Macromolecular bioscience最新文献

The combination of gelatin and hydroxyapatite (HA) has emerged as a promising strategy in dental tissue engineering due to its favorable biocompatibility, mechanical properties, and ability to support cellular activities essential for tissue regeneration, rendering them ideal components for hard tissue applications. Besides, precise control over interconnecting porosity is of paramount importance for tissue engineering materials. Conventional methods for creating porous scaffolds frequently encounter difficulties in regulating pore size distribution. This study demonstrates the fabrication of gelatin-nano HA scaffolds with uniform porosity using a T-type junction microfluidic device in a single-step process. Significant improvements in control over the pore size distribution are achieved by regulating the flow parameters, resulting in effective and time-efficient manufacturing comparable in quality to the innovative 3D bioprinting techniques. The overall porosity of the scaffolds exceeded 60%, with a remarkably narrow size distribution. The incorporation of nano-HAinto 3D porous gelatin scaffolds successfully induced osteogenic differentiation in stem cells at both the protein and gene levels, as evidenced by the significant increase in osteocalcin (OCN), an important marker of osteogenic differentiation. The OCN levels are 26 and 43 times higher for gelatin and gelatin-HA scaffolds, respectively, compared to the control group.

Due to the increasing challenges posed by the growing immunity to poly(ethylene glycol) (PEG), there is growing interest in innovative polymer-based materials as viable alternatives. In this study, the advantages of lipids and polymers are combined to allow efficient and rapid cytoplasmic drug delivery. Specifically, poly(2-methyl-2-oxazoline) is modified with a cholesteryl hemisuccinate group as a lipid anchor (CHEMSPOx). The CHEMSPOx is additionally functionalized with a coumarin group (CHEMSPOx-coumarin). Both polymers self-assembled in water into vesicles of ≈100 nm and are successfully loaded with a hydrophobic model drug. The loaded vesicles reveal high cellular internalization across variant cell lines within 1 h at 37 °C as well as 4 °C, albeit to a lesser extent. A kinetic study confirms the fast internalization within 5 min after the sample's addition. Therefore, different internalization pathways are involved, e.g., active uptake but also nonenergy dependent mechanisms. CHEMSPOx and CHEMSPOx-coumarin further demonstrate excellent cyto-, hemo-, and membrane compatibility, as well as a membrane-protecting effect, which underlines their good safety profile for potential biological intravenous application. Overall, CHEMSPOx, as a lipopolyoxazoline, holds great potential for versatile biological applications such as fast and direct intracellular delivery or cellular lysis protection.

A major limitation in the development of mucosal drug delivery systems is the design of in vitro models that accurately reflect in vivo conditions. Traditionally, models seek to mimic characteristics of physiological mucus, often focusing on property-specific trial metrics such as rheological behavior or diffusion of a nanoparticle of interest. Despite the success of these models, translation from in vitro results to in vivo trials is limited. As a result, several authors have called for work to develop standardized testing methodologies and characterize the influence of model properties on drug delivery performance. To this end, a series of trials is performed on 12 mucomimetic hydrogels reproduced from literature. Experiments show that there is no consistent correlation between barrier performance and rheological or microstructural properties of the tested mucomimetic hydrogels. In addition, the permeability of both mucopenetrating and mucoadhesive nanoparticles is assessed, revealing non-obvious variations in barrier properties such as the relative contributions of electrostatic and hydrophobic interactions in different models. These results demonstrate the limitations of predicting mucomimetic behavior with common characterization techniques and highlight the importance of testing barrier performance with multiple nanoparticle formulations.

Sortase-mediated ligation (SML) has become a powerful tool for site-specific protein modification. However, sortase A (SrtA) suffers from low catalytic efficiency and mediates an equilibrium reaction. Therefore, ligations with large macromolecules may be challenging. Here, the synthesis of polymeric building blocks for sortase-mediated ligation constituting peptide-polymers with either the recognition sequence for sortase A (LPX₁TGX₂) or its nucleophilic counterpart (G_x) is demonstrated. The peptide-polymers are synthesized by solid-phase peptide synthesis followed by photo-iniferter (PI) reversible addition-fragmentation chain-transfer (RAFT) polymerization of various monomers. The building blocks are subsequently utilized to investigate possibilities and limitations when using macromolecules in SML. In particular, diblock copolymers are obtained even when using the orthogonal building blocks in equimolar ratio by exploiting a technique to shift the reaction equilibrium. However, ligations of two polymers can not be achieved when the degree of polymerization exceeds 100. Subsequently, C-terminal protein-polymer conjugates are synthesized. Several polymers are utilized that can replace the omnipresent polyethylene glycol (PEG) in future therapeutics. The conjugation is exemplified with a nanobody that is known for efficient neutralization of SARS-CoV-2. The study demonstrates a universal approach to polymer-LPX₁TGX₂ and G_x-polymer building blocks and gives insight into their application in SML.

Self-assembling peptide-based materials with ordered nanostructures possess advantages such as good biocompatibility and biodegradability, superior controllability, and ease of chemical modification. Through covalent conjugation or non-covalent encapsulation, photosensitizers (PSs) can be carried by self-assembling peptide-based nanomaterials for targeted delivery towards tumor tissues. This improves the stability, solubility, and tumor accumulation of PSs, as well as reduces their dark toxicity. More importantly, these nanomaterials can be tailored with responsiveness to tumor microenvironment, which enables smart release of PSs for precise and enhanced photodynamic therapy (PDT). In this review, the self-assembly of peptide from the perspective of driving forces is first described, and various self-assembling peptide materials with zero to 3D nanostructures are subsequently highlighted for PDT of cancers in recent years. Finally, an outlook in this field is provided to motivate fabrication of advanced PDT nanomaterials.

Topical treatment of oral inflammatory diseases is challenging due to the intrinsic physicochemical barriers of the mucosa and the continuous flow of saliva, which dilute drugs and limit their bioavailability. Nanocarrier technology can be an innovative approach to circumvent these problems and thus improve the efficacy of topical drug delivery to the mucosa. Core-multishell (CMS) nanocarriers are putative delivery systems with high biocompatibility and the ability to adhere to and penetrate the oral mucosa. Ester-based CMS nanocarriers release the anti-inflammatory compound dexamethasone (Dx) more efficiently than a conventional cream. Mussel-inspired functionalization of a CMS nanocarrier with catechol further improves the adhesion of the nanocarrier and may enhance the efficacy of the loaded drugs. In the present study, the properties of the ester-based CMS 10-E-15-350 nanocarrier (CMS-NC) are further evaluated in comparison to the catechol-functionalized variant (CMS-C_0.08). While the mucoadhesion of CMS-NC is inhibited by saliva, CMS-C_0.08 exhibits better mucoadhesion in the presence of saliva. Due to the improved adhesion properties, CMS-C_0.08 loaded with dexamethasone (Dx-CMS-C_0.08) shows a better anti-inflammatory effect than Dx-CMS-NC when applied dynamically. These results highlight the superiority of CMS-C_0.08 over CMS-NC as an innovative drug delivery system (DDS) for the treatment of oral mucosal diseases.

Bone pelvis tumor resection and reconstruction is a complex surgical procedure that poses challenges in soft tissue reconstruction despite advancements in stabilizing pelvic structure. This study aims to investigate the potential of using Polyetheretherketone (PEEK) material in repairing and reconstructing soft tissues surrounding pelvic implants. Specifically, the study focuses on exploring the effectiveness of 3D printed porous PEEK material in promoting cell growth and adhesion. The interaction between PEEK materials with different pore sizes (200, 400, 600 µm) and different specifications (through-hole (T)/non-through-hole (C)) is evaluated by cell experiments and animal experiments. The soft tissue ingrowth potential of PEEK materials is evaluated by cell growth and adhesion observation. The findings indicate that PEEK material, particularly the T400 variant, exhibits stronger interaction with muscle tissue compared to its interaction with bone and fibrous tissue. The moderately sized pores present in the T400 material facilitate enhanced cell adhesion and penetration, thereby promoting cell growth and differentiation. PEEK materials with through-hole structures show promise for applications involving the repair and reconstruction of soft tissues and muscle tissue. The study provides valuable insights into the development and application of biomedical materials, specifically PEEK, contributing to the advancement of pelvic tumor resection and reconstruction techniques.

The incidence of nerve tissue injuries, such as peripheral nerve injury, spinal cord injury, traumatic brain injury, and various neurodegenerative diseases (NDs), is continuously increasing because of stress, physical and chemical trauma, and the aging population worldwide. Restoration of the damaged nervous system is challenging because of its structural and functional complexity and limited regenerative ability. Additionally, there is no cure available for NDs except for medications that provide symptomatic relief. Stem cells offer an alternative approach for promoting damage repair, but their efficacy is limited by a compromised survival rate and neurogenesis process. To address these challenges, neural tissue engineering has emerged as a promising strategy in which stem cells are seeded or encapsulated within a suitable biomaterial construct, increasing cell survival and neurogenesis. Numerous biomaterials are utilized to create different types of constructs for this purpose. Researchers are trying to develop ideal scaffolds that combine biomaterials, cells, and molecules that exactly mimic the biological and mechanical properties of the tissue to achieve functional recovery associated with neurological dysfunction. This review focuses on exploring the development and applications of different biomaterials for their potential use in the diagnosis, therapy, nerve tissue regeneration, and treatment of neurological disorders.

The study aimed to develop thiolated pluronic-based self-emulsifying drug delivery system (SNEDDS) targeted delivery of Rifampicin coated by arginine for enhanced drug loading, mucoadhesion, muco penetration, site-specific delivery, stabilized delivery against intracellular mycobacterium tuberculosis (M. tb), decreased bacterial burden and production by intracellular targeting. Oleic oil, PEG 200 and Tween 80 are selected as oil, co-surfactant and surfactant based on solubilizing capacity and pseudo ternary diagram region. Coating of thiolated polymer on SNEDDS with ligand arginine (Arg-Th-F407 SNEDDDS) decreased bacterial burden and production by intracellular targeting in macrophages. Formulation are evaluated through scanning electron microscope (SEM), EDAX analysis, diffraction laser scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, and thermal analysis (DSC & TGA). Hydrodynamic diameter of thiolated polymeric SNEDDS (Th-F407 SNEDDS) and Arg-Th-F407 SNEDDS is observed to be 148.4 and 188.5 nm with low PDI of 0.4 and 0.3, respectively. Invitro drug release study from Arg-Th-F407 SNEDDS indicates 80% sustained release in 72 h under controlled conditions. Arg-Th-F407 SNEDDDS shows excellent capability of killing M.tb strains in macrophages even at low dose as compared to traditional rifampicin (RIF) and is found biocompatible, non-cytotoxic, and hemocompatible. Therefore, Arg-Th-F407 SNEDDDS of RIF proved ideal for targeting and treating M.tb strains within macrophages.