Sophia Loeffelsend, Chien-Hsin Yu, Jeanette Weigelt, Stephan Hauschild, Joerg Tessmar, Stephan Foerster, Juergen Groll
{"title":"Optimizing the Cross-Linking of Poly(2-oxazoline)-Based Hybrid Microgels for Cell Encapsulation via Radiation-free Thiol-Michael-Addition Reaction","authors":"Sophia Loeffelsend, Chien-Hsin Yu, Jeanette Weigelt, Stephan Hauschild, Joerg Tessmar, Stephan Foerster, Juergen Groll","doi":"10.1002/mabi.202500403","DOIUrl":"10.1002/mabi.202500403","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oksana K. Savchak, Ruth M. C. Verbroekken, Burcu Gumuscu, Albert P. H. J. Schenning
{"title":"Light-Responsive Surface Topographies Modulate Macrophage Immune Responses Through Dynamic Mechanical Cues","authors":"Oksana K. Savchak, Ruth M. C. Verbroekken, Burcu Gumuscu, Albert P. H. J. Schenning","doi":"10.1002/mabi.202500657","DOIUrl":"10.1002/mabi.202500657","url":null,"abstract":"<p>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.</p>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Łukasz Mazurek, Mateusz Rybka, Mikołaj Zajdel, Jan Jurak, Mateusz Szudzik, Anna Laskowska, Joanna Czuwara, Dorota Sulejczak, Szymon Salagierski, Michał Dziadek, Antoni Sureda, Robert Schwartz, Marek Konop
{"title":"Keratin-Acetate Dressing Accelerates Diabetic Wound Healing, Promotes M2 Macrophage Polarization and Increases Cytokeratins 16 and 17 Expression–In Vitro and In Vivo Studies","authors":"Łukasz Mazurek, Mateusz Rybka, Mikołaj Zajdel, Jan Jurak, Mateusz Szudzik, Anna Laskowska, Joanna Czuwara, Dorota Sulejczak, Szymon Salagierski, Michał Dziadek, Antoni Sureda, Robert Schwartz, Marek Konop","doi":"10.1002/mabi.202500351","DOIUrl":"10.1002/mabi.202500351","url":null,"abstract":"<div>\u0000 \u0000 <p>A novel keratin-based wound dressing enriched with sodium acetate (FKDP+0.1%Act) was developed to address the constant challenges of chronic wound healing in diabetes. By combining bioactive keratin fibers with the anti-inflammatory properties of acetate, this study explored the material's regenerative and immunomodulatory potential using in vitro models of keratinocytes and macrophages, alongside full-thickness wounds in diabetic rats. FKDP+0.1%Act markedly accelerated wound closure and improved tissue architecture during early healing. It promoted a shift toward pro-regenerative M2 macrophage polarization, reduced M1-associated markers and tumor necrosis factor α (TNFα) expression, and significantly upregulated vascular endothelial growth factor (VEGF) and cytokeratins 16 and 17 (KRT16/17) – key angiogenesis and epidermal repair mediators. These effects were consistently observed across in vivo and in vitro methods, highlighting a synergistic interaction between keratin and acetate. The dressing preserved structural integrity, demonstrated favorable cytocompatibility, and modulated key inflammatory and regenerative pathways. These findings underscore the translational potential of FKDP+0.1%Act as a dual-functional biomaterial capable of enhancing epithelial regeneration and reprogramming inflammatory responses in impaired diabetic wound environments.</p>\u0000 </div>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the Therapeutic Potential of Recombinant Lasioglossin-III Peptide: A Theoretical and Experimental Approach","authors":"Atul Kumar, Anindya Basu","doi":"10.1002/mabi.202500060","DOIUrl":"10.1002/mabi.202500060","url":null,"abstract":"<div>\u0000 \u0000 <p>Antimicrobial peptides are increasingly being recognized as a promising solution for antibiotic resistance owing to their membranolytic properties. The Lasioglossin-III (LL-III) peptide in this regard is known to be a highly potent broad-spectrum antimicrobial and has shown its potential for diversified applications. Hence, to support its cost-effective recombinant production, in this paper, we rationally evaluated the therapeutic potential of the latter through experimental and molecular simulation-based approaches. We first evaluated the structural and functional mechanisms of the peptide using computation-based approaches; thereafter, the safety and