Boronate Ester Bonds Research Articles

Polydiacetylene Liposome-Based Dual-Output Optical Sensor for ppb Level Detection of Dopamine in Solution and Solid Phases.

Dopamine (DA), a neurotransmitter, plays a crucial role in regulating motor functions and emotions and can serve as a marker for several diseases. In this study, we report a highly sensitive polydiacetylenes (PDA)-based dual-output sensor for dopamine detection in both solution and solid phases that was developed by modifying PDA liposomes with boronic acid groups at the termini. This sensor exploits the high affinity between the catechol residue of dopamine and the -B(OH)2 group of the PDA-based probe (PDA-PhBA) to form boronate ester bonds, causing a stress-induced blue-to-red color change along with a steady increase in fluorescence response at λmax 622 nm. The PDA-PhBA-based sensor displays high sensitivity toward dopamine with low limit of detection of 6.2 ppb in colorimetric analysis and 0.6 ppb in fluorimetric measurements, demonstrating its dual optical output ability. The sensor works well for adrenaline, another catecholamine, with similar efficacy. Its practical applicability was validated by the successful recovery of trace level dopamine in blood serum and real water samples. Additionally, immobilizing PDA-PhBA liposomes in sodium alginate produced PDA beads for the solid-phase detection of dopamine with an limit of detection (LOD) of 59 nM (9.0 ppb) in colorimetric detection using a smartphone for capturing images and ImageJ software for analysis.

Boronic ester bonds hydrogel with temperature and pH responsiveness for controlled release fertilizer

The growth of plants can be severely restricted by insufficient water and fertilizers in pure soil. There exists a significant demand for developing a hydrogel to enhance water retention and enable control release fertilizer. In this study, we synthesized the boronic ester bonds hydrogel with temperature and pH responsiveness using sodium alginate, borax pentahydrate and carboxymethyl chitosan (CMCS) via a one-pot method. Urea was loaded in the hydrogel as a model fertilizer. The dual responsive hydrogel exhibited a rapid release behavior of fertilizer due to the dissociation of boronic ester bonds at 40 °C and pH 5.5. The incorporation of CMCS improved the non-covalent interaction within the hydrogel, accompanied by a reduction in the pore size and swelling ratio to 74 μm and 11.3 g/g, respectively. The hydrogel exhibited desirable water retention capacity in soil with a weight loss of only 41.9 % at day 15, while the degradation rate of hydrogel was 49.0 %. Additionally, the hydrogel displayed good antibacterial activity against both Rhizobium and Bacillus cereus strains while being non-toxic to plants. The dual responsive hydrogel holds promising applications in agriculture, forestry, and horticulture.

3D printing of reprogrammable liquid crystal elastomers with exchangeable boronic ester bonds

Liquid crystal elastomers (LCEs) are a kind of soft actuating materials with large reversible deformation ability, which can work as the “motor” to exhibit complex deformations and drive the locomotion of soft robots. The deformation of LCEs depends on the three-dimensional (3D) shape of whole structure and alignment patterns of mesogens. Various methods have been employed to fabricate the LCE structure with desired shapes and mesogen alignments. However, conventional 3D printed LCEs require continuous thermal energy input to maintain their actuated shapes. The LCEs cannot be reprocessed and reprogrammed once cured. Herein, we introduce dynamic boronic ester bonds into the ink, with which the printed LCE structures are capable of being reprogrammed from polydomain into monodomain state and vice versa. We further explore the effects of printing parameters and content of dynamic covalent bonds on the actuation performance and reprogramming ability. The actuated shape could be well predicted with finite element method. The dynamic printable LCEs developed here offer new strategy and large design space for LCE structures.

Covalent Adaptable Networks Containing Nitrogen-Coordinated Boronic Ester and Imine Bonds

Covalent Adaptable Networks Containing Nitrogen-Coordinated Boronic Ester and Imine Bonds

Dynamic Covalent Boronic-Acid-Functionalized Alginate/PVA Hydrogels for pH and Shear-Responsive Drug Delivery.

