Biomaterials Science最新文献

Engineering skeletal muscle tissue with precisely defined alignment is of significant importance for applications ranging from drug screening to biohybrid robotics. Aligning 2D contractile muscle monolayers, which are compatible with high-content imaging and can be deployed in planar soft robots, typically requires micropatterned cues. However, current protocols for integrating microscale topographical features in extracellular matrix hydrogels require expensive microfabrication equipment and multi-step procedures involving error-prone manual handling steps. To address this challenge, we present STAMP (simple templating of actuators via micro-topographical patterning), an easily accessible and cost-effective one-step method to pattern microtopography of various sizes and configurations on the surface of hydrogels using reusable 3D printed stamps. We demonstrate that STAMP enables precisely controlling the alignment of mouse and human skeletal muscle fibers without negatively impacting their maturation or function. To showcase the versatility of our technique, we designed a planar soft robot inspired by the iris, which leverages spatially segregated regions of concentric and radial muscle fibers to control pupil dilation. Optogenetic skeletal muscle fibers grown on a STAMPed iris substrates formed a multi-oriented actuator, and selective light stimulation of the radial and concentric fibers was used to control the function of the iris, including pupil constriction. Computational modeling of the biohybrid robot as an active bilayer matched experimental outcomes, showcasing the robustness of our STAMP method for designing, fabricating, and testing planar biohybrid robots capable of complex multi-DOF motion.

Hernia typically does not heal spontaneously. Large-pore patches, most notably polypropylene patches (PP patches), are the gold standard in hernia repair surgery. However, a single patch is insufficient for both anti-adhesion and tissue fusion, leading to complications such as organ adhesions. In this study, a chemically stable and biocompatible modified fluorinated poly(aryl ether) (FPAE-F) was prepared by grafting perfluoroalkyl groups onto a fluorinated poly(aryl ether) via nucleophilic aromatic substitution. A porous FPAE-F fiber film (eFPAE-F) was fabricated by electrospinning and combined with a PP patch to produce a modified fluorinated poly(aryl ether)/polypropylene (FPAE-F/PP) composite patch. The eFPAE-F layer of the composite patch, which faces the abdominal viscera, exhibits a water contact angle of 151.3 ± 1.2°. This superhydrophobic surface prevents protein adhesion, thereby inhibiting rapid fibroblast proliferation. The small pore size (3.22 ± 1.25 μm) of the eFPAE-F layer effectively impedes fibroblast infiltration while permitting the transport and metabolism of nutrients. In vivo experiments have demonstrated that the composite patch is a viable anti-adhesion material, resulting in no adhesions and low inflammation levels after 2 weeks. Due to its outstanding anti-adhesion properties, eFPAE-F/PP is expected to be applied in the field of hernia repair.

Biodegradable scaffolds with tailored mechanical and structural properties are essential for scaffold-guided soft tissue regeneration (SGSTR). SGSTR requires scaffolds with controllable degradation and erosion characteristics to maintain mechanical and structural integrity and strength for at least four to six months. Additionally, these scaffolds must allow for porosity expansion to create space for the growing tissue and exhibit increased mechanical compliance to match the properties of the newly formed tissue. Although progress has been made in this area, previous studies have yet to fully explore these aspects using biodegradable polymers that are synthesized and 3D printed into filaments classified as medical-grade. In this study, we optimized scaffold design based on the properties of biodegradable materials and employed digital-assisted 3D printing to adjust the degradation pathway of dual-material scaffolds dynamically, thereby modulating mechanical and structural changes. Two medical-grade 3D printing filaments were utilized: Dioxaprene® (DIO), which has a degradation rate of approximately six months, and Caproprene™ (CAP), which has a degradation rate of about 36 months. The scaffolds were 3D printed with these materials to create the desired architecture. An in vitro degradation study showed the increasing pore size and compliance (>90% increase) of the scaffold architecture via the breakdown of DIO. Meanwhile, the slow-degrading CAP maintained long-term mechanical and structural integrity. Furthermore, over six months of subcutaneous implantation in rats, the dual material showed an approximately two-fold increase in mechanical compliance and free volume expansion, with the pore size increasing from 1 mm to 2 mm to accommodate the growing tissue. The scaffold remained structurally intact and provided mechanical support for the newly formed tissue. Histological and immunohistochemical analyses indicated good in vivo biocompatibility, tissue guidance, and the formation of organized soft tissue architecture, supported by an extensive network of blood vessels.

Vascularization is a crucial aspect of biofabrication, as the development of vascular networks is essential for tissue survival and the optimization of cellular functions. Spheroids have emerged as versatile units for vascularization, demonstrating significant potential in angiogenesis and prevascularization for tissue engineering and regenerative medicine. However, a major challenge in creating customized vascularized spheroids is the construction of a biomimetic extracellular matrix (ECM) microenvironment. This process requires careful regulation of environmental factors, including the modulation of growth factors, the selection of culture media, and the co-culture of diverse cell types. Recent advancements in biofabrication have expanded the potential applications of vascularized spheroids. The integration of microfluidic technology with bioprinting offers promising solutions to existing challenges in regenerative medicine. Spheroids have been widely studied for their ability to promote vascularization in in vitro models. This review highlights the latest developments in vascularized biofabrication, and systematically explores strategies for constructing vascularized spheroids. We provide a comprehensive analysis of spheroid applications in specific tissues, including skin, liver, bone, cardiac, and tumor models. Finally, the review addresses the major challenges and future directions in the field.

Temperature is a crucial physical parameter in living organisms, directly associated with cellular activities. Elevated temperatures induce cell death, thereby establishing hyperthermia as a viable modality for cancer therapy. The demand for determining appropriate cancer types for hyperthermia lies in identifying cancer cells that exhibit poorer heat tolerance compared to normal cells. Herein, we have designed NaNdF₄:4%Yb@NaYF₄ with bright luminescence in the near-infrared region for the purpose of achieving in situ cellular temperature detection. The Nd-Yb nanothermometer provides temperature feedback based on a ratiometric luminescence intensity signal. By employing a universal cytobiology method to assess the heat resistance differences between cancer cells and normal cells across various organs, it has been observed that lung epithelial cells exhibit superior heat resistance compared to lung cancer cells. Once the Nd-Yb nanothermometer incubates within lung cells, the temperature differences between live and dead cells can be detected. The absolute temperature differences between live and dead lung cancer cells (0.1 °C) and lung epithelial cells (1.4 °C) under identical thermal stimulation (50 °C) are detected by the Nd-Yb co-doped nanothermometer, confirming that the heat resistance of normal lung cells is significantly superior to that of lung cancer cells. The differential heat resistance of lung cells enables selective hyperthermia for killing A549 cells while maximally protecting BEAS-2B cells. This research may establish rare earth nanothermometry as a valuable protocol for assessing cellular heat resistance, thereby guiding selective hyperthermia for precise lung cancer treatment.

Photodynamic therapy (PDT) has received much attention as a promising modality for tumor treatment. However, the weak targeting ability of conventional photosensitisers and the metastasis of malignant tumors have severely limited the development of PDT. To address this, an esterase-activated prodrug (BPYM) has been developed for imaging-guided photodynamic therapy cascade immunotherapy for the treatment of pancreatic cancer. Upon reaction with esterase, BPYM releases the photosensitiser BPY and exhibits strong red fluorescence emission, which is further enhanced by the aggregation-induced emission (AIE) characteristics of BPY. Interestingly, the activation of the fluorescence signal simultaneously indicates the activation of photosensitivity capabilities. Under white light irradiation, activated BPYM can generate large amounts of reactive oxygen species (ROS) to induce apoptosis in pancreatic cancer cells. More importantly, BPYM-mediated PDT can trigger immunogenic cell death (ICD) and elicit a systemic anti-tumor immune response. Ultimately, this imaging-guided PDT not only precisely ablates the primary pancreatic cancer tumors, but also inhibits the growth of distant tumors through an immune response. In summary, we report a strategy to achieve photodynamic immunotherapy for the treatment of pancreatic cancer through the rational design of an esterase-activated prodrug.

Cartilage tissue engineering based on the combination of biomaterials, adult or stem cells and bioactive factors is a challenging approach for regenerative medicine with the aim of achieving the formation of a functional neotissue stable in the long term. Various 3D scaffolds have been developed to mimic the extracellular matrix environment and promote cartilage repair. In addition, bioactive factors have been extensively employed to induce and maintain the cartilage phenotype. However, the spatiotemporal control of bioactive factor release remains critical for maximizing the regenerative potential of multipotent cells, such as mesenchymal stromal cells (MSCs), and achieving efficient chondrogenesis and sustained tissue homeostasis, which are essential for the repair of hyaline cartilage. Despite advances, the effective delivery of bioactive factors is limited by challenges such as insufficient retention at the site of injury and the loss of therapeutic efficacy due to uncontrolled drug release. These limitations have prompted research on biomolecule-scaffold interactions to develop advanced delivery systems that provide sustained release and controlled bioavailability of biological factors, thereby improving therapeutic outcomes. This review focuses specifically on biomaterials (natural, hybrid and synthetic) and biomolecules (molecules, proteins, nucleic acids) of interest for cartilage engineering. Herein, we review in detail the approaches developed to maintain the biomolecules in scaffolds and control their release, based on their chemical nature and structure, through steric, non-covalent and/or covalent interactions, with a view to their application in cartilage repair.

α-Synuclein (α-Syn) is a primary pathological indicator for Parkinson's disease (PD). The α-Syn oligomer is even more toxic and is responsible for PD. Hence, identifying α-Syn and its oligomers is an interesting approach to diagnosing PD. The prevention strategies for oligomer formation could be therapeutic in treating PD. Various conventional strategies have been developed for the management of PD. However, their clinical applications are limited due to toxicity, off-targeting, side effects, and poor bioavailability. Recently, nanomaterials have gained significant attention due to unique physicochemical characteristics such as nanoscale size, large surface area, flexibility of functionalization, and ability to protect and control a loaded payload. Functionalizing the surface of nanoparticles with a desired targeting agent could offer targeted delivery of the payload at the site of action due to specificity and selectivity against complementary molecules. Among various functionalization approaches, biomolecule-functionalized nanomaterials offer benefits such as enhanced bioavailability, improved internalization into target cells through receptor-mediated endocytosis, and delivery of therapeutics across the BBB (blood-brain barrier). In this review, we initially discussed the major milestones related to PD and highlighted the therapeutic strategies focused on clinical trials. The strategies of biomolecule functionalization of nanomaterials and their application in detecting and preventing α-Syn oligomer for the diagnosis and therapy of PD, respectively, have been reviewed comprehensively. Ultimately, we have outlined the conclusions, highlighted the limitations and challenges, and provided insight into future perspectives and alternative approaches that must be investigated.

Tendon degeneration remains an intricate pathological process characterized by the coexistence of multiple dysregulated homeostasis processes, including the increase in collagen III production in comparison with collagen I. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) remain a promising therapeutic tool thanks to their pro-regenerative properties and applicability as drug delivery systems, despite their drug loading limitations. Herein, we developed MSC-EV-derived hybrid lipid nanoparticles (MSC-Hyb NPs) using a microfluidic-sonication technique as an alternative platform for the delivery of collagen type I (COL 1A1) mRNA into pathological TSPCs. The MSC-Hyb NPs produced had LNP-like physicochemical characteristics and were 178.6 nm in size with a PDI value of 0.245. Moreover, MSC-Hyb NPs encapsulated mRNA and included EV-derived surface proteins such as CD63, CD81 and CD144. MSC-Hyb NPs remained highly biocompatible with TSPCs and proved to be functional mRNA delivery agents with certain limitations in comparison with lipid nanoparticles (LNPs). In vitro efficacy studies on TSPCs showed a 2-fold increase in procollagen type I carboxy-terminal peptide production comparable with the effect caused by LNPs. Therefore, our work provides an alternative production method for MSC-EV-derived hybrid NPs and supports their potential use as drug delivery systems for tendon regeneration.

High expression of externally injected in vitro transcribed (IVT) mRNA in natural killer (NK) cells is a prerequisite for NK cell-mediated cell therapy. To enhance the transfection efficacy of IVT mRNA-loaded polyplexes, we exposed NK cells to a hypertonic condition during transfection, which facilitated endo/exocytosis to maintain the isotonic state of the cells. The transfection efficacy of IVT mRNA was significantly enhanced after 24 h, which was mainly due to the facilitated cellular uptake and endosomal escape of the polyplexes. Interestingly, osmotic alterations in NK cells significantly affect the expression levels of endosome-escape-related genes in ion channels. Treatment with a mild hypertonic condition exhibited negligible toxicity to NK cells, without disturbing the integrity of the cellular membranes or the innate cytotoxic abilities of NK cells against cancer cells. These results demonstrate that the hypertonic treatment of NK cells enhances the transfection efficacy of IVT mRNA to produce genetically engineered NK cells.