Bioadhesive Hydrogel Research Articles

An inhaled bioadhesive hydrogel to shield non-human primates from SARS-CoV-2 infection.

The surge of fast-spreading SARS-CoV-2 mutated variants highlights the need for fast, broad-spectrum strategies to counteract viral infections. In this work, we report a physical barrier against SARS-CoV-2 infection based on an inhalable bioadhesive hydrogel, named spherical hydrogel inhalation for enhanced lung defence (SHIELD). Conveniently delivered via a dry powder inhaler, SHIELD particles form a dense hydrogel network that coats the airway, enhancing the diffusional barrier properties and restricting virus penetration. SHIELD's protective effect is first demonstrated in mice against two SARS-CoV-2 pseudo-viruses with different mutated spike proteins. Strikingly, in African green monkeys, a single SHIELD inhalation provides protection for up to 8 hours, efficiently reducing infection by the SARS-CoV-2 WA1 and B.1.617.2 (Delta) variants. Notably, SHIELD is made with food-grade materials and does not affect normal respiratory functions. This approach could offer additional protection to the population against SARS-CoV-2 and other respiratory pathogens.

Dual-crosslinked bioadhesive hydrogel as NIR/pH stimulus-responsiveness platform for effectively accelerating wound healing

Adhesive hydrogels have emerged as promising candidates to solve life-threatening infectious skin injuries. However, the inadequate mechanical characteristics and biological adherence limit the traditional wound dressing unable to adapt to high-frequency movement and real-time monitoring of wound healing, calling for the development of bioadhesive materials guided wound healing. In this work, a multifunctional bioadhesive hydrogel with double colorimetric-integrated of polyethylene glycol (PVA)-dextran (Dex)-borax-bromothymol blue (BTB)-fluorescein thiocyanate (FITC) and functionalization by tungsten disulfide-catechol nanozyme (CL/WS2) was created. Hydrogel is a perfect biological adhesive, which can achieve repeatable and strong tissue adhesion strength (8.3 ± 0.6 kPa), which is 1.66 times that of commercial dressings. Based on the strong biological adhesion of the hydrogel, a sensor is integrated into the hydrogel to collect visual image of bacterial infection from a smartphone and transform it into an on-site pH signal for remote evaluation of the wound's dynamic status in real time. Ultimately, the adhesiveness hydrogel has high worth in managing the burden related to wound healing and paving the way for intelligent wound management in the future.

Robust Neural Interfaces with Photopatternable, Bioadhesive, and Highly Conductive Hydrogels for Stable Chronic Neuromodulation.

A robust neural interface with intimate electrical coupling between neural electrodes and neural tissues is critical for stable chronic neuromodulation. The development of bioadhesive hydrogel neural electrodes is a potential approach for tightly fixing the neural electrodes on the epineurium surface to construct a robust neural interface. Herein, we construct a photopatternable, antifouling, conductive (∼6 S cm-1), bioadhesive (interfacial toughness ∼100 J m-2), soft, and elastic (∼290% strain, Young's modulus of 7.25 kPa) hydrogel to establish a robust neural interface for bioelectronics. The UV-sensitive zwitterionic monomer can facilitate the formation of an electrostatic-assembled conductive polymer PEDOT:PSS network, and it can be further photo-cross-linked into elastic polymer network. Such a semi-interpenetrating network endows the hydrogel electrodes with good conductivity. Especially, the photopatternable feature enables the facile microfabrication processes of multifunctional hydrogel (MH) interface with a characteristic size of 50 μm. The MH neural electrodes, which show improved performance of impedance, charge storage capacity, and charge injection capability, can produce effective electrical stimulation with high current density (1 mA cm-2) at ultralow voltages (±25 mV). The MH interface could realize high-efficient electrical communication at the chronic neural interface for stable recording and stimulation of a sciatic nerve in the rat model.

Long-term antibacterial, antioxidative, and bioadhesive hydrogel wound dressing for infected wound healing applications.

