Biomedical materials (Bristol, England)最新文献

Nanoparticles (NPs)¹have been explored as drugs carriers for treating tumors and central nervous system (CNS)²diseases and for oral administration. However, they lack satisfactory clinical efficacy due to poor extravasation and infiltration through biological barriers to target tissues. Most clinical antitumor NPs have been designed based on enhanced permeability and retention effects which are insufficient and heterogeneous in human tumors. The tight junctions³3TJs: tight junctionsof the blood-brain barrier⁴4BBB: blood-brain barrierand the small intestinal epithelium severely impede NPs from being transported into the CNS and blood circulation, respectively. By contrast, transcytosis enables NPs to bypass these physiological barriers and enhances their infiltration into target tissues by active transport. Here, we systematically review the mechanisms and putative application of NP transcytosis for targeting tumor and CNS tissues, explore oral NP administration, and propose future research directions in the field of NP transcytosis.

Biodegradable medical devices undergo degradation following implantation, potentially leading to clinical failure. Consequently, it is necessary to assess the change in their properties post-implantation. However, a standardized method for the precise evaluation of the changes in their physicochemical properties is currently lacking. In this study, we aimed to establish precisely simulated oral physiological conditions (SOPCs) and investigate the physicochemical property changes to predict the performance alterations of biodegradable dental barrier membranes (BDBMs) following human implantation. We investigated changes in physicochemical properties of BDBM after exposure to SOPC for 24 weeks. When BDBM was exposed to SOPC for 24 weeks, there was a significant decrease in mass (-1.37%), molecular weight (-19.54%) and tensile load (-72.84%). Among the physicochemical properties, molecular weight decreased similarly after 24 weeks of implantation in rats (-15.78%) and after 24 weeks of exposure to SOPC (-19.54%). Changes in the physicochemical properties of BDBM in simulatedin vitrooral conditions and in thein vivoenvironment were similar. Overall, the evaluation of physicochemical property changes after exposing BDBM to the proposed SOPC demonstrates novelty in its ability to accurately predict performance changes post-implantation. This approach may provide significant insights not only for the development of BDBM but also for various types of biodegradable medical devices.

Cell micro-patterning controls cell fate and function and has potential for generating therapeutically usable mesenchymal stromal cell (MSC) populations with precise functions. However, to date, the micro-patterning of human cells in a translational context has been impossible because only ruminant media supplements, e.g. fetal bovine serum (FBS), are established for use with micro-patterns (MPs). Thus, there are currently no good manufacturing practice (GMP)-compliant media available for MPs. This study tested a xenogenic-free human plasma and platelet lysate (hP + PL) medium supplement to determine its compatibility with MPs. Unfiltered hP + PL medium resulted in significant protein deposition, creating a 'carpet-like' layer that rendered MPs ineffective. Filtration (3×/5×) eliminated this effect. Importantly, quantitative comparison using droplet digital PCR revealed that human MSCs in all media types exhibited similar profiles with strong myogenic Calponin 1/Transgelin 2 (TAGLN2) and weaker osteogenic alkaline phosphatase/Runt-related transcription factor 2 marker expression, and much weaker adipogenic (lipoprotein lipase/peroxisome proliferator-activated receptor gamma) and chondrogenic (collagen type II/aggrecan) expression, with profiles being dominated by myogenic markers. Within these similar profiles, an even stronger induction of the myogenic marker TAGLN2 by all hP + PL- compared to FBS-containing media. Overall, this suggested that FBS can be replaced with hP + PL without altering differentiation profiles. However, assessing individual MSC responses to various MP types with defined categories revealed that unfiltered hP + PL medium was unusable. Importantly, FBS- and 3× filtered hP + PL media were comparable in each differentiation category. Summarized, this study recommends 3× filtered hP + PL as a xenogenic-free and potentially GMP-compliant alternative to FBS as a culture medium supplement for micro-patterning cell populations in both basic and translational research that will ensure consistent and reliable MSC micro-patterning for therapeutic use.

Machine learning (ML) has emerged as a transformative tool in various industries, driving advancements in key tasks like classification, regression, and clustering. In the field of chemical engineering, particularly in the creation of biomedical devices, personalization is essential for ensuring successful patient recovery and rehabilitation. Polylactic acid (PLA) is a material with promising potential for applications like tissue engineering, orthopedic implants, drug delivery systems, and cardiovascular stents due to its biocompatibility and biodegradability. Additive manufacturing (AM) allows for adjusting print parameters to optimize the properties of PLA components for different applications. Although past research has explored the integration of ML and AM, there remains a gap in comprehensive analyses focusing on the impact of ML on PLA-based biomedical devices. This review examines the most recent developments in ML applications within AM, highlighting its ability to revolutionize the utilization of PLA in biomedical engineering by enhancing material properties and optimizing manufacturing processes. Moreover, this review is in line with the journal's emphasis on bio-based polymers, polymer functionalization, and their biomedical uses, enriching the understanding of polymer chemistry and materials science.

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.

The advancement in the arena of bone tissue engineering persuades us to develop novel nanocomposite scaffolds in order to improve antibacterial, osteogenic, and angiogenic properties that show resemblance to natural bone extracellular matrix. Here, we focused on the development of novel zinc-doped hydroxyapatite (ZnHAP) nanoparticles (1, 2 and 3 wt%; size: 50-60 nm) incorporated chitosan-gelatin (CG) nanocomposite scaffold, with an interconnected porous structure. The addition of ZnHAP nanoparticles decreases the pore size (∼30 µm) of the CG scaffolds. It was observed that with the increase in the concentration of ZnHAP nanoparticles (3 wt%) in CG scaffolds, the swelling ratio (1760% ± 2.0%), porosity (71% ± 0.98%) and degradation rate (35%) decreased, whereas mechanical property (1 MPa) increased, which was better as compared to control (CG) samples. Similarly, the high deposition of apatite crystals especially CG-ZnHAP₃nanocomposite scaffold revealed the excellent osteoconductive potential among all other scaffolds. MC3T3-E1 osteoblastic cells seeded with CG-ZnHAP nanocomposite scaffolds depicted better cell adhesion, proliferation and differentiation to osteogenic lineages. Finally, the chorioallantoic membrane (CAM) assay revealed better angiogenesis of ZnHAP nanoparticles (3 wt%) loaded CG scaffolds supporting vascularization after 7th day incubation in the CAM area. Overall, the results showed that the CG-ZnHAP₃nanocomposite scaffold could be a potential candidate for bone defect repair.

