It examines their synthesis techniques, advantages as drug delivery systems, incorporation into scaffold materials, and the challenges that remain in the field.

Osteoarthritis has become a common degenerative joint disease, lacking clinical means to alleviate this disease. Melittin, taken from natural honeybee venom, possesses outstanding anti-inflammatory properties and has great potential to treat OA. However, its high toxicity and hemolytic properties limit its application. In this work, a biocompatible hydrogel was prepared from extracellular matrix of rib cartilage, possessing fibrous mesh structure characteristics, which was beneficial for melittin loading. It was found that the use of extracellular matrix hydrogel loaded with melittin can reduce the intrinsic toxicity of melittin and prolong the release behavior, simultaneously. The in vitro study demonstrated that melittin-hydrogel could effectively inhibit phosphorylation-ERK/JNK, prevent the exacerbation of TNF-α-induced apoptosis in ATDC5 cells, and reduce their inflammatory markers, effectively alleviating osteoarthritis and preventing cartilage degradation.&#xD;Subsequently, in vivo studies have demonstrated that injecting melittin-hydrogel into the joint cavity of OA mice can effectively reduce cartilage degeneration. These findings suggest that melittin-hydrogel plays a critical role in the development of osteoarthritis and may provide a therapeutic option for the treatment of OA disease.&#xD;

Nanoparticle-mediated drug delivery has revolutionized nano-therapeutics. It ensures improved biodistribution, longer blood circulation, and improved bioavailability inside the body. The loading efficiency and stability of the drug within the carrier are the major challenges for ideal drug delivery. In this study, we have synthesized indocyanine green (ICG) loaded Poly-L-Lysine (PLL) nanoparticles by a two-step self-assembly process using a green chemistry approach, where water-based solvents were used for fabrication such as phosphate-buffered saline (PBS, pH 7.4), deionized water (DI), and Milli-Q water (MQ). The effect of these solvents on the morphology, stability and loading efficiency of ICG was investigated using UV-visible spectroscopy, fluorescence spectroscopy, scanning electron microscopy (SEM), and dynamic light scattering (DLS). The results demonstrated that nanoparticles can be fabricated using all the three solvents, however, there was a huge difference between their functional and morphological properties. These functional and morphological properties play important role in their biomedical applications. It was found that PBS-based NPs showed the maximum loading of ICG followed by deionized water and Milli-Q water respectively. The PBS suspended ICG-loaded PLL nanoparticles were highly monodispersed with the mean diameter of ~200 nm and showed highest photothermal efficiency. The green synthesized biocompatible and biodegradable NPs were designed to treat solid tumors via local hyperthermia due to photothermal property of these NPs. The photothermal cytotoxicity assessment of PBS-based PLL-ICG NPs in both 2D and 3D in vitro cultures displayed notable efficacy. Therefore, we conclusively demonstrate that selection of right solvent is crucial to realize the full potential of green-synthesized polymeric nanoparticles.

Although conventional chemotherapeutic drugs exhibit broad-spectrum antitumor efficacy, their toxic effects on normal cells cannot be ignored, and there is an urgent need to develop novel drugs to improve therapeutic efficacy and reduce side effects. In this study, we prepared PLGA/TA microspheres with tannin as the target drug and PLGA as the carrier, and evaluated their physicochemical properties, including particle size, morphology, and release behavior, with the aim of exploring the potential of PLGA/TA microspheres for tumor therapy. The results of RNA sequencing showed that PLGA/TA microspheres may act on tumor cells mainly through the pathway of PI3K-Akt, and do not interfere with the synthesis of DNA directly. synthesis. Overall, PLGA/TA microspheres, as a novel drug delivery system, showed good anti-tumor potential and provided new ideas and directions for cancer therapy.&#xD;

Periodontitis seriously affects people's daily health, and the development of a non-antibiotic bio-adhesive with antimicrobial and periodontitis regeneration for periodontal pockets will effectively promote the treatment of periodontitis. In this study, we constructed a hybrid hydrogel (GelMA-BC-PL) by introducing aldehyde bacterial cellulose (BC) short nanofibers into the photosensitive hydrogel (GelMA), which binds to periodontal tissues to play an adhesive role through the Schiff base reaction, and further introducing ε-polylysine (PL), which could achieve the adhesive, antibacterial, and regenerative effect. Pigskin adhesion experiments showed that the adhesion of GelMA hydrogel to pigskin was only 0.39 N, while that of GelMA-BC-PL reached 1.42 N. The adhesion performance of the hydrogel was significantly improved by adding aldehyde BC nanofibers. Due to the introduction of ε-polylysine, the antimicrobial properties of the hybrid hydrogel against two typical periodontitis bacteria (porphyromanas gingivalis and fusobacterium nucleatum), were significantly improved. Experiments with human periodontal membrane fibroblasts showed that the hybrid hydrogel had excellent cell spreading and proliferation promotion properties. The hybrid hydrogel simultaneously achieves adhesion, antimicrobial properties and promotes periodontal regeneration, which has great potential for application in the treatment of periodontitis diseases.&#xD;

