ACS Applied Bio Materials最新文献

Patients and healthcare systems face significant social and financial challenges due to the increasing number of individuals with chronic external and internal wounds that fail to heal. The complexity of the healing process remains a serious health concern, despite the effectiveness of conventional wound dressings in promoting healing. Recent advancements in materials science and fabrication techniques have led to the development of innovative dressings that enhance wound healing. To further expedite the healing process, novel approaches such as nanoparticles, 3D-printed wound dressings, and biomolecule-infused dressings have emerged, along with cell-based methods. Additionally, gene therapy technologies are being harnessed to generate stem cell derivatives that are more functional, selective, and responsive than their natural counterparts. This review highlights the significant potential of biomaterials, nanoparticles, 3D bioprinting, and gene- and cell-based therapies in wound healing. However, it also underscores the necessity for further research to address the existing challenges and integrate these strategies into standard clinical practice.

With the rising incidence of cancer, chemotherapy has become a widely used treatment approach. However, the use of anticancer drugs such as doxorubicin (DOX) poses significant long-term risks due to its nonspecific distribution and severe side effects. Therefore, developing a nanoparticle-based drug delivery system (DDS) that enhances the bioavailability of DOX specifically to cancer cells is crucial while minimizing its side effects on normal cells. This study employed zeolitic imidazolate framework-8 (ZIF-8) as a DDS to encapsulate DOX using a one-pot method. The surface of this system was subsequently modified with a copper-gallic acid (Cu-GA) complex to form the Cu-GA/DOX@ZIF-8 (CGDZ) system. The CGDZ system effectively encapsulates DOX and demonstrates pH-responsive drug release, facilitating controlled drug release in the acidic environment of cancer cells. Furthermore, the Cu-GA coating enhances the biocompatibility of the material, reduces drug toxicity in normal endothelial cells (BAECs) due to the antioxidant feature of modified GA, and maintains the efficacy and intracellular trafficking of DOX in colon cancer cells (C-26). Interestingly, CGDZ nanoparticles showed significantly higher toxicity against cancer cells as compared to unmodified systems and free DOX. Overall, CGDZ exhibited significant in vitro efficacy in targeting cancer cell lines while reducing the toxicity of DOX, offering a novel and effective nanoparticle system for targeted cancer treatment.

The rapid spread and mutation of SARS-CoV-2, the virus responsible for COVID-19, has set the foundation for extensive research into next-generation therapeutic strategies. A critical component of SARS-CoV-2 is the trimeric Spike (S) glycoprotein, which facilitates viral entry into host cells by interacting with the receptor-binding domain (RBD). To inhibit and block viral entry, we designed and developed molecularly imprinted synthetic nanogel antibodies (MIP-SNAs) that cap the Spike S1 RBD. This aims to provide a versatile, biosecure, and effective therapeutic tool for the prevention and treatment of SARS-CoV-2 infection. Herein, we employed reverse miniemulsion polymerization to synthesize MIP-SNAs using poly(ethylene glycol) diacrylate (PEGDA), a nontoxic, nonimmunogenic and FDA-approved polymer, able to interact noncovalently with the functional groups of template Spike S1 RBD. In addition, the formulation of MIP-SNAs was based on a preliminary investigation of protein conformation by circular dichroism. Characterization of the SNAs was conducted using several techniques to investigate the chemical structure, thermal stability, size, and morphology. Under optimal conditions, the MIP-SNAs exhibited high specificity, with rebinding capacities up to 6-fold higher compared to the control nonimprinted synthetic nanogel antibodies. MIP-SNAs also demonstrated notable selectivity toward the SARS-CoV-2 Spike S1 RBD protein compared to the structural resembling Spike proteins of Bat-CoV, while cytocompatibility assays confirmed the biocompatible character of the SNAs. Given the excellent features of the recently developed MIP-SNAs, we are one step closer to finding efficient but also patient-friendly prevention and treatment solutions for SARS-CoV-2 infection. Beyond immediate applications, this technology offers the potential for broader diagnostic and therapeutic uses against related viral pathogens.

