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.

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.

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.

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.

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.

Rapid and strategic cell placement is necessary for high throughput tissue fabrication. Current adhesive cell patterning systems rely on fluidic shear flow to remove cells outside of the patterned regions, but limitations in washing complexity and uniformity prevent adhesive patterns from being widely applied. Centrifugation is commonly used to study the adhesive strength of cells to various substrates; however, the approach has not been applied to selective cell adhesion systems to create highly organized cell patterns. This study shows centrifugation as a promising method to wash cellular patterns after selective binding of cells to the surface has taken place. After patterning H9C2 cells using biotin-streptavidin as a model adhesive patterning system and washing with centrifugation, there is a significant number of cells removed outside of the patterned areas of the substrate compared to the initial seeding, while there is not a significant number removed from the desired patterned areas. This method is effective in patterning multiple size and linear structures from line widths of 50–200 μm without compromising immediate cell viability below 80%. We also test this procedure on a variety of tube-forming cell lines (MPCs, HUVECs) on various tissue-like surface materials (collagen 1 and Matrigel) with no significant differences in their respective tube formation metrics when the cells were seeded directly on their unconjugated surface versus patterned and washed through centrifugation. This result demonstrates that our patterning and centrifugation system can be adapted to a variety of cell types and substrates to create patterns tailored to many biological applications.

The reconstruction of large-sized soft tissue defects remains a substantial clinical challenge, with adipose tissue engineering emerging as a promising solution. The acellular dermal matrix (ADM), known for its intricate spatial arrangement and active cytokine involvement, is widely employed as a scaffold in soft tissue engineering. Since ADM shares high similarity with decellularized adipose matrix, it holds potential as a substitute for adipose tissue. This study explores the adipogenic ability of a spongy material derived from ADM via vacuum-thermal crosslinking (T-ADM), characterized by high porosity, adjustable thickness, and suitable mechanical strength. Adipose-derived stem cells (ADSCs) are considered ideal seed cells in adipose tissue engineering. Nevertheless, whether pre-adipogenic induction is necessary before their incorporation remains debatable. In this context, ADSCs, both with and without pre-adipogenic induction, were seeded into T-ADM to regenerate vascularized adipose tissue. A comparative analysis of the two constructs was performed to evaluate angiogenesis and adipogenesis in vitro, and tissue regeneration efficacy in vivo. Additionally, RNA-seq analysis was utilized to investigate the potential mechanisms. The results showed that T-ADM exhibited good performance in terms of volume retention and maintenance of adipocyte phenotype, confirming its suitability as a scaffold for adipose tissue engineering. In-vitro outcomes demonstrated that pre-adipogenic induction enhanced the adipogenic level of ADSCs, but reduced their ability to promote vascularization. Furthermore, constructs utilizing pre-induced ADSCs showed an insignificant superiority in in-vivo fat formation, and neovascularization compared with those with non-induced ADSCs, which may be attributed to similar macrophage regulation, and balanced modulation of the proliferator-activated receptor-γ and hypoxia-inducible factor 1 α pathways. Consequently, the direct use of ADSCs is advocated to streamline the engineering process and reduce associated costs. The combined strategy of T-ADM with ADSCs proves to be feasible, convenient and effective, offering substantial potential for addressing large-sized tissue deficits and facilitating clinical applications.

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.

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.

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.