Bone injury presents a prevalent challenge in clinical settings, with traditional treatment modalities exhibiting inherent limitations. Recent advancements have highlighted the potential of combining physical exercise intervention and innovative materials to enhance bone repair and recovery. This review explores the synergistic effects of physical exercise and novel materials in promoting bone regeneration, with a particular focus on the role of neurovascular coupling mechanisms. Physical exercise not only stimulates bone cell function and blood circulation but also enhances the bioactivity of novel materials, such as nanofiber membranes and smart materials, which provide supportive scaffolds for bone cell attachment, proliferation, and differentiation. Neurovascular coupling, involving the interaction between neural activity and blood flow, is integral to the bone repair process, ensuring the supply of nutrients and oxygen to the injured site. Studies demonstrate that the combination of physical exercise and novel materials can accelerate bone tissue regeneration, with exercise potentially enhancing the bioactivity of materials and materials improving the effectiveness of exercise. However, challenges remain in clinical applications, including patient variability, material biocompatibility, and long-term stability. Optimizing the integration of physical exercise and novel materials for optimal therapeutic outcomes is a key focus for future research. This review examines the collaborative mechanisms between physical exercise, novel materials, and neurovascular coupling, emphasizing their potential and the ongoing challenges in clinical settings. Further exploration is needed to refine their application and improve bone repair strategies.

Osteoarthritis has become a common degenerative joint disease, lacking clinical means to alleviate this disease. Melittin, taken from natural honeybee venom, possesses outstanding anti-inflammatory properties and has great potential to treat OA. However, its high toxicity and hemolytic properties limit its application. In this work, a biocompatible hydrogel was prepared from extracellular matrix of rib cartilage, possessing fibrous mesh structure characteristics, which was beneficial for melittin loading. It was found that the use of extracellular matrix hydrogel loaded with melittin can reduce the intrinsic toxicity of melittin and prolong the release behavior, simultaneously. The in vitro study demonstrated that melittin-hydrogel could effectively inhibit phosphorylation-ERK/JNK, prevent the exacerbation of TNF-α-induced apoptosis in ATDC5 cells, and reduce their inflammatory markers, effectively alleviating osteoarthritis and preventing cartilage degradation.&#xD;Subsequently, in vivo studies have demonstrated that injecting melittin-hydrogel into the joint cavity of OA mice can effectively reduce cartilage degeneration. These findings suggest that melittin-hydrogel plays a critical role in the development of osteoarthritis and may provide a therapeutic option for the treatment of OA disease.&#xD;

Periodontitis seriously affects people's daily health, and the development of a non-antibiotic bio-adhesive with antimicrobial and periodontitis regeneration for periodontal pockets will effectively promote the treatment of periodontitis. In this study, we constructed a hybrid hydrogel (GelMA-BC-PL) by introducing aldehyde bacterial cellulose (BC) short nanofibers into the photosensitive hydrogel (GelMA), which binds to periodontal tissues to play an adhesive role through the Schiff base reaction, and further introducing ε-polylysine (PL), which could achieve the adhesive, antibacterial, and regenerative effect. Pigskin adhesion experiments showed that the adhesion of GelMA hydrogel to pigskin was only 0.39 N, while that of GelMA-BC-PL reached 1.42 N. The adhesion performance of the hydrogel was significantly improved by adding aldehyde BC nanofibers. Due to the introduction of ε-polylysine, the antimicrobial properties of the hybrid hydrogel against two typical periodontitis bacteria (porphyromanas gingivalis and fusobacterium nucleatum), were significantly improved. Experiments with human periodontal membrane fibroblasts showed that the hybrid hydrogel had excellent cell spreading and proliferation promotion properties. The hybrid hydrogel simultaneously achieves adhesion, antimicrobial properties and promotes periodontal regeneration, which has great potential for application in the treatment of periodontitis diseases.&#xD;

Osteoporosis poses a significant public health challenge, necessitating advanced bone regeneration solutions. While gelatin methacrylate (GelMA) hydrogels show promise, conventional fabrication methods using aqueous two-phase systems (ATPS) often result in inconsistent mechanical properties and structural irregularities. This study presents an approach synthesizing new methods and parameters for bR-GelMA, utilizing stop-flow lithography (SFL) to fabricate highly elastic micro-particles incorporating bioactive glass particles. SFL, in contrast to ATPS, offers precise control over micro-particle formation, enabling the production of uniform and stable structures ideal for biomedical applications. The resulting elastic micro-particles demonstrate rapid degradation, enhanced cell proliferation, and improved mechanical strength without compromising flexibility. This innovative approach using SFL to fabricate GelMA-based micro-particles holds significant promise for bone regeneration and other critical therapeutic applications.

