Injectable hydrogels are widely investigated as carriers for mesenchymal stem cells (MSCs)

The gap

Evidence profile

Sourced from the future work and abstract of the source papers, classified as general, drawn from work published between 2025 and 2026, spanning 3 journals. Those papers have been cited 12 times in total.

Supporting evidence — 3 representative gaps

• Functional metal nanozyme-hydrogel for biomedical applications (2026) · Soft Science · doi

  The metal nanozyme-hydrogel composite system represents an emerging intersection of biomimetic catalysis and biomaterials engineering. As detailed in this review, through well-established top-down or bottom-up strategies, various metal nanozymes have been successfully integrated into hydrogel networks, achieving multifunctional synergy. The core advantage of this system lies in the fact that the hydrogel matrix not only provides structural protection to mitigate deactivation, dilution, aggregation, and nonspecific clearance in complex biological environments, but its adjustable 3D network also facilitates mass transport, including substrate diffusion and product removal. Conversely, nanozymes, as built-in catalytic engines, endow hydrogels with enhanced biocatalytic activities, such as reactive oxygen species regulation, immune regulation, and tissue regeneration capabilities. At the application level, 3D printing technology makes it possible to construct personalized implants with bionic structures, while injectable in situ gels have become an ideal choice for filling deep or irregular tissue defects. Their promising potential in tumor co-therapy, infected wound management, and biosensing fully demonstrates their value as next-generation intelligent diagnosis and treatment platforms. However, from laboratory proof-of-concept to clinically applicable therapies, this field still faces a series of severe core challenges. Critical challenges in catalytic efficacy and biosafety The primary challenge lies in the gap of catalytic efficacy: despite the continuous improvement of design strategies, the catalytic efficiency and substrate specificity of most nanozymes are still far inferior to those of natural enzymes. Furthermore, the selection of an optimal nanozyme material necessitates a complex balance between competing performance metrics. Precious metal nanozymes (e.g., Pt, Pd) often exhibit superior catalytic activity and stability but face challenges related to high cost, potential long-term bioaccumulation, and limited biodegradability. Iron-based nanozymes (e.g., Fe3O4) generally offer better biocompatibility, lower cost, and potential metabolic pathways, yet their catalytic activity may be lower or more condition-dependent. MOF-based nanozymes provide highly tunable structures and multifunctionality but can suffer from instability in acidic microenvironments or complex degradation profiles. Therefore, maximizing therapeutic outcomes requires carefully weighing catalytic efficiency against biosafety, manufacturing scalability, and overall cost-effectiveness. Beyond intrinsic material properties, biological barriers present further impediments. Once inside the body, the surface of the nanozyme will rapidly adsorb proteins to form a protein corona. This dynamic biomolecular mask can occlude active sites, leading to a sharp decline in catalytic activity. Equally critical is the long-term biosafety of the delivery system. Hydrogels, as delivery ca

  generalfuture work
  Keywords: catalytic nanozymes metal nanozyme hydrogel system complex potential challenges biosafety activity cost strategies core lies
• Beyond Biomaterials: Engineering Bioactive Hydrogels as Immuno-Mechanobiological Niches for Osteochondral Regeneration (2025) · Gels · cited 12× · doi