DNA-related enzymes are associated with various diseases and have been potential biomarkers for clinical diagnosis. Developing robust and ultrasensitive methods is extremely favorable for the detection of these biomarkers. To this purpose, a primer-regulated rolling circle amplification (RCA) strategy was ingeniously proposed. Briefly, the RCA primer, which was invalidated with 3'-inverted dT (locked state) and unable to initiate an amplification reaction by phi29 DNA polymerase, was embedded with the recognition substrate of the specific enzyme. In the presence of the target, the recognition and cleavage process of the enzyme prompted the release of the 3'-inverted dT and the regeneration of 3'-OH (unlocked state), satisfying the vital prerequisite for RCA. By adopting this programmable and modular design, the recognition substrate can be either single base sites or a specific sequence for different types of enzymes. This also enables us to conduct single or multiple enzyme detection conveniently, relying on a logic-controlled manner including YES, OR, AND, and AND-OR operations. Overall, the proposed strategy is uniquely insightful and provides a universal tool for multiple analyses of diverse DNA-related enzymes.

This study reports a facile approach for the green synthesis of a high-performance magnetic resonance/computed tomography (MR/CT) dual-modal imaging nanoprobe. The probe, designated as NPs-TCZ, is synthesized via one-step self-assembly of two amphiphilic block copolymers, namely, PEG-DTIPA-TCZ and pal-GGGGHHHHD. The NPs-TCZ exhibits a high longitudinal relaxivity (9.60 mM^-1 s^-1) and X-ray absorption (58.2 Hu mM^-1), as well as excellent water solubility and biocompatibility. The MR/CT dual-modal imaging can synergistically visualize synovial inflammation and bone erosion, which are both important clinical indicators for assessing arthritis severity, enabling sensitive diagnosis and prognostic assessments of rheumatoid arthritis (RA). The active targeting capability of tocilizumab (TCZ) enables the specific accumulation of NPs-TCZ at inflamed joints rather than healthy joints, significantly enhancing the imaging signals and minimizing its potential side effects. In vivo assays using both collagen-induced arthritis mice and acute arthritis mice demonstrate high performance and effectiveness in MR/CT dual-modal imaging of inflamed joints. This study provides insights into not only RA diagnosis in a more accurate manner but also the synthesis of multifunctional nanoprobes in a more robust and mild manner.

A material that was able to simultaneously sense a bacterial presence and to release antimicrobial peptides (AMP) on demand in a tunable amount was developed. Simultaneous sensing and release were achieved by the combination of a bacteria-sensing hydrogel with antimicrobial-peptide-carrying mesoporous silica particles or coatings. The mesoporous silica with a mesopore diameter of 22 nm was functionalized with a covalently grafted green light-sensitive linker, to which antimicrobial peptides were covalently attached. The gelatin-based hydrogel, which contains C14R-functionalized mesoporous silica particles, is designed to respond to bacterial presence as it may occur, e.g., in a wound's microbiological environment. In the presence of bacteria and 0.1% trypsin, a protease enzyme simulating bacterial presence, the hydrogel, deposited in a donut shape, undergoes a shape loss as the bacteria cleave cross-linking bonds within the hydrogel. When observing hydrogel shape loss after 2 h as a readout of a bacterial infection, subsequent irradiation triggers the release of antimicrobial peptides on demand with adjustable concentration-time profiles. The sensing and on-demand release are integrated into commercially available wound dressing fabrics, demonstrating an application proof-of-concept. Characterization using ATR-IR spectroscopy, TGA, and BCA validates the successful fabrication and release. The H1.6P composite released antimicrobial agents, reaching concentrations of up to 298 μg/mL at pH 7.4 from a 300 μL sample. The efficacy of the released C14R against E. coli BL21(DE3) is illustrated. Overall, the multifunctionality of this approach presents a promising step toward on-demand wound care and thus for reducing side effects and antibiotic resistance.

During the wound healing process, complications such as bacterial attachment or inflammation may occur, potentially leading to surgical site infections. To reduce this risk, many commercial sutures contain biocides such as triclosan; however, this chemical has been linked to toxicity and contributes to the occurrence of bacterial resistance. In response to the need for more biocompatible alternatives, we here present an approach inspired by the innate human defense system: utilizing mucin glycoproteins derived from porcine mucus to create more cytocompatible suture coatings with antibiofouling properties. By attaching manually purified mucin to commercially available sutures through a simple and rapid coating process, we obtain sutures with cell-repellent and antibacterial properties toward Gram-positive bacteria. Importantly, our approach preserves the very good mechanical and tribological properties of the sutures while offering options for further modifications: the mucin matrix can either be condensed for controlled localized drug release or covalently functionalized with inorganic nanoparticles for hard tissue applications, which allows for tailoring a commercial suture for specific biomedical use cases.

Piezoelectricity is reported to be able to promote bone scaffolds with excellent osteogenic performance. Herein, barium titanate/β-tricalcium phosphate (BTO/β-TCP) piezoelectric composite scaffolds were 3D printed, and their osteogenic performances were investigated in detail. The fabrication of BTO/β-TCP piezoelectric composite scaffolds employed cutting-edge DLP 3D printing technology. The scaffolds, featuring a triply periodic minimal surface (TPMS) design with a porosity of 60%, offered a unique structural framework. A comprehensive assessment of the composition, piezoelectric properties, and mechanical characteristics of the BTO/β-TCP scaffolds was conducted. Notably, an increase in the BTO volume fraction from 50 to 80 vol % within the scaffolds led to a reduction in compressive strength, decreasing from 2.47 to 1.74 MPa. However, this variation was accompanied by a substantial enhancement in the piezoelectric constant d₃₃, soaring from 1.4 pC/N to 21.6 pC/N. Utilizing mouse osteoblasts (MC3T3-E1) in a live/dead cell staining assay, under the influence of external ultrasound, demonstrated the commendable biocompatibility of these piezoelectric composite ceramic bone scaffolds. Furthermore, thorough analyses of alkaline phosphatase (ALP) activity and polymerase chain reaction (PCR) findings provided compelling evidence of the scaffolds' superior osteogenic properties, underpinning their effectiveness at the cellular protein and gene levels. In conclusion, this study offers a groundbreaking strategy for the employment of BTO/β-TCP piezoelectric composite scaffolds in bone implant applications, harnessing their unique blend of biocompatibility, piezoelectricity, and osteogenic potential.

This research aimed to evaluate the potency of preparation based on heparinized iron oxide nanoparticles (hIONPs) in combination with radiation therapy, including magnetic delivery via the applied magnetic field (AMF), in sarcoma and cervical cancer models. For in vitro studies, cells of rhabdomyosarcoma (RD), fibrosarcoma (HT1080), and cervical cancer (HeLa S3) were treated with hIONPs and analyzed for survival rate and hIONP uptake. Then, cell morphology, cell cycle, increase of reactive oxygen species, mitochondria depolarization, and ability to form colonies were assessed for combined treatment (hIONPs + 3Gy). For in vivo research, hIONPs were administered once in the hybrids of CBAxC57Bl/6j mice, grafted with sarcoma (S37) and cervical cancer (CC5) strains. The ultimate in vivo treatment modes were: (1) i.v. hIONPs (14 μg/kg) + 5 Gy; (2) i.v. hIONPs (14 μg/kg) + AMF + 5 Gy; and (3) i.t. hIONPs (2,8 μg/kg) + 5 Gy. The overall survival rates, increase in life expectancy, inhibition of tumor growth (tumor growth inhibition), and degree of inhibition (T/C) were determined, and pathomorphological changes were assessed in experimental groups. The combined treatment in vitro (hIONPs + 3Gy) promotes multiple tumor cell death with high-severity peroxide effects compared with other groups. The sarcoma cells were more sensitive than cervical cancer cells. For in vivo, an enhancing effect was revealed by the combination of radiotherapy and magnetic-delivered hIONPs. For S37 tumor, the treatment regimen was characterized as having a high antitumor effect, ≪++++ ≫, with a 20% cure rate of mice. For the CC5 tumor, the effect was accompanied by the inhibition of tumor growth, an increase in the life expectancy of animals, and was characterized as a significant antitumor effect, ≪+++/++ ≫. From the data obtained, it can be concluded that the radiosensitizing potential of hIONPs may be taken as a basis of combined radiation treatment protocols.