Biomedical materials (Bristol, England)最新文献

The production of artificial bone constructs using human mesenchymal stem cells (hMSCs) is a promising approach for tissue engineering and regenerative medicine. However, the development of a suitable 3D bioreactor system that can mimic thein vivoenvironment and promote osteogenic differentiation of hMSCs remains a significant challenge. The 3D cell culture system established in this study consists of a bioreactor with an included vascular-mimetic perfusion system for hydrogel cultures and enables to study the effect of different hydrogels and the addition of cell matrix components (in this study Collagen type 1) or the 3D environment itself on the osteogenesis process. Our results show that the 3D bioreactor system can promote osteogenic differentiation of hMSCs, as evidenced by increased expression of osteogenic markers and mineralization of the hydrogel matrix. We also observed a positive effect of collagen type I on cell morphology. The results of this study demonstrate the potential of the 3D bioreactor system for the production of artificial bone constructs using hMSCs and provide a basis for further optimization and scaling up of the system. Our reactor system is an easy and reproducible system that can be used conventionally in laboratories to form or assemble histocompatible tissue substitutes to research artificial bone constructs and could reduce animal experiments in the near future.

Development of biomimetic scaffolds that mimic the complex structures and compositions of extracellular matrices is a promising approach in tissue engineering. This comprehensive review delves into the evolving and advancing field of gradient and hierarchical scaffolds in tissue engineering, with a particular emphasis on electrospinning-based and extrusion-based fabrication techniques, as well as their hybrid methodologies. We first introduce the fundamental concepts of biomimetic scaffold design in tissue engineering. Subsequently, we provide an overview of the design principles, mechanical considerations, and fabrication methods for creating gradient and hierarchical scaffolds that closely mimic the complex structures found in natural tissues. The applications of gradient and hierarchical scaffolds in various areas of tissue engineering, such as bone, cartilage, tendon, ligament, and vascular tissues, are also highlighted. Furthermore, the paper addresses current challenges in the field, including limitations in fabrication techniques, scalability issues, and the integration of smart and stimuli-responsive materials. It concludes by discussing emerging trends and future research directions, emphasizing the potential of these advanced scaffolds to revolutionize tissue engineering and regenerative medicine. This review aims to provide researchers and practitioners with clear insights into recent advancements, current challenges, and prospective directions in gradient and hierarchical scaffold design and fabrication.

The global health crisis posed by antimicrobial resistance and biofilm-protected infections demands urgent development of biocompatible antibacterial materials. The traditional antimicrobial substances are challenged by their higher cytotoxicity, poorer biofilm penetration, or resistance induction. This review highlights the transformative potential of highly biocompatible and antibacterial polymers, which achieve broad-spectrum efficacy while minimizing toxicity. The parameter of selectivity index (SI) is emphasized in assessing the balance between antimicrobial efficacy and biocompatibility of antimicrobial materials. A higher SI value indicates that the material retains potent antimicrobial activity while exhibiting superior biocompatibility. Representative examples of antimicrobial materials with high SI values are also summarized. The polymeric quaternary ammonium salts, chitosan derivatives, polyamino acids such as hyperbranched polylysine, and N-halamine polymers demonstrate synergistic antibacterial actions through membrane destabilization, oxidative stress induction, and biofilm suppression, exhibiting tunable degradation, immune tolerance, and selective targeting, enabling applications in medical devices and tissue materials, encompassing both fundamental research and commercial applications in biomedicine, to serve as a comprehensive reference for relevant researchers. Challenges in scalable manufacturing, regulatory classification, and long-term biosafety assessment, and future perspectives on multifunctional polymer design and smart responsive systems are finally discussed.

Postoperative infection and insufficient osseointegration of orthopedic implants are core challenges leading to surgical failure, and endowing implants with drug storage and release functions has become a key innovative direction to break through this bottleneck. As the core carrier of the drug storage and release system, the size, morphology, and porosity of micro/nano topological structures directly determine the drug-loading efficiency and release kinetics. With its unique advantages of precise controllability and the ability to achieve multi-level topological structure integration in a single step, laser processing technology has received much attention in the integrated application of multifunctional design and drug storage/release for orthopedic implants. This review systematically summarizes the research progress of laser technology in constructing drug storage and release microstructures on the surface of orthopedic implants: first, it introduces the development history of implant surface microstructure design and mainstream preparation methods; then it focuses on the use of ultrafast lasers to construct surface micro/nano topological structures to achieve antibacterial and sustained drug release; it emphasizes the discussion on the preparation of implant scaffolds with complex microstructures and graded porosity by laser additive manufacturing technology, and their application in improving drug-loading capacity and achieving on-demand drug release; finally, it analyzes the existing challenges in this field and looks forward to future development trends and research directions.

The clinical application of injectable hydrogels as drug delivery vehicles is limited by persistent pain and discomfort at the injection site, which are critical issues that affect long-term patient compliance. This pain primarily originates from thein situswelling of the hydrogel within the tissue post-injection. However, the complex biomechanical mechanisms underlying this process remain uncertain. This study utilized the COMSOL Multiphysics platform to construct a multiphysics model that couples the large-deformation swelling of the hydrogel with the poro-viscoelastic interactions of subcutaneous tissue, aiming to investigate the evolution of tissue stress during the quasi-static phase post-injection. The simulation results reproduce the characteristic rise-and-fall dynamics of tissue stress. The stress peaks at approximately 60-100 min post-injection, driven by hydrogel swelling, reaching a peak stress of approximately 10.8 kPa, a level clearly exceeding the reported ∼6-9 kPa threshold for activating nociceptors. Subsequently, it gradually decreased owing to the poro-viscoelastic relaxation effects of the tissue, reaching a stress equilibrium phase after approximately 400 min. Parametric studies further reveal two key design principles for low-pain formulations: (1) An optimal injection depth window exists (6-12 mm in this model) that effectively disperses stress and facilitates the formation of a morphologically regular drug depot, whereas injections that are too shallow or too deep lead to stress concentration due to boundary constraints; (2) A smaller hydrogel radius (volume) can trigger higher local peak stress due to a point-like pressure source effect. This study provided a theoretical foundation for the design of low-pain injectable formulations. By synergistically optimizing parameters such as injection depth and volume, the poromechanical microenvironment induced by hydrogel swelling can be actively managed, thereby enhancing patient comfort and compliance while ensuring therapeutic efficacy.

Pollen grains are being explored as innovative biomaterials for different applications, ranging from oral drug delivery to encapsulation of food additives, with the production of pollen-based building blocks standing on its robust, chemically inert, and mechanically durable sporopollenin wall. Yet, concerns remain regarding the safety of sporopollenin microcapsules (SMCs) or derivatized sporopollenin materials purified from pollen grains, traditionally linked to allergies. Herein, we address the critical question of whether sporopollenin shells purified from bee pollen may cause allergic reactions by evaluating their interaction with human immunoglobulin E (IgE) antibodies in sera from patients with and without allergic sensitization to pollen of specific species. Clean SMCs fromCastanea sativa, Amaranthaceae (Chenopodium album), andOlea europaeapollen grains were successfully produced using a species-independent chemical treatment and characterized. The Covaris Adaptive Focused Acoustics™ (AFA) technology was employed for protein extraction from the bee pollen and the SMCs, yielding 0.72-1.25 ng and 0.026 ng-0.028 ng of protein per pollen grain, respectively. X-ray photoelectron spectroscopy (XPS) analysis also confirmed that the surface nitrogen content of the SMCs was minimal, ranging from 0.9% to 2.7%. SDS-PAGE, followed by immunoblotting analysis, showed that proteins extracted from bee pollen strongly reacted with IgE antibodies in human sera, whereas SMCs did not trigger allergic sensitization. Overall, our findings suggest that while bee pollen proteins could elicit allergic reactions in sensitive patients, SMCs do not, highlighting their potential as safe biomaterials for various applications and offering valuable insights into the allergenic potential of bee pollen.

Avascular necrosis (AVN) is a bone degenerative condition characterized by disrupted blood supply, leading to bone necrosis and subsequent bone collapse. Current AVN treatments, such as core decompression and surgical interventions, exhibited limited success rates due to donor site morbidity, infection, and structural mismatch. Existing treatments fail to regenerate the necrotic bone and prevent bone collapse. Thus, the current study explores the potential of 3D-printed composite scaffolds consisting of calcium peroxide nanoparticles (CaO₂NPs) and manganese dioxide (MnO₂) within a polylactide (PLA) matrix. These 3D-printed composite scaffolds can provide mechanical support to the collapsing bone, while CaO₂NPs and MnO₂particles can provide a localized and sustained molecular oxygen delivery at the site of necrosis. PLA/Mn/Ca4% exhibited the highest mechanical strength compared with other tested compositions (2% and 6%). Moreover, the 4% composition demonstrated consistent and sustained oxygen release.In vitrostudies with MG-63 cells demonstrated excellent biocompatibility and cell proliferation under hypoxic conditions. Also, enhanced mineralization on the 4% composite scaffolds suggested osteogenic potential of these scaffolds in a hypoxic environment. These findings suggest that these 3D printed composite scaffolds can effectively promote bone regeneration in hypoxic conditions, potentially offering a promising clinical strategy for treating AVN.

