Regenerative Biomaterials最新文献

Neurological injuries and diseases are a leading cause of disability worldwide, underscoring the urgent need for effective therapies. Neural regaining and enhancement therapies are seen as the most promising strategies for restoring neural function, offering hope for individuals affected by these conditions. Despite their promise, the path from animal research to clinical application is fraught with challenges. Neuroengineering, particularly through the use of biomaterials, has emerged as a key field that is paving the way for innovative solutions to these challenges. It seeks to understand and treat neurological disorders, unravel the nature of consciousness, and explore the mechanisms of memory and the brain's relationship with behavior, offering solutions for neural tissue engineering, neural interfaces and targeted drug delivery systems. These biomaterials, including both natural and synthetic types, are designed to replicate the cellular environment of the brain, thereby facilitating neural repair. This review aims to provide a comprehensive overview for biomaterials in neuroengineering, highlighting their application in neural functional regaining and enhancement across both basic research and clinical practice. It covers recent developments in biomaterial-based products, including 2D to 3D bioprinted scaffolds for cell and organoid culture, brain-on-a-chip systems, biomimetic electrodes and brain-computer interfaces. It also explores artificial synapses and neural networks, discussing their applications in modeling neural microenvironments for repair and regeneration, neural modulation and manipulation and the integration of traditional Chinese medicine. This review serves as a comprehensive guide to the role of biomaterials in advancing neuroengineering solutions, providing insights into the ongoing efforts to bridge the gap between innovation and clinical application.

Effective reconstruction of large bone defects, particularly in thickness, remains one of the major challenges in orthopedic and dental fields. We previously produced an Escherichia coli-based industrial-scale GMP-grade recombinant human bone morphogenetic protein-2 (E-rhBMP-2) and showed that the combination of E-rhBMP-2 with beta-tricalcium phosphate (β-TCP/E-rhBMP-2) can effectively promote bone reconstruction. However, the limited mechanical strength and poor morphology retention of β-TCP granules are key points that need optimization to obtain more effective grafts and further expand its clinical applications. Therefore, we combined β-TCP/E-rhBMP-2 with fibrin gel to enhance its mechanical properties and usability for vertical bone regeneration. We investigated the mechanical properties and vertical bone regeneration effects of the materials applied, with or without fibrin containing E-rhBMP-2, in a calvarial defect model in mice. Compression tests were conducted to assess the initial stability of the materials. Scanning electron microscopy and Fourier transform infrared spectroscopy were conducted to characterize the presence of fibrin on the scaffold. After 4 and 12 weeks of implantation, micro-computed tomography and histological and immunofluorescent analyses were performed to assess the morphology and volume of the newly formed bone. The fibrin-containing groups had significantly higher initial mechanical strength and higher ability to maintain their morphology in vivo compared to the counterparts without fibrin. However, fibrin gel alone suppressed the bone formation ability of β-TCP/E-rhBMP-2 whereas the presence of high doses of E-rhBMP-2 in fibrin gel resulted in material resorption and enhanced new bone formation. In conclusion, fibrin gel significantly improved the mechanical strength and surgical manageability of the β-TCP/E-rhBMP-2 scaffold, and the addition of E-rhBMP-2 to the fibrin gel further enhanced the vertical bone regeneration and initial structural integrity of the scaffold.