Herein, we investigated hydrogels composed of boronic-acid-functionalized alginate and blended with polyvinyl alcohol (PVA) of different molecular weights to control the release of metoclopramide hydrochloride as a function of pH and shear stress. The functionalization of alginate introduced dynamic covalent bonding and pH-responsive properties that can modulate network connectivity. The study investigated the viscoelastic properties of the hydrogels, their drug release profiles, and their responsiveness to changes in pH and shear forces. The results showed that a higher PVA molecular weight and alkaline pH conditions increased hydrogel viscosity and stiffness due to a more stable and interconnected network structure than acidic pH. Metoclopramide release revealed that the hydrogels exhibited pH-responsive drug release behavior. The drug was more readily released under acidic conditions due to the instability of sp2-hybridized boronate ester bonds. The influence of shear forces on the release of metoclopramide was also investigated at shear rates of 1, 10, and 100 s-1, revealing their effect on matrix stiffening. Research shows that AlgBA/PVA hydrogels have unique properties, such as dynamic covalent bonding, that make them sensitive to external mechanical forces. This sensitivity makes them ideal for applications where physiological conditions trigger drug release.

Mussel‐inspired stretchable, anti‐fatigue, self‐healing and biocompatible hydrogel adhesives

AbstractHydrogels can form physically or chemically interactions with tissues and are widely used in the design of bioadhesive material. Polydopamine (PDA)/polyacrylamide (PAM)‐based adhesion hydrogels have emerged as one of the hydrogel adhesive materials with great potential for development. However, this type of hydrogel has low mechanical and adhesion properties, which has certain limitations in practical applications. Herein, inspired by the mussel adhesion mechanism, we introduced PDA into PAM/3‐aminophenylboronic acid grafted sodium alginate (SA‐PBA) double network system prepared a series of adhesive hydrogels, PDA was crosslinked by dynamic boronic ester bonds with SA‐PBA. The experimental results established that the hydrogels have favorable adhesive, anti‐fatigue, stretchable, and self‐healing properties. Cytocompatibility assay and in vitro hemolysis assay also indicated that the multifunctional hydrogel has excellent cytocompatibility and hemocompatibility.

Fully synthetic hydrogels promote robust crypt formation in intestinal organoids.

Initial landmark studies in the design of synthetic hydrogels for intestinal organoid culture identified precise matrix requirements for differentiation, namely decompression of matrix-imposed forces and supplementation of laminin. But beyond stating the necessity of laminin, organoid-laminin interactions have gone largely unstudied, as this ubiquitous requirement of exogenous laminin hinders investigation. In this work, we exploit a fast stress relaxing, boronate ester based synthetic hydrogel for the culture of intestinal organoids, and fortuitously discover that unlike all other synthetic hydrogels to date, laminin does not need to be supplemented for crypt formation. This highly defined material provides a unique opportunity to investigate laminin-organoid interactions and how it influences crypt evolution and organoid function. Via fluorescent labeling of non-canonical amino acids, we further show that adaptable boronate ester bonds increase deposition of nascent proteins, including laminin. Collectively, these results advance the understanding of how mechanical and matricellular signaling influence intestinal organoid development.

A Sprayable Janus Hydrogel as an Effective Bioadhesive for Gastrointestinal Perforation Repair

AbstractAdvancements in hydrogel bioadhesives for sealing gastrointestinal perforations (GP) face challenges due to weak mechanical properties, causing leakage, especially on uneven wound surfaces. Herein, a Janus hydrogel is introduced featuring a two‐step cross‐linking process, designed to serve as an efficient bioadhesive using a sprayable method. This Janus hydrogel formulation is achieved by modifying a photocurable hyaluronic acid hydrogel with dopamine (DA) and phenylboronic acid (PBA) groups, enabling reversible boronate ester bonds. These dynamic cross‐linking bonds facilitate shear‐thinning and self‐healing abilities, ensuring secure adhesion to complex wounds. A subsequent photocurable irreversible cross‐linking stage results in the formation of a hydrogel barrier with asymmetric adhesive properties, imparting inherent mechanical strength for postoperative anti‐adhesion. To enhance the clinical practicality of this hydrogel, an integrated sprayer device is further developed, enabling the efficient delivery of hydrogel at any angle and over long distances under minimally invasive conditions. Therefore, the HADP hydrogel, integrated with the sprayer device, successfully addressed the limitations associated with hydrogel bioadhesives in clinical applications concerning angles and terrains. This integrated approach presents a compelling solution for repairing gastrointestinal perforations in clinical settings. Moreover, it demonstrates significant potential for diverse applications in repairing complex wound surfaces.

