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.

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 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, and human retinal pigment epithelial cells (ARPE19). The stability of bevacizumab with pure magnesium (Mg) was investigated through an indirect enzyme-linked immunosorbent assay 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 h 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.

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.

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

With the advent of nanotechnology, there has been an extensive interest in the antimicrobial potential of metals. The rapid and widespread development of antimicrobial-resistant and multidrug-resistant bacteria has prompted recent research into developing novel or alternative antimicrobial agents. In this study, the antimicrobial efficacy of metallic copper, cobalt, silver and zinc nanoparticles was assessed against Escherichia coli (NCTC 10538), S. aureus (ATCC 6538) along with three clinical isolates of Staphylococcus epidermidis (A37, A57 and A91) and three clinical isolates of E. coli (Strains 1, 2 and 3) recovered from bone marrow transplant patients and patients with cystitis respectively. Antimicrobial sensitivity assays, including agar diffusion and broth macro-dilution to determine minimum inhibitory and bactericidal concentrations (MIC/MBC) and time-kill/synergy assays, were used to assess the antimicrobial efficacy of the agents. The panel of test microorganisms, including antibiotic-resistant strains, demonstrated a broad range of sensitivity to the metals investigated. MICs of the type culture strains were in the range of 0.625–5.0 mg ml⁻¹. While copper and cobalt exhibited no difference in sensitivity between Gram-positive and Gram-negative microorganisms, silver and zinc showed strain specificity. A significant decrease (p < 0.001) in the bacterial density of E. coli and S. aureus was demonstrated by silver, copper and zinc in as little as two hours. Furthermore, combining metal nanoparticles reduced the time required to achieve a complete kill.

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.

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.

The erosion and drug release behavior of an injectable hydrogel composed of ethoxylated trimethylolpropane tri-3-mercaptopropionate (ETTMP) and poly(ethylene glycol) diacrylate were determined under physiological conditions. 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 to predict the eroding mass change and equilibrium water content across different compositions. Three easily detectable model drugs (methylene blue (MB), 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 drug release were 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 MB because of 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.

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.

Osteoarthritis (OA) 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 (ECM) of rib cartilage, possessing fibrous mesh structure characteristics, which was beneficial for melittin loading. It was found that the use of ECM 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 OA and preventing cartilage degradation. 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 OA and may provide a therapeutic option for the treatment of OA disease.

Despite their impact on cancer therapy, limitations such as systemic toxicity and drug resistance are encountered with platinum-based drugs. This study explores the potential of combining Pt^IV-based NP with carmofur (Car) to address these issues. In this study, platinum nanoparticles (PtNPs) and Car-loaded PtNP (Car@PtNP) were synthesized and their cytotoxic and apoptotic effects on colorectal and breast cancer cells were evaluated. Following characterization of the synthesized NPs by dynamic light scattering, UV–VIS spectroscopy, FTIR, and STEM, it was found that the average size of PtNPs was 55.42 nm and the size increased to approximately 186.06 nm upon synthesis of Car@PtNP. MTT assays demonstrated that Car@PtNP exhibited higher levels of cellular toxicity than carmofur alone. While it significantly decreased cell viability in both colon and breast cancer cells, its toxicity to HUVEC cells was minimal. Treatment of MCF-7 and HCT116 cells with 50 µg ml⁻¹ of free Car resulted in cell viabilities of 65.2% and 76.93%, respectively, whereas the viability of cells treated with Car@PtNP decreased to 49.60% and 55.47%. Flow cytometric analysis confirmed that apoptosis was increased in healthy HCT116 cells treated with Car@PtNP, with a marked increase in both early and late apoptotic cell populations. Furthermore, these results were confirmed by Hoescht and Rhodamin123 immunofluorescence staining, and significant mitochondrial dysfunction and apoptotic morphological changes were observed in treated cells. The findings underscore the promise of Car@PtNP as a novel chemotherapeutic approach, integrating the benefits of Pt^IV complexes and Car to enhance antitumor efficacy while mitigating the drawbacks of conventional platinum-based therapies.

Although human periodontal ligament stem cell (hPDLSC)-based tissue engineering have been promising for regenerating periodontal bone tissue, their effectiveness is limited by the lack of an optimal delivery vehicle for these cells. Therefore, this study reports a gelatin methacryloyl microsphere system, incorporating injectable platelet-rich fibrin and nano-hydroxyapatite (nHA) as carriers for hPDLSCs. These hybrid microspheres were effectively produced using droplet microfluidics technology, achieving a size range of 100–300 μm. Importantly, the release profile of multiple growth factors (GFs) from the microspheres was significantly extended, lasting up to 28 d. Moreover, the released GFs and nHA considerably enhanced the proliferation of encapsulated hPDLSCs along with their spreading and osteogenic differentiation. The microspheres facilitated the development of Spheroid-like cell aggregates within two weeks of culture, demonstrating a promising approach for advanced periodontal bone tissue regeneration.

Cardiovascular diseases (CVD) can cause narrowing or blockage in small diameter blood vessels (less than 6 millimeters in diameter). Bypass surgery, which involves replacing damaged native blood vessels, can address various CVD. Recent advancements in manufacturing techniques and the application of new materials have led to the creation of artificial blood vessels that more closely resemble native vessels. By combining different materials and manufacturing methods, it is possible to mimic the structure and function of native blood vessels. Surface coating technologies are also employed in the production of artificial blood vessels to replicate certain vascular functions, such as regulating thrombosis and dissolution. Although most products are not yet ready for clinical use, research and development in artificial blood vessels are progressing faster than ever before (figure 1).

Pancreatic duct strictures, which can arise from trauma, inflammation, or malignancy, often result in complications such as duct obstruction, pancreatic parenchymal hypertension, and ischemia. Endoscopic stenting is an effective therapeutic approach for managing these strictures. However, traditional plastic pancreatic duct stents fail to conform to the physiological curvature of the pancreas, while metal pancreatic duct stents with flared ends reduce migration but are associated with complications such as de novo strictures. Additionally, plastic and metal pancreatic duct stents require surgical removal. Whereas biodegradable pancreatic duct stents present a promising alternative due to their superior biocompatibility and ability to decompose into non-toxic materials, potentially eliminating the need for additional surgeries. Despite these advantages, biodegradable pancreatic duct stents remain in the experiment stage. This review assesses current materials of pancreatic duct stents, and emphasizes recent advancements in biodegradable options and emerging trends in clinical applications.

Biomedical implants are extensively utilized to replace hard-tissue defects owing to their biocompatibility and remarkable tissue-affinity. The materials and functional design are selected based on the resultant osseointegration level and resistance to infection, and these considerations constitute the dominant research topic in this field. However, high rates of implantation failure and peri-implantitis have been reported. Current research on biomedical-implant design encompasses enhancement of the implant surface properties, such as the roughness, nano/micro topography, and hydrophilicity, along with the realization of advanced features including antibacterial properties and cell and immunomodulation regulation. This review considers the two achievements of contemporary implant manufacturing; namely, osseointegration and the realization of antibacterial properties. Present mainstream surface modifications and coatings are discussed, along with functional design technologies and achievements. The impacts of direct surface-treatment techniques and osteogenic functional coatings on osseointegration performance and antibacterial surface structures are elucidated, considering inorganic and organic coatings with antibacterial properties as well as antibiotic-releasing coatings. Furthermore, this review highlights recent advancements in physically driven antimicrobial strategies. Expanding upon existing research, future directions for implant studies are proposed, including the realization of comprehensive functionality that integrates osseointegration and antibacterial properties, as well as patient-specific design. Our study presents a comprehensive review and offers a novel perspective on the design of biomedical implants for enhanced versatility. An in-depth exploration of future research directions will also stimulate subsequent investigations.

Cardiovascular diseases (CVD) can cause narrowing or blockage in small diameter blood vessels (less than 6 millimeters in diameter). Bypass surgery, which involves replacing damaged native blood vessels, can address various CVD. Recent advancements in manufacturing techniques and the application of new materials have led to the creation of artificial blood vessels that more closely resemble native vessels. By combining different materials and manufacturing methods, it is possible to mimic the structure and function of native blood vessels. Surface coating technologies are also employed in the production of artificial blood vessels to replicate certain vascular functions, such as regulating thrombosis and dissolution. Although most products are not yet ready for clinical use, research and development in artificial blood vessels are progressing faster than ever before (figure 1).

Pancreatic duct strictures, which can arise from trauma, inflammation, or malignancy, often result in complications such as duct obstruction, pancreatic parenchymal hypertension, and ischemia. Endoscopic stenting is an effective therapeutic approach for managing these strictures. However, traditional plastic pancreatic duct stents fail to conform to the physiological curvature of the pancreas, while metal pancreatic duct stents with flared ends reduce migration but are associated with complications such as de novo strictures. Additionally, plastic and metal pancreatic duct stents require surgical removal. Whereas biodegradable pancreatic duct stents present a promising alternative due to their superior biocompatibility and ability to decompose into non-toxic materials, potentially eliminating the need for additional surgeries. Despite these advantages, biodegradable pancreatic duct stents remain in the experiment stage. This review assesses current materials of pancreatic duct stents, and emphasizes recent advancements in biodegradable options and emerging trends in clinical applications.

Biomedical implants are extensively utilized to replace hard-tissue defects owing to their biocompatibility and remarkable tissue-affinity. The materials and functional design are selected based on the resultant osseointegration level and resistance to infection, and these considerations constitute the dominant research topic in this field. However, high rates of implantation failure and peri-implantitis have been reported. Current research on biomedical-implant design encompasses enhancement of the implant surface properties, such as the roughness, nano/micro topography, and hydrophilicity, along with the realization of advanced features including antibacterial properties and cell and immunomodulation regulation. This review considers the two achievements of contemporary implant manufacturing; namely, osseointegration and the realization of antibacterial properties. Present mainstream surface modifications and coatings are discussed, along with functional design technologies and achievements. The impacts of direct surface-treatment techniques and osteogenic functional coatings on osseointegration performance and antibacterial surface structures are elucidated, considering inorganic and organic coatings with antibacterial properties as well as antibiotic-releasing coatings. Furthermore, this review highlights recent advancements in physically driven antimicrobial strategies. Expanding upon existing research, future directions for implant studies are proposed, including the realization of comprehensive functionality that integrates osseointegration and antibacterial properties, as well as patient-specific design. Our study presents a comprehensive review and offers a novel perspective on the design of biomedical implants for enhanced versatility. An in-depth exploration of future research directions will also stimulate subsequent investigations.

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 (NVC) 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. NVC, 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 NVC, emphasizing their potential and the ongoing challenges in clinical settings. Further exploration is needed to refine their application and improve bone repair strategies.

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.

The incorporation of electroconductive and magnetic materials into scaffolds for tissue engineering has emerged as an innovative approach to enhance nerve tissue regeneration. In this study, the freeze-drying technique was used to fabricate a bifunctional 3D neural scaffold based on biodegradable polyvinyl alcohol (PVA), incorporating magnetite nanoparticles (Fe₃O₄ NPs) and the conductive polymer polypyrrole (PPy). Microstructural and chemical analyses using FESEM/EDS, XRD, and FTIR revealed scaffolds with a homogeneous structure, interconnected pores averaging 100 µm, and over 80% porosity, with magnetite evenly distributed in the PVA matrix. The incorporation of Fe₃O₄ nanoparticles significantly enhanced the scaffold's compressive strength and elastic modulus, while PPy increased conductivity to levels comparable to those of native neural tissue. The scaffold also exhibited superparamagnetic properties due to Fe₃O₄ NPs, as confirmed by VSM analysis. PBS submersion demonstrated water absorption and a 30% weight loss over 24 days. In vitro cytotoxicity tests on SH-SY5Y human neuroblastoma cells cultured on composite scaffolds confirmed cell viability, both with and without pulsed electromagnetic field stimulation. Overall, these results suggest that this scaffold is a promising candidate for neural tissue regeneration.

Macrophage polarisation is crucial for initiating inflammation in response to biomaterial scaffolds, significantly influencing tissue integration and regeneration in vivo. Modulating macrophage polarisation towards a tissue-regeneration-favouring phenotype through the physical properties of scaffolds offers a promising strategy to enhance tissue regeneration while minimizing unfavourable immune responses. However, the critical impact of scaffold physical properties, such as size-scale dimensions, orientation of architectural cues, and local stiffness of these cues on macrophage polarization, remains largely unexplored and inadequately understood. This study investigates the combinatorial effects of the physical properties of 3D scaffolds made from Poly (ε-caprolactone) on human macrophage polarisation. Our findings indicate that the size-scale dimensions and orientation of the architectural cues of the scaffold play crucial roles in determining cell shape, attachment, and the modulation of key gene expression (iNOS, IL-1β, MRC1, ARG), as well as cytokines (TNF-α, IL-10) release associated with the polarisation of human macrophages. Specifically, in scaffolds with architectural cues at larger scales (≥ 300 µm diameter), macrophage polarisation is primarily determined by the size-scale of the architectural cues and scaffold stiffness, rather than orientation. Conversely, at smaller scales (≤ 15 µm), the orientation of the scaffold's architectural cues plays a more critical role. These insights underscore the pivotal role of scaffold design in modulating immune responses for enhanced tissue regeneration, offering valuable guidance for the rational development of biomaterial scaffolds in regenerative medicine.

