With advances in tissue engineering, the possibility of regenerating injured tissue or failing organs has become a realistic prospect for the first time in medical history. Tissue engineering - the combination of bioactive materials with cells to generate engineered constructs that functionally replace lost and/or damaged tissue - is a major strategy to achieve this goal. One facet of tissue engineering is biofabrication, where three-dimensional tissue-like structures composed of biomaterials and cells in a single manufacturing procedure are generated. Cell-laden hydrogels are commonly used in biofabrication and are termed "bioinks". Hydrogels are particularly attractive for biofabrication as they recapitulate several features of the natural extracellular matrix and allow cell encapsulation in a highly hydrated mechanically supportive three-dimensional environment. Additionally, they allow for efficient and homogeneous cell seeding, can provide biologically-relevant chemical and physical signals, and can be formed in various shapes and biomechanical characteristics. However, despite the progress made in modifying hydrogels for enhanced bioactivation, cell survival and tissue formation, little attention has so far been paid to optimize hydrogels for the physico-chemical demands of the biofabrication process. The resulting lack of hydrogel bioinks have been identified as one major hurdle for a more rapid progress of the field. In this review we summarize and focus on the deposition process, the parameters and demands of hydrogels in biofabrication, with special attention to robotic dispensing as an approach that generates constructs of clinically relevant dimensions. We aim to highlight this current lack of effectual hydrogels within biofabrication and initiate new ideas and developments in the design and tailoring of hydrogels. The successful development of a "printable" hydrogel that supports cell adhesion, migration, and differentiation will significantly advance this exciting and promising approach for tissue engineering.

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25th Anniversary Article: Engineering Hydrogels for Biofabrication

CONSPECTUS: Cyclodextrins (CDs) have many attractive functions, including molecular recognition, hydrolysis, catalysis, and polymerization. One of the most important uses of CDs is for the molecular recognition of hydrophobic organic guest molecules in aqueous solutions. CDs are desirable host molecules because they are environmentally benign and offer diverse functions. This Account demonstrates some of the great advances in the development of supramolecular materials through host-guest interactions within the last 10 years. In 1990, we developed topological supramolecular complexes with CDs, polyrotaxane, and CD tubes, and these preparation methods take advantage of self-organization between the CDs and the polymers. The combination of polyrotaxane with αCD forms a hydrogel through the interaction of αCDs with the OH groups on poly(ethylene glycol). We categorized these polyrotaxane chemistries within main chain type complexes. At the same time, we studied the interactions of side chain type supramolecular complexes with CDs. In these systems the guest molecules modified the polymers and selectively formed inclusion complexes with CDs. The systems that used low molecular weight compounds did not show such selectivity with CDs. The multivalency available within the complex cooperatively enhances the selective binding of CD with guest molecules via the polymer side chains, a phenomenon that is analogous to binding patterns observed in antigen-antibody complexes. To incorporate the molecular recognition properties of CDs within the polymer side chains, we first prepared stimuli-responsive sol-gel switching materials through host-guest interactions. We chose azobenzene derivatives for their response to light and ferrocene derivatives for their response to redox conditions. The supramolecular materials were both redox-responsive and self-healing, and these properties resulted from host-guest interactions. These sol-gels with built in switches gave us insight for creating materials that were self-healing or could serve as artificial muscle. Furthermore, we developed another self-healing material with CD inclusion complexes that showed selective self-healing properties after its surface was cut. These CD self-healing materials do not include chemical cross-linkers; instead the inclusion complex of CDs with guest molecules stabilized the material's strength. However, by introducing chemical cross-linkers into the hydrogels, we produced materials that could expand and contract. The chemical cross-linked hydrogels with responsive groups bent in response to external stimuli, and the cross-linkers controlled the ratio of inclusion complexes. Furthermore, we used the molecular recognition of CDs to achieve macroscopic self-assemblies, and this chemistry can direct these macroscopic objects into even larger aggregated structures. As we have demonstrated, reversible host-guest interactions have tremendous potential for the creation of a wide variety of functional materials.

Supramolecular polymeric materials via cyclodextrin-guest interactions.

Synthesis and Applications of Boronic Acid-Containing Polymers: From Materials to Medicine.

Cyclodextrin-based polymeric materials: synthesis, properties, and pharmaceutical/biomedical applications.

Flexible, tough, and self-healable polymeric materials are promising to be a solution to the energy problem by substituting for conventional heavy materials. A fusion of supramolecular chemistry and polymer chemistry is a powerful method to create such intelligent materials. Here, a supramolecular polymeric material using multipoint molecular recognition between cyclodextrin (CD) and hydrophobic guest molecules at polymer side chain is reported. A transparent, flexible, and tough hydrogel (host-guest gel) is formed by a simple preparation procedure. The host-guest gel shows self-healing property in both wet state and dry state due to reversible nature of host-guest interaction. The practical utility of the host-guest gel as a scratch curable coating is demonstrated.