The erosion and drug release behavior of an injectable hydrogel composed of ethoxylated trimethylolpropane tri-3-mercaptopropionate (ETTMP) and poly(ethylene glycol) diacrylate (PEGDA) were determined under physiological conditions. The water and polymer mass changes were monitored over time to characterize the swelling/deswelling and erosion of the hydrogel tablets. Experimental data were collected for hydrogels with varying polymer fractions. These data were used to develop an empirical model for predicting the eroding mass change and equilibrium water content across different compositions. Three easily detectable model drugs (methylene blue, sulforhodamine 101, and chloroquine) were loaded into 25, 35, and 50 wt% polymer hydrogels to understand their drug release behavior. The gelation time and time for total release was dependent on the weight fraction of the polymer in the hydrogel and varied with the pH of the drug solutions, with more acidic drugs increasing gelation time. Complete drug release was not observed for methylene blue due to the reaction with ETTMP thiol groups, demonstrating the importance of understanding the potential interactions between the drug and polymer. Drug-loaded hydrogels were also monitored for erosion and were found to swell more than their neat counterparts for all drugs tested, suggesting an effect of drug loading on the extent of hydrogel crosslinking.&#xD;

The development of magnesium-based intraocular drug delivery devices holds significant promise for biomedical applications, particularly in treating wet age-related macular degeneration (AMD) using vascular endothelial growth factor (VEGF) inhibitors such as bevacizumab. Magnesium's rapid degradation, which can be finely tuned to achieve the controlled release required for AMD treatment, along with its well-established biocompatibility and biodegradable properties, positioning it as an ideal material for these applications. The study aimed to evaluate magnesium's potential as a carrier for ocular drug delivery systems by demontrating the stability of monoclonal antibodies, specifically bevacizumab, in the presence of magnesium corrosion products and the biocompatibility of these products with various cell lines, including murine fibroblasts (3T3), rat retinal Müller cells (RMC-1), and human retinal pigment epithelial cells (ARPE19). The stability of bevacizumab with pure magnesium (Mg) was investigated through an indirect ELISA protocol, developed and customized for this specific aim. The biocompatibility of Mg corrosion products was assessed by toxicological evaluations through MTT and Trypan Blue Viability assays, along with cell cycle analysis. Results demonstrated no significant impact of Mg corrosion products on bevacizumab stability, with changes in mean values consistently below or equal to 10%. Furthermore, Mg extracts showed minimal cytotoxicity, as metabolic activity exceeded 80% across all cell lines, classified as Grade 0/1 cytotoxicity under ISO 10993–5 standards. Cell viability, proliferation, and morphology remained unaffected for up to 72 hours of exposure. This study provides the first in vitro evaluation of bevacizumab's stability in the presence of magnesium corrosion products and its biocompatibility with retinal cell lines, laying the foundation for future ophthalmic research and underscoring magnesium's potential as a material for intraocular drug delivery systems.

Temporary anchorage devices (TADs) have evolved as useful anchorage providers for orthodontic tooth movements. To improve the stability of TADs, a number of modifications on their surface have been developed and investigated. This review comprehensively summarizes recent findings of clinically applied surface modifications of TADs and compared the biological improvement of these modifications. We focused on sandblasting, large-grit, acid etching (SLA), anodic oxidation (AO) and ultraviolet photofunctionalization (UVP). In vitro, in vivo and clinical studies of these surface modifications on TADs with clear explanations, low possibility of bias and published in English were included. Studies demonstrated that SLA, AO and UVP enhance cell attachment, proliferation, and differentiation in vitro. The biocompatibility and osteoconductivity of TAD surface are improved in vivo. However, in clinical studies, the changes are generally not so impressive. Furthermore, this review highlights the promising potential in combinations of different modifications. In addition, some other surface modifications, for instance, the biomimetic calcium phosphate coating, deserve to be proposed as future strategies.

Bioprinting, an advanced additive manufacturing technology, enables the fabrication of complex, viable three-dimensional (3D) tissues using bioinks composed of biomaterials and cells. This technology has transformative applications in regenerative medicine, drug screening, disease modeling, and biohybrid robotics. In particular, in situ bioprinting has emerged as a promising approach for directly repairing damaged tissues or organs at the defect site. Unlike traditional 3D bioprinting, which is confined to flat surfaces and require complex equipment, in situ techniques accommodate irregular geometries, dynamic environments and simple apparatus, offering greater versatility for clinical applications. In situ bioprinting via hand-held devices prioritize flexibility, portability, and real-time adaptability while allowing clinicians to directly deposit bioinks in anatomically complex areas, making them cost-effective, accessible, and suitable for diverse environments, including field surgeries. This review explores the principles, advancements, and comparative advantages of robotic and hand-held in situ bioprinting, emphasizing their clinical relevance. While robotic systems excel in precision and scalability, hand-held bioprinters offer unparalleled flexibility, affordability, and ease of use, making them a valuable tool for personalized and minimally invasive tissue engineering. Future research should focus on improving biosafety, aseptic properties, and bioink formulations to optimize these technologies for widespread clinical adoption.

Curcumin is a natural polyphenol extracted from plants that interacts with various molecular targets and exhibits antioxidant, antibacterial, anticancer, and anti-aging properties. Due to its various pharmacological activities and high safety margin, curcumin has been used in the prevention and treatment of various diseases, including Alzheimer's, heart, and rheumatic immune diseases. To develop curcumin eye drops that can be used as antioxidant and antibacterial agents after phacoemulsification, we designed a nano-based drug delivery system to improve curcumin bioavailability and duration of action. We successfully prepared a zeolitic imidazolate framework-8 (ZIF-8) coated with chitosan-liposome for curcumin delivery (Cur@ZIF-8/CS-Lip). This system enables sustained curcumin release for over 20 h in vitro and exhibits excellent biosafety, antioxidant, and antibacterial activities. Therefore, we proposed that Cur@ZIF-8/CS-Lip may reduce the incidence of oxidative stress and infections following cataract surgery.&#xD;

NanoMIPs are nanoscale molecularly imprinted polymers (MIPs) ranging in size between 30 to 300 nm offering a high affinity binding reagent as an alternative to antibodies. They are being extensively researched for applications in biological extraction, disease diagnostics and biosensors. Various methodologies for nanoMIP production have been reported demonstrating variable timescales required, sustainability, ease of synthesis and final yields. We report herein a fast (<2 h) method for one pot aqueous phase synthesis of nanoMIPs using an acrylamide-based monomer and N,N'-methylenebisacrylamide crosslinker. NanoMIPs were produced for a model protein template namely haemoglobin from bovine species. We demonstrate that nanoMIPs can be produced within 15 min. We investigated reaction quenching times between 5 and 20 min. Dynamic light scattering results demonstrate a distribution of particle sizes (30–900 nm) depending on reaction termination time, with hydrodynamic particle diameter increasing with increasing reaction time. We attribute this to not only particle growth due to polymer chain growth but based on AFM analysis, also a tendency (after reaction termination) for particles to agglomerate at longer reaction times. Batches of nanoMIPs ranging 400–800 nm, 200–400 nm and 100–200 nm were isolated using membrane filtration. The batches were captured serially on decreasing pore size microporous polycarbonate membranes (800–100 nm) and then released with sonication to isolate nanoMIP batches in the aforementioned ranges. Rebinding affinities of each batch were determined using electrochemical impedance spectroscopy, by first trapping nanoMIP particles within an electropolymerized thin layer. Binding constants determined for NanoMIPs using the E-MIP sensor approach are in good agreement with surface plasmon resonance results. We offer a rapid (<2 h) and scalable method for the mass production (40–80 mg per batch) of high affinity nanoMIPs.

This study aims to employ poly-L-lactic acid (PLLA) and poly(p-dioxanone) (PPDO), loaded with naringin (NAR) to fabricate a functionalized degradable mesh which can promote abdominal wall hernia (AWH) repair. Three meshes named PPDO, PLLA/PPDO, and PLLA/PPDO/NAR were fabricated by electrospinning. The physical and chemical properties of the meshes were evaluated from the aspects of morphology, wettability, chemical composition, mechanical properties, and in vitro degradation. Then, the meshes were implanted into rats to evaluate their repair effects on abdominal wall defect models. The mechanical properties of PLLA/PPDO/NAR mesh were superior to the other two meshes, with a fixed tensile strength of 36.47 ± 2.40 N cm⁻¹ and an elongation at break of 287.98% ± 51.67%, which adequately met the mechanical strength required for the human abdominal wall. The core–shell structure effectively delayed the degradation of PLLA/PPDO as well as PLLA/PPDO/NAR mesh, and drug release of PLLA/PPDO/NAR mesh. On the 7th, 14th, and 28th day after implantation, more neovascularization and tissue formation were observed in the PLLA/PPDO/NAR group and the newborn collagen was arranged in a regular and neat manner compared to the other two groups. The immunohistochemical results showed that the PLLA/PPDO/NAR mesh promoted abdominal wall repair by inhibiting the expression of matrix metalloproteinase2 as well as interleukin-6, and increasing the expression of vascular endothelial growth factor. The PLLA/PPDO/NAR mesh is promising for application in AWH repair.