efficacy of the target peptide was confirmed through in vitro and in vivo experiments. Our results indicated that the recombinant peptide rapidly and stably binds to both Gram-positive and Gram-negative bacterial membranes, leading to significant membrane perturbations whilst retaining its biocompatibility. Upon confirming the in vitro activity of the peptide under physiologically relevant conditions, the same was further tested upon local infection on mice. The peptide was found to exhibit remarkable healing effects, comparable to those of a commercially available antimicrobial product. Hence, overall, it can be said that the recombinant LL-III can be used as a potent antimicrobial molecule and can be further used for diversified therapeutic applications.</p>\u0000 </div>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145377835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Low-Molecular-Weight Polysaccharide From Cremastra Appendiculata: Extraction, Structural Characterization, and Anti-HCC Activity","authors":"Haoyue Kong, Wenna Li, Yufei Wang, Yuwen Wang, Guanghui Jiang, Jing Wang, Junfeng Niu","doi":"10.1002/mabi.202500376","DOIUrl":"10.1002/mabi.202500376","url":null,"abstract":"<div>\u0000 \u0000 <p>The medicinal benefits of <i>Cremastra appendiculata</i> include antipyretic effects, detoxification, the elimination of phlegm and masses, and it is extensively used for the treatment of various cancers. However, the underlying mechanisms for the antitumor effects of <i>C. appendiculata</i> polysaccharide (CAP; one of the primary substances of its water-soluble components) remain unknown. This study involved CAP preparation and characterization as well as the investigation of its anti-hepatocellular carcinoma (HCC) activities. Structural analysis revealed that CAP (Mw = 8,058 Da) is a linear glucomannan that is composed of → 4) -β-D-Glc<i>p</i>- (1 → 4) -β-D-Man<i>p</i>- (1 →. In an anti-HCC trial, the use of the CAP-mediated mediated macrophage-conditioned medium significantly inhibited Hepa1-6 cell migration and proliferation. CAP inhibits tumor growth in mice, and at high-doses, mitigated 5-fluorouracil-induce immune-organ damage. CAP enhances the immune-organ index of mice, increased the levels of TNF-α and IFN-γ, and improve their immune functions, whereby it indirectly eliminated tumors. This study provides theoretical and experimental evidence in support of the use of CAP for the treatment of HCC and thereby promotes the development of natural polysaccharides from traditional medicines.</p>\u0000 </div>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Věra Hedvičáková, Manikandan Sivan, Divyabharathi Madheswaran, Kristýna Havlíčková, Šárka Hauzerová, Maxim Lisnenko, Jan Valtera, Jaroslav Mikule, Kateřina Strnadová, Věra Jenčová, Eva Kuželová Košťáková, David Lukáš
{"title":"Antimicrobial Functionalization of Composite Nanofibrous Yarns as Surgical Sutures","authors":"Věra Hedvičáková, Manikandan Sivan, Divyabharathi Madheswaran, Kristýna Havlíčková, Šárka Hauzerová, Maxim Lisnenko, Jan Valtera, Jaroslav Mikule, Kateřina Strnadová, Věra Jenčová, Eva Kuželová Košťáková, David Lukáš","doi":"10.1002/mabi.202500510","DOIUrl":"10.1002/mabi.202500510","url":null,"abstract":"<p>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.</p>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Álvaro Hidalgo-Yerga, Leonor Resina, Jordi Casanovas, Carlos Alemán, Maria M. Pérez-Madrigal
{"title":"PLA/PCL Tubes Filled with Polysaccharide Hydrogels as Robust Hybrid Nerve Guidance Conduits with Controlled Swelling","authors":"Álvaro Hidalgo-Yerga, Leonor Resina, Jordi Casanovas, Carlos Alemán, Maria M. Pérez-Madrigal","doi":"10.1002/mabi.202500613","DOIUrl":"10.1002/mabi.202500613","url":null,"abstract":"<div>\u0000 \u0000 <p>Peripheral nerve injuries (PNIs) cause severe loss of motor and sensory functions, with limited recovery achievable through current surgical options. Nerve guidance conduits (NGCs) represent a promising alternative for bridging nerve gaps, particularly when integrating bioactive and mechanically stable