Boronic acid-modified alginate enables direct formation of injectable, self-healing and multistimuli-responsive hydrogels

Abstract

Abstract. One-step functionalization of alginate with boronic acid groups allowed spontaneous formation of biocompatible hydrogels under basic conditions without additional complementary molecules or crosslinking agents. The dynamic nature of boronate ester bonds formed with vicinal diols present on alginate pyranose rings provided remarkable self-healing, injectable and multi-stimuli responsive properties to the material.Stimuli-responsive hydrogels are characterized by the ability to respond to external triggers (e.g. pH, temperature, light, specific molecules, etc.), a major property typically associated with their potential use for biomedical applications.1,2 In addition, the development of biomimetic gelbased materials with self-healing properties has extended their prospect for new applications. Nature relies on the use of reversible sacrificial bonds that allow for a better adaptation of a biomaterial to specific environments as well as for self-reparation upon damage. [3][4][5][6] This has inspired an emerging research area devoted to the fabrication of self-healable hydrogel networks based on dynamic covalent chemistry. [7][8][9] In sharp contrast to covalently crosslinked hydrogels, whose stable bonds do not undergo exchange reactions, gels based on dynamic bonds are able to reform bonds around a damaged zone, allowing the restitution of their functional properties. 9Within this context, boronic acids have been extensively studied due to their excellent ability to interact reversibly with diols, forming boronate

Transiently malleable multi-healable hydrogel nanocomposites based on responsive boronic acid copolymers

“…Next, we sought to study the gels as cell encapsulants, as several studies have shown that soft hydrogels can support the retention of viable cells within polymeric matrices for cell delivery/therapy and tissue engineering applications. 60,69,72,102,[108][109][110] Optical microscopy images showed that H9c2 cells could spread evenly within the gel matrix, retained their morphology and apparently increased their density when cultured for 48 hours (Fig. 8b and c); also, the cells predominantly remained alive throughout the culture period as evidenced by the intense green fluorescent signal ( Fig.…”

“…Finally, we demonstrate that these materials can be used as bulk cell encapsulants for cell delivery applications aimed to soft tissue engineering applications, [69][70][71][72] owing to the mild mixing and recovery conditions for their preparation and reconstruction. Such functionalities in terms of multi-responsiveness and healability, combined with excellent cytocompatible properties, have not been extensively exploited in previous boronic acid-based studies, 33,60,64,73 and hence, we anticipate that our study will be inspirational towards the development of functionally more complex, yet synthetically accessible, materials for the biomedical field.…”

“…Boronic acids in the form of polymers and hydrogels have been widely used in the biomedical field, [47][48][49][50] for example, as pH-responsive hydrogels, [51][52][53][54] carbohydrate biosensors, [55][56][57] cell encapsulation systems, 58 and as targeting motifs for drug delivery and diagnostics. 59,60 Recently, soft healable gels based on the reversible bonding of boronic acids with diols have also emerged in the form of multi-responsive polymer blends. [61][62][63][64] Inspired by these studies and our previous work on boronate ester constructs for chemical logic operations 65 and cell surface engineering, 66,67 we designed a simple boronic acidbased nanocomposite that exhibits complex, albeit predictable, physicochemical and mechanical behaviour as a multihealable model platform for cell encapsulation.…”

Cross‐Linking Building Blocks Using a “Boronate Bridge” to Build Functional Hybrid Materials

“…Pettignano et al. reported injectable, self‐healable, and multistimuli‐responsive hydrogels consisting of alginate modified with PBA moieties . Reversible bonds between the boronate and diol of the alginate enabled the gel to form under basic conditions, be responsive to pH and competitive sugar, exhibit self‐healing after cutting, and have high cell viability inside the gel.…”

Redox‐Active Dynamic Self‐Supporting Thixotropic 3D‐Printable G‐Quadruplex Hydrogels

“…[17,21,22] Ferrocene-functionalised hydrogel can change its hydrophilicity and hydrophobicity by changing the oxidation state of the Fe centre. Boronate ester mediated LMW G4 hydrogels are dynamic, self-healablea nd thixotropic in nature owing to the dynamic behaviour of the boronic acid-boronate ester equilibrium in aqueous medium.…”