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.

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.

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

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

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 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.

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.

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.

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, denoted as Hep-Brij 58, to facilitate self-assembly into stable nanoparticles in an aqueous environment. The self-assembled formation of Hep-Brij nanoparticles was demonstrated through dynamic light scattering and TEM, while the iodine method identified the critical concentration for the self-assembled process. PTX was incorporated into Hep-Brij nanoparticles through 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 more effective in terms of the amount of PTX loaded. Hep-Brij 58/PTX was stable over two weeks of storage in distilled water. In vitro release of PTX from Hep-Brij 58 exhibited a controlled drug release effect following the diffusion kinetics. Furthermore, Hep-Brij 58 was non-toxic to primary healthy cells and cancer cells. The in vitro anticancer test with Hela cells indicated remarkable anticancer activity of PTX-loaded Hep-Brij 58 nanoparticles compared to free PTX. In summary, Hep-Brij 58 nanoparticles hold considerable potential for use as a delivery system for managing PTX therapy.

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

The 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 significantly activated the mitochondrial apoptosis pathway and inhibited 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.

Diabetes is now a global chronic disease, with the number of people with diabetes expected to reach 643 million by the end of 2030. Semaglutide, a human glucagon-like peptide-1 (GLP-1) analogue with 94% similarity to human GLP-1, can promote insulin secretion and repress glucagon secretion in a glucose concentration-dependent manner, resulting in substantial improvement of blood glucose levels and reducing the risk of hypoglycemia in patients with type 2 diabetes. To improve the absorption efficiency of semaglutide in oral delivery, we developed chitosan hydrochloride-coated and nonionic surfactant-modified niosomes (CS.HCL-NSPEs-NIO) as a new way to encapsulate it. The results showed that CS.HCL-NSPEs-NIO could efficiently penetrate the cell junctions in the intestinal endothelium and therefore promote drug absorbance. In addition, gastrointestinal distribution studies revealed that CS. HCL-NSPEs-NIO could stay in the intestine for more than 4 h, thus allowing for long-term glucose regulation. Effective reduction of blood glucose levels and weight loss were observed in db/db mice while no toxicity was detected in major organs. On the whole, our recommendation is that CS.HCL-NSPEs-NIO shows promise as an oral delivery tool for enhancing the hypoglycemic effects of semaglutide.

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, PVA20SF10SPI, PVA15SF15SPI, PVA10SF20SPI, 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 Fourier transform infrared spectroscopy and their morphology was observed using scanning electron microscopy. 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, alkaline phosphatase (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.

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

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

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

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

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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.