components. In this study, a multi-component NGC is developed by combining rolled-up poly(lactic acid)/poly(caprolactone) (PLA/PCL) microfilms, providing mechanical reinforcement and shape-memory behavior, with polysaccharide-based hydrogels (alginate (ALG), hyaluronic acid (HA), or carboxymethyl cellulose (CMC)) that act as lumen fillers to mimic the extracellular matrix (ECM). The hydrogel formulations display appropriate viscosity, straightforward gelation, and enhanced mechanical properties while maintaining cytocompatibility. Although all three composite conduits exhibit non-toxic degradation by-products and mechanical performance comparable to that of native human nerves, the NGC containing the HA click-hydrogel displays a more porous structure, with an elastic modulus of 19.2 ± 2.9 kPa and ultimate compressive strength of 29.2 ± 8.2 kPa. Moreover, the HA hydrogel shows prolonged stability in physiological conditions, and a stable swelling ratio is achieved within 2 h and maintained for at least 20 days. Overall, our cost-effective fabrication strategy, which integrates polysaccharide-based hydrogels and biodegradable polymer microfilms, offers a promising platform for advancing nerve tissue engineering.</p>\u0000 </div>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julia Eichermüller, Jessica Faber, Xuen Ng, Camilla Mussoni, Julian Bauer, Jonas Röder, Alessandro Cianciosi, Philipp Stahlhut, Tomasz Jungst, Jürgen Groll, Dominik Steiner, Thomas Scheibel, Oliver Friedrich, Taufiq Ahmad, Aldo R. Boccaccini, Silvia Budday, Janina Müller-Deile
{"title":"Biocompatibility of Hydrogels for Glomerular 3D Co-Culture: A Comparative Analysis","authors":"Julia Eichermüller, Jessica Faber, Xuen Ng, Camilla Mussoni, Julian Bauer, Jonas Röder, Alessandro Cianciosi, Philipp Stahlhut, Tomasz Jungst, Jürgen Groll, Dominik Steiner, Thomas Scheibel, Oliver Friedrich, Taufiq Ahmad, Aldo R. Boccaccini, Silvia Budday, Janina Müller-Deile","doi":"10.1002/mabi.202500460","DOIUrl":"10.1002/mabi.202500460","url":null,"abstract":"<p>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 <i>in vivo</i> 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.</p>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mabi.202500460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Design and Evaluation of Chitosan-Coated Liposomal Microneedle Capsules for Oral Insulin Delivery: A Proof of Concept","authors":"Kirthana Gopal, Melbha Starlin Chellathurai, Zarif Mohamed Sofian, Pornanong Aramwit, Syed Mahmood","doi":"10.1002/mabi.202500661","DOIUrl":"10.1002/mabi.202500661","url":null,"abstract":"<div>\u0000 \u0000 <p>The study presents a proof-of-concept for novel protein drug delivery system by formulating layer-coated liposomes with chitosan oligosaccharide (COS) and insulin, infused in dissolvable microneedles (DMNs), and packed in an enteric-coated capsule for oral delivery of insulin. Cellular uptake studies using CCD841 showed time-dependent internalization, while cytotoxicity assays confirmed over 80% cell viability, indicating biocompatibility. The fabricated hydroxypropyl methylcellulose (HPMC) and Aloe vera (AV) based DMN had a pyramidal shape with a height of 464.25 ± 1.48 µm. Permeability studies revealed a sustained release profile in SIF for both layer-coated liposomes (80.08% ± 3.02) and DMN-containing layer-coated liposomes (75.06% ± 1.06). In contrast, a burst release in SGF for layer-coated liposomes and for DMNs is attributed to charge interactions and polymer solubility. Enteric-coated capsules demonstrated no insulin release in SGF for 1 h, indicating effective gastric protection. The release for an enteric-coated capsule containing DMN infused with layer-coated liposomes in SIF reached 79.24% ± 1.22, mirroring the release profile of DMNs. This multilayered system effectively protects insulin from gastric degradation, facilitates delivery of insulin to the intestine, and achieves a sustained release profile, offering a promising strategy for oral insulin delivery.</p>\u0000 </div>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}