Mitigating Critical Peripheral Nerve Deficit Therapy with Reactive Oxygen Species/Ca2+-Responsive Dynamic Hydrogel-Mediated mRNA Delivery.

Critical peripheral nerve deficiencies present as one of the most formidable conundrums in the realm of clinical medicine, frequently culminating in structural degradation and derangement of the neuromuscular apparatus. Engineered extracellular vesicles (EVs) exhibit the potential to ameliorate nerve impairments. However, the advent of Wallerian degeneration (WD), an inexorable phenomenon that ensues post peripheral nerve injury, serves as an insurmountable impediment to the direct therapeutic efficacy of EVs. In this investigation, we have fashioned a dynamic network for the conveyance of PTEN-induced kinase 1 (PINK1) mRNA (E-EV-P@HPCEP) using an adaptive hydrogel with reactive oxygen species (ROS)/Ca2+ responsive ability as the vehicle, bearing dual-targeted, engineered EVs. This intricate system is to precisely deliver PINK1 to senescent Schwann cells (SCs) while concurrently orchestrating a transformation in the inflammatory-senescent milieu following injury, thereby stymying the progression of WD in peripheral nerve fibers through the stimulation of autophagy within the mitochondria of the injured cells and the maintenance of mitochondrial mass equilibrium. WD, conventionally regarded as an inexorable process, E-EV-P@HPCEP achieved functionalized EV targeting, orchestrating a dual-response dynamic release mechanism via boronate ester bonds and calcium chelation, effectuating an enhancement in the inflammatory-senescent microenvironment, which expedites the therapeutic management of nerve deficiencies and augments the overall reparative outcome.

Marine‐Derived Nanozyme‐Crosslinked Self‐Adaptive Hydrogels for Programmed Regulating the Regeneration Process

AbstractSelf‐adaptive hydrogels that can specifically respond to pathological cues and match the highly ordered tissue regeneration process are significantly on‐demand for effective wound management. Herein, multifunctional marine‐derived gold clusterzyme (AuNCs)‐based self‐adaptive hydrogels with microenvironment triggered release behavior are elaborately fabricated for on‐demand antioxidant, anti‐inflammatory and immunoregulation. The marine mussel‐derived catechol ligands (L‐3,4‐dihydroxyphenylalanine) endow AuNCs with enhanced superoxide dismutase‐mimic activity due to their high affinity to superoxide anion free radical (O2−•) and unique electron transfer mechanism, leading to 100% inhibition of O2−•. Upon uniformly crosslinking with phenylboronic acid‐modified marine‐derived sodium alginate (PBA‐Sa), the obtained AuNCs@PBA‐Sa hydrogels exhibit outstanding self‐healing property, tunable degradation and good removability. Meanwhile, AuNCs can greatly enhance the mechanical property and confer the hydrogel with favorable tissue adhesion for rapid hemostasis. Furthermore, injectable AuNCs@PBA‐Sa hydrogels can not only adapt their shape to the irregular wound, but also smartly adapt their microstructure to the physiological microenvironment of diabetic wound, leading to the responsive release of AuNCs upon the break of boronate ester bonds. The released gold clusterzymes can actively induce the generation of M2‐macrophage, demonstrating an outstanding anti‐inflammatory and pro‐regeneration effect. Therefore, the present multifunctional clusterzyme‐based self‐adaptive hydrogels hold great potential for remolding the dynamic tissue regeneration microenvironment and smart wound management.

Dynamic Covalent Boronate Chemistry Accelerates the Screening of Polymeric Gene Delivery Vectors via In Situ Complexation of Nucleic Acids.

