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International Journal of Bioprinting                                   Supramolecular hydrogels as bioinks




            can be challenging in developing advanced bioinks.   real-world applications, especially in tissue engineering
            Designing functional building polymer blocks that can   and regenerative medicine.
            assemble in a predictable and programmable manner     Advancing  the  clinical  translation  of  supramolecular
            requires in-depth knowledge of non-covalent interactions   hydrogels and related complexes presents numerous
            and their influence on the assembly process. However,   obstacles, including biocompatibility and safety concerns,
            as previously indicated, weak non-covalent interactions,   production scale constraints, regulatory compliance,
            typically responsible for maintaining supramolecular   understanding in vivo behavior, and ensuring therapeutic
            groups, could influence bioink stability and reversibility.   efficacy. Addressing these challenges necessitates
            Ensuring the stability of these assemblies in different   rigorous review, efficient manufacturing processes, clear
            environments, such as in solution or at interfaces, can be   regulatory requirements, a better understanding of
            a challenge. Additionally, controlling the reversibility of   biological interactions, and optimization methodologies
            the assembly/disassembly processes is crucial for their   for consistent therapeutic outcomes. Interdisciplinary
            practical applications.                            approaches are essential for overcoming these challenges.
               Achieving the desired supramolecular structure often   Hence, continued research and innovation are necessary
            involves a balance between kinetic and thermodynamic   to unlock the full potential of supramolecular hydrogel
            factors. Kinetic control directs the assembly pathway,   bioink synthesis and translate it into clinical applications
            while thermodynamic control stabilizes the most favorable   across various biomedical fields.
            structure.  Striking  this  balance  can  be  challenging  and
            requires careful consideration when selecting the bioink   8. Conclusion
            composition. Scaling up supramolecular bioink synthesis   In summary, this review has explored advancements in
            to produce larger quantities of functional structures   supramolecular hydrogels, emphasizing their crucial role in
            and maintaining reproducibility across batches pose   tissue engineering, especially in the context of 3D bioprinting.
            additional difficulties.                           The formulation of adaptable supramolecular polymer-
               Supramolecular hydrogels hold great potential in   NP hydrogels represents a significant stride, providing
            tissue engineering, yet they face several challenges.   versatile features like biodegradability, cytocompatibility,
            The  comparatively  feeble  mechanical  properties  of   and  customizable  composition.  Positioned  as  promising
            supramolecular  hydrogels  compared  to  other  hydrogels   bioinks, these hydrogels demonstrate cytocompatibility,
            can restrict their use in load-bearing applications.    fostering cell growth and differentiation, thereby making
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            Additionally, devising novel and efficient methods   them attractive for 3D bioprinting applications. These
            to regulate hydrogel degradation is essential, as   hydrogels have the capability to confer self-healing
            supramolecular hydrogels are often more susceptible to   properties, shear-thinning behavior, tunable  mechanical
            degradation than covalently crosslinked hydrogels. 169  properties, and adjustable degradability. The incorporation
                                                               of relevant biological macromolecules further enhances
               Characterizing supramolecular hydrogel bioinks can   the usefulness of these materials. The exploration of
            be technically challenging due to their dynamic nature   different chemistries, such as CB[n]-based, CD-based,
            and transient interactions. Traditional characterization   peptide-based, and DNA-based hydrogels, reveals a diverse
            techniques, such as X-ray crystallography and nuclear   landscape. These hydrogels, extending beyond tissue
            magnetic resonance (NMR) spectroscopy, may not always   engineering, demonstrate applications in drug delivery,
            be applicable. Combining different techniques or adapting   wound healing, and other innovative uses, highlighting their
            existing methods to study the structural and dynamic   broad potential and versatility. Despite these advancements,
            properties of supramolecular assemblies is an ongoing   challenges remain in characterizing the dynamic nature of
            challenge. Optimization is needed for compatibility   supramolecular assemblies and addressing compatibility
            with various physiological environments and systems, as   issues for seamless integration into devices or materials.
            incorporating supramolecular structures  into bioprinted   Nevertheless, the future of supramolecular hydrogel
            constructs requires addressing stability, processability,   synthesis and applications appears promising. As we
            and interface compatibility challenges. Ensuring the   venture into this exciting frontier, interdisciplinary research
            desired  functional performance  with properties,  such as   will be essential to shape the trajectory of supramolecular
            selectivity, responsiveness, and stability over extended   hydrogel development and utilization. Future research may
            periods, is critical for their successful implementation in   focus on precision in tuning hydrogel properties for specific





            Volume 10 Issue 3 (2024)                        28                                doi: 10.36922/ijb.3223
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