Macromolecular bioscience最新文献

Poly(2-oxazoline)s (POx) are an emerging class of synthetic polymers with potential in biomedical applications as most of them are characterized by biocompatibility, stealth properties, and structural tunability. Similarly, microgels gain attention for cell encapsulation, drug delivery, and as building blocks for physical hydrogels and tissue constructs. However, the predominant cross-linking methods for both POx and microgels rely on UV light and radicals, which can harm cells. This study aims to integrate the trends of POx and microgels and to overcome limitations of UV-based methods. It introduces a radiation-free cross-linking mechanism via thiol-Michael-addition for POx-based microgels, tailored for cell-friendly cell encapsulation. Therefore, a hybrid polymer system of thiolated POx, gelatin, and acrylated hyaluronic acid is chosen and its cross-linking kinetics is optimized for microfluidic procedures. Subsequently, hydrogels and microgels of different molar ratios of the functional groups are prepared. These differ in stiffness and degradation. Cell encapsulation tests with fibroblasts show cell viabilities >90% and that the gel systems support cell spreading and proliferation, irrespective of molar ratio. This confirms that the proposed cross-linking strategy is effective for creating POx-based microgels suitable for cell-friendly cell encapsulation.

Vascularization remains a fundamental challenge in tissue engineering, directly impacting the survival, integration, and function of engineered grafts across diverse organ systems. This comprehensive review explores the latest advancements in promoting angiogenesis within tissue-engineered constructs, focusing on strategies that emulate natural vascular development to overcome ischemic limitations post-implantation. We examine three core domains of pro-angiogenic intervention: controlled delivery of growth factors (e.g., VEGF, FGF, PDGF), development of bioactive and mechanically tuned biomaterials (such as collagen, gelatin, hyaluronic acid, and decellularized matrices), and cell-based approaches leveraging stem and progenitor cells, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. Novel technologies such as 3D bioprinting, nanofabrication, and the use of extracellular vesicles have further enabled spatial and temporal control over vascular network formation. Organ-specific applications in cardiac, hepatic, dermal, osseous, pancreatic, musculoskeletal, adipose, and corneal tissues illustrate the translational potential of these techniques, while also highlighting the unique vascular requirements of each tissue type. Additionally, unconventional angiogenic inducers, such as parasite-derived proteins, are emerging as potential therapeutic tools. Despite significant progress, challenges remain in achieving long-term vessel stability, synchronizing vascularization with lymphangiogenesis and immunomodulation, and navigating regulatory complexities for clinical implementation. This review underscores the centrality of angiogenesis in regenerative medicine and advocates for continued interdisciplinary efforts to refine vascular integration strategies that will enable durable, functional, and patient-specific tissue replacements.

Vegetable oils are natural and renewable resources, mostly composed of triglycerides (fatty acid esters of glycerol). These molecules possess multiple reactive sites, which can be used for chemical functionalization to form epoxides, hydroxyls, and cyclic carbonates. Thanks to these added functions, polymerization can take place in order to form vegetable oil-based materials, such as polyesters, polyurethanes, or hybrid materials. The development of vegetable oil-based polymers has provided access to new materials with properties such as flexibility, biocompatibility, and biodegradability. Thus, these characteristics make them particularly well-suited for biomedical applications. In this review, we are focusing on vegetable oil-based materials developed as drug delivery systems and wound dressings.

Understanding macrophage phenotype regulation by mechanical stimuli is a promising way to elucidate the body's inflammatory response and design new therapies. However, creating dynamic interfaces that allow precise, real-time, and reversible control over mechanical cues remains a challenge. In this study, we report the immunomodulatory effects of dynamic liquid crystal (LC) polymer films on in vitro macrophage responses. By utilizing reversible light-induced LC surface topographies, we generate dynamic mechanical stimuli on cells during topography formation and removal, enabling on-demand and reversible reprogramming of cell behavior. Our findings reveal a strong topographical shape-dependent cell response by examining the effects of flat, pillared, and grooved LC films on THP-1-derived macrophages. A strong increase in both pro- and anti-inflammatory markers is observed on grooves, while pillars maintain the anti-inflammatory profile without broad activation. Macrophages on LC film-generated topographies furthermore present distinct cytokine expression profiles. Notably, light-induced grooves triggered a stronger pro-remodeling cellular response, while pillars appeared to exert an inhibitory effect on macrophage activation. The dynamic topographies remarkably induced distinct changes in the macrophage membrane morphology, triggering migration-associated blebbing of the cell membrane in all cases except for grooves that promoted an increased degree of lamellipodia and filopodia formation. Overall, these results demonstrate that light-responsive LC surfaces provide a controllable platform for topography-dependent and adaptive immune modulation, opening opportunities for rational design of immunoregulatory scaffolds that exploit macrophage plasticity for regenerative medicine.

