Regenerative Biomaterials最新文献

Developing bioactive materials with multifunctional properties is crucial for enhancing their biomedical applications in regenerative medicine. Bioactive glass nanoparticle (BGN) is a new generation of biomaterials that demonstrate high biocompatibility and tissue-inducing capacity. However, the hard nanoparticle surface and single surface property limited their wide biomedical applications. In recent years, the surface functional strategy has been employed to decorate the BGN and improve its biomedical applications in bone tissue repair, bioimaging, tumor therapy and wound repair. This review summarizes the progress of surface-interface design strategy, customized multifunctional properties and biomedical applications in detail. We also discussed the current challenges and further development of multifunctional BGN to meet the requirements of various biomedical applications.

The decellularized extracellular matrix (dECM) has emerged as an effective medium for replicating the in vivo-like conditions of the tumor microenvironment (TME), thus enhancing the screening accuracy of chemotherapeutic agents. However, recent dECM-based tumor models have exhibited challenges such as uncontrollable morphology and diminished cell viability, hindering the precise evaluation of chemotherapeutic efficacy. Herein, we utilized a tailor-made microfluidic approach to encapsulate dECM from porcine liver in highly poly(lactic-co-glycolic acid) (PLGA) porous microspheres (dECM-PLGA PMs) to engineer a three-dimensional (3D) tumor model. These dECM-PLGA PMs-based microtumors exhibited significant promotion of hepatoma carcinoma cells (HepG2) proliferation compared to PLGA PMs alone, since the infusion of extracellular matrix (ECM) microfibers and biomolecular constituents within the PMs. Proteomic analysis of the dECM further revealed the potential effects of these bioactive fragments embedded in the PMs. Notably, dECM-PLGA PMs-based microtissues effectively replicated the drug resistance traits of tumors, showing pronounced disparities in half-maximal inhibitory concentration (IC₅₀) values, which could correspond with certain aspects of the TME. Collectively, these dECM-PLGA PMs substantially surmounted the prevalent challenges of unregulated microstructure and suboptimal cell viability in conventional 3D tumor models. They also offer a sustainable and scalable platform for drug testing, holding promise for future pharmaceutical evaluations.

With mechanical strength close to cortical bone, biodegradable and osteopromotive properties, magnesium (Mg)-based implants are promising biomaterials for orthopedic applications. However, during the degradation of such implants, there are still concerns on the potential adverse effects such as formation of cavities, osteolytic phenomena and chronic inflammation. Therefore, to transform Mg-based implants into clinical practice, the present study evaluated the local effects of high-purity Mg screws (HP-Mg, 99.99 wt%) by comparing with clinically approved polylactic acid (PLA) screws in epiphyseal trabecular bone of rabbits. After implantation of screws at the rabbit distal femur, bone microstructural, histomorphometric and biomechanical properties were measured at various time points (weeks 4, 8 and 16) using micro-CT, histology and histomorphometry, micro-indentation and scanning electron microscope. HP-Mg screws promoted peri-implant bone ingrowth with higher bone mass (BV/TV at week 4: 0.189 ± 0.022 in PLA group versus 0.313 ± 0.053 in Mg group), higher biomechanical properties (hardness at week 4: 35.045 ± 1.000 HV in PLA group versus 51.975 ± 2.565 HV in Mg group), more mature osteocyte LCN architecture, accelerated bone remodeling process and alleviated immunoreactive score (IRS of Ram11 at week 4: 5.8 ± 0.712 in PLA group versus 3.75 ± 0.866 in Mg group) as compared to PLA screws. Furthermore, we conducted finite element analysis to validate the superiority of HP-Mg screws as orthopedic implants by demonstrating reduced stress concentration and uniform stress distribution around the bone tunnel, which led to lower risks of trabecular microfractures. In conclusion, HP-Mg screws demonstrated greater osteogenic bioactivity and limited inflammatory response compared to PLA screws in the epiphyseal trabecular bone of rabbits. Our findings have paved a promising way for the clinical application of Mg-based implants.

