Multifunctional Biomaterials Research Articles

Cu2O/H2Ti3O7/Cellulose biohybrid film with efficient photocatalytic and antibacterial activities in solar-driven environmental decontamination

Increasing efforts have been devoted to cellulose-based multifunctional biomaterials for environmental applications. In this study, solvothermal method combined with impregnation reduction process of Cu2+ has been developed to create versatile Cu2O/H2Ti3O7/CP (cellulose paper) biocomposite films that demonstrates efficacy in treating wastewater from organic compounds, disinfecting it from microbes and also purifying the air from volatile organic compounds (VOCs). H2Ti3O7 nanosheets decorated with Cu2O nanoparticles exhibit an excellent visible-light responsibility. Furthermore, the Cu2O/H2Ti3O7/CP biocomposite film demonstrated enhanced efficacy in removing aniline in the liquid phase and 1-propanol in the gaseous phase compared to the H2Ti3O7/CP. This enhanced photocatalytic activity is primarily due to the synergistic effect between Cu2O and H2Ti3O7, which suppresses the recombination of charge carriers and improves their mobility. Reuse tests confirm the stability of the prepared hybrid photocatalyst. Moreover, the biocomposite exhibits good antimicrobial properties, which contributed to the effective inactivation of Escherichia coli. This proves its versatility as a photocatalyst for a broad range of biological and environmental applications.

Regenerative Medicine Approaches for Skin Wound Healing: from Allografts to Engineered Skin Substitutes

Abstract Purpose of the Review Recent advancements in tissue engineering and regenerative medicine have paved the way for innovative solutions in skin regeneration, particularly for extensive burns and full-thickness wounds where traditional approaches are limited. The purpose of the review is to explore the integration of bioactive materials, stem cell therapies, and tissue-engineered skin substitutes and their role in revolutionizing wound healing and skin transplantation. Recent Findings Studies leveraging natural and synthetic biomaterials as scaffolds, alongside the regenerative capabilities of mesenchymal stem cells (MSCs) and other cellular therapies, underscore the potential to enhance tissue repair, minimize scarring, and improve overall clinical outcomes. The development of multifunctional biomaterials and the advent of cutting-edge techniques such as 3D bioprinting and nanomedicine further propel the field, offering personalized and effective solutions. As these technologies evolve, they hold promise for more efficient, patient-specific skin grafting, reducing the need for systemic immunosuppression and enhancing graft survival. Summary The critical advancements in biomaterials, stem cell therapies, and tissue engineering, outline a course toward more effective and personalized skin regeneration therapies.

Customizable Lyophilized Agent for Radiotherapy Imaging and TherapY (CLARITY).

Smart radiotherapy biomaterials (SRBs) include seed and liquid biomaterials designed to be employed as fiducial markers during radiotherapy while also delivering therapeutic drug payloads to enhance treatment outcomes. In this study, we investigate a novel Customizable Lyophilized Agent for Radiotherapy Imaging and TherapY (CLARITY) biomaterial, which can be loaded with immunoadjuvants (anti-CD40 monoclonal antibody or Caflanone (FBL-03G)) at the point of care. The CLARITY biomaterial was investigated in an animal model of pancreatic cancer using C57BL6 mice. Mice were imaged before and at different points of time post-treatment to evaluate the potential of CLARITY biomaterial to provide imaging contrast similar to fiducials. This study also used cadavers to assess CLARITY's potential to provide imaging contrast in humans. Results showed imaging contrast from computed tomography (CT) and magnetic resonance imaging (MRI) modalities for up to 30 days post-treatment, demonstrating potential for use as fiducials. A significant increase in survival (***, p = 0.0006) was observed for mice treated with CLARITY biomaterial loaded with immunoadjuvant for up to 10 weeks post-treatment compared to those without treatment. These initial results demonstrate the potential of CLARITY biomaterial to serve as a smart multifunctional radiotherapy biomaterial and provide the impetus for further development and optimization as a point-of-care technology for combination radiotherapy and immunotherapy.

Silk Sericin is a Potent, Multifunctional Biomaterial for Endothelialization of Tissue‐Engineered Heart Valves (Adv. Funct. Mater. 32/2024)

Silk Sericin is a Potent, Multifunctional Biomaterial for Endothelialization of Tissue‐Engineered Heart Valves (Adv. Funct. Mater. 32/2024)

Photothermal switch by gallic acid-calcium grafts synthesized by coordination chemistry for sequential treatment of bone tumor and regeneration

The residual bone tumor and defects which is caused by surgical therapy of bone tumor is a major and important problem in clinicals. And the sequential treatment for irradiating residual tumor and repairing bone defects has wildly prospects. In this study, we developed a general modification strategy by gallic acid (GA)-assisted coordination chemistry to prepare black calcium-based materials, which combines the sequential photothermal therapy of bone tumor and bone defects. The GA modification endows the materials remarkable photothermal properties. Under the near-infrared (NIR) irradiation with different power densities, the black GA-modified bone matrix (GBM) did not merely display an excellent performance in eliminating bone tumor with high temperature, but showed a facile effect of the mild-heat stimulation to accelerate bone regeneration. GBM can efficiently regulate the microenvironments of bone regeneration in a spatial-temporal manner, including inflammation/immune response, vascularization and osteogenic differentiation. Meanwhile, the integrin/PI3K/Akt signaling pathway of bone marrow mesenchymal stem cells (BMSCs) was revealed to be involved in the effect of osteogenesis induced by the mild-heat stimulation. The outcome of this study not only provides a serial of new multifunctional biomaterials, but also demonstrates a general strategy for designing novel blacked calcium-based biomaterials with great potential for clinical use.

Multifunctional Biocomposites: Synthesis, Characterization, and Prospects for Regenerative Medicine and Controlled Drug Delivery.

This article presents a new method for preparing multifunctional composite biomaterials with applications in advanced biomedical fields. The biomaterials consist of dicalcium phosphate (DCPD) and bioactive silicate glasses (SiO2/Na2O and SiO2/K2O), containing the antibiotic streptomycin sulfate. Materials were deeply characterized by X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy, and zeta potential analysis, UV-visible spectrophotometry, and ion-exchange measurement were applied in a simulating body fluid (SBF) solution. The main results include an in situ chemical transformation of dicalcium phosphate into an apatitic phase under the influence of silicate solutions and the incorporation of the antibiotic. The zeta potential showed a decrease in surface charge from ζ = -24.6 mV to ζ = -16.5 mV. In addition, a controlled and prolonged release of antibiotics was observed over a period of 37 days, with a released concentration of up to 755 ppm. Toxicity tests in mice demonstrated good tolerance of the biomaterials, with no significant adverse effects. Moreover, these biomaterials have shown potent antibacterial activity against various bacterial strains, including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, suggesting their potential use in tissue engineering, drug delivery, and orthopedic and dental implants. By integrating the antibiotic into the biomaterial composites, we achieved controlled release and prolonged antibacterial efficacy. This research contributes to advancing biomaterials by exploring innovative synthetic routes and showcasing their promise in regenerative medicine and controlled drug delivery.

Adoption of a Tetrahedral DNA Nanostructure as a Multifunctional Biomaterial for Drug Delivery.

DNA nanostructures have been widely researched in recent years as emerging biomedical materials for drug delivery, biosensing, and cancer therapy, in addition to their hereditary function. Multiple precisely designed single-strand DNAs can be fabricated into complex, three-dimensional DNA nanostructures through a simple self-assembly process. Among all of the synthetic DNA nanostructures, tetrahedral DNA nanostructures (TDNs) stand out as the most promising biomedical nanomaterial. TDNs possess the merits of structural stability, cell membrane permeability, and natural biocompatibility due to their compact structures and DNA origin. In addition to their inherent advantages, TDNs were shown to have great potential in delivering therapeutic agents through multiple functional modifications. As a multifunctional material, TDNs have enabled innovative pharmaceutical applications, including antimicrobial therapy, anticancer treatment, immune modulation, and cartilage regeneration. Given the rapid development of TDNs in the biomedical field, it is critical to understand how to successfully produce and fine-tune the properties of TDNs for specific therapeutic needs and clinical translation. This article provides insights into the synthesis and functionalization of TDNs and summarizes the approaches for TDN-based therapeutics delivery as well as their broad applications in the field of pharmaceutics and nanomedicine, challenges, and future directions.

Emerging 2D Nanomaterials-Integrated Hydrogels: Advancements in Designing Theragenerative Materials for Bone Regeneration and Disease Therapy.

This review highlights recent advancements in the synthesis, processing, properties, and applications of 2D-material integrated hydrogels, with a focus on their performance in bone-related applications. Various synthesis methods and types of 2D nanomaterials, including graphene, graphene oxide, transition metal dichalcogenides, black phosphorus, and MXene are discussed, along with strategies for their incorporation into hydrogel matrices. These composite hydrogels exhibit tunable mechanical properties, high surface area, strong near-infrared (NIR) photon absorption and controlled release capabilities, making them suitable for a range of regeneration and therapeutic applications. In cancer therapy, 2D-material-based hydrogels show promise for photothermal and photodynamic therapies, and drug delivery (chemotherapy). The photothermal properties of these materials enable selective tumor ablation upon NIR irradiation, while their high drug-loading capacity facilitates targeted and controlled release of chemotherapeutic agents. Additionally, 2D-materials -infused hydrogels exhibit potent antibacterial activity, making them effective against multidrug-resistant infections and disruption of biofilm generated on implant surface. Moreover, their synergistic therapy approach combines multiple treatment modalities such as photothermal, chemo, and immunotherapy to enhance therapeutic outcomes. In bio-imaging, these materials serve as versatile contrast agents and imaging probes, enabling their real-time monitoring during tumor imaging. Furthermore, in bone regeneration, most 2D-materials incorporated hydrogels promote osteogenesis and tissue regeneration, offering potential solutions for bone defects repair. Overall, the integration of 2D materials into hydrogels presents a promising platform for developing multifunctional theragenerative biomaterials.

Calcium Orthophosphate (CaPO4) Containing Composites for Biomedical Applications: Formulations, Properties, and Applications

The goal of this review is to present a wide range of hybrid formulations and composites containing calcium orthophosphates (abbreviated as CaPO4) that are suitable for use in biomedical applications and currently on the market. The bioactive, biocompatible, and osteoconductive properties of various CaPO4-based formulations make them valuable in the rapidly developing field of biomedical research, both in vitro and in vivo. Due to the brittleness of CaPO4, it is essential to combine the desired osteologic properties of ceramic CaPO4 with those of other compounds to create novel, multifunctional bone graft biomaterials. Consequently, this analysis offers a thorough overview of the hybrid formulations and CaPO4-based composites that are currently known. To do this, a comprehensive search of the literature on the subject was carried out in all significant databases to extract pertinent papers. There have been many formulations found with different material compositions, production methods, structural and bioactive features, and in vitro and in vivo properties. When these formulations contain additional biofunctional ingredients, such as drugs, proteins, enzymes, or antibacterial agents, they offer improved biomedical applications. Moreover, a lot of these formulations allow cell loading and promote the development of smart formulations based on CaPO4. This evaluation also discusses basic problems and scientific difficulties that call for more investigation and advancements. It also indicates perspectives for the future.

Engineered Robust Hydrophobic/Hydrophilic Nanofibrous Scaffolds with Drug-Eluting, Antioxidant, and Antimicrobial Capacity.