Diabetes, a metabolic disease that is becoming increasingly severe globally, presents a significant challenge in the medical field. Diabetic wounds are characterized by their chronicity, difficulty healing, and complex microenvironment that harbors multiple adverse factors, including elevated hyperglycemia, persistent inflammation, susceptibility to infections, and oxidative stress, all of which contribute to the impaired healing process. Nanocomposite hydrogels, as materials with unique physicochemical properties and biocompatibility, have gained growing attention in recent years for their potential applications in diabetic wound healing. These hydrogels provide a moist healing environment for wounds and regulate cellular behavior and signaling pathways, promoting wound repair and healing. By introducing specific functional groups and nanoparticles, nanocomposite hydrogels can respond to pathological features of wounds, enabling adaptive drug release. Owing to their diverse bioactive functions, nanocomposite hydrogels are powerful tools for the treatment of diabetic wounds. Thus, this article provides an overview of recent progress in the use of nanocomposite hydrogels for diabetic wound healing.

The growing interest in peripheral nerve regeneration and developing post-traumatic repair methods under diabetes was the impetus for this study, which aims to investigate the effect of curcumin and Garcinia kola on the transected and diabetic sciatic nerves. 35 male Wistar albino rats were used. The animals were divided into five groups; each consisted of seven rats. The sciatic nerve was transected in all groups of rats except for the control (Cont) group, which underwent no treatment. In the transected animals, a 10 mm nerve stump was removed from the two cm distal to the sciatic notch. The external jugular vein was used as a conduit to repair the gap between the two ends of the sciatic nerve. Diabetes was induced in the transected + diabetes mellitus (T+DM), the transected + diabetes mellitus + Garcinia kola (T+DM+GK), and the transected + diabetes mellitus + Curcumin (T+DM+Cur) groups except for the sham group. A dose of 300 mg/kg/day of curcumin dissolved in olive oil was administered to the T+DM+Cur group (via oral gavage every day for 28 days) and 200 mg/kg/day of Garcinia kola to the T+DM+GK group (via oral gavage every day for seven days). All animals were sacrificed after three months. Stereological analysis and functional and microscopic evaluations were done to evaluate the sciatic nerve regeneration and function. In the T+DM+GK and the sham groups, the number of axons increased. A slight improvement in the axonal area in the T+DM+Cur and the sham groups was also observed, and an increase in the myelin sheath thickness was found in the T+DM+GK and the sham group. When the SFI test results were evaluated, it was seen that GK had a stronger effect than curcumin in terms of functional regeneration. Additionally, no significant difference was observed between T+DM and Cont groups when the electrophysiological results were examined. The study showed GK's efficiency in treating diabetic peripheral nerve regeneration.&#xD;

The middle ear, which lies between the external auditory canal and the inner ear, comprises the tympanic membrane, the ossicular chain, as well as the associated muscles, ligaments, and the middle ear cavity. Its primary function is to transmit vibratory energy from the air to the cochlear fluids via the ossicular chain. This part of the ear can be damaged by cholesteatoma, which can affect all three ossicles,necessitating ossiculoplasty to restore sound transmission. Ossiculoplasty is the preferred intervention for restoring the mechanism of sound transmission in patients with ossicular deformities. However, the complexity and extended duration of the surgery can significantly impact the patient's quality of life. To address these challenges, our work employs 3D printing technology for the reconstruction of the patient's ear ossicles. This involves detailed 3D modeling and reconstruction of the ear ossicles to obtain precise measurements and visualize the unique anatomical structure of each patient.The model presented in this study is a prototype designed to validate the form and dimensions of a total ossicular replacement prosthesis. Our radiologists and traumatologists reviewed both the form and dimensions and deemed them realistic, ensuring they aligned with clinical requirements. It is important that medical devices,especially those designed for long-term implantation,must undergo strict regulatory testing, which can take several years. Standards such as ISO 13485, ISO 14971and ISO 5832 require thorough validation to ensure safety, effectiveness, and quality. While this prototype represents an important step, further testing, and regulatory approval will be necessary before it can be used in clinical settings. By leveraging advanced materials and precise 3D printing techniques, these custom-made prostheses simplify the surgical procedure and enhance patient outcomes by providing tailored solutions that meet specific anatomical and functional needs. This innovative approach represents a significant advancement in treating ossicular deformities, ensuring both efficacy and improved patient satisfaction.

Macrophage polarisation is crucial for initiating inflammation in response to biomaterial scaffolds, significantly influencing tissue integration and regeneration in vivo. Modulating macrophage polarisation towards a tissue-regeneration-favouring phenotype through the physical properties of scaffolds offers a promising strategy to enhance tissue regeneration while minimizing unfavourable immune responses. However, the critical impact of scaffold physical properties, such as size-scale dimensions, orientation of architectural cues, and local stiffness of these cues on macrophage polarization, remains largely unexplored and inadequately understood. This study investigates the combinatorial effects of the physical properties of 3D scaffolds made from Poly (ε-caprolactone) on human macrophage polarisation. Our findings indicate that the size-scale dimensions and orientation of the architectural cues of the scaffold play crucial roles in determining cell shape, attachment, and the modulation of key gene expression (iNOS, IL-1β, MRC1, ARG), as well as cytokines (TNF-α, IL-10) release associated with the polarisation of human macrophages. Specifically, in scaffolds with architectural cues at larger scales (≥ 300 µm diameter), macrophage polarisation is primarily determined by the size-scale of the architectural cues and scaffold stiffness, rather than orientation. Conversely, at smaller scales (≤ 15 µm), the orientation of the scaffold's architectural cues plays a more critical role. These insights underscore the pivotal role of scaffold design in modulating immune responses for enhanced tissue regeneration, offering valuable guidance for the rational development of biomaterial scaffolds in regenerative medicine.

The success of tumor prosthesis relies on the preclusion of deep infection and local recurrence in limb sparing surgery. The orthopedic implants enabling to simultaneously possess the antibacterial function and anticancer ability have become a desirable local therapy in the treatment of bone cancer. In this regard, we proposed a promising concept of the sequential release in a dual-drug system by combing titania nanotubes and chitosan as drug nanoreservoirs and sustained release films, respectively. An electrochemical anodization technique, controlled by anodization voltage, electrolyte composition, and processing time, was used to fabricate self-ordered titania nanotubes on the titanium surface, with their lengths simply tuned by the processing time, for drug loading. Two drugs of cisplatin and vancomycin as model anticancer and antibiotic, respectively, were sequentially loaded in nanotubes to investigate the release kinetics. The release profiles of cisplatin and vancomycin were found to be related to the spatial positioning of each drug on the nanotubes. Such a release sequence can be attributed to the anisotropic diffusion of drugs from the nanotubes, which can be further sustained for over 4 weeks through chitosan coverage. The drug release behavior was first evaluated in water using ultraviolet–visible spectroscopy for the quantitative analysis of release kinetics over time. The influence of dual-drug-loaded nanotubes on the growth of Staphylococcus aureus and osteogenic sarcoma in vitro was systematically evaluated for the therapeutic efficacy of bone cancer treatment. A high correlation between the viabilities of bacteria and cells and dual-drug release profiles was observed, indicating the feasibility of our nanotube-based concept utilizing a sequential release pattern to combat initial bacterial infection and prevent local recurrence.

Osteoarthritis (OA) 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 (ECM) of rib cartilage, possessing fibrous mesh structure characteristics, which was beneficial for melittin loading. It was found that the use of ECM 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 OA and preventing cartilage degradation. 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 OA and may provide a therapeutic option for the treatment of OA disease.

The erosion and drug release behavior of an injectable hydrogel composed of ethoxylated trimethylolpropane tri-3-mercaptopropionate (ETTMP) and poly(ethylene glycol) diacrylate were determined under physiological conditions. 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 to predict the eroding mass change and equilibrium water content across different compositions. Three easily detectable model drugs (methylene blue (MB), 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 drug release were 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 MB because of 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.

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 gelatin methacryloyl (GelMA), which binds to periodontal tissues to play an adhesive role through the Schiff base reaction, and further introducing -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 PL, 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.

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

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 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, and human retinal pigment epithelial cells (ARPE19). The stability of bevacizumab with pure magnesium (Mg) was investigated through an indirect enzyme-linked immunosorbent assay 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 h 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.

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.

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.