Dendritic cells (DCs) are the most potent antigen-presenting cells with multifaceted functions in controlling immune activation and tolerance. Graves' disease, particularly Graves' ophthalmopathy, is recognized as a refractory autoimmune thyroid disease. Therefore, DC-targeted therapies aimed at inducing specific immune tolerance are important for the treatment of Graves' disease. Therefore, we utilized polylactic acid glycolic acid polymer (PLGA) polymer nanoparticles (NPs) encapsulating Graves' disease auto-antigen thyrotropin receptor A (TSHR-A) peptide and the immune tolerance inducer rapamycin (Rapa) to synthesize drug-loaded NPs (NP (TSHR-A + Rapa)). We first characterized the synthesized nanodrugs using transmission electron microscopy and dynamic light scattering techniques and tested the uptake capacity of DCs for NPs after co-culturing the NPs with DCs. And the safe concentration of NPs to DCs was detected using Cell counting kit-8 (CCK-8) assay. Subsequently, we tested the targeting and safety of the NPs in mice. And the effects of NPs on the proportion and proliferation of DCs and regulatory T (Treg) cells were examined in vivo and in vitro using flow cytometry and 5-ethynyl-2'-deoxyuridine (EdU) method, respectively. Enzyme linked immunosorbent assay (ELISA) assays were used to detect the effect of NPs on cytokine release from DCs. Finally, we tested the preventive and therapeutic effects of the synthesized NPs on disease models. Our results showed that the synthesized NPs were well taken up by DCs in vitro, while in vivo they were mainly targeted to the spleen of mice. The NPs were able to relatively inhibit the maturation of DCs in vivo and in vitro, while affecting the release of relevant cellular functional factors from DCs, and the NPs also promoted the proportion and proliferation of Treg cells in vivo and in vitro. In addition, the synthesized NPs were able to prevent and improve the mouse disease model well without toxic side effects on mouse organs and other physiological indicators. Therefore, the synthesis of NP (TSHR-A + Rapa) NPs using PLGA encapsulated TSHR-A and rapamycin could be used as targeting DCs to alter immune tolerance and as a new potential approach for the treatment of Graves' disease.

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.

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.

Orthopaedic applications require materials that balance mechanical strength, biocompatibility, and controlled degradation, particularly for bone regeneration and load-bearing purposes. This study investigates the effects of varying weight percentages of Al₂O₃ and TiO₂ (25:75, 50:50, and 75:25) on the characteristics of Al₂TiO₅ biomaterials synthesized via the sol–gel method. Structural and chemical characterizations, including XRD and FTIR, confirmed the successful synthesis of phase-pure Al₂TiO₅, highlighting functional groups such as Al–O and Ti–O. Among the tested compositions, the 50:50 ratio exhibited the strongest antibacterial efficacy against S. aureus and E. coli, comparable to a commercial antibiotic, while also promoting hydroxyapatite (HAp) deposition in simulated body fluid (SBF). Additionally, cytotoxicity assessments using the L929 murine fibroblast cell line revealed that the 50:50 composition had the lowest toxicity. All formulations demonstrated controlled degradation, minimizing pH fluctuations and enhancing bioactivation and biocompatibility. Zeta potential analysis indicated that the 50:50 composition exhibited the most negative values over time, suggesting strong surface interactions with SBF and a favorable environment for HAp nucleation. Furthermore, the compressive strength of all formulations (71–74 MPa) was sufficient for load-bearing applications. These findings suggest that optimizing the 50:50 weight ratio enhances bioactivity, mechanical stability, and biocompatibility, making it a promising candidate for orthopedic and bone tissue engineering applications.

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.

A mere glance at the foundation of the sericulture industry to produce silk and the consequent establishment of the Silk Road to transport it; elucidates the significant role that this material has played in human history. Owing to its exceptional robustness, silk was introduced into medicine as a surgical suture approximately two millennia ago. During the last decades, silk has garnered attention as a possible source of biological-based materials that can be effectively used in regenerative medicine. Silk's unique characteristics, like its low immunogenicity, suitable adhesive properties, exceptional tensile strength, perfect hemostatic properties, adequate permeability to oxygen and water, resistance to microbial colonization, and most importantly, excellent biodegradability; make it an outstanding choice for biomedical applications. Although there are many different types of silk in nature, Bombyx mori (B. mori) silk accounts for about 90% of global production and is the most thoroughly investigated and the most commonly used. Silk fibroin (SF) and silk sericin (SS) are the two main protein constituents of silk. SF has been manufactured in various morphologic forms (e.g. hydrogels, sponges, films, etc) and has been widely used in the biomedical field, especially as a scaffold in tissue engineering. Similarly, SS has demonstrated a vast potential as a suitable biomaterial in tissue engineering and regenerative medicine. Initial studies on SF and SS as wound dressings have shown encouraging results. This review aims to comprehensively discuss the potential role of silk proteins in refining wound healing and skin regeneration.

Peri-implantitis represents an inflammatory condition characterized by the presence of plaque-related soft and hard tissue damage surrounding dental implants, often resulting in progressive alveolar bone loss and, ultimately, implant failure. Black phosphorus (BP), a novel two-dimensional (2D) material that has recently emerged in the biomedical field, has attracted increasing attention due to its unique osteogenic properties and exceptional antibacterial and antioxidant characteristics. Additionally, its outstanding biomedical attributes enhance angiogenesis and nerve regeneration. Compared to other biomaterials, its high specific surface area, high photothermal conversion efficiency, and complete biodegradability make BP a promising candidate for treating infection-related bone defects. This article reviews the biological properties of BP nanosheets (BPNSs) and discusses their potential applications in the context of peri-implantitis, aiming to provide fresh insights for future research and applications of BPNS.

Extracellular vesicles (EVs) are nanoscale phospholipid-based particles secreted by cells and are essential mediators responsible for intercellular signal communication. The rapid development of EV nanotechnology has brought unprecedented opportunities for nanomedicine. Among various administration methods, oral administration is the most convenient and simplest. However, most drugs (peptides, small molecule drugs, nucleic acids, and therapeutic proteins) greatly reduce their oral bioavailability due to the harsh gastrointestinal environment. Notably, some EVs have been shown to cross biological barriers, including the gastrointestinal tract. The distinctive biological properties of EVs make them a promising natural carrier for oral drug delivery. This review introduces the characteristics of EVs, covering their classification, production methods, and therapeutic efficacy in oral administration. Additionally, we explore the potential roles of EVs in disease prevention and treatment, as well as their future prospects in pharmaceutical applications. This comprehensive overview aims to provide insights into the application of EVs in oral drug delivery, highlighting their advantages, current progress, and the challenges that need to be overcome for successful clinical translation.

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.

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.&#xD;

A paclitaxel (PTX) nano-delivery system using modified heparin and polyethylene glycol hexadecyl ether (Brij 58) was developed in this study. Brij 58 was conjugated to the heparin backbone via the cystamine bridge and donated as Hep-Brij 58 to facilitate the self-assembly into stable nanoparticles in aqueous. The self-assembled formation of Hep-Brij nanoparticles was demonstrated through DLS and TEM, whereas the iodine method identified the critical concentration for the self-assembled process. PTX was incorporated into Hep-Brij nanoparticles through the physical entrapment. The PTX-loaded Hep-Brij nanoparticles were then characterized according to particle size and size distribution, drug-loading content, and efficiency. Compared to Brij 58, Hep-Brij 58 was outperformed in term of the amount PTX loaded. Hep-Brij 58/PTX was stable during 2 weeks of storage in distilled water. In vitro release of PTX from Hep-Brij 58 exhibited a control drug release effect following the diffusion kinetic. Furthermore, Hep-Brij 58 was non-toxic to primary healthy cells and cancer cells. The in vitro anticancer with Hela cell indicated remarkable anticancer activity of PTX-loaded Hep-Brij 58 nanoparticles compared to free PTX. Altogether, Hep-Brij 58 nanoparticles holds considerable potential for delivery system for managing PTX therapy

