Hydrogel adhesion inherently relies on engineering the contact surface at soft and hydrated interfaces. Upon contact, adhesion normally occurs through the formation of chemical or physical interactions between the disparate surfaces. The ability to form these adhesion junctions is challenging for hydrogels as the interfaces are wet and deformable and often contain low densities of functional groups. In this Review, we link the design of the binding chemistries or adhesion junctions, whether covalent, dynamic covalent, supramolecular, or physical, to the emergent adhesive properties of soft and hydrated interfaces. Wet adhesion is useful for bonding to or between tissues and implants for a range of biomedical applications. We highlight several recent and emerging adhesive hydrogels for use in biomedicine in the context of efficient junction design. The main focus is on engineering hydrogel adhesion through molecular design of the junctions to tailor the adhesion strength, reversibility, stability, and response to environmental stimuli.

Injectable hydrogels from biocompatible materials are in demand for tissue engineering and drug delivery systems. Here, we produce hydrogels from mere cellulose nanocrystals (CNCs) by salt-induced charge screening. The injectability of CNC hydrogels was assessed by a combination of shear and capillary rheology, revealing that CNC hydrogels are conveyed via plug flow in capillaries allowing injection with minimal impact on mechanical properties. The potential of CNC hydrogels as drug carriers was elaborated by the in vitro release of the model protein bovine serum albumin (BSA), poorly water soluble tetracycline (TC), and readily soluble doxorubicin (DOX) into physiological saline and simulated gastric juice. For TC, a burst release was observed within 2 days, whereas BSA and DOX both showed a sustained release for 2 weeks. Only DOX was released fully from the hydrogels. The different release patterns were attributed to drug size, solubility, and specific drug–CNC interactions. The biocompatibility of CNC hydrogels and maintained bioactivity of released DOX were confirmed in a HeLa cell assay. The drug release was modulated by the incorporation of sucrose or xanthan gum in CNC hydrogels, whereas altering CNC concentration showed minor effects. The release into simulated gastric juice at pH 2 ceased for BSA due to charge inversion and electrostatic complexation, but not for smaller TC. Thus, CNC hydrogels may act as pH-responsive delivery systems that preserve drugs under gastric conditions followed by pH-triggered release in the duodenum.

Polymeric nanoparticles (NPs) are versatile and effective drug delivery systems (DDS) that can be produced via nanoprecipitation of block copolymers. Yet, translation into clinical products has been limited. Thus, methods for NP production that enable rapid formulation screening and continuous production are needed. Toward this end, we engineered a coaxial jet mixer (CJM) for controlled and continuous nanoprecipitation in flow. The CJM enabled continuous assembly of poly(ethylene glycol)-block-polylactide NPs with various co-solvents and was compared to batch nanoprecipitation. Other fabricated microfluidic devices were suitable for small scale formulation screening but more limited in scalable and continuous processes. In contrast, the CJM was tolerant to all water-miscible solvents tested, enabled formulation screening, and scalable production of NPs and DDS. In total, the CJM provides a complementary approach to the process engineering of polymeric NP formation that can be used broadly for formulation screening and production. K E Y W O R D Sbiomedical engineering, controlled release formulations, microfluidics, nanotechnology, self assembly

Ink engineering is a fundamental area of research within additive manufacturing (AM) that designs next‐generation biomaterials tailored for additive processes. During the design of new inks, specific requirements must be considered, such as flowability, postfabrication stability, biointegration, and controlled release of therapeutic molecules. To date, many (bio)inks have been developed; however, few are sufficiently versatile to address a broad range of applications. In this work, a universal nanocarrier ink platform is presented that provides tailored rheology for extrusion‐based AM and facilitates the formulation of biofunctional inks. The universal nanocarrier ink (UNI) leverages reversible polymer–nanoparticle interactions to form a transient physical network with shear‐thinning and self‐healing properties engineered for direct ink writing (DIW). The unique advantage of the material is that a range of functional secondary polymers can be combined with the UNI to enable stabilization of printed constructs via secondary cross‐linking as well as customized biofunctionality for tissue engineering and drug delivery applications. Specific UNI formulations are used for bioprinting of living tissue constructs and DIW of controlled release devices. The robust and versatile nature of the UNI platform enables rapid formulation of a broad range of functional inks for AM of advanced biomaterials.