Bacterial infection and oxidative stress hinder clinical wound healing. Therefore, wound dressings with antibacterial and antioxidative properties are urgently needed. In this study, a type of quaternized lignin (QL) functionalized poly(hexamethylene biguanide) hydrochloride (PHMB) complex incorporated polyacrylamide (QL-PHMB-PAM) hydrogel was developed as a multifunctional dressing material for the promotion of infected wound repair. Owing to the abundant catechol groups of quaternized lignin, the QL-PHMB-PAM hydrogel exhibited robust repeatable adhesiveness to various substrates with antioxidative properties. Additionally, the antibacterial components of PHMB in the QL-PHMB-PAM composite hydrogel showed high efficiency and long-term antibacterial activity against Staphylococcus aureus (S.aureus), Escherichia coli (E.coli), and methicillin-resistant S. aureus (MRSA; up to 100%). Furthermore, in vivo experiments indicated that this multifunctional hydrogel accelerated the healing of S. aureus-infected wounds by promoting the reconstruction of blood vessels and hair follicles. These results demonstrate that this antioxidative, antibacterial, and bioadhesive hydrogel is a promising alternative wound dressing material for the prevention of bacterial infections and the acceleration of infected wound regeneration.

Acceleration of Oral Wound Healing under Diabetes Mellitus Conditions Using Bioadhesive Hydrogel

Oral wounds under diabetic conditions display a significant delay during the healing process, mainly due to oxidative stress-induced inflammatory status and abnormal immune responses. Besides, the wet and complicated dynamic environment of the oral cavity impedes stable treatment of oral wounds. To overcome these, a biomimetic hydrogel adhesive was innovatively developed based on a mussel-inspired multifunctional structure. The adhesive displays efficient adhesion and mechanical harmony on the oral mucosa through enhanced bonding in an acidic proinflammatory environment. The bioadhesive hydrogel exhibits excellent antioxidative properties by mimicking antioxidative enzymatic activities to reverse reactive oxygen species (ROS)-mediated immune disorders. Experiments on oral wounds of diabetic rats showed that this hydrogel adhesive could effectively protect against mucosal wounds and obviously shorten the inflammatory phase, thus promoting the wound-healing process. Therefore, this study offers a promising therapeutic choice with the potential to advance the clinical treatment of diabetic oral wounds.

Degradable Bioadhesives Based on Star PEG-PLA Hydrogels for Soft Tissue Applications.

Tissue adhesives are interesting materials for wound treatment as they present numerous advantages compared to traditional methods of wound closure such as suturing and stapling. Nowadays, fibrin and cyanoacrylate glues are the most widespread commercial biomedical adhesives, but these systems display some drawbacks. In this study, degradable bioadhesives based on PEG-PLA star-shaped hydrogels are designed. Acrylate, methacrylate, and catechol functional copolymers are synthesized and used to design various bioadhesive hydrogels. Various types of mechanisms responsible for adhesion are investigated (physical entanglement and interlocking, physical interactions, chemical bonds), and the adhesive properties of the different systems are first studied on a gelatin model and compared to fibrin and cyanoacrylate references. Hydrogels based on acrylate and methacrylate reached adhesion strength close to cyanoacrylate (332 kPa) with values of 343 and 293 kPa, respectively, whereas catechol systems displayed higher values (11 and 19 kPa) compared to fibrin glue (7 kPa). Bioadhesives were then tested on mouse skin and human cadaveric colonic tissue. The results on mouse skin confirmed the potential of acrylate and methacrylate gels with adhesion strength close to commercial glues (15-30 kPa), whereas none of the systems led to high levels of adhesion on the colon. These data confirm that we designed a family of degradable bioadhesives with adhesion strength in the range of commercial glues. The low level of cytotoxicity of these materials is also demonstrated and confirm the potential of these hydrogels to be used as surgical adhesives.

