Immobilization of coacervate microcapsules in multilayer sodium alginate beads for efficient oral anticancer drug delivery.

We have designed and evaluated coacervate microcapsules-immobilized multilayer sodium alginate beads (CMs-M-ALG-Beads) for oral drug delivery. The CMs-M-ALG-Beads were prepared by immobilization of doxorubicin hydrochloride (DOX) loaded chitosan/carboxymethyl coacervate microcapsules (DOX:CS/CMCS-CMs) in the core and layers of the multilayer sodium alginate beads. The obtained CMs-M-ALG-beads exhibited layer-by-layer structure and rough surface with many nanoscale particles. The swelling characteristic and drug release results indicated that 4-layer CMs-M-ALG-Beads possessed favorable gastric acid tolerance (the swelling rate <5%, the cumulative drug release rate <3.8%). In small intestine, the intact DOX:CS/CMCS-CMs were able to rapidly release from CMs-M-ALG-Beads with the dissolution of ALG matrix. Ex vivo intestinal mucoadhesive and permeation showed that CMs-M-ALG-Beads exhibited continued growth for P(app) values of DOX, which was 1.07-1.15 folds and 1.28-1.38 folds higher than DOX:CS:CMCS-CMs in rat jejunum and ileum, respectively, demonstrating that CMs-M-ALG-Beads were able to enhance the absorption of DOX by controlled releasing DOX:CS/CMCS-CMs and prolonging the contact time between the DOX:CS/CMCS-CMs and small intestinal mucosa.

Construction of mPt/ICG-αA nanoparticles with enhanced phototherapeutic activities for multidrug-resistant bacterial eradication and wound healing.

The emergence of multidrug-resistant (MDR) bacterial infections calls for novel strategies for effective bacterial inhibition and wound healing. Phototherapeutic approaches are promising in treating bacterial infection because of their high efficiency, noninvasiveness, and few side effects; however, their antibacterial effect is limited by the formation of biofilms in wounds. Herein, we report novel composite nanoparticles (mPt/ICG-αA NPs) combining mesoporous platinum (mPt) nanoparticles, indocyanine green (ICG) and α-amylase (αA) for combating MDR bacteria and treating wound infection, which integrates a triple bacterial inhibition mechanism arising from the combination of photodynamic therapy (PDT), photothermal therapy (PTT) and α-amylase enzymatic activities. The combination of mPt and ICG significantly enhances the effect of PTT and the temperature can be increased up to 80.8 °C to induce efficacious bacterial degeneration. Meanwhile, mPt/ICG-αA (mPIA) NPs with a low concentration of 25 µg mL-1 exhibited a remarkable catalase activity (CAT) and could continuously decompose endogenous H2O2 into O2 in a hypoxic microenvironment, thereby enhancing the PDT effect to achieve broad-spectrum bactericidal activity. mPIA NPs showed excellent MDR antibacterial efficiency against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli), and the bactericidal rate reached up to 99.0% and 97.2% with single 808 nm near-infrared light irradiation, respectively. mPIA NPs also exhibited an excellent ability to destroy biofilms and biocompatibility. Animal experiments further suggested that mPIA NPs could achieve the successful repairment of wounds infected with S. aureus in living systems, while this platform demonstrated negligible toxicity towards mice. Considering the superior performances of mPIA NPs, the synergistic αA-CAT-PDT-PTT boosted therapeutic activity presented in the current work provides a promising method to effectively fight against biofilm-related infectious diseases and wound healing.

High-Strength Collagen-Based Composite Films Regulated by Water-Soluble Recombinant Spider Silk Proteins and Water Annealing.

