Biomaterials Science最新文献

PEGylation is a promising strategy for modulating the physicochemical properties and improving the therapeutic efficacy of protein drugs. However, the application of multi-PEGylation frequently results in diminished protein activity. A single low molecular weight PEG (5 kDa) modified at the amino terminus of the B chain preserves the biological activity of insulin and moderately improves its pharmacokinetics. Nonetheless, this modification offers limited protein stabilization. Furthermore, overdoses still carry the risk of hypoglycemia, posing challenges for the clinical application of PEGylated insulin. Here, we constructed multifunctional nanochaperones featuring phenylboronic acid (PBA) modified hydrophobic microdomains and nitrilotriacetic acid (NTA)-based coordination domains (PN-nChaps) for PEGylated insulin delivery. This delivery strategy effectively overcomes the limitations associated with PEGylation by enhancing the stability and reducing the immunogenicity of PEGylated insulin, while enabling glucose-responsive controlled release. PEGylated insulin with nanochaperone carrier demonstrates a prolonged half-life (t_1/2 = 18.66 h), facilitates on-demand release, and minimizes the risk of hypoglycemia. This approach provides a safe and effective strategy for long-term glycemic management in diabetic patients.

Radionuclide-contaminated wounds face clinical dilemmas such as repeated erosion and ulceration and are difficult to heal. In this work, we aimed to develop a biodegradable hydrogel with a beneficial effect on radionuclide-contaminated wounds and initially investigated the mechanism of action of the hydrogel. The hydrogel was produced through the ring-opening polymerization of polycaprolactone (PCL) triggered by polyethylene glycol (PEG), and its physicochemical properties were characterized by gel permeation chromatography, nuclear magnetic resonance, rheological properties testing, and other techniques. The low critical solution temperatures were 30 °C and 46 °C, which are suitable for the human body to realize the degradable properties of the hydrogel. A radionuclide-contaminated wound model was established, which proved that the biodegradable hydrogel had good healing properties and did not form secondary lesions. The effect was better than clinically used EGF or VB12. Pathological results showed that mature granulation tissue formed on the 7th day after the injury, and by the 10th day after the injury, the scab had completely fallen off, the epithelial coverage had reached over 70% and the wound was essentially completely healed. Additionally, the hydrogel affects immune metabolism, regulates immune cell function, promotes the formation of new blood vessels and granular tissue, and effectively accelerates the healing process of radionuclide-contaminated wounds.

Natural products, which are compounds extracted and/or refined from plants and microbes in nature, have great potential for the discovery of therapeutic agents, especially for infectious diseases and cancer. In recent years, natural products have been reported to induce multiple cell death pathways to exhibit antitumor effects. Among them, pyroptosis is a unique programmed cell death (PCD) characterized by continuous cell membrane permeability and intracellular content leakage. According to the canonical and noncanonical pathways, the formation of gasdermin-N pores involves a variety of transcriptional targets and post-translational modifications. Thus, tailored control of PCD may facilitate dying cells with sufficient immunogenicity to activate the immune system to eliminate other tumor cells. Therefore, we summarized the currently reported natural products or their derivatives and their nano-drugs that induce pyroptosis-related signaling pathways. We reviewed six main categories of bioactive compounds extracted from natural products, including flavonoids, terpenoids, polyphenols, quinones, artemisinins, and alkaloids. Correspondingly, the underlying mechanisms of how these compounds and their derivatives engage in pyroptosis are also discussed. Moreover, the synergistic effect of natural bioactive compounds with other antitumor therapies is proposed as a novel therapeutic strategy for traditional chemotherapy, radiotherapy, chemodynamic therapy, photodynamic therapy, photothermal therapy, hyperthermal therapy, and sonodynamic therapy. Consequently, we provide insights into natural products to develop a novel antitumor therapy or qualified adjuvant agents by inducing pyroptosis, which may eventually be applied clinically.

Granular hydrogels comprised of jammed, crosslinked microgels offer great potential as biomaterial scaffolds for cell-based therapies, including for cartilage tissue regeneration. As stiffness and porosity of hydrogels affect the phenotype of encapsulated cells and the extent of tissue regeneration, the design of tunable granular hydrogels to control and optimize these parameters is highly desirable. We hypothesized that chondrogenesis could be modulated using a granular hydrogel platform based on biocompatible, zwitterionic materials with independent intra- and inter-microgel crosslinking mechanisms. Microgels are made with mechanical fragmentation of photocrosslinked zwitterionic carboxybetaine acrylamide (CBAA) and sulfobetaine methacrylate (SBMA) hydrogels, and secondarily crosslinked in the presence of cells using horseradish peroxide (HRP) to produce cell-laden granular hydrogels. We varied the intra-microgel crosslinking density to produce microgels with varied stiffnesses (1–3 kPa) and swelling properties. These microgels, when resuspended at the same weight fraction and secondarily crosslinked, resulted in granular hydrogels with distinct porosities (5–40%) due to differing swelling properties. The greatest extent of chondrogenesis was achieved in scaffolds with the highest microgel stiffness and highest porosity. However, when scaffold porosity was kept constant and just microgel stiffness varied, cell phenotype and chondrogenesis were similar across scaffolds. These results indicate the dominant role of granular scaffold porosity on chondrogenesis, whereas microgel stiffness appears to play a relatively minor role. These observations are in contrast to cells encapsulated within conventional bulk hydrogels, where stiffness has been shown to significantly affect chondrocyte response. In summary, we introduce chemically-defined, zwitterionic biomaterials to fabricate versatile granular hydrogels allowing for tunable scaffold porosity and microgel stiffness to study and influence chondrogenesis.

