Biomaterials Science最新文献

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.

Treating sunburn and other UV-induced skin damage issues remains a significant challenge in the field of dermatology. In this study, we synthesized a highly bioactive recombinant type III collagen (rCol III) to accelerate the healing of UV-damaged skin. The high-purity rCol III demonstrated excellent biocompatibility and bioactivity, significantly promoting the adhesion, proliferation, and migration of HFF-1 cells. In a mouse UV-damage model, Combo evaluations demonstrated that rCol III contributed to restore transepidermal water loss (TEWL) values of UV-damaged skin to normal levels. Histological analysis further confirmed that rCol III substantially accelerated skin repair by enhancing collagen regeneration. Additionally, rCol III facilitated the regeneration of zebrafish tail fin tissue and alleviated shrinkage caused by excessive UV exposure. The biocompatible and bioactive rCol III offers a novel strategy for treating UV-induced skin damage, holding immense potential for applications in skin tissue engineering.

Tauopathies are neurodegenerative diseases that involve tau misfolding and aggregation in the brain. These diseases, including Alzheimer's disease (AD), are some of the least understood and most difficult to treat neurodegenerative disorders. Antibodies and antibody fragments that target tau oligomers, which are especially toxic forms of tau, are promising options for immunotherapies and diagnostic tools for tauopathies. In this study, we have developed conformational, tau oligomer-specific nanobodies, or single-domain antibodies. We demonstrate that these nanobodies, OT2.4 and OT2.6, are highly specific for tau oligomers relative to tau monomers and fibrils. We used epitope mapping to verify that these nanobodies bind to discontinuous epitopes on tau and to support the idea that they interact with a conformation present in the oligomeric, and not monomeric or fibrillar, forms of tau. We show that these nanobodies interact with tau oligomers in brain samples from AD patients and from healthy older adults with primary age-related tauopathy. Our results demonstrate the potential of these nanobodies as tau oligomer-specific binding reagents and future tauopathy therapeutics and diagnostics.

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.

It remains a challenge to endow a polymeric material with antithrombotic ability by surface grafting without disturbing the bulk properties of the substrate. Heparin-based functional structures of less than 80 nm were fabricated and covalently grafted on a polyethylene terephthalate surface via carbene chemistry (Hep-g-PET). Heparin was oxidized with the minimum antithrombrin sequence retained, creating an aldehyde group on the chain terminus. Oxidized heparin was then covalently attached to a poly(amidoamine) (PAMAM)-grafted PET substrate. The interface between blood and PET was improved by the surface functionality, and the amount of attached platelets decreased to 29 ± 12.1% of its initial value. The bulk properties of the functionalized film were hardly influenced, and the visible light transmittance remained more than 96%. The tethered structures also showed the ability to kill attached S. aureus and E. coli efficiently. The functionalized membrane showed negligible ex vivo cell cytotoxicity and a low hemolysis ratio. Hep-g-PET was implanted in between rat skin and muscle, and showed an outstanding histological response and antimicrobial ability. The influences of the graft thickness and the heparin chain length were explored. The strategies reported in this work may help to improve the design of polymeric implant bio-devices.

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.

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.

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.

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.

Over the last 20 years, mesoporous silica nanoparticles (MSNs) have drawn considerable attention in the biomedical field due to their large surface area, porous network, biocompatibility, and abundant modification possibilities. In situ MSN modification refers to the incorporation of materials such as alkoxysilanes, ions and nanoparticles (NPs) in the silica matrix during synthesis. Matrix modification is a popular approach for endowing MSNs with additional functionalities such as imaging properties, bioactivity, and degradability, while leaving the mesopores free for drug loading. As such, in situ modified MSNs are considered promising theranostic agents. This review provides an extensive overview of different materials and modification strategies that have been used and their effect on MSN properties. We also highlight how in situ modified MSNs have been applied in theranostic applications, oncology and regenerative medicine. We conclude with perspectives on the future outlooks and current challenges for the widespread clinical use of in situ modified MSNs.