Gene therapy provides exciting new therapeutic opportunities beyond the reach of traditional treatments. Despite the tremendous progress of viral vectors, their high cost, complex manufacturing, and side effects have encouraged the development of nonviral alternatives, including cationic polymers. However, these are less efficient in overcoming cellular barriers, resulting in lower transfection efficiencies. Although the exquisite structural tunability of polymers might be envisaged as a versatile tool for improving transfection, the need to fine-tune several structural parameters represents a bottleneck in current screening technologies. By taking advantage of the fast-forming and strong boronate ester bond, an archetypal example of dynamic covalent chemistry, a highly adaptable gene delivery platform is presented, in which the polycation synthesis and pDNA complexation occur in situ. The robustness of the strategy entitles the simultaneous evaluation of several structural parameters at will, enabling the accelerated screening and adaptive optimization of lead polymeric vectors using dynamic covalent libraries.

Cancer intra and extracellular microenvironment-responsive electrical signal of touchable conductive hydrogel

A wireless-integrated tumor microenvironment-responsive sensor designed from diselenide-functionalized carbon dot (dsCD) and hyaluronic acid polymer dot (PD(HA)) loaded in a mineralized conductive hydrogel (dsCD-PD(HA) Hydrogel) for detecting cellular reactive oxygen species (ROS) and pH detection. The manufactured ROS/pH responsive conductive hydrogel efficiently differentiated between cancer cells and normal cells in response to cellular factors through changes in fluorescence, electrical and mechanical response. Tumor microenvironment acidity and high ROS concentrations caused fluorescence recovery via boronate ester and diselenide bond cleavage alongside a change in electrical resistivity from 78.9 kΩ (pH 7.4) to 38.8 kΩ (0.1 mM H2O2/pH 6.8) due to disintegration of molecular interaction in the sensor. In vitro electrochemical analysis revealed different ΔR/R0 bending profiles between cancer (26.2 % and 25.9 % for HeLa and PC-3, respectively) and normal cells (17.9 %), alongside the optical performance demonstrating higher regain of fluorescence of cancer cells (HeLa and PC-3) compared to the normal cells (CHO-K1). Additionally, the dsCD-PD(HA) Hydrogel demonstrated favorable biocompatibility and in vitro ROS scavenging, with selective targeting of cancer cells. A wireless sensing platform was developed by connecting the dsCD-PD(HA) Hydrogel sensor to a smartphone, showing a precise signal during detection via resistance or electro-mechanical signals.

Recycling of Polydicyclopentadiene Enabled with N-Coordinated Boronic EsterBonds.

In this contribution, the transformation of polydicyclopentadiene (PDCPD) from thermoset into vitrimer is introduced. First, two N-coordinated diboronic diols are successfully synthesized via the reaction of N,N,N-tri(2-hydroxyethyl)amine and/or N,N,N",N"-tetrakis(2-hydroxyethyl)ethylene diamine with 4-(hydroxymethyl) phenylboronic acid and then they are transformed into two N-coordinated cyclic boronic diacrylates. The latter two dienes carrying electron-withdrawing substituents are used for the ring opening insertion metathesis copolymerization (ROIMP) of dicyclopentadiene to afford the crosslinked PDCPD. In the crosslinked PDCPD networks, N-coordinated cyclic boronic ester bonds are integrated. It is found that the as-obtained PDCPD networks displayed the excellent reprocessing properties. In the meantime, the fracture toughness is significantly improved. Owing to the inclusion of N-coordinated cyclic boronic ester bonds, the modified PDCPDs have the thermal stability much superior to plain PDCPD. The results reported in this work demonstrate that PDCPD can successfully be transformed into the vitrimers via the introduction of N-coordinated cyclic boronic ester bonds.

Damage-Tolerant and Self-Repairing Web-Like Borate Type Binder Enable Stable Operation of Efficient Si-Based Anodes.