Spider silk has attracted extensive attention in the development of high-performance tissue engineering materials because of its excellent physical properties, biocompatibility, and biodegradability. Although high-molecular-weight recombinant spider silk proteins can be obtained through metabolic engineering of host bacteria, the solubility of the recombinant protein products is always poor. Strong denaturants and organic solvents have thus had to be exploited for their dissolution, and this seriously limits the applications of recombinant spider silk protein-based composite biomaterials. Herein, through adjusting the temperature, ionic strength, and denaturation time during the refolding process, we successfully prepared water-soluble recombinant spider major ampullate spidroin 1 (sMaSp1) with different repeat modules (24mer, 48mer, 72mer, and 96mer). Then, MaSp1 was introduced into the collagen matrix for fabricating MaSp1-collagen composite films. The introduction of spider silk proteins was demonstrated to clearly alter the internal structure of the composite films and improve the mechanical properties of the collagen-based films and turn the opaque protein films into transparency ones. More interestingly, the composite film prepared with sMaSp1 exhibited better performance in mechanical strength and cell adhesion compared to that prepared with water-insoluble MaSp1 (pMaSp1), which might be attributed to the effect of the initial dissolved state of MaSp1 on the microstructure of composite films. Additionally, the molecular weight of MaSp1 was also shown to significantly influence the mechanical strength (enhanced to 1.1- to 2.3-fold) and cell adhesion of composite films, and 72mer of sMaSp1 showed the best physical properties with good bioactivity. This study provides a method to produce recombinant spider silk protein with excellent water solubility, making it possible to utilize this protein under environmentally benign, mild conditions. This paves the way for the application of recombinant spider silk proteins in the development of diverse composite biomaterials.

The recent progress of tissue adhesives in design strategies, adhesive mechanism and applications.

Tissue adhesives have emerged as an effective method for wound closure and hemostasis in recent decades, due to their ability to bond tissues together, preventing separation from one tissue to another. However, existing tissue adhesives still have several limitations. Tremendous efforts have been invested into developing new tissue adhesives by improving upon existing adhesives through different strategies. Therefore, highlighting and analyzing these design strategies are essential for developing the next generation of advanced adhesives. To this end, we reviewed the available strategies for modifying traditional adhesives (including cyanoacrylate glues, fibrin sealants and BioGlue), as well as design of emerging adhesives (including gelatin sealants, methacrylated sealants and bioinspired adhesives), focusing on their structures, adhesive mechanisms, advantages, limitations, and current applications. The bioinspired adhesives have numerous advantages over traditional adhesives, which will be a wise direction for achieving tissue adhesives with superior properties.

Enhanced anticoagulant activity of hirudin-i analogue co-expressed with arylsulfotransferase in periplasm of E. coli BL21(DE3).

Hirudin, a blood anticoagulant, is the most potent natural thrombin inhibitor of leech origin. Its application is limited because it is difficult to obtain abundant natural hirudin directly from the leech. Although some bioengineering methods can significantly increase the production of hirudin, the reduced efficacy of recombinant hirudin (rH) remains a critical shortcoming. The lack of sulfation of tyrosine 63 in rH is an important cause of its inadequate performance. This article is the first report of periplasmic co-expression of an rH-I analogue with arylsulfotransferase (ASST) in E. coli BL21(DE3). Co-expressed rH-I analogue with sulfate donor substrate (p-nitrophenyl sulfate potassium) showed anticoagulant (rabbit and goat serum) activity twice more than rH-I analogue expressed without ASST, indicating its potential periplasmic sulfation. Moreover, purified rH-I analogue showed above 4.5 times higher anticoagulant activity compared to therapeutic anti-thrombotic heparin (HE). At the same time, pH-dependent differential solubility was employed to purify rH analogues from fermentation broth, which is a simple, fast and inexpensive purification technology, and can potentially be used for larger scale purification. This will also greatly improve the application of rH in clinical treatment.

Development of tilapia collagen and chitosan composite hydrogels for nanobody delivery.

Recently, injectable hydrogels have shown great potential in cell therapy and drug delivery. They can easily fill in any irregular-shaped defects and remain in desired positions after implantation using minimally invasive strategies. Here, we developed hydrogels prepared from tilapia skin collagen and chitosan (HCC). The residual mass rate of HCC was affected by the pH at the time of preparation, which was 29.1 % at pH 7 in 36 h. By comparison, the residual mass ratios of HCC at pH values of 6 and 5 were only approximately 8.4 % and 0, respectively. In addition, the stability of HCC was also affected by the concentration of these two components. HCC10 catalyzed by 10 mg mL-1 tilapia skin collagen and 10 mg mL-1 chitosan was more stable than HCC5 catalyzed by 5 mg mL-1 tilapia skin collagen and 10 mg mL-1 chitosan; therefore, we studied that ability of HCC10 to deliver two model nanobodies: 2D5 and KPU. As the concentration of nanobodies increased, the cumulative release rate of 2D5 decreased, and the release rate of KPU increased. Meanwhile, the cumulative release rate of 2D5 was the highest (68.3 %) at pH 5.5, followed by pH 6.8 (56.4 %) and 7.4 (28.4 %). However, the cumulative release rates of KPU were similar at pH 5.5 (45.1 %), 6.8 (46.5 %), and 7.4 (44.9 %). HCC is biodegradable, and can facilitate the release nanobodies; thus, HCC could be developed into an intelligent responsive tumor treatment matrix for use in cancer therapy.