Poloxamer 407, also known as Pluronic^® F127, is gaining interest in the cosmetic, biomedical and pharmaceutical fields for its biocompatibility, safety and thermo-sensitive properties. Ensuring sterility is critical in clinical applications, and sterilization is often preferred over aseptic processing. However, sterilization can impact the functional properties of the hydrogel. In this study, we investigate the effects of steam heat (121°C, 20 min), dry heat (160°C, 1 h), gamma irradiation (25 kGy) and electron beam (e-beam) irradiation (15 and 25 kGy) on a 30% w/v Poloxamer 407 hydrogel formulation. Our analysis encompasses gelling properties, pH, Fourier-transform infrared spectroscopy, gel permeation chromatography, small-angle X-ray scattering, rheology, swelling, degradation by-products and lactate dehydrogenase release of the sterilized hydrogels, comparing them to a non-sterile counterpart. We demonstrated that heat sterilization alters the hydrogel's gelling and structural properties due to water evaporation and oxidation under harsh temperature conditions, especially when applying the dry heat method. Gamma irradiation proved unsuitable, resulting in an acidic and cytotoxic hydrogel due to oxidative degradation. In contrast, e-beam irradiation preserves the hydrogel's elasticity, gelling and structural properties while enhancing mechanical resilience and moderating swelling. Therefore, e-beam irradiation within the 15-25 kGy range appears to be the most suitable method for sterilizing a 30% w/v Poloxamer 407 hydrogel.

Biodegradable Zn alloy has recently gained attention for use in bone implants considering its biodegradability, attractive mechanical properties and bioactivity. However, excessive corrosion of Zn alloy at the early stage of implantation may cause severe cytotoxicity, resulting in insufficient osseointegration, which hinders the clinical use of Zn alloy. In this study, we designed a photothermally controlled degradative hybrid coating as a corrosion-protective barrier with the intention of preventing Zn ion burst release during the early stages of implantation and regaining the alloy's corrosion advantage later on. The coating consists of zeolite imidazole skeleton-encapsulated indocyanine green core-shell-structured nanoparticles and polylactic coglycolic acid (ICG@ZIF-8/PLGA) on pristine Zn-0.8 (wt.%) Li (ZL) alloy. The electrochemical test results indicated that coating ZL with ICG@ZIF-8/PLGA can effectively reduce its corrosion current density (i_corr) from 2.48 × 10^-5 A·cm^-2 to 2.10 × 10^-8 A·cm^-2. After near-infrared (NIR) light irradiation, ICG@ZIF-8 heated PLGA coating to reach Tg, causing the coating to degrade and the i_corr of the coated ZL alloy decreased to 2.50 × 10^-7 A·cm^-2, thus restoring corrosion advantage. Both in vitro and in vivo investigations showed that the coated ZL alloy had acceptable biocompatibility. Overall, the developed photothermally controlled coating improved the Zn alloy's resistance to corrosion and allowed for the adjustment of the Zn alloy's degradation rate through 808-nm NIR light irradiation.

Fibroblast growth factor-2 (FGF-2) is a critical molecule for sustaining the pluripotency of human pluripotent stem (PS) cells. However, FGF-2 is extremely unstable and cannot be stored long periods at room temperature. Therefore, the following FGF-2-conjugated cell culture materials were developed to stabilize FGF-2: FGF-2-conjugated polyvinyl alcohol (PVAI-C-FGF) hydrogels and FGF-2-conjugated carboxymethyl cellulose-coated (CMC-C-FGF) dishes. Human induced pluripotent stem (iPS) cells were proliferated on recombinant vitronectin (rVN)-coated PVAI-C-FGF hydrogels and CMC-C-FGF dishes in medium without FGF-2. Human iPS cells could not be cultivated on rVN-coated PVAI-C-FGF hydrogels for more than two passages but could proliferate on rVN-coated CMC-C-FGF dishes. These results indicated that the amount of immobilized FGF-2 and the base cell materials are important, including the amount of immobilized rVN and the conformation of FGF-2 on the surfaces. When human iPS cells were proliferated on rVN-coated CMC-C-FGF surfaces in medium containing no FGF-2 for 10 passages, their pluripotency and potential to differentiate into cells originating from three germ layers were maintained in vivo and in vitro. Furthermore, the cells could extensively differentiate into cardiomyocytes, which can be used for cardiac infarction treatment in future and retinal pigment epithelium for retinal pigmentosa treatment in future. The FGF-2-immobilized surface could enable human PS cell culture in medium that does not need to contain unstable FGF-2. The amount of FGF-2 immobilization on the rVN-coated CMC-C-5FGF and CMC-C-20FGF dishes was reduced to 93.6 and 52.2 times, respectively, which is less than the conventional amount of FGF-2 used in culture medium for one passage (6 days) of human iPS cell culture. This reduction resulted from the stabilization of unstable FGF-2 by the immobilization of FGF-2, which was achieved by utilizing optimal base materials (CMC), coating materials (rVN) and long-joint segment (PEG4-SPDP) design.

This study investigates a novel pH-responsive hydrogel composed of polyvinyl alcohol (PVA) and boric acid (BA) designed for the controlled release of salvianolic acid B (SAB), addressing the critical challenge of scar formation and skin regeneration. The dual-crosslinked network architecture of the hydrogel exhibits remarkable pH sensitivity, enabling it to achieve a peak SAB release within 48 hours in the acidic microenvironment characteristic of early-stage wound healing. In vitro assessments demonstrated that the PVA-BA-SAB hydrogel significantly inhibits fibroblast activation and mitigates abnormal collagen deposition, effectively preventing excessive scar formation. Transcriptome sequencing reveals the potential role of PVA-BA-SAB hydrogel in balancing TGF-β and Wnt signaling pathways. Furthermore, in vivo studies revealed enhanced tissue regeneration, characterized by improved collagen organization and increased vascularization, as well as the promotion of mature hair follicle development. The hydrogel's biocompatibility, mechanical robustness and adhesive properties were also thoroughly evaluated, confirming its suitability for clinical applications. These findings suggest that the PVA-BA-SAB hydrogel fully exerts the excellent characteristics of biomaterials and maximizes the pharmacological effect of SAB. Our innovative drug delivery system not only facilitates enhanced wound healing but also offers a strategic approach to minimize scarring. This research provides valuable insights into innovative therapeutic strategies for effective wound management and tissue repair.

Poly (l-lactic acid) (PLLA) is a biocompatible, biodegradable material with piezoelectric properties, making it a promising candidate for providing self-powered stimulation to accelerate tissue repair. Repairs to various tissues, such as bone, cartilage and nerve, necessitate distinct piezoelectric characteristics even from the same material. However, the extensive utilization of PLLA piezoelectric scaffolds in various tissue is hindered by their low and single piezoelectric constants. In this study, PLLA nanofiber membranes with enhanced and adjustable piezoelectric constants (d ₃₃) were fabricated through oriented electrospinning. By carefully controlling the parameters of the spinning solution, a steady increase in d ₃₃ values from 0 to 30 pC/N was achieved. This advancement allows tailoring of PLLA nanofiber membranes to meet various piezoelectric requirements of different tissues. As an example of tailoring the optimal piezoelectric constants, we developed PLLA-2-0, PLLA-2-10, PLLA-2-15 and PLLA-2-20 nanofiber membranes with d ₃₃ values of 0, 5, 10 and 15 pC/N, respectively. The impact of varying piezoelectric constants of PLLA nanofiber membranes on cellular behavior and repair efficacy were validated through in vitro cellular experiments and in vivo mandibular critical defect repair. The results indicated that PLLA-2-20 demonstrated superior cell proliferation rate up to 130% and an osteogenic differentiation level approximately twice of the control. In addition, PLLA-2-20 significantly promoted cell adhesion and migration, and the cell aspect ratio was about five times higher than that of the control group. In vivo, PLLA-2-20 optimal restorative effects on rat mandibles via endogenous mechanical force-mediated piezoelectric stimulation, leading to complete histological restoration within 8 weeks. These findings highlight the potential of the PLLA membranes with high and adjustable d ₃₃ by a straightforward process. This study provides a novel approach for the development of highly electroactive membranes tailored to specific tissue repair needs.

During the implantation process of cardiovascular implants, vascular damage caused by inflammation occurs, and the inflammatory process is accompanied by oxidative stress. Currently, carbon monoxide (CO) has been demonstrated to exhibit various biological effects including vasodilatation, antithrombotic, anti-inflammatory, apoptosis-inducing and antiproliferative properties. In this study, hemoglobin/epigallocatechin-3-gallate (EGCG) core-shell nanoparticle-containing coating on stainless steel was prepared for CO loading and inflammation modulation. Inspired by strong coordination ability with CO, hemoglobin nanoparticle was first prepared and encapsulated into EGCG metal-phenolic networks. A polydopamine (PDA) linking layer was then coated on 316 stainless steel, and the hemoglobin/EGCG nanoparticles were loaded with the subsequent PDA deposition. It showed that the maximum release amount of CO by the coating was 17.0 nmol/cm² in 48 h. In vitro evaluations conducted in a simulated inflammatory environment revealed that the coating, which released CO from hemoglobin/EGCG nanoparticles, effectively mitigated the lipopolysaccharide-induced inflammatory response in macrophages. Specifically, it decreased the expression of tumor necrosis factor-α, increased the expression of interleukin-10, suppressed the polarization of macrophages toward the M1 phenotype and reduced intracellular reactive oxygen species (ROS). Furthermore, under simulated oxidative stress conditions, the coating decreased the apoptosis of endothelial cells induced by oxidative stress and down-regulated intracellular ROS levels. In vivo implantation results further confirmed that the coating, with its hemoglobin/EGCG nanoparticles and CO release capabilities, reduced macrophage-mediated inflammatory responses and modulated the polarization phenotype of macrophages.

The detection of residual nuclei in decellularized extracellular matrix (dECM) biomaterials is critical for ensuring their quality and biocompatibility. However, current evaluation methods have limitations in addressing impurity interference and providing intelligent analysis. In this study, we utilized four staining techniques-hematoxylin-eosin staining, acetocarmine staining, the Feulgen reaction and 4',6-diamidino-2-phenylindole staining-to detect residual nuclei in dECM biomaterials. Each staining method was quantitatively evaluated across multiple parameters, including area, perimeter and grayscale values, to establish a semi-quantitative scoring system for residual nuclei. These quantitative data were further employed as learning indicators in machine learning models designed to automatically identify residual nuclei. The experimental results demonstrated that no single staining method alone could accurately differentiate between nuclei and impurities. In this study, a semi-quantitative scoring table was developed. With this table, the accuracy of determining whether a single suspicious point is a cell nucleus has reached over 98%. By combining four staining methods, false positives caused by impurity contamination were eliminated. The automatic recognition model trained based on nuclear parameter features reached the optimal index of the model after several iterations of training in 172 epochs. The trained artificial intelligence model achieved a recognition accuracy of over 90% for detecting residual nuclei. The use of multidimensional parameters, integrated with machine learning, significantly improved the accuracy of identifying nuclear residues in dECM slices. This approach provides a more reliable and objective method for evaluating dECM biomaterials, while also increasing detection efficiency.

Osteoarthritis (OA) is a frequent chronic illness in orthopedics that poses a major hazard to patient health. In situ cell therapy is emerging as a therapeutic option, but its efficacy is influenced by both the inflammatory milieu and the amount of stem cells, limiting its use. In this study, we designed a novel injectable porous microsphere (PM) based on microfluidic technology that can support in situ mesenchymal stem cells (MSCs) therapy by combining polylactic-glycolic acid copolymer, kartogenin, polydopamine, stromal cell-derived factor-1, and copper-doped bioactive glass (CuBG). The ex vivo tests demonstrated that PMs@CuBG microspheres were biocompatible and facilitated the transformation of synovial macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotypes by releasing CuBG to reduce joint inflammation. At the same time, the microspheres are able to recruit MSCs into the joint cavity and encourage their differentiation into chondrocytes, thereby treating articular cartilage injury. The in vivo rat experimental results show that intra-articular injection of PMs@CuBG in rats with OA improves OARSI scores, aggrecan content and the ratio of col-2α-positive cells, indicating a reparative effect on damaged cartilage within the joint. As a result, PMs@CuBG microspheres are predicted to provide a novel and successful approach to in situ cell therapy for OA.