ACS Applied Bio Materials最新文献

A titanium alloy is widely used in implants for its excellent mechanical properties and corrosion resistance. However, the bonding strength between a titanium alloy and bone tissue is low, and the bacterial adhesion is easily triggered on the implant surface, which may cause the failure of implants. Therefore, surface modification is necessary to improve the biological activity and antibacterial properties. In this work, four different types of laser-induced periodic surface structure (LIPSS) surfaces are designed and fabricated on the TiNi alloy by a femtosecond laser according to the size of MC3T3-E1 mouse embryonic osteoblasts. The in vitro osteogenic activity of the LIPSS surface is investigated. It is found that the LIPSS helps improve the in vitro osteogenic activity, and bonelike apatite tends to deposit and distribute on the LIPSS. The biological activity and antibacterial activity of the LIPSS surface are evaluated through cell culture experiments and Escherichia coli culture experiments. It is demonstrated that the horizontal LIPSS sample with a width of 30 μm has the highest cell proliferation rate (142.5% after 1 day, 132.3% after 3 days) and a good antibacterial rate (50.2%). These results provide guidance for the application of the LIPSS in biocompatibility and antibacterial aspects.

STAT3 is an important protein responsible for cellular proliferation, motility, and immune tolerance and is hyperactive in colorectal cancer, instigating metastasis, cellular proliferation, migration, as well as inhibition. It helps in proliferation of myeloid-derived suppressor cells (MDSCs), which within the tumor microenvironment (TME) suppress T cells to encourage tumor growth, metastasis, and resistance to immunotherapy, besides playing dynamic role in regulating macrophages within the tumor. Thus, MDSC is a potential target to augment immune surveillance within the TME. Herein, we report targeting both colorectal cancer and MDSCs using a glucocorticoid receptor (GR)-targeted nanoliposomal formulation carrying GR-ligand, dexamethasone (Dex), and a STAT3 inhibitor, niclosamide (N). Our main objective was to selectively inhibit STAT3, the key immunomodulatory factor in most TME-associated cells including MDSCs, and also repurpose the use of this antihelminthic, low-cost drug N for cancer treatment. The resultant formulation D1XN exhibited better tumor regression and survivability compared to GR nontargeted formulation. Further, bone marrow cell-derived MDSCs were engineered by D1XN treatment ex vivo and were inoculated back to tumor-bearing mice. Significant tumor growth inhibition with enhanced antiproliferative immune cell signatures, such as T cell infiltration, decrease in T_reg cells, and increased M1/M2 macrophage ratio within the TME were observed. This reveals the effectiveness of engineered MDSCs to modulate tumor surveillance besides reversing the aggressiveness of the tumor. Therefore, D1XN and D1XN-mediated engineered MDSCs alone or in combination can be considered as potent selective chemo-immunotherapeutic nanoliposomal agent(s) against colorectal cancer.

The encapsulation of bacteria in metal-organic frameworks (MOFs) is being studied for use in biomedicine and bioremediation. However, biocompatibility could be improved, as much of the research focuses on ZIF-8 and Escherichia coli. MIL-88A, composed of fumaric acid and iron, offers a safer alternative. This study investigates encapsulation of the probiotic strain Lactiplantibacillus plantarum 299v in a nanocrystalline matrix via a simple one-pot synthesis. The encapsulated bacteria show improved stability in saline, lysozyme and pepsin compared to uncoated cells. These findings highlight the potential of the iron(III) fumarate matrix for bacterial protection and controlled release for biological applications.

The encapsulation of bacteria in metal–organic frameworks (MOFs) is being studied for use in biomedicine and bioremediation. However, biocompatibility could be improved, as much of the research focuses on ZIF-8 and Escherichia coli. MIL-88A, composed of fumaric acid and iron, offers a safer alternative. This study investigates encapsulation of the probiotic strain Lactiplantibacillus plantarum 299v in a nanocrystalline matrix via a simple one-pot synthesis. The encapsulated bacteria show improved stability in saline, lysozyme and pepsin compared to uncoated cells. These findings highlight the potential of the iron(III) fumarate matrix for bacterial protection and controlled release for biological applications.

STAT3 is an important protein responsible for cellular proliferation, motility, and immune tolerance and is hyperactive in colorectal cancer, instigating metastasis, cellular proliferation, migration, as well as inhibition. It helps in proliferation of myeloid-derived suppressor cells (MDSCs), which within the tumor microenvironment (TME) suppress T cells to encourage tumor growth, metastasis, and resistance to immunotherapy, besides playing dynamic role in regulating macrophages within the tumor. Thus, MDSC is a potential target to augment immune surveillance within the TME. Herein, we report targeting both colorectal cancer and MDSCs using a glucocorticoid receptor (GR)-targeted nanoliposomal formulation carrying GR-ligand, dexamethasone (Dex), and a STAT3 inhibitor, niclosamide (N). Our main objective was to selectively inhibit STAT3, the key immunomodulatory factor in most TME-associated cells including MDSCs, and also repurpose the use of this antihelminthic, low-cost drug N for cancer treatment. The resultant formulation D1XN exhibited better tumor regression and survivability compared to GR nontargeted formulation. Further, bone marrow cell-derived MDSCs were engineered by D1XN treatment ex vivo and were inoculated back to tumor-bearing mice. Significant tumor growth inhibition with enhanced antiproliferative immune cell signatures, such as T cell infiltration, decrease in T_reg cells, and increased M1/M2 macrophage ratio within the TME were observed. This reveals the effectiveness of engineered MDSCs to modulate tumor surveillance besides reversing the aggressiveness of the tumor. Therefore, D1XN and D1XN-mediated engineered MDSCs alone or in combination can be considered as potent selective chemo-immunotherapeutic nanoliposomal agent(s) against colorectal cancer.

A titanium alloy is widely used in implants for its excellent mechanical properties and corrosion resistance. However, the bonding strength between a titanium alloy and bone tissue is low, and the bacterial adhesion is easily triggered on the implant surface, which may cause the failure of implants. Therefore, surface modification is necessary to improve the biological activity and antibacterial properties. In this work, four different types of laser-induced periodic surface structure (LIPSS) surfaces are designed and fabricated on the TiNi alloy by a femtosecond laser according to the size of MC3T3-E1 mouse embryonic osteoblasts. The in vitro osteogenic activity of the LIPSS surface is investigated. It is found that the LIPSS helps improve the in vitro osteogenic activity, and bonelike apatite tends to deposit and distribute on the LIPSS. The biological activity and antibacterial activity of the LIPSS surface are evaluated through cell culture experiments and Escherichia coli culture experiments. It is demonstrated that the horizontal LIPSS sample with a width of 30 μm has the highest cell proliferation rate (142.5% after 1 day, 132.3% after 3 days) and a good antibacterial rate (50.2%). These results provide guidance for the application of the LIPSS in biocompatibility and antibacterial aspects.

Oxygen anions (superoxide and peroxide anions) are naturally unstable and prone to chemical interactions. These reactive oxygen species (ROS) are formed during long-term storage in olive oil (OO), the structural properties of which extend the ROS lifespan more effectively than those of other vegetable oils. In wound treatment, superoxide anions serve as precursors for hydrogen peroxide and play a crucial role in cell proliferation, migration, and angiogenesis. These anions were encapsulated within the OO medium for crystallization. Piezoelectric actuators were employed to distribute the trapped bubbles evenly throughout the crystallized OO. The ROS-filled OO microcapsules eliminated volatile organic compounds and particulate matter (from the air). Samples stored in crystallized OO were utilized to investigate the antibacterial effects. Both Escherichia coli and Staphylococcus aureus were implicated in skin infections (with S. aureus as the primary pathogen and E. coli as the secondary pathogen) and were selected for antibacterial testing. Microcapsules applied to cultured E. coli and S. aureus resulted in different inhibition zones. Two groups [control (C-) and treatment (T-)] of second-degree burn wounds were created on the dorsal area of 15 Wistar rats. Over a period of 2 weeks, statistical analysis using a t-test demonstrated a significant reduction in the wound size in the T-zones. Histological examination with hematoxylin, eosin, and trichrome staining of tissue samples from the wound areas revealed a notable reduction in inflammation, enhanced epidermal cell proliferation, improved activity in producing hair follicles, and increased collagen deposition in the treated regions on different days of observation.

Implant-associated infections pose significant challenges due to bacterial resistance to antibiotics. Recent research highlights the potential of immobilizing antimicrobial peptides (AMPs) onto implants as an alternative to conventional antibiotics for the prevention of bacterial infection. While various AMP immobilization methodologies have been investigated, they lack responsiveness to biological cues. This study proposes an enzyme-responsive antimicrobial coating for orthopedic devices using KR-12, an AMP derived from Cathelicidin LL-37, coupled with the Human Elastin-Like Polypeptide (HELP) as a biomimetic and stimuli-responsive linker, while mimicking the extracellular matrix (ECM). During implantation, these customized interfaces encounter the innate immune response triggering elastase release, which degrades HELP biopolymers, enabling the controlled release of KR-12. After coupling KR-12 with HELP to titanium surfaces, the antimicrobial activity against four pathogenic bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa) was assessed, revealing an inhibition ratio of bacterial adhesion and colonization exceeding 92% for all tested strains, compared with surfaces functionalized with KR-12 only. It is thought that the enhanced antimicrobial activity was due to the improved mobility of KR-12 when coupled with HELP. Furthermore, the prepared coatings boosted the adhesion and proliferation of human osteoblasts, confirming the cytocompatibility. These findings suggest the potential for smart coatings that combine the antimicrobial functions of AMPs with HELP's biological properties for use in a variety of settings, including medical devices.

Implant-associated infections pose significant challenges due to bacterial resistance to antibiotics. Recent research highlights the potential of immobilizing antimicrobial peptides (AMPs) onto implants as an alternative to conventional antibiotics for the prevention of bacterial infection. While various AMP immobilization methodologies have been investigated, they lack responsiveness to biological cues. This study proposes an enzyme-responsive antimicrobial coating for orthopedic devices using KR-12, an AMP derived from Cathelicidin LL-37, coupled with the Human Elastin-Like Polypeptide (HELP) as a biomimetic and stimuli-responsive linker, while mimicking the extracellular matrix (ECM). During implantation, these customized interfaces encounter the innate immune response triggering elastase release, which degrades HELP biopolymers, enabling the controlled release of KR-12. After coupling KR-12 with HELP to titanium surfaces, the antimicrobial activity against four pathogenic bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa) was assessed, revealing an inhibition ratio of bacterial adhesion and colonization exceeding 92% for all tested strains, compared with surfaces functionalized with KR-12 only. It is thought that the enhanced antimicrobial activity was due to the improved mobility of KR-12 when coupled with HELP. Furthermore, the prepared coatings boosted the adhesion and proliferation of human osteoblasts, confirming the cytocompatibility. These findings suggest the potential for smart coatings that combine the antimicrobial functions of AMPs with HELP’s biological properties for use in a variety of settings, including medical devices.

Oxygen anions (superoxide and peroxide anions) are naturally unstable and prone to chemical interactions. These reactive oxygen species (ROS) are formed during long-term storage in olive oil (OO), the structural properties of which extend the ROS lifespan more effectively than those of other vegetable oils. In wound treatment, superoxide anions serve as precursors for hydrogen peroxide and play a crucial role in cell proliferation, migration, and angiogenesis. These anions were encapsulated within the OO medium for crystallization. Piezoelectric actuators were employed to distribute the trapped bubbles evenly throughout the crystallized OO. The ROS-filled OO microcapsules eliminated volatile organic compounds and particulate matter (from the air). Samples stored in crystallized OO were utilized to investigate the antibacterial effects. Both Escherichia coli and Staphylococcus aureus were implicated in skin infections (with S. aureus as the primary pathogen and E. coli as the secondary pathogen) and were selected for antibacterial testing. Microcapsules applied to cultured E. coli and S. aureus resulted in different inhibition zones. Two groups [control (C-) and treatment (T-)] of second-degree burn wounds were created on the dorsal area of 15 Wistar rats. Over a period of 2 weeks, statistical analysis using a t-test demonstrated a significant reduction in the wound size in the T-zones. Histological examination with hematoxylin, eosin, and trichrome staining of tissue samples from the wound areas revealed a notable reduction in inflammation, enhanced epidermal cell proliferation, improved activity in producing hair follicles, and increased collagen deposition in the treated regions on different days of observation.