Endoscopy Deliverable and Mushroom-Cap-Inspired Hyperboloid-Shaped Drug-Laden Bioadhesive Hydrogel for Stomach Perforation Repair.

Gastrointestinal tract perforation is a full-thickness injury that causes bleeding and fatal infection of the peritoneum. This condition worsens in an acidic gastric environment which interferes with the normal coagulation cascade. Current endoscopic clips to repair gastric perforations are ineffective, and metal or plastic occluders need secondary surgery to remove them. Herein, we report a self-expandable, endoscopy deliverable, adhesive hydrogel to block gastric perforation. We found the nanosilica coating significantly enhanced the adhesive strength even under a simulated strong acidic stomach environment. The developed device was disulfide cross-linked for the reducible degraded gel. By loading with vonoprazan fumarate (VF) and acidic fibroblast growth factor (AFGF), the hyperboloid-shaped device can have a sustained drug release to regulate intragastric pH and promote wound healing. The gel device can be compressed and then expanded like a mushroom when applied in an acute gastric perforation model in both rabbits and minipigs. By utilizing a stomach capsule robot for remotely monitoring the pH and by immunohistochemical analysis, we demonstrated that the compressible hyperboloid-shaped gel could stably block the perforation and promoted wound healing during the 28 days of observation. The real-time pH meter demonstrated that the gel could control intragastric pH above 4 for nearly 60 h to prevent bleeding.

Sutureless transplantation using a semi-interpenetrating polymer network bioadhesive for ocular surface reconstruction

The conjunctiva covers the largest area of ocular surface and is responsible for tear balance and clear vision. After trauma or surgery, the conjunctiva is prone to scarring and contracture. Transplantation with suture often implies numerous complications, such as inflammation, suture erosion, granuloma. And the suture needs to be removed, which means a secondary trauma. In this study, a bioadhesive hydrogel (GMO) for sutureless conjunctival transplantation was developed based on a semi-interpenetrating polymer network (sIPN) consisting of gelatin methacrylate (GelMA) and oxidized hyaluronic acid (OHA). The maximum adhesion strength was 157 ± 17 kPa, and the burst pressure was 357 ± 29 kPa, which was 15 times higher than the human intraocular pressure (IOP). GMO bioadhesive hydrogel significantly improved surgical efficiency and secured the collagen scaffold firmly to a rabbit conjunctival defect. The sutureless transplantation approach revealed the promoted tissue repair without scar. In conclusion, GMO bioadhesive may be an attractive alternative to suture for ocular surface reconstruction by avoiding suture-related complications and improving clinical outcome. Statement of significanceConjunctival tissue is prone to scarring and contracture after trauma, and surgery with sutures often implies numerous complications. In this study, the ocular surface reconstruction was achieved by sutureless transplantation of conjunctival scaffold using bioadhesive hydrogel. The prepared GMO bioadhesive based on the semi-interpenetrating network of gelatin methacrylate (GelMA) and oxidized hyaluronic acid (OHA) had favorable adhesion and mechanical properties. The sutureless transplantation approach significantly improved the operation efficiency, avoided suture-related complications, and promoted the regeneration of conjunctiva. This study highlights the great potential of the sutureless repair strategy for clinical application in ocular surface reconstruction.

Natural Dual-Crosslinking Bioadhesive Hydrogel for Corneal Regeneration in Large-Size Defects.

Corneal injectable hydrogels represent a promising alternative to alleviate donor shortage and simplify traditional surgeries. However, most hydrogels focus on repairing focal corneal defects (≤3.5mm) and leave many clinical requirements unmet. Herein, a novel ion-activated bioadhesive hydrogel (IonBAH) is designed and its long-term performance of repairing large corneal defects (6mm) is evaluated in rabbits for 6 months. The IonBAH is a dual-network hydrogel composed of natural corneal extracellular matrix and peptide-modified alginate, which enables its desirable transparency and biocompatibility, tunable mechanics, and robust adhesion. Moreover, the IonBAH maintains the secretory phenotype of quiescent keratocytes, while preventing their myofibroblastic differentiation in vitro. Upon application in situ, it rapidly seals the 6mm corneal defect and forms normal curvature through the coverage of a contact lens impregnated with calcium ions. During the 6 months follow-up, the IonBAH promotes rapid regeneration of corneal epithelium, stroma, and nerves with restored transparency, equivalent to the outcome of donor corneal transplantation. In addition, the suitability of IonBAH as an adhesive and patch for various clinical requirements are also evaluated with a pleasing outcome. Collectively, IonBAH may provide a clinically applicable scaffold for corneal surgeries, especially in large defect repair.