Retraction of ‘Cytocompatible, soft and thick brush-modified scaffolds with prolonged antibacterial effect to mitigate wound infections’ by Shaifali Dhingra et al., Biomater. Sci., 2022, 10, 3856–3877, https://doi.org/10.1039/D2BM00245K.

Spinal cord injury is a serious disease of the central nervous system. The electrophysiological properties of the spinal cord that are essential to maintaining neurotransmission can be impaired after the injury. Therefore, electrophysiological evaluation is becoming an important indicator of the injury extent or the therapeutic outcomes by reflecting the potential propagation of neural pathways. On the other hand, the repair of damaged nerves is one of the main goals of spinal cord injury treatment. Growing research interest has been concentrated on developing effective therapeutic solutions to restore the normal electrophysiological function of the injured spinal cord by using conductive materials and/or exerting the merits of electrical stimulation. Accordingly, this review introduces the current common electrophysiological evaluation in spinal cord injury. Then the cutting-edge therapeutic strategies aiming at electrophysiological improvement in spinal cord injury are summarized. Finally, the challenges and future prospects of neural restoration after spinal cord injury are presented.

The human body possesses natural barriers, such as skin and mucosa, which limit the effective delivery of therapeutics and integration of medical devices to target tissues. Various strategies have been deployed to breach these barriers mechanically, chemically, or electronically. The development of various penetration enhancers (PEs) offers a promising solution due to their ability to increase tissue permeability using readily available reagents. However, existing PE-mediated delivery methods often rely on weak gel or liquid drug formulations, which are not ideal for sustained local delivery. Hydrogel adhesives that can seamlessly interface biological tissues with controlled drug delivery could potentially resolve these issues. Here, we demonstrate that tough adhesion between drug-laden hydrogels and biological tissue (e.g. skin and tumours) can lead to effective local delivery of drugs deep into targeted tissues by leveraging the enhanced tissue penetration mediated by PEs. The drug release profile of the hydrogel adhesives can be fine-tuned by further engineering the nanocomposite hydrogel matrix to elute chemotherapeutics from 2 weeks to 2 months. Using a 3D tumour spheroid model, we demonstrated that PEs increased the cancer-killing effectiveness of doxorubicin by facilitating its delivery into tumour microtissues. Therefore, the proposed tough bioadhesion and drug delivery strategy modulated by PEs holds promise as a platform technique to develop next-generation wearable and implantable devices for cancer management and regenerative medicine.

Injectable hydrogels, as a class of highly hydrated soft materials, are of interest for biomedicine due to their precise implantation and minimally invasive local drug delivery at the implantation site. The combination of in situ gelation ability and versatile therapeutic agent/cell loading capabilities makes injectable hydrogels ideal materials for drug delivery, tissue engineering, wound dressing and tumor treatment. In particular, the stimuli-responsive injectable hydrogels that can respond to different stimuli in and out of the body (e.g., temperature, pH, redox conditions, light, magnetic fields, etc.) have significant advantages in biomedicine. Here, we summarize the design strategies, advantages, and recent developments of stimuli-responsive injectable hydrogels in different biomedical fields. Challenges and future perspectives of stimuli-responsive injectable hydrogels are also discussed and the future steps necessary to fulfill the potential of these promising materials are highlighted.

Bacterial colonization and biofilm formation on medical devices represent one of the most urgent and critical challenges in modern healthcare. These issues not only pose serious threats to patient health by increasing the risk of infections but also exert a considerable economic burden on national healthcare systems due to prolonged hospital stays and additional treatments. To address this challenge, there is a need for smart, customized biomaterials for medical device fabrication, particularly through the development of surface modification strategies that prevent bacterial adhesion and the growth of mature biofilms. This review explores three bioinspired approaches through which antibacterial and antiadhesive coatings can be engineered to exhibit smart, stimuli-responsive features. This responsiveness is greatly valuable as it provides the coatings with a controlled, on-demand antibacterial response that is activated only in the presence of bacteria, functioning as self-defensive coatings. Such coatings can be designed to release antibacterial agents or change their surface properties/conformation in response to specific stimuli, like changes in pH, temperature, or the presence of bacterial enzymes. This targeted approach minimizes the risk of developing antibiotic resistance and reduces the need for continuous, high-dose antibacterial treatments, thereby preserving the natural microbiome and further reducing healthcare costs. The final part of the review reports a critical analysis highlighting the potential improvements and future evolutions regarding antimicrobial self-defensive coatings and their validation.

LAPONITE®-based drug delivery systems offer many advantages due to the unique ionic and physical properties of LAPONITE®. The high ionicity and large surface area of LAPONITE® nanoparticles enable the intercalation and dissolution of biomolecules. In this study, we explored the potential of LAPONITE® as a carrier for FG-4592 to support angiogenesis and as a carrier for bone morphogenic protein-2 (BMP-2) to support osteogenesis. Interestingly, we found that LAPONITE® promoted the FG-4592 induced upregulation of vascular endothelial growth factor (VEGF) gene expression of human umbilical cord endothelial cells (HUVECs). Additionally, we observed that LAPONITE® could provide a sustained release of BMP-2 and significantly potentiate the osteogenic effects of BMP-2 on adipose derived mesenchymal stem cells (AMSCs). Overall, current findings on the LAPONITE®-drug/protein model system provide a unique way to potentiate the angiogenic activities of FG-4592 on HUVECs and osteogenic effects of BMP-2 on AMSCs for tissue engineering application. Future studies will be directed towards gaining a deeper understanding of these effects on a co-culture system of HUVECs and AMSCs.