  The evolution of osteochondral regeneration strategies from reductionist, cell- or ECM-centric models toward dynamic, system-level approaches represents a promising but inherently more complex path. Designing hydrogels as bioinstructive environments— capable of guiding immune responses, modulating mechanical signaling, and supporting spatially distinct yet interconnected tissue compartments—requires not only deeper biologi- cal understanding, but also a profound shift in how biomaterials are conceptualized, tested, and translated. The incorporation of multiple functionalities, such as immunomodulation, mechanosensitivity, and zonal architecture, increases the design space exponentially but also introduces significant challenges in terms of material fabrication, reproducibility, and regulatory approval. Ensuring consistency across batches of complex hydrogels—especially those containing gradients, responsive elements, or live cells—poses significant hurdles for standardization and upscaling. From a translational perspective, hydrogel biocompatibility is well-supported locally in most preclinical models, with inflammation typically tied to specific chemistries or byproducts [78]. Degradation products appear to clear safely—particularly when hy- drophilic components are used—though systemic organ-specific data remains limited. Functional lifespans range from weeks to months, depending on degradation mecha- Gels 2025, 11, 658 12 of 16 nisms and matrix design [79]. Key translational hurdles include synchronizing scaffold degradation with tissue healing, preventing fibrotic encapsulation, and ensuring inter- face integration. These challenges are emphasized in recent reviews of multifunctional osteochondral hydrogels [11]. Moreover, the dynamic and patient-specific nature of os- teoimmunological responses introduces biological variability that is difficult to model preclinically. Regulatory frameworks are not yet fully equipped to assess the safety and effi- cacy of multifunctional, responsive biomaterials that interact with host tissues in non-linear ways. From a translational perspective, integrating these hydrogels into surgical workflows, ensuring their mechanical integrity under joint loading, and predicting their long-term performance remain unresolved challenges. Additionally, the preclinical models typically used in cartilage or bone research often fail to capture the full physiological complexity of the osteochondral interface or the chronic inflammatory environment seen in human disease. Addressing these obstacles will require interdisciplinary collaboration, innovative in vitro and in vivo models, and new regulatory paradigms that can accommodate the biological and functional sophistication of next-generation biomaterials. Despite these hur- dles, the field stands at a pivotal moment: embracing complexity—rather than simplifying it—may ultimately be the only way to achieve robust, integrated, and clinically meaningful osteochondral regeneration. Though variability in immune responses and long-term inte- gration remain challenges, the ability to tailor hydrogel properties to patient-specific needs offers exciting opportunities for personalized regenerative therapies. Ultimately, embracing complexity is not a barrier but a necessary evolution: it empowers us to move beyond simplistic hydrogels toward truly adaptive, multifunctional platforms capable of guiding coordinated cartilage and bone healing. This complexity-driven approach, supported by ongoing technological and scientific advances, holds the greatest promise to overcome longstanding limitations and achieve durable, clinically meaningful osteochondral repair. Author Contributions: Conceptualization, F.S., A.D.G., and N.R.; methodology, F.S., V.R.H.M.; investigation, F.S., and V.R.H.M.; writing—original draft preparation, F.S., V.R.H.M., and L.I.; writing— review and editing, F.S., V.R.H.M., L.I., L.A., M.S., N.R., A.D.G., L.M., and G.M.P.; visualization, F.S., M.S., L.A.; supervision, N.R., A.D.G., L.M., G.M.P.; project administration, N.R., and A.D.G. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: This review does not involve the generation or analysis of new data. Therefore, no data are available. Acknowledgments: During the preparation of this manuscript, the authors used ChatGPT-4o for the purposes of enhancing the language and overall clarity of the text. The authors have reviewed and edited the output and take full responsibility for the content of this publication. Conflicts of Interest: The authors declare no conflicts of interest.

  generalfuture work
  Keywords: osteochondral hydrogels models challenges specific complexity authors responses biomaterials regulatory ensuring translational degradation used multifunctional
• Engineering injectable alginate hydrogels for mesenchymal stem cell delivery: comparative evaluation of ionic crosslinking strategies and early in vitro outcomes (2026) · Biomedical Materials · doi

  Abstract Injectable hydrogels are widely investigated as carriers for mesenchymal stem cells (MSCs); however, the influence of ionic crosslinking strategy on injectability-relevant properties and early in vitro cell responses remains insufficiently defined from a design perspective.

  generalabstractevidence 5/5
  Keywords: abstract injectable hydrogels widely investigated carriers mesenchymal stem cells mscs influence ionic crosslinking strategy injectability

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