Preparation of a Bioadhesive Poly(Acrylic Acid)/Polyvinylpyrrolidone Complex Gel and Its Clinical Effect on Dental Hemostasis.

Poly(acrylic acid) (PAA) is a water-soluble synthetic polymer that exhibits bioadhesive properties and has been applied in various novel medical devices, such as drug-delivery carriers and hemostatic agents. PAA forms a water-insoluble complex when mixed with polyvinylpyrrolidone (PVP). If PAA and PVP are mixed in water, they form an aggregated precipitate, which neither swells nor adheres to tissues. The formation of the hydrophobic complex was caused by hydrophobic interactions between the main chains of both polymers aligned the same as a zipper. To hinder the zipper-like alignment of the polymer main chains, hyaluronic acid (HA), a macromolecular viscous polysaccharide, was added to the PVP solution prior to complex formation. When the initial concentration of PAA was lower than 0.05%, HA effectively prevented the aggregation of PAA/PVP complexes and resulted in a slightly clouded suspension. Freeze-drying of the mixture yielded a soft white sponge, which could immediately swell in water to form a highly bioadhesive hydrogel. The PAA/PVP complex prepared with HA exhibited high hemostatic efficiency in clinical studies, even in patients on antithrombotic drugs.

EE338 Cost-Effectiveness Analysis of Arthroscopic Injection of a Bioadhesive Hydrogel Implant in Conjunction with Microfracture for the Treatment of Focal Chondral Defects of the Knee: An Australian Perspective

JointRep is a bioadhesive hydrogel arthroscopically injected to facilitate cartilage regeneration. The cost-effectiveness of JointRep with microfracture surgery compared to microfracture alone was evaluated from the Australian healthcare system perspective, in patients with symptomatic focal osteochondral defects (Outerbridge Grade 3 or 4) of the knee who had failed conservative treatment and were indicated for surgery.

Cost-effectiveness analysis of arthroscopic injection of a bioadhesive hydrogel implant in conjunction with microfracture for the treatment of focal chondral defects of the knee – an Australian perspective

Aim JointRep is a bioadhesive hydrogel arthroscopically injected to facilitate cartilage regeneration. The cost-effectiveness of JointRep with microfracture surgery compared to microfracture alone was evaluated from the Australian healthcare system perspective, in patients with symptomatic focal chondral defects (Outerbridge Grade 3 or 4) of the knee who had failed conservative treatment and were indicated for surgery. Materials and methods A de novo Markov model comprising two health states- ‘Alive’ and ‘Dead’ was developed. Model transition probability was based on the general population mortality rates. Clinical outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, a validated patient-reported tool measuring pain, stiffness, and physical function. The utility was derived by mapping WOMAC scores to EQ-5D scores using a published algorithm. Cost inputs were based on published Australian costs from AR-DRGs, Medicare Benefits Schedule, and Prostheses List. Model outcomes included costs, Quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Base-case analysis was conducted for a time horizon of 3 years and a cycle length of 1 year. Cost and health outcomes were discounted at 5% per annum. Sensitivity and scenario analyses were also conducted. Results Total QALYs were estimated to be higher for JointRep with microfracture surgery (2.61) compared to microfracture surgery alone (1.66), an incremental gain of 0.95 QALY. JointRep with microfracture surgery was associated with an incremental cost of $6,022 compared to microfracture surgery alone, thus leading to an ICER of $6,328. Results were substantially robust to varying parameters in the sensitivity analyses conducted, alternative model settings and assumptions in scenario analyses. Limitations The clinical inputs used in the model were based on data from short duration, non-randomized, post-market clinical trial. Conclusions JointRep with microfracture surgery is a cost-effective treatment option compared to microfracture alone from the Australian health care system perspective.

Sutureless neurorrhaphy system using a macrophage-polarizing in situ visible light-crosslinkable adhesive protein hydrogel for functional nerve regeneration

Surgical intervention after traumatic peripheral nerve injury relies heavily on sutures. While the suture method often burdens functional nerve regeneration by causing secondary traumatic damage and eliciting prolonged inflammatory immune responses, replacing sutures has rarely been considered because secure anastomosis between severed nerve ends has been the utmost priority in neurorrhaphy. In the present work, a macrophage-polarizing sutureless neurorrhaphy system was proposed by using an in situ visible light-crosslinkable protein-based bioadhesive hydrogel containing a functional neurotransmitter peptide. The efficacy of the proposed bioadhesive hydrogel as a successful sutureless neurorrhaphy system was intensively evaluated in vitro and in vivo. Using a rat sciatic nerve defect model, our findings suggested that this macrophage-polarizing bioadhesive hydrogel offered effective sutureless anastomosis and the capability to induce M2 macrophage polarization for effective tissue remodeling, significantly enhancing functional nerve regeneration compared with conventional sutures. Taken together, these results suggest that our macrophage-polarizing functional bioadhesive hydrogel system can be utilized as a promising alternative to surgical sutures for nerve regenerative medicine applications.

Multi-crosslinking hydrogels with robust bio-adhesion and pro-coagulant activity for first-aid hemostasis and infected wound healing

Bio-adhesive polysaccharide-based hydrogels have attracted much attention in first-aid hemostasis and wound healing for excellent biocompatibility, antibacterial property and pro-healing bioactivity. Yet, the inadequate mechanical properties and bio-adhesion limit their applications. Herein, based on dynamic covalent bonds, photo-triggered covalent bonds and hydrogen bonds, multifunctional bio-adhesive hydrogels comprising modified carboxymethyl chitosan, modified sodium alginate and tannic acid are developed. Multi-crosslinking strategy endows hydrogels with improved strength and flexibility simultaneously. Owing to cohesion enhancement strategy and self-healing ability, considerable bio-adhesion is presented by the hydrogel with a maximal adhesion strength of 162.6 kPa, 12.3-fold that of commercial fibrin glue. Based on bio-adhesion and pro-coagulant activity (e.g., the stimulative aggregation and adhesion of erythrocytes and platelets), the hydrogel reveals superior hemostatic performance in rabbit liver injury model with blood loss of 0.32 g, only 54.2% of that in fibrin glue. The healing efficiency of hydrogel for infected wounds is markedly better than commercial EGF Gel and Ag+ Gel due to the enhanced antibacterial and antioxidant properties. Through the multi-crosslinking strategy, the hydrogels show enhanced mechanical properties, fabulous bio-adhesion, superior hemostatic performance and promoting healing ability, thereby have an appealing application value for the first-aid hemostasis and infected wound healing.

Soft armour-like layer-protected hydrogels for wet tissue adhesion and biological imaging

Hydrogels with high water contents have been widely used as ultrasound couplants for medical imaging due to their acoustic impedance compatibility with biological tissues. However, their functional reliability is compromised by unstable adhesion to wet tissues, as surrounding water disrupts the surface bonding. Herein, we report a novel strategy to fabricate a bioadhesive hydrogel by assembling a soft armour-like hydrophobic surface as the outermost adhesive layer to achieve instant and robust wet tissue adhesion. The external catechol-containing hydrophobic layer generates a water depletion region at the contact interface, which promotes rapid adhesion (within 5 s) and prevents the weakening of interfacial bonds from water penetration even under high hydraulic pressures. The internal hydrogel matrix reduces the signal attenuation in ultrasound imaging due to its high water content of 86.7 wt%. The porcine model further demonstrates that the as-prepared hydrogel adhesive enables both the stable attachment and high-contrast imaging for ultrasound diagnosis in wet intraoral environments. This work devises a new pathway for building the human-machine interface for biomedical applications.

Bioadhesive injectable hydrogel with phenolic carbon quantum dot supported Pd single atom nanozymes as a localized immunomodulation niche for cancer catalytic immunotherapy

Immunotherapy is a powerful way to treat cancer, however, systemic treatment-associated adverse effects remain a major concern. In this study, a bioadhesive injectable hydrogel is developed to provide localized immune niches for tumor microenvironment immunomodulation and cancer catalytic immunotherapy. First, a phenolic single atom nanozyme (SAN) was developed by in situ synthesis of Pd single atom on catechol-grafted carbon-quantum-dot (DA-CQD@Pd) templates. Then, the bioadhesive injectable hydrogel consisting of DA-CQD@Pd SAN and immune adjuvant CpGODN was formed through SAN-catalyzed free-radical polymerization. The SAN exhibited peroxidase-like activity to generate ROS and kill tumor cells through catalytic therapy. The hydrogel locally released CpGODN in a sustained manner, which limited the risk of systemic exposure, reducing the impact of CpGODN toxicity, and protecting CpGODN from degradation. The bioadhesive hydrogel immobilized around solid tumor to provide an immune response site after injection. When combined it with the administration of immune checkpoint inhibitor anti-PD-L1, the hydrogel realized localized immunomodulation, maximized therapeutic efficacy and prevents tumor metastasis via a catalytic immunotherapy.

Thermosensitive Bioadhesive Hydrogels Based on Poly(N-isopropylacrilamide) and Poly(methyl vinyl ether-alt-maleic anhydride) for the Controlled Release of Metronidazole in the Vaginal Environment.

The development of thermosensitive bioadhesive hydrogels as multifunctional platforms for the controlled delivery of microbicides is a valuable contribution for the in situ treatment of vagina infections. In this work, novel semi-interpenetrating network (s-IPN) hydrogels were prepared by the entrapment of linear poly(methyl vinyl ether-alt-maleic anhydride) (PVME-MA) chains within crosslinked 3D structures of poly(N-isopropylacrylamide) (PNIPAAm). The multifunctional platforms were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermal techniques, rheological analysis, swelling kinetic measurements, and bioadhesion tests on porcine skin. The hydrogels exhibited an interconnected porous structure with defined boundaries. An elastic, solid-like behavior was predominant in all formulations. The swelling kinetics were strongly dependent on temperature (25 °C and 37 °C) and pH (7.4 and 4.5) conditions. The s-IPN with the highest content of PVME-MA displayed a significantly higher detachment force (0.413 ± 0.014 N) than the rest of the systems. The metronidazole loading in the s-IPN improved its bioadhesiveness. In vitro experiments showed a sustained release of the antibiotic molecules from the s-IPN up to 48 h (94%) in a medium simulating vaginal fluid, at 37 °C. The thermosensitive and bioadhesive PNIPAAm/PVME-MA systems showed a promising performance for the controlled release of metronidazole in the vaginal environment.

Natural polymer-derived photocurable bioadhesive hydrogels for sutureless keratoplasty

Keratoplasty is the gold standard treatment for visual impairment caused by corneal damage. The use of suturing as the bonding method is the source of many complications following keratoplasty. Currently available corneal adhesives do not have both adequate adhesive strength and acceptable biocompatibility. Herein, we developed a photocurable bioadhesive hydrogel which was composed of gelatin methacryloyl and oxidized dextran for sutureless keratoplasty. The bioadhesive hydrogel exhibited high light transmittance, resistance to enzymatic degradation and excellent biocompatibility. It also had higher adhesive strength than commercial adhesives (fibrin glue). In a rabbit model of lamellar keratoplasty, donor corneal grafts could be closely bonded to the recipient corneal bed and remained attached for 56 days by using of this in situ photopolymerized bioadhesive hydrogel. The operated cornea maintained transparent and noninflamed. Sutureless keratoplasty using bioadhesive hydrogel allowed rapid graft re-epithelialization, typically within 7 days. In vivo confocal microscopic and histological evaluation of the operated cornea did not show any apparent abnormalities in terms of corneal cells and ultrastructure. Thus, this bioadhesive hydrogel is exhibited to be an appealing alternative to sutures for keratoplasty and other corneal surgeries.

Dual-Dynamic-Bond Cross-Linked Antibacterial Adhesive Hydrogel Sealants with On-Demand Removability for Post-Wound-Closure and Infected Wound Healing.

The design and development of a smart bioadhesive hydrogel sealant with self-healing and excellent antibacterial activity to achieve high wound closure effectiveness and post-wound-closure care is highly desirable in clinical applications. In this work, a series of adhesive antioxidant antibacterial self-healing hydrogels with promising traits were designed through dual-dynamic-bond cross-linking among ferric iron (Fe), protocatechualdehyde (PA) containing catechol and aldehyde groups and quaternized chitosan (QCS) to enable the closure of skin incisions and promotion of methicillin-resistant Staphylococcus aureus (MRSA)-infected wound healing. The dual-dynamic-bond cross-linking of a pH-sensitive coordinate bond (catechol-Fe) and dynamic Schiff base bonds with reversible breakage and re-formation equips the hydrogel with excellent autonomous healing and on-demand dissolution or removal properties. Additionally, the hydrogel presents injectability, good biocompatibility and antibacterial activity, multifunctional adhesiveness, and hemostasis as well as NIR responsiveness. The in vivo evaluation in a rat skin incision model and infected full-thickness skin wound model revealed the high wound closure effectiveness and post-wound-closure care of the smart hydrogels, demonstrating its great potential in dealing with skin incisions and infected full-thickness skin wounds.

Bioadhesive hydrogel comprising bilirubin/β-cyclodextrin inclusion complexes promote diabetic wound healing

Context Chronic non-healing diabetic wound therapy is an important clinical challenge. Manipulating the release of bioactive factors from an adhesive hydrogel is an effective approach to repair chronic wounds. As an endogenous antioxidant, bilirubin (BR) has been shown to promote wound healing. Nonetheless, its application is limited by its low water solubility and oxidative degradation. Objective This study developed a bilirubin-based formulation for diabetic wound healing. Materials and methods Bilirubin was incorporated into β-CD-based inclusion complex (BR/β-CD) which was then loaded into a bioadhesive hydrogel matrix (BR/β-CD/SGP). Scratch wound assays were performed to examine the in vitro pro-healing activity of BR/β-CD/SGP (25 μg/mL of BR). Wounds of diabetic or non-diabetic rats were covered with BR or BR/β-CD/SGP hydrogels (1 mg/mL of BR) and changed every day for a period of 7 or 21 days. Histological assays were conducted to evaluate the in vivo effect of BR/β-CD/SGP. Results Compared to untreated (18.7%) and BR (55.2%) groups, wound closure was more pronounced (65.0%) in BR/β-CD/SGP group. In diabetic rats, the wound length in BR/β-CD/SGP group was smaller throughout the experimental period than untreated groups. Moreover, BR/β-CD/SGP decreased TNF-α levels to 7.7% on day 3, and elevated collagen deposition and VEGF expression to 11.9- and 8.2-fold on day 14. The therapeutic effects of BR/β-CD/SGP were much better than those of the BR group. Similar observations were made in the non-diabetic model. Discussion and conclusion BR/β-CD/SGP promotes wound healing and tissue remodelling in both diabetic and non-diabetic rats, indicating an ideal wound-dressing agent.