Highly Flexible, Tough, and Self-Healing Supramolecular Polymeric Materials Using Host-Guest Interaction

Polymer networks have been constructed through host−guest inclusion between β-cyclodextrin (β-CD) and 1-(2-aminoethyl)amidoadmantyl (ADen) substituents on poly(acrylic acid) (PAA). The structure of the networks and the host−guest interactions between the β-CD and ADen groups were studied by rheology and 2D 1H NOESY NMR spectroscopy. The maximum viscosity of the mixture of β-CD substituted PAA (β-CDPAA) and ADen substituted PAA (ADenPAA) occurred at a 1:1 β-CD:ADen substituent ratio which confirmed their binary inclusion. The viscosity of the mixture of the two polymers decreased upon addition of native β-CD due to its ability to compete favorably with the β-CD substituents of β-CDPAA in the inclusion of the ADen substituents of ADenPAA and the consequent disintegration of the polymer network. The rheological properties of the polymer networks were temperature sensitive. In the temperature range 10−35 °C, the storage modulus and the loss modulus obeyed a time−temperature superposition. The horizontal and v...

Polymer Networks Assembled by Host−Guest Inclusion between Adamantyl and β-Cyclodextrin Substituents on Poly(acrylic acid) in Aqueous Solution

Polymeric hydrogels were prepared based on the inclusive complexation between α-cyclodextrin (α-CD) and poly(ethylene glycol) (PEG). Because the rheological property of a thermodynamic stable hydrogel should be gap-independent, it is found in this work that the uniformed hydrogel can be distinguished from gel-like aggregation by changing the plate gap during the rheological measurement. By this rheological method it is determined that suitable storage duration is necessary for the preparation of uniform hydrogels. However, the sonication technique after mixing CD and PEG solutions or increasing PEG concentration can shorten the time to form stable hydrogels. Moreover, the molecular weight of PEG should be high enough (≥8000 g/mol) for sol-gel transition. The higher the molecular weight of PEG is, the longer storage time is needed to obtain a uniform hydrogel. From the observation by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) of prepared hydrogels, we concluded that the driving force of networks should be attributed to the crystallization of complexed α-CDs in the α-CD/PEG pseudo-polyrotaxanes. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd.

Hydrogels assembled by inclusion complexation of poly(ethylene glycol) with alpha-cyclodextrin

In this article we demonstrated that the viscosities of modified poly (acrylic acid) (PAA) solutions were tunable by modulating the hydrophobic and inclusion association between alkyl groups and β-cyclodextrin (β-CD) groups grafted to PAA. The viscosity can be controlled by changing the host–guest molar ratio, alkyl chain length, polymer concentration, salt concentration, pH value, temperature, or addition of native β-CD. A viscosity maximum for inclusive polymer networks constructed by mixing hydrophobically modified PAA (HMPAA) and β-CD–modified PAA (β-CDPAA) appeared at the alkyl : β-CD molar ratio of 1:1, which implies the inclusion association between HM and β-CD grafts is binary. Longer side chain length or higher polymer concentration led to higher viscosity for aqueous HMPAA solution with only hydrophobic association or its mixture with β-CDPAA with inclusion association. Monotonically increasing the ionic strength or pH value resulted in a viscosity maximum due to the competition between electrostatic repulsion and hydrophobic or inclusive association. The hydrophobic interactions of alkyl groups could be masked by native β-CD, and the networks of HMPAA and β-CDPAA mixture deconstructed upon addition of native β-CD molecules. The storage modulus and loss modulus of hydrophobic HMPAA and inclusive HMPAA + β-CDPAA solutions obey time–temperature superposition. The horizontal and vertical temperature shift factors obeyed a simple-exponential Arrhenius relationship, where the activation energies for hydrophobic association system were found to be 3.4 and − 12.1 kJ/mol, and for inclusive association system 53.9 and − 2.9 kJ/mol, respectively. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/apj.279

Rheology control by modulating hydrophobic and inclusive associations of side‐groups in poly (acrylic acid)

Pitches with different contents of light component were obtained from the high-temperature coal tar by distillation. The effect of the light component on the thermal polymerization of pitch was investigated using a laboratory autoclave. The component distribution in the original pitch was determined by gel permeation chromatography. The variation of carbon distribution in the modified pitch was monitored by solid-state 13C nuclear magnetic resonance. The results show that the variation of quinoline insolubility (QI) in the modified pitch during thermal treatment is markedly influenced by the amount of light component. When the light components exist in the original pitch, the QI in the modified pitch decreases at a low temperature (below 683 K) during the initial reaction stage and subsequently increases. The toluene insolubility of the modified pitch invariably increases. When the light components are added in the original pitch with a higher softening point, the results show the same trend of decrease of QI in the modified pitch. It can be included that the QI content in the modified pitch can be regulated by both the thermal polymerization conditions and the contents of the light component in the original pitch. Copyright © 2016 Curtin University of Technology and John Wiley & Sons, Ltd.

Peng Liu

Papers

Polymer Networks Assembled by Host−Guest Inclusion between Adamantyl and β-Cyclodextrin Substituents on Poly(acrylic acid) in Aqueous Solution

Hydrogels assembled by inclusion complexation of poly(ethylene glycol) with alpha-cyclodextrin

Rheology control by modulating hydrophobic and inclusive associations of side‐groups in poly (acrylic acid)

Effect of light component on the regulation of quinoline insolubility in pitch during thermal treatment