Three-dimensional (3D) cell printing is rapidly redefining how we engineer tissues by enabling the precise delivery of living cells within bio-inks to build complex, cell-laden structures. Unlike traditional approaches that seed cells onto inert scaffolds, this technique allows direct integration of cells into the construct, promoting enhanced cell infiltration, extracellular matrix (ECM) remodeling, and tissue-like functionality. Despite the explosion of interest, the field remains fragmented, with limited efforts to unify emerging data across platforms and applications. Our review addresses this gap by synthesizing recent advances in 3D cell printing in terms of key printing factors and parameters and adaptive bioprinting, presenting consensus and translative information such as printing parameters, identifying current established applications, and proposing future research directions based on the currentin vivoor clinical results. We map current trends across biomaterial choices-including gelatin, decellularized ECM, alginate, collagen I, and fibrin-and explore how diverse cell types, from primary human cells to engineered stem cell derivatives, are shaping the future of tissue fabrication. These innovations are already influencingin vivoresearch in skin regeneration, cartilage repair, and vascular grafts, while the high-resolution capabilities of 3D printing are powering next-generation organ-on-chip models. We conclude with key translational challenges and propose future research priorities to move from bench to bedside.

Bioceramic-incorporated polymer-based scaffolds have gained more interest as a promising and effective approach in bone tissue engineering (BTE) applications. This study is the first to investigate the role of incorporated manganese-doped hydroxyapatite (Mn-HA) and gelatin coating in increased bioactivity and biological properties, specifically the cell attachment potencies of three-dimensional (3D) porous electrospun polycaprolactone (PCL). In this context, novel 3D porous composite scaffolds were synthesized by wet electrospinning of PCL incorporated with Mn-HA. The scaffolds were then coated with a thin gelatin layer to enhance the cell adhesion capacity. The effects of Mn-HA and the gelatin coating were evaluated in terms of structural, physicochemical, and biological properties. The results demonstrated that Mn-HA was successfully synthesized with doping of 2 mol% Mn, with MnSO₄(manganese sulfate) and MnCl₂(manganese chloride) precursors. Mn-HA powder with a MnSO₄precursor indicated better cell viability results. Therefore, Mn-HA/PCL scaffolds with 2.5% and 5% (w/w) bioceramic content were prepared with the MnSO₄precursor. The scaffolds' porosity increased from 24% (PCL/gelatin group) to approximately 34% in both the 2.5% and 5% (w/w) bioceramic-containing groups. The addition of Mn-HA powder improved thein vitrobioactivity and degradation rate of the scaffolds. Specifically, the 5% and 2.5% (w/w) Mn-HA incorporated scaffolds indicated 40% and 30% weight loss after 21 d of incubation, respectively. In contrast to the PCL/gelatin and HA-containing groups, the Mn-doped HA containing scaffolds exhibited a weight loss of around 17%-20%, indicating a decrease in degradation. The presence of the Mn-HA powder and gelatin coating elevated the cell viability results significantly, as opposed to the PCL scaffolds. Incorporation of 5% (w/w) Mn-HA improved the alkaline phosphatase activity and intracellular calcium levels, contrary to other groups. Thus, the incorporation of Mn-doped HA and gelatin into the PCL scaffold supports the potency towards properties required for BTE applications and suggests it as a prospective biomaterial for further evaluations.

Chronic wounds represent a significant clinical challenge, necessitating the development of multifunctional dressings with bioactive compounds to accelerate healing. Carotenoids-natural pigments with potent antioxidant and anti-inflammatory properties-are emerging as promising agents for tissue repair. This study explores the therapeutic potential of carotenoid pigments biosynthesized by Kocuria sp. and their integration into a chitosan/alginate/polyvinyl alcohol (Cs/Alg/PVA) nanocomposite for wound healing applications. Carotenoids were extracted and optimized under varying conditions of temperature, salinity, pH, and culture media. The pigments were incorporated into a Cs/Alg/PVA matrix and characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry (DSC), andin vitrorelease studies. Antioxidant capacity was evaluated via DPPH assay, and anti-inflammatory properties were assessed using hemolysis assays. Cell viability and proliferation were analyzed on L929 and human dermal fibroblast cells using MTT assay.In vivowound healing efficacy was evaluated in a murine excisional wound model with histological and morphometric analyses. The carotenoid-enriched composite exhibited strong antioxidant activity, significant anti-hemolytic effects, and enhanced biocompatibility with fibroblasts. Release kinetics revealed sustained and pH-responsive delivery of carotenoids.In vivo, the composite significantly accelerated wound contraction and epithelialization compared to controls, with histopathological analysis confirming increased fibroblast presence, collagen deposition, and reduced inflammation. This study highlights the therapeutic potential of microbial carotenoids embedded in Cs/Alg/PVA dressings as a biocompatible, antioxidant-rich platform for enhanced wound healing. The approach offers a sustainable, natural alternative to synthetic additives in wound care biomaterials.