The selection of appropriate cell sources is vital for the regeneration and repair of tendons using stem cell-based approaches. Human adipose-derived stem cells (hADSCs) have emerged as a promising therapeutic strategy for tendon injuries. However, the heterogeneity of hADSCs can lead to inconsistent or suboptimal therapeutic outcomes. In this study, we isolated and identified a tenomodulin (TNMD)-positive subpopulation from hADSCs (TNMD⁺hADSCs) using flow cytometry and then assessed the cellular response of this subpopulation to decellularized tendon slices (DTSs), including cell proliferation, migration, and tenogenic differentiation, using the CCK-8 assay, transwell migration assay, and quantitative real-time polymerase chain reaction. Our findings revealed that TNMD⁺hADSCs maintained the general characteristics of stem cells and exhibited significantly higher expressions of tendon-related markers compared to hADSCs. Importantly, DTSs significantly enhanced the proliferation, migration, and tenogenic differentiation of TNMD⁺hADSCs. This study provides preliminary experimental evidence for the translational application of ADSCs for tendon regeneration and repair.

Multimodal bioimaging is beneficial for clinical diagnosis and research due to the provision of comprehensive diagnostic information. However, the design of multifunctional bio-probes aggregating multiple bioimaging functions is greatly challenging. In this study, a multifunctional bio-probe based on lanthanide-based nanomaterials Sr₂GdF₇: Yb³⁺/Er³⁺/Tm³⁺(abbreviated as SGF) was developed forin vivomultimodal imaging by co-adopting apropos lanthanides and tuning their molar ratio. The experimental results indicate that SGF incorporates multiple excellent properties, such as 10 nm small size, optimal red-NIR region emissions, strong paramagnetism, excellent x-ray absorption ability and high biological safety. More importantly, SGF successfully realizedin vivomultimodal imaging of upconversion luminescence, magnetic resonance and x-ray computed tomography at the animal level. Thus, SGF is expected to become a multifunctional bio-probe for clinical research/diagnosis. This research would promote the application and transformation of lanthanide fluorides nanomaterials in the field of clinical diagnosis to a certain extent.

Articular cartilage and osteochondral defect repair and regeneration presents significant challenges to the field of tissue engineering (TE). TE and regenerative medicine strategies utilizing natural and synthetic-based engineered scaffolds have shown potential for repair, however, they face limitations in replicating the intricate native microenvironment and structure to achieve optimal regenerative capacity and functional recovery. Herein, we report the development of a cartilage extracellular matrix (ECM) as a printable biomaterial for tissue regeneration. The biomaterial was prepared through decellularization and solubilization of articular cartilage. The effects of two different viscosity modifiers, xanthan gum and Laponite®, and the introduction of a secondary photo-crosslinkable component on the rheological behavior and stability were studied. dcECM-Laponite® bioink formulations demonstrated storage modulus (G') ranging from 750 to 4000 Pa, which is three orders of magnitude higher than that of the dcECM-XG bioink formulations. The rheological evaluation of the bioinks demonstrated the tunability of the bioinks in terms of their viscosity and degree of shear thinning, allowing the formulations to be readily extruded during 3D printing. Also, a spreadable ink composition was identified to form a uniform cartilage layer post-printing. The choice of viscosity modifier along with UV cross-linking warrants shape fidelity of the structure post-printing, as well as improvements in the storage and loss moduli. The modified ECM-based bioink also significantly improved the stability and allowed for prolonged and sustained release of loaded growth factors through the addition of Laponite®. The ECM-based bioink supported human bone-marrow derived stromal cell and chondrocyte viability and increased chondrogenic differentiationin vitro. By forming decellularized cartilage ECM biomaterials in a printable and stable bioink form, we develop a 'Cartilage Ink' that can support cartilaginous tissue formation by closely resembling the native cartilage ECM in structure and function.

3D-printed customized titanium alloy (Ti6Al4V, TC4) as load-bearing prostheses and implants, such as intervertebral cages, have been widely used in clinical practice. Native biological inertia and inadequate bone in-growth of porous titanium alloy scaffolds hampered their clinical application efficiency and then extended the healing period. To improve the osseointegration capacity of 3D-printed intervertebral cages, sandblasting was selected to execute their surface treatment. On the one hand, sandblasting treatment can efficiently eliminate incomplete unmelted powder that adheres to struts in intervertebral cages during the manufacture of 3D printing, resulting in high surface area and low surface flatness induced by the rough surface could favor osseointegration. On the other hand, sandblasting can also induce ultrafine grains and nanograins in the near-surface layer that are conductive to mechanical strength enhancement. This can be verified by both microhardness and residual compressive stress reaching peak values (404.2 HV, 539.1 MPa) in the transverse section of its near-surface layer along the depth from the surface. This is attributed to the fact that more grain boundaries can impede dislocation movement. Sandblasting surfaces in intervertebral cages could favor osseointegration and in-growth, providing a foundation for sandblasting treatment of 3D-printed intervertebral cages in clinical applications.