Novel binder designs are shown to be fruitful in improving the electrochemical performance of silicon (Si)-based anodes. However, issues with mechanical damage from dramatic volume change and poor lithium-ion (Li+) diffusion kinetics in Si-based materials still need to be addressed. Herein, an aqueous self-repairing borate-type binder (SBG) with a web-like architecture and high ionic conductivity is designed for Si and SiO electrodes. The 3D web-like architecture of the SBG binder enables uniform stress distribution, while its self-repairing ability promotes effective stress dissipation and mechanical damage repair, thereby enhancing the damage tolerance of the electrode. The tetracoordinate boron ions ( ) in the SBG binder boosts the Li transportation kinetics of Si-based electrodes. Based on dynamic covalent and ionic conductive boronic ester bonds, the diverse requirements of the binder, including uniform stress distribution, self-repairing ability, and high ionic conductivity, can be met by simple components. Consequently, the proposed straightforward multifunction design strategy for binders based on dynamic boron chemistry provides valuable insights into fabricating high-performance Si-based anodes.

Ligand Dissociation of Metal-Complex Photocatalysts toward pH-Photomanipulation in Dynamic Covalent Hydrogels for Printing Reprocessable and Recyclable Devices.

Dynamic covalent hydrogels are gaining attention for their potential in smart materials, soft devices, electronics, and more thanks to their impressive mechanical properties, biomimetic structures, and dynamic behavior. However, a significant challenge lies in designing precise and efficient dynamic photochemistry for their preparation, allowing for complex structures and control over the dynamic process. Herein, we propose a general and straightforward orthogonal dynamic covalent photochemistry strategy for preparing high-performance printable dynamic covalent hydrogels, thereby broadening their advanced applications. This photochemical strategy uses a bifunctional photocatalyst to initiate radical polymerization and release ligands through a rapid light-mediated dissociation mechanism. This process leads to a controlled increase in system pH from mildly acidic to alkaline conditions within one hundred seconds, which in turn triggers the pH-sensitive model reactions of boronic acid/diol complexation and Knoevenagel condensation. The orthogonal photochemistry enables the formation of interpenetrated and conjoined networks, significantly enhancing the mechanical properties of the hydrogels. The reversible bonds formed during the process, i.e., boronic ester and unsaturated ketone bonds, confer excellent self-healing, reprocessable, and recyclable properties on the hydrogels through photochemical pH variations. Furthermore, this rapid, controlled fabrication process and dynamic behavior are highly compatible with printing techniques, enabling the design of adaptive and recyclable sensors with different structures. These advancements are promising for various material science, medicine, and engineering applications.

Borate bonds-containing pH-responsive chitosan hydrogel for postoperative tumor recurrence and wound infection prevention

Chitosan has been widely used in biomedical fields due to its good antibacterial properties, excellent biocompatibility, and biodegradability. In this study, a pH-responsive and self-healing hydrogel was synthesized from 3-carboxyphenylboronic acid grafted with chitosan (CS-BA) and polyvinyl alcohol (PVA). The dynamic boronic ester bonds and intermolecular hydrogen bonds are responsible for the hydrogel formation. By changing the mass ratio of CS-BA and PVA, the tensile stress and compressive stress of hydrogel can controlled in the range of 0.61 kPa - 0.74 kPa and 295.28 kPa - 1108.1 kPa, respectively. After doping with tannic acid (TA)/iron nanocomplex (TAFe), the hydrogel successful killed tumor cells through the near infrared laser-induced photothermal conversion and the TAFe-triggered reactive oxygen species generation. Moreover, the photothermal conversion of the hydrogel and the antibacterial effect of CS and TA give the hydrogel a good antibacterial effect. The CS-BA/PVA/TAFe hydrogel exhibit good in vivo and in vitro anti-tumor recurrence and antibacterial ability, and therefore has the potential to be used as a powerful tool for the prevention of local tumor recurrence and bacterial infection after surgery.

Seeking Cells, Targeting Bacteria: A Cascade-Targeting Bacteria-Responsive Nanosystem for Combating Intracellular Bacterial Infections.

Intracellular bacteria pose a great challenge to antimicrobial therapy due to various physiological barriers at both cellular and bacterial levels, which impede drug penetration and intracellular targeting, thereby fostering antibiotic resistance and yielding suboptimal treatment outcomes. Herein, a cascade-target bacterial-responsive drug delivery nanosystem, MM@SPE NPs, comprising a macrophage membrane (MM) shell and a core of SPE NPs. SPE NPs consist of phenylboronic acid-grafted dendritic mesoporous silica nanoparticles (SP NPs) encapsulated with epigallocatechin-3-gallate (EGCG), a non-antibiotic antibacterial component, via pH-sensitive boronic ester bonds are introduced. Upon administration, MM@SPE NPs actively home in on infected macrophages due to the homologous targeting properties of the MM shell, which is subsequently disrupted during cellular endocytosis. Within the cellular environment, SPE NPs expose and spontaneously accumulate around intracellular bacteria through their bacteria-targeting phenylboronic acid groups. The acidic bacterial microenvironment further triggers the breakage of boronic ester bonds between SP NPs and EGCG, allowing the bacterial-responsive release of EGCG for localized intracellular antibacterial effects. The efficacy of MM@SPE NPs in precisely eliminating intracellular bacteria is validated in two rat models of intracellular bacterial infections. This cascade-targeting responsive system offers new solutions for treating intracellular bacterial infections while minimizing the risk of drug resistance.

A novel acid-responsive polymer coating with antibacterial and antifouling properties for the prevention of biofilm-associated infections

Chronic infections caused by the pathogenic biofilms on implantable medical devices pose an increasing challenge. To combat long-term biofilm-associated infections, we developed a novel dual-functional polymer coating with antibacterial and antifouling properties. The coating consists of N-vinylpyrrolidone (NVP) and 3-(acrylamido)phenylboronic acid (APBA) copolymer brushes, which bind to curcumin (Cur) as antibacterial molecules through acid-responsive boronate ester bonds. In this surface design, the hydrophilic poly (N-vinylpyrrolidone) (PVP) component improved antifouling performance and effectively prevented bacterial adhesion and aggregation during the initial phases. The poly (3-(acrylamido) phenylboronic acid) (PAPBA, abbreviated PB) component provided binding sites for Cur by forming acid-responsive boronate ester bonds. When fewer bacteria overcame the anti-adhesion barrier and colonized, the surface responded to the decreased microenvironmental pH by breaking the boronate ester bonds and releasing curcumin. This responsive mechanism enabled Cur to interfere with biofilm formation and provide a multilayer anti-biofilm protection system. The coating showed excellent antibacterial properties against Escherichia coli and Staphylococcus aureus, preventing biofilm formation for up to 7 days. The coating also inhibited protein adsorption and platelet adhesion significantly. This coating also exhibited high biocompatibility with animal erythrocytes and pre-osteoblasts. This research offers a promising approach for developing novel smart anti-biofilm coating materials.

Macrophage membrane-camouflaged pH-sensitive nanoparticles for targeted therapy of oral squamous cell carcinoma

BackgroundOral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX.ResultsThe results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility.ConclusionsTherefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.

High-strength self-healing hydrogels based on boronate-diol complexation cross-linking with good bioavailability

In this report, new self-healing hydrogels were obtained through simple one-pot free radical polymerization of acrylamide, phenylboronic acid, and 2-hydroxyethyl acrylate as copolymer monomers, potassium persulfate (KPS) as initiator, and tetramethylethylenediamine (TEMED) as promoter under low-temperature alkaline (pH = 9) conditions. The boronic acid group of phenylboronic acid (PBA) can interact with the hydroxyl group of hydroxyethyl acrylate (HEA) to form dynamic boronic ester bonds instead of the conventional bis acrylate crosslinkers. The effect of PBA content on the mechanical strength of the hydrogels was systematically investigated. The hydrogels exhibited higher stress, elongation, and self-healing properties due to the synergistic effect of H-bonds and boronate-diol complexation. Further studies revealed that the A–H–0.2–P–0.08 hydrogels exhibited excellent resistance to compression fatigue and also showed good biocompatibility through in vitro cytotoxicity tests.