Implant-associated osteomyelitis (IAO) is a major clinical challenge due to persistent biofilms, antibiotic resistance, and impaired osteogenesis. Hydrogels, with tunable physicochemical properties, biocompatibility, and localized drug delivery capabilities, offer advanced solutions to these problems. This review systematically examines advanced hydrogel-based strategies for IAO treatment, categorized into two primary approaches. Antibiotic-loaded hydrogels leverage nanomaterial integration and hybrid composites to achieve precise, spatiotemporal drug release, thereby minimizing toxicity and resistance. Non-antibiotic approaches, including nanomaterial-based agents such as metals and photothermal nanohybrids, as well as peptides, plant polyphenols, and phage therapy, provide alternative options to circumvent antibiotic resistance. Crucially, we highlight key optimization strategies that encompass controlled cross-linking, stimuli-responsive systems (e.g., pH and temperature), anti-biofilm mechanisms, and biomimicry, synergistically enhancing both antibacterial and osteogenic functions in these platforms. Collectively, these advances signify a shift from passive drug carriers to multifunctional, bioactive platforms that both eradicate resistant bacteria and support bone regeneration. This transformative shift, however, reveals persistent challenges while suggesting promising research avenues for advancing hydrogel-based therapies against IAO.

Antimicrobial drug-releasing sutures have the potential to minimize the risk of postoperative inflammation and infection development. Using such medical devices is patient-considerate and cost-effective, reducing the need for oral drug administration and secondary surgical interventions. Nowadays, antimicrobial coatings on surgical sutures exist, however, they typically provide short-term drug release with limited concentrations. In this study, alternating current electrospinning was utilized to produce pristine and chlorhexidine (CHX) loaded composite polycaprolactone nanofibrous yarns with a mechanically resistant polyamide 6 core. Production speed between 10 and 30 m/min resulted in varying linear densities of yarns inversely proportional to the production speed and consequently with different concentrations of CHX. A prolonged release lasting one month was achieved, attributed to the dual relaxation times. Morphological analyses showed a composite character of yarns with a uniform pristine or CHX-loaded fibrous envelope that was susceptible to enzymatic degradation. The yarns exhibited high porosity, exceeding values typical for conventional fibers and displayed mechanical properties compatible with thin monofilaments sutures. The estimated curvature and torsion of the fibers, combined with the nanofibrous envelope resulted in a 3D yarn structure that closely mimics the extracellular environment. The 3D nature of composite nanofibrous yarns together with adsorbed proteins supported fibroblast adhesion and proliferation indicating biocompatibility. Proposed composite nanofibrous yarns represent an alternative to conventional smooth dip-coated antimicrobial sutures.

Conventional 2D mono-cultures fall short in replicating the complex microenvironment of glomerular tissue, where cell–cell and cell–matrix interactions are critical. To better mimic in vivo conditions, the development of robust 3D co-culture systems is essential. Here, we systematically evaluate five hydrogel matrices—Matrigel, alginate dialdehyde-gelatin (ADA-GEL), fibrin, recombinantly produced spider silk protein eADF4(C16)-RGD, and allyl-modified gelatin (GelAGE)—for their suitability in supporting glomerular 3D co-culture. The hydrogels are assessed for handling properties, cell viability, and the support of physiological cell behavior using bright-field microscopy, live/dead assays, immunofluorescence, and multiphoton imaging. Among the tested hydrogels, GelAGE and eADF4(C16)-RGD demonstrate superior biocompatibility and structural support. Due to its ease of use and comparable biological performance, GelAGE and spider silk protein eADF(C16)-RGD are selected for further mechanical characterization, revealing favorable viscoelastic properties. These findings position both hydrogels as a promising candidate for engineering physiologically relevant 3D glomerular models and advancing kidney tissue research.

Hydrogels mimicking the mechanical and biochemical features of the cellular microenvironment allow cell encapsulation and facilitate in vitro 3D culture. In addition to biocompatibility and reactivity in physiological conditions, a key criterion for crosslinking chemistry is appropriate gelation kinetics to allow mixing and homogeneous distribution of cells with the hydrogel precursors. We have previously presented aryl methylsulfone/thiol (MS/SH) reaction as a thiol-reactive cross-linking system for cell encapsulation in star polyethylene glycol (PEG4) hydrogels with a gelation kinetics in minutes time scale. Remaining experimental challenges for this system are a finer modulation of gelation kinetics and streamlining the synthesis of the prepolymer. Here we present the possibility to tune the gelation kinetics by introducing an electron-withdrawing substituent at p-position of the aryl MS ring. This variant also presents synthetic advantages. We study the influence of the p-substituent on the physicochemical properties of MS/SH crosslinked hydrogels, and their performance for cell encapsulation. We compare these properties with the PEG-MS variant containing an electron-donating linker. The new star poly(ethylene glycol)-4-(5-(methylsulfonyl)-1H-tetrazol-1-yl)benzamide (PEG4-CONH-TzMS) shows superior properties as cell encapsulating hydrogel in terms of ease of mixing polymer precursors, faster gelation, homogenous cell distribution and high enzymatic stability.