Multifunctional nanofibrous architectures have attracted extensive attention for biomedical applications due to their adjustable and versatile properties. Electrospun fabrics stand out as key building blocks for these structures, yet improving their mechanobiological and physicochemical performance is a challenge. Here, we introduce biodegradable engineered hydrophobic/hydrophilic scaffolds consisting of electrospun polylactide nanofibers coated with drug-eluting synthetic (poly(vinyl alcohol)) and natural (starch) polymers. The microstructure of these composite scaffolds was tailored for an increased hydrophilicity, optimized permeability, water retention capacity of up to 5.1 g/g, and enhanced mechanical properties under both dry and wet conditions. Regarding the latter, normalized tensile strengths of up to 32.4 MPa were achieved thanks to the improved fiber interactions and fiber-coating stress transfer. Curcumin was employed as a model drug, and its sustained release in a pure aqueous medium was investigated for 35 days. An in-depth study of the release kinetics revealed the outstanding water solubility and bioavailability of curcumin, owing to its complexation with the hydrophilic polymers and further delineated the role of the hydrophobic nanofibrous network in regulating its release rate. The modified curcumin endowed the composites with antioxidant activities up to 5.7 times higher than that of free curcumin as well as promising anti-inflammatory and bacteriostatic activities. The cytocompatibility and cell proliferation capability on human dermal fibroblasts also evidenced the safe use of the constructs. Finally, the fabrics present pH-responsive color-changing behavior easily distinguishable within the pH range of 5-9. Thus, these designs offer a facile and cost-effective roadmap for the fabrication of smart multifunctional biomaterials, especially for chronic wound healing.

Self-Healing Guar Gum-Based Nanocomposite Hydrogel Promotes Infected Wound Healing through Photothermal Antibacterial Therapy.

Preventing bacterial infections is a crucial aspect of wound healing. There is an urgent need for multifunctional biomaterials without antibiotics to promote wound healing. In this study, we fabricated a guar gum (GG)-based nanocomposite hydrogel, termed GBTF, which exhibited photothermal antibacterial therapy for infected wound healing. The GBTF hydrogel formed a cross-linked network through dynamic borate/diol interactions between GG and borax, thereby exhibiting simultaneously self-healing, adaptable, and injectable properties. Additionally, tannic acid (TA)/Fe3+ nanocomplexes (NCs) were incorporated into the hydrogel to confer photothermal antibacterial properties. Under the irradiation of an 808 nm near-infrared laser, the TA/Fe3+ NCs in the hydrogel could rapidly generate heat, leading to the disruption of bacterial cell membranes and subsequent bacterial eradication. Furthermore, the hydrogels exhibited good cytocompatibility and hemocompatibility, making them a precandidate for preclinical and clinical applications. Finally, they could significantly promote bacteria-infected wound healing by reducing bacterial viability, accelerating collagen deposition, and promoting epithelial remodeling. Therefore, the multifunctional GBTF hydrogel, which was composed entirely of natural substances including guar gum, borax, and polyphenol/ferric ion NCs, showed great potential for regenerating infected skin wounds in clinical applications.

Silver and silicon doped βTCP scaffolds with gentamicin or ceftazidime loaded P(3HB) coatings as multifunctional biomaterials for bone regeneration

The risk of bacterial infections is a significant challenge faced frequently in the use of implants or scaffolds for bone regeneration. Therefore, this study focusses on the development and characterisation of novel β tricalcium phosphate (βTCP) scaffolds co-doped with silver and silicon, along with composites coated with antibiotic-loaded poly(3-hydroxybutyrate) (P(3HB)) layers. The successful incorporation of silver and silicon dopants while maintaining the formation of βTCP phase was confirmed using X-ray fluorescence (XRF), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS) analysis. The developed materials demonstrated comparable total and open porosity (∼64–70 vol%), suggesting high interconnectivity between pores conducive to nutrient transport and tissue repair. The increase in compressive strength was achieved for both doped (4.73 ± 0.79 MPa) and P(3HB) coated (5.79 ± 0.92 MPa) scaffolds due to the fine bioceramic microstructure and polymeric coating. Silver and silicon-modified βTCP demonstrated enhanced growth inhibition of Gram-negative (Pseudomonas aeruginosa, Escherichia coli) and Gram-positive (Staphylococcus aureus) bacterial strains in vitro compared to the pure βTCP. P(3HB) coatings, enriched with gentamicin or ceftazidime, exhibited burst and sustained release of the antibiotics from the scaffolds up to 120 h further intensifying the bacteria-killing capability, with evident inhibition zones observed in vitro. Moreover, the composites exhibited apatite-forming ability, suggesting their bioactive potential. In vivo evaluation using Caenorhabditis elegans demonstrated the lack of toxicity of the tested materials. The simultaneous incorporation of the dopants and antibiotic-loaded P(3HB) coatings not only offer a dual antibacterial approach but may also facilitate bone regeneration. However, further in vitro and in vivo investigations are needed to assess their potential in clinical application.

Photothermal-antibacterial bioactive noncrystalline nanosystem promotes infected wound tissue regeneration through thermo-ions activation

The efficient repair and tissue regeneration of chronic infected wounds is still a major challenge, among which the bacterial infection, inflammation and oxidative stress induced poor angiogenesis are the key obstacles. The nanosystem with single repair pathway could not meet the requirement of regenerating complicated wound tissue. Herein, we construct an photothermal multifunctional bioactive nanoglass (BGN) with the metal polyphenol coordination surface to treat methicillin-resistant Staphylococcus aureus（MRSA）infected wound. The BGN was coated with copper (Cu) coordinated polydopamine (PDA-Cu) to bioactive BGN@PDA-Cu nanoparticles, which release bioactive ions (Ca2+, SiO44- and Cu2+) and show the robust antibacterial/antioxidant/mild photothermal activities. BGN@PDA-Cu possesses the strong MRSA inhibition, reactive oxygen species scavenging, mild photothermal stimulation (41℃) and hemostatic ability. The antioxidant activity, thermal stimulation and sustainable bioactive ions release could significantly reverse the inflammatory phenotype of macrophage and enhance the angiogenesis through the activation of hypoxia-inducible factor HIF-1α and heat shock protein HSP90 pathways. The in vivo MRSA infected wound model demonstrated that BGN@PDA-Cu could significantly inhibit the MRSA infection and accelerate the wound repair which has 2 times improvement on healing rate compared with commercial bioglass dressing. This work demonstrates that bioactive ions release combined with mild thermal stimulation is a promising strategy to design multifunctional bioactive biomaterials for angiogenetic tissue regeneration.

Biocompatible adipose extracellular matrix and reduced graphene oxide nanocomposite for tissue engineering applications

Despite the immense need for effective treatment of spinal cord injury (SCI), no successful repair strategy has yet been clinically implemented. Multifunctional biomaterials, based on porcine adipose tissue-derived extracellular matrix (adECM) and reduced graphene oxide (rGO), were recently shown to stimulate in vitro neural stem cell growth and differentiation. Nevertheless, their functional performance in clinically more relevant in vivo conditions remains largely unknown. Before clinical application of these adECM-rGO nanocomposites can be considered, a rigorous assessment of the cytotoxicity and biocompatibility of these biomaterials is required. For instance, xenogeneic adECM scaffolds could still harbour potential immunogenicity following decellularization. In addition, the toxicity of rGO has been studied before, yet often in experimental settings that do not bear relevance to regenerative medicine. Therefore, the present study aimed to assess both the in vitro as well as in vivo safety of adECM and adECM-rGO scaffolds. First, pulmonary, renal and hepato-cytotoxicity as well as macrophage polarization studies showed that scaffolds were benign invitro. Then, a laminectomy was performed at the 10th thoracic vertebra, and scaffolds were implanted directly contacting the spinal cord. For a total duration of 6 weeks, animal welfare was not negatively affected. Histological analysis demonstrated the degradation of adECM scaffolds and subsequent tissue remodeling. Graphene-based scaffolds showed a very limited fibrous encapsulation, while rGO sheets were engulfed by foreign body giant cells. Furthermore, all scaffolds were infiltrated by macrophages, which were largely polarized towards a pro-regenerative phenotype. Lastly, organ-specific histopathology and biochemical analysis of blood did not reveal any adverse effects. In summary, both adECM and adECM-rGO implants were biocompatible upon laminectomy while establishing a pro-regenerative microenvironment, which justifies further research on their therapeutic potential for treatment of SCI.

Biomimetically ordered ultralong hydroxyapatite nanowires-based hierarchical hydrogel scaffold with osteoimmunomodulatory and osteogenesis abilities for augmenting bone regeneration

Artificial construction of tissue engineering implants with bone-mimicking structure and osteogenic function is of great significance for bone regeneration, but it remains a formidable challenge. Herein, inspired by natural bone, a biomimetically hierarchical hydrogel scaffold with highly ordered arrangement and multi-layered concentric circular structure is constructed by a convenient free-injection method for osteoimmunomodulation and bone defect regeneration. Ultralong hydroxyapatite nanowires act as skeleton unit to assemble into the hierarchically ordered nanowire bundles and further hybridization with hyaluronic acid methacrylate and loading with layered double hydroxide nanosheets to form the stable biomimetic scaffold. The biomimetic scaffold exhibits anisotropic structure, high water content and porosity, mechanical robustness, and sustained release of bioactive ions. In particular, the excellent biocompatibility together with ordered topography and biochemical cue can guide recruitment and directional migration of stem cells, and effectively promote osteogenic differentiation and vascularization in vitro. Moreover, the biomimetic scaffold induces M2 phenotype polarization of macrophages, thus creating a favorable osteoimmune environment. The in vivo study proves that the biomimetic scaffold can attenuate inflammation, promote vascularized ossification, and further accelerate new bone formation. This study provides an innovative strategy to construct multifunctional anisotropic biomaterials for bone tissue engineering.

Silk Sericin is a Potent, Multifunctional Biomaterial for Endothelialization of Tissue‐Engineered Heart Valves

AbstractEndothelialization is important for offering an anticoagulant surface, which is crucial for the construction of tissue‐engineered heart valves. Silk sericin is extensively investigated in the biomedical field due to its remarkable biological activities and diverse functional groups, favoring chemical modifications for the formation of versatile constructs. Herein, a sericin covalently modified valve (SCMV) is successfully fabricated by coupling maleylated silk sericin (MSS) with thiolated decellularized heart valve (DHV) through a Michael addition reaction. The results demonstrate that SCMV exhibits a smooth surface, higher hydrophilicity, and excellent resistance to platelets adhesion compared to DHV. Additionally, SCMV promotes endothelial cells (ECs) adhesion under both static and flow conditions and enhances their survival in a mouse subcutaneous implant model. The study also discovered that MSS‐stimulated ECs exhibit increased RhoA activation, expression of rho‐associated protein kinase 2 (ROCK2) and phosphorylated myosin light chain 2 (MLC2), actin polymerization, and cell adhesion; whereas actin organization and cell adhesion are significantly reduced by treatment with Y‐27632, a ROCK inhibitor. Furthermore, several integrin subunits, including α1, α2, α3, α5, α6, β1, β3, and β5, are involved in this regulatory process. Collectively, the findings highlight the potential application of silk sericin in promoting endothelialization of DHV while uncovering novel mechanisms underlying its regulatory effect on ECs adhesion.

An Injectable Magnesium-Based Cement Stimulated with NIR for Drug-Controlled Release and Osteogenic Potential.

Magnesium phosphate bone cement (MPC) has gained widespread usage in orthopedic implantation due to its fast-setting and high initial strength benefits. However, the simultaneous attainment of drug-controlled release and osteogenic potential in MPC remains a significant challenge. Herein, a strategy to create a smart injectable cement system using nanocontainers and chondroitin sulfate is proposed. It employs nanocontainers containing alendronate-loaded mesoporous silica nanoparticles, which are surface-modified with polypyrrole to control drug release in response to near-infrared (NIR) stimulation. The alendronate-incorporated cement (ACMPC) exhibits improved compressive strength (70.6 ± 5.9 MPa), prolonged setting time (913 s), and exceptional injectability (96.5% of injection rate and 242 s of injection time). It also shows the capability to prevent degradation, thus preserving mechanical properties. Under NIR irradiation, the cement shows good antibacterial properties due to the combined impact of hyperthermia, reactive oxygen species, and alendronate. Furthermore, the ACMPC (NIR) group displays good biocompatibility and osteogenesis capabilities, which also lead to an increase in alkaline phosphatase activity, extracellular matrix mineralization, and the upregulation of osteogenic genes. This research has significant implications for developing multifunctional biomaterials and clinical applications.

Application of Bioactive Materials for Osteogenic Function in Bone Tissue Engineering.

Bone tissue defects present a major challenge in orthopedic surgery. Bone tissue engineering using multiple versatile bioactive materials is a potential strategy for bone-defect repair and regeneration. Due to their unique physicochemical and mechanical properties, biofunctional materials can enhance cellular adhesion, proliferation, and osteogenic differentiation, thereby supporting and stimulating the formation of new bone tissue. 3D bioprinting and physical stimuli-responsive strategies have been employed in various studies on bone regeneration for the fabrication of desired multifunctional biomaterials with integrated bone tissue repair and regeneration properties. In this review, biomaterials applied to bone tissue engineering, emerging 3D bioprinting techniques, and physical stimuli-responsive strategies for the rational manufacturing of novel biomaterials with bone therapeutic and regenerative functions are summarized. Furthermore, the impact of biomaterials on the osteogenic differentiation of stem cells and the potential pathways associated with biomaterial-induced osteogenesis are discussed.

Chitosan/NH2-MIL-125 (Ti) scaffold loaded with doxorubicin for postoperative bone tumor clearance and osteogenesis: An in vitro study

Surgical resection remains the primary treatment modality for bone tumors. However, it is prone to local bone defects and tumor recurrence. Therefore, there is an urgent need for multifunctional biomaterials that combine tumor treatment and bone repair after bone tumor surgery. Herein, a chitosan composite scaffold (CS/DOX@Ti-MOF) was designed for both tumor therapy and bone repair. Among them, the amino-functionalized Ti-based metal-organic framework (NH2-MIL-125 (Ti), Ti-MOF) has a high specific surface area of 1116 m2/g and excellent biocompatibility, and promotes osteogenic differentiation. The doxorubicin (DOX) loading capacity of Ti-MOF was 322 ± 21 mg/g, and DOX@Ti-MOF has perfect antitumor activity. Furthermore, the incorporation of DOX@Ti-MOF improved the physical and mechanical properties of the composite scaffolds, making the scaffold surface rough and favorable for cells to attach. CS/DOX@Ti-MOF retains the unique properties of each component. It responds to the release of DOX in the tumor microenvironment to remove residual tumor cells, followed by providing a site for cell attachment, proliferation, and differentiation. This promotes bone repair and achieves the sequential treatment of postoperative bone tumors. Overall, CS/DOX@Ti-MOF may be a promising substitute for postoperative bone tumor clearance and bone defect repair. It also provides a possible strategy for postoperative bone tumor treatment.

Capturing cerium ions via hydrogel microspheres promotes vascularization for bone regeneration

The rational design of multifunctional biomaterials with hierarchical porous structure and on-demand biological activity is of great consequence for bone tissue engineering (BTE) in the contemporary world. The advanced combination of trace element cerium ions (Ce3+) with bone repair materials makes the composite material capable of promoting angiogenesis and enhancing osteoblast activity. Herein, a living and phosphorylated injectable porous hydrogel microsphere (P-GelMA-Ce@BMSCs) is constructed by microfluidic technology and coordination reaction with metal ion ligands while loaded with exogenous BMSCs. Exogenous stem cells can adhere to and proliferate on hydrogel microspheres, thus promoting cell-extracellular matrix (ECM) and cell-cell interactions. The active ingredient Ce3+ promotes the proliferation, osteogenic differentiation of rat BMSCs, and angiogenesis of endotheliocytes by promoting mineral deposition, osteogenic gene expression, and VEGF secretion. The enhancement of osteogenesis and improvement of angiogenesis of the P-GelMA-Ce scaffold is mainly associated with the activation of the Wnt/β-catenin pathway. This study could provide novel and meaningful insights for treating bone defects with biofunctional materials on the basis of metal ions.