The skin, being the body's primary defense mechanism, is susceptible to various injuries such as epidermal wounds, natural aging, and ultraviolet-induced damage. As a result, there is growing interest in researching skin repair methods. Traditional animal-derived collagen, widely available on the market, poses risks due to its immunogenicity and potential for viral contamination. In contrast, recombinant collagen sourced from human genes offers a safer alternative. To investigate the potential of human recombinant collagen in skin repair, our research team applied two types, type I human collagen (Col I) and CF-1552(I), to two different skin injury models: a wound-healing model and a photo-aging model. Our findings indicate that both Col I and CF-1552(I) effectively enhance wound healing and repair skin damaged by ultraviolet exposure. Notably, CF-1552(I) showed effects comparable to Col I in promoting cell proliferation in the wound-healing model and increasing malondialdehyde content in the photo-aging model, suggesting that CF-1552(I) may offer greater potential for skin repair compared to the larger Col I molecule.

Mechanical adaptation of tissue engineering scaffolds is critically important since natural tissue regeneration is highly regulated by mechanical signals. Herein, we report a facile and convenient strategy to tune the modulus of waterborne biodegradable polyurethanes (WBPU) via cross-linking manipulation of phase separation and water infiltration for constructing mechanically adaptable tissue engineering scaffolds. Amorphous aliphatic polycarbonate and trifunctional trimethylolpropane were introduced to polycaprolactone-based WBPUs to interrupt interchain hydrogen bonds in the polymer segments and suppress microphase separation, inhibiting the crystallization process and enhancing covalent cross-linking. Intriguingly, as the crosslinking density of WBPU increases and the extent of microphase separation decreases, the material exhibits a surprisingly soft modulus and enhanced water infiltration. Based on this strategy, we constructed WBPU scaffolds with a tunable modulus to adapt various cells for tissue regeneration and regulate the immune response. As a representative application of brain tissue regeneration model in vivo, it was demonstrated that the mechanically adaptable WBPU scaffolds can guide the migration and differentiation of endogenous neural progenitor cells into mature neurons and neuronal neurites and regulate immunostimulation with low inflammation. Therefore, the proposed strategy of tuning the modulus of WBPU can inspire the development of novel mechanically adaptable biomaterials, which has very broad application value.

Hydrogels are highly promising due to their soft texture and excellent biocompatibility. However, the designation and optimization of hydrogels involve numerous experimental parameters, posing challenges in achieving rapid optimization through conventional experimental methods. In this study, we leverage machine learning algorithms to optimize a dual-network hydrogel based on a blend of acrylamide (AM) and alginate, targeting applications in flexible electronics. By treating the concentrations of components as experimental parameters and utilizing five material properties as evaluation criteria, we conduct a comprehensive property assessment of the material using a linear weighting method. Subsequently, we design a series of experimental plans using the Bayesian optimization algorithm and validate them experimentally. Through iterative refinement, we optimize the experimental parameters, resulting in a hydrogel with superior overall properties, including heightened strain sensitivity and flexibility. Leveraging the available experimental data, we employ a classification algorithm to separate the cutoff data. The feature importance identified by the classification model highlights the pronounced impact of AM, ammonium persulfate, and N,N-methylene on the classification outcomes. Additionally, we develop a regression model and demonstrate its utility in predicting and analyzing the relationship between experimental parameters and hydrogel properties through experimental validation.

Facilitating an appropriate immune response is crucial for promoting bone tissue regeneration upon biomaterial implantation. In this study, the Mg²⁺-containing nanostructures on the surface of Ti-1.25Mg alloy were prepared by a one-step hydrothermal reaction method via regulating pH value to enhance the immunomodulatory osteogenic properties of Ti-Mg alloys. In neutral (HT7) or alkaline (HT9) hydrothermal treatment (HT) solution, the size of MgTiO₃ nanostructures formed on the surface of Ti-1.25Mg alloy is smaller than that in acidic HT solution (HT5), and lamellar Mg(OH)₂ nanostructures are found in HT7 and HT9. In addition, the sample surface has a lower roughness and higher wettability with increasing pH value. The Mg²⁺-containing nanostructures on the Ti-1.25Mg alloy inhibited inflammatory response by promoting the polarization of M2 macrophages, thereby promoting osteogenesis in vitro. The micro-CT and histological assessment proved that the regeneration of bone defect was faster in HT7 than the Ti-1.25Mg in vivo. Mechanically, Mg²⁺-containing nanostructures can mediate the immune response of macrophages via upregulating integrins α5β1 and inhibiting Toll-like receptors (TLR-4), subsequently inhibiting the NF-κB signaling pathway. Overall, osteoimmunity-regulating Mg²⁺-containing nanostructures on Ti-1.25Mg present a promising biomaterial for bone repair.

Cartilage defects are frequently caused by trauma, illness and degradation of the cartilage. If these defects are not sufficiently treated, the joints will degrade irreversibly, possibly resulting in disability. Articular cartilage lacks blood vessels and nerves and is unable to regenerate itself, so the repair of cartilage defects is extremely challenging in clinical treatment. Tissue engineering technology is an emerging technology in cartilage repair and cartilage regeneration. 3D-printed hydrogels show great potential in cartilage tissue engineering for the fabrication of 3D cell culture scaffolds to mimic extracellular matrix. In this study, we construct a 3D-printed hydrogel loaded with nanoparticles by electrostatic interaction and photo cross-linking for the regeneration of cartilage, which has adaptable and drug-continuous release behavior. A photopolymerizable bioink was prepared using recombinant collagen, chitosan, nanoclay Laponite-XLG and nanoparticles loaded with Kartogenin (KGN). This bioink was added with KGN, a small molecule drug that promotes cartilage differentiation, and as a result, the 3D-printed CF/CM/3%LAP/KGN scaffolds obtained by extrusion printing is expected to be used for cartilage repair. It was shown that the 3D-printed scaffolds had good cytocompatibility for human bone marrow mesenchymal stem cells (hBMSCs) and exhibited excellent antimicrobial properties, the continuous release of KGN in the scaffold induced the hBMSCs differentiation into chondrocytes, which significantly enhanced the expression of collagen II and glycosaminoglycan. In vivo studies have shown that implantation of KGN-loaded scaffolds into cartilage-injured tissues promoted cartilage tissue regeneration. This study demonstrated that 3D-printed CF/CM/3%LAP/KGN scaffolds can be used for cartilage repair, which is expected to lead to new healing opportunities for cartilage injury-based diseases.

Bioactive microspheres coated with acellular extracellular matrix (aECM) have received extensive attention in bone tissue engineering. In this work, biomimetic microspheres with different aECM ratios, uniform size and controllable size were prepared easily by blending natural porcine dermal aECM and poly (lactic-co-glycolic acid) (PLGA) using electrohydrodynamic spraying and solidification actuated by solvent extraction method. In this work, the appropriate polymer concentration and preparation voltage were investigated, and the surface morphology of the microspheres was observed by scanning electron microscope. Sirius red was used to visualize aECM exposure on the surface of the microspheres. The in vitro and in vivo experiments were carried out to evaluate the bioactivity and osteogenic properties of the microspheres. The results showed that the morphology and size of PLGA microspheres had little influence on the aECM blending. In vitro experiments showed that the higher the content of aECM, the better the cell adhesion performance. In vivo, rat calvarial defect models were observed and characterized at 4 and 8 weeks postoperatively, and the values of BV/TV of 50aECM/PLGA were 47.57 ± 1.14% and 72.92 ± 2.19%, respectively. The results showed that the skull healing effect was better in aECM-containing microspheres. In conclusion, aECM/PLGA composite microspheres can increase cell adhesion performance through the addition of aECM. Moreover, in vivo experiments have proved that aECM/PLGA microspheres are beneficial to bone repair, which means the aECM/PLGA microspheres are a promising bone tissue engineering material.

To address the uneven nutrient distribution within three-dimensional (3D) tissue models and organoids currently used in medical research, this study introduces a microvascular network based on the Hilbert curve. Our aim was to develop innovative solutions for enhancing nutrient supply in thick tissue models in vitro. By using 3D bioprinting, we engineered microvascular networks of varying Hilbert orders and validated their efficacy in enhancing nutrient uniformity through numerical simulations and experiments. These networks facilitated broader and more uniform nutrient distribution throughout the thick tissue models, particularly the 2° Hilbert microvascular structure, which occupies less space and significantly reduces regions of cellular death. Furthermore, we explored the potential of assembling larger tissue constructs using the 2° Hilbert microvascular network, showcasing its applicability in constructing large-scale biological models. The findings suggest that the 2° Hilbert microvascular structure is particularly effective in ensuring adequate nutrient delivery, thus enhancing the viability and functionality of large-volume tissue models. These innovations hold significant promise for advancing the fields of tissue engineering and regenerative medicine by improving nutrient delivery to in vitro thick tissue block models. This provides a robust foundation for future in vitro research and clinical applications, potentially leading to more effective treatments and interventions in the medical field. The development of these microvascular networks represents a crucial step forward in overcoming the limitations of current 3D tissue models and organoids, paving the way for more sophisticated and reliable biomedical research tools.