Mimicking bone remodeling scaffolds were developed as supportive biomaterials to promote tissue formation at defect sites in osteoporosis. Scaffolds made of polyvinyl alcohol (PVA) were mixed with varying weight ratios of silk fibroin (SF) and a phytoactive compound-based soy protein isolate (SPI); PVA30SF, PVA10SF20SPI, PVA20SF10SPI, PVA30SPI. PVA was used as control. These components were mixed into aqueous solution and crosslinking with EDC before freeze thawing and freeze drying, respectively. Then, the scaffolds were characterized at the molecular level using FTIR and their morphology was observed using SEM. Physical properties including swelling and degradation were tested, as well as mechanical properties like stress-strain behavior and modulus. The biological performance of the scaffolds was evaluated through osteoblast cell culturing, assessing cell viability, proliferation, ALP activity, calcium content, and calcium deposition. The results demonstrate that the scaffolds with both SF and SPI had greater molecular mobility of –OH, amide I, II, and III groups, compared to the scaffold with only SF or SPI. These scaffolds also displayed larger pore sizes. Scaffolds with both SF and SPI showed higher swelling and degradation rates than those with only SF or SPI. Additionally, they exhibited better cell viability and calcium deposition, along with increased cell proliferation, ALP activity, and calcium content. Notably, the scaffold with a higher amount of SPI, PVA10SF20SPI, exhibited the most suitable performance for enhancing cell response, thereby promoting bone formation. This scaffold is proposed as a supportive biomaterial to be incorporated with plates and screws for bone fixation at defect sites in osteoporosis.&#xD;

The traditional treatment for cervical cancer involves aggressive surgery combined with radiotherapy and chemotherapy. Nevertheless, these treatments have certain limitations and side effects, thus breakthroughs and advances are required in cervical cancer therapy. Magnesium alloy is a promising antitumor biomaterial with excellent biocompatibility and biodegradability. However, the potential effects of magnesium alloy on cervical tumors have not been extensively explored. Recent studies have demonstrated that adding a small amount of calcium to the magnesium matrix can reduce grain size and corrosion rate while providing good biocompatibility. We conducted in vivo and in vitro experiments to test the antitumor properties of Mg-1%Ca alloys. The results indicated that the Mg-1%Ca alloy released Mg2+ and OH- more slowly, inhibited the proliferation of SiHa and HeLa cells, induced apoptosis in tumor cells, disrupted the cytoskeleton, and inhibited cell migration and invasion. At the molecular level, Mg-1%Ca alloy&#xD;the MAPK/ERK signaling pathway. In the future, Mg-1%Ca may be employed in the treatment of cervical cancer as a novel adjuvant therapeutic material with anticancer function to prevent the occurrence and progression of cancer proliferation and metastasis.&#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.

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.

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.&#xD;

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.

Rapid and strategic cell placement is necessary for high throughput tissue fabrication. Current adhesive cell patterning systems rely on fluidic shear flow to remove cells outside of the patterned regions, but limitations in washing complexity and uniformity prevent adhesive patterns from being widely applied. Centrifugation is commonly used to study the adhesive strength of cells to various substrates; however, the approach has not been applied to selective cell adhesion systems to create highly organized cell patterns. This study shows centrifugation as a promising method to wash cellular patterns after selective binding of cells to the surface has taken place. After patterning H9C2 cells using biotin-streptavidin as a model adhesive patterning system and washing with centrifugation, there is a significant number of cells removed outside of the patterned areas of the substrate compared to the initial seeding, while there is not a significant number removed from the desired patterned areas. This method is effective in patterning multiple size and linear structures from line widths of 50–200 μm without compromising immediate cell viability below 80%. We also test this procedure on a variety of tube-forming cell lines (MPCs, HUVECs) on various tissue-like surface materials (collagen 1 and Matrigel) with no significant differences in their respective tube formation metrics when the cells were seeded directly on their unconjugated surface versus patterned and washed through centrifugation. This result demonstrates that our patterning and centrifugation system can be adapted to a variety of cell types and substrates to create patterns tailored to many biological applications.

The reconstruction of large-sized soft tissue defects remains a substantial clinical challenge, with adipose tissue engineering emerging as a promising solution. The acellular dermal matrix (ADM), known for its intricate spatial arrangement and active cytokine involvement, is widely employed as a scaffold in soft tissue engineering. Since ADM shares high similarity with decellularized adipose matrix, it holds potential as a substitute for adipose tissue. This study explores the adipogenic ability of a spongy material derived from ADM via vacuum-thermal crosslinking (T-ADM), characterized by high porosity, adjustable thickness, and suitable mechanical strength. Adipose-derived stem cells (ADSCs) are considered ideal seed cells in adipose tissue engineering. Nevertheless, whether pre-adipogenic induction is necessary before their incorporation remains debatable. In this context, ADSCs, both with and without pre-adipogenic induction, were seeded into T-ADM to regenerate vascularized adipose tissue. A comparative analysis of the two constructs was performed to evaluate angiogenesis and adipogenesis in vitro, and tissue regeneration efficacy in vivo. Additionally, RNA-seq analysis was utilized to investigate the potential mechanisms. The results showed that T-ADM exhibited good performance in terms of volume retention and maintenance of adipocyte phenotype, confirming its suitability as a scaffold for adipose tissue engineering. In-vitro outcomes demonstrated that pre-adipogenic induction enhanced the adipogenic level of ADSCs, but reduced their ability to promote vascularization. Furthermore, constructs utilizing pre-induced ADSCs showed an insignificant superiority in in-vivo fat formation, and neovascularization compared with those with non-induced ADSCs, which may be attributed to similar macrophage regulation, and balanced modulation of the proliferator-activated receptor-γ and hypoxia-inducible factor 1 α pathways. Consequently, the direct use of ADSCs is advocated to streamline the engineering process and reduce associated costs. The combined strategy of T-ADM with ADSCs proves to be feasible, convenient and effective, offering substantial potential for addressing large-sized tissue deficits and facilitating clinical applications.

Bioabsorbable textile scaffolds are promising for bone tissue engineering applications. Their tuneable, porous, fibre-based architecture resembles that of native extracellular matrix, and they can sustain tissue growth while being gradually absorbed in the body. In this work, immortalized mouse calvaria preosteoblast MC3T3-E1 cells were cultured in vitro on two warp-knitted bioabsorbable spacer fabric scaffolds made of poly(lactic acid) (PLA) and poly-4-hydroxybutyrate (P4HB), to investigate their osteogenic properties. Scaffold structure and yarn properties were characterized after manufacturing. Cells were seeded on the two scaffolds and treated with osteogenic media for up to 35 days. Both scaffolds supported similar cell growth patterns, featuring a higher cell density on multifilament yarns, which could be beneficial to drive cell proliferation or related phenomena in localized area of the construct. The increase in alkaline phosphatase activity and the calcium deposition observed on some PLA and P4HB scaffolds after 28 and 35 days of culture, confirm their potential to support MC3T3-E1 cells differentiation, however inconsistent mineralization was observed on the scaffolds. Due to their structural and morphological features, ability to support cell attachment and growth, and their limited osteogenic potential, these PLA and P4HB bioabsorbable textile scaffolds are recommended for further investigation for bone tissue engineering applications.

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.

Biodegradable medical devices undergo degradation following implantation, potentially leading to clinical failure. Consequently, it is necessary to assess the change in their properties post-implantation. However, a standardized method for the precise evaluation of the changes in their physicochemical properties is currently lacking. In this study, we aimed to establish precisely simulated oral physiological conditions (SOPCs) and investigate the physicochemical property changes to predict the performance alterations of biodegradable dental barrier membranes (BDBMs) following human implantation. We investigated changes in physicochemical properties of BDBM after exposure to SOPC for 24 weeks. When BDBM was exposed to SOPC for 24 weeks, there was a significant decrease in mass (−1.37%), molecular weight (−19.54%) and tensile load (−72.84%). Among the physicochemical properties, molecular weight decreased similarly after 24 weeks of implantation in rats (−15.78%) and after 24 weeks of exposure to SOPC (−19.54%). Changes in the physicochemical properties of BDBM in simulated in vitro oral conditions and in the in vivo environment were similar. Overall, the evaluation of physicochemical property changes after exposing BDBM to the proposed SOPC demonstrates novelty in its ability to accurately predict performance changes post-implantation. This approach may provide significant insights not only for the development of BDBM but also for various types of biodegradable medical devices.