Development and characterization of a photo-cross-linked functionalized type-I collagen (Oreochromis niloticus) and polyethylene glycol diacrylate hydrogel.

Collagen hydrogels have been widely investigated as scaffolds for tissue engineering due to their biocompatibility and capacity to promote cell adhesion. However, insufficient mechanical strength and rapid degradation properties remain the major obstacles for their applications. In the present study, type-I tilapia collagen (TC) was functionalized to form methacrylated tilapia collagen (MATC) by introducing methacrylic acid, developing a photo-cross-linked PEGDA-MATC hydrogel. The mechanical strength of PEGDA-MATC hydrogel could be tuned by adjusting the pH of the precursor solutions, which was decreased with the pH increased. At a pH 5 condition, PEGDA-MATC showed the highest compressive fracture stress (1.31 MPa). Compared to the PEGDA-TC hydrogel, PEGDA-MATC hydrogel exhibited similar swelling behavior to PEGDA-TC hydrogel in PBS solutions, but higher residual mass ratio (PEGDA-MATC, 213.2 ± 2.8%) than PEGDA-TC hydrogel (199.4 ± 3.8%) when cultured with type-I collagenase. PEGDA-MATC hydrogel showed sustained BSA release capacity for 6 days, and the BSA release ratio was significantly (p < 0.05) decreased with increasing concentration of loaded-BSA (68.6% at 4 mg mL-1, 42.2% at 8 mg mL-1). The PEGDA-MATC hydrogel allowed cell adhesion and proliferation in vitro. These results demonstrated that PEGDA-MATC hydrogel might be a potential scaffold for tissue engineering applications.

Improved Cell Viability and Biocompatibility of Bacterial Cellulose through in Situ Carboxymethylation.

Bacterial cellulose (BC) is a natural product with multiple properties, which has been utilized in tissue engineering. However, cell adhesion and proliferation are reported to be weaker on native BC, providing less support compared to other types of biomaterials, like collagen. To increase the biocompatibility and the medical performance of BC, in situ modification is used to add carboxymethyl group to BC. By partially changing the structure and physical properties of BC, carboxymethylation significantly increases cell affinity and viability, especially on the initial cell adhesion. Furthermore, in the in vivo implantation, the tissue reaction shows that carboxymethylation significantly increases the biocompatibility of BC, exhibiting better tissue condition and a lower inflammatory reaction which are proved through HE staining and immunohistochemistry. The data prove that in situ carboxymethylation is a simple and direct way of improving the performance of BC in medical applications.

A natural in situ fabrication method of functional bacterial cellulose using a microorganism.

The functionalization methods of materials based on bacterial cellulose (BC) mainly focus on the chemical modification or physical coating of fermentation products, which may cause several problems, such as environment pollution, low reaction efficiency and easy loss of functional moieties during application. Here, we develop a modification method utilizing the in situ microbial fermentation method combined with 6-carboxyfluorescein-modified glucose (6CF-Glc) as a substrate using Komagataeibacter sucrofermentans to produce functional BC with a nonnatural characteristic fluorescence. Our results indicate that the microbial synthesis method is more efficient, controllable and environmentally friendly than traditional modification methods. Therefore, this work confirms that BC can be functionalized by using a microbial synthesis system with functionalized glucose, which provides insights not only for the functionalization of BC but also for the in situ synthesis of other functional materials through microbial synthetic systems.

A thermosensitive RGD-modified hydroxybutyl chitosan hydrogel as a 3D scaffold for BMSCs culture on keloid treatment.

Cell therapy with bone marrow-derived mesenchymal stem cells (BMSCs) is a potential method for many disease treatments, including keloid. In the present study, an Arg-Gly-Asp (RGD) modified hydroxybutyl chitosan (HBC) hydrogel (HBC-RGD) was developed to enhance the adhesion and proliferation of BMSCs within the hydrogel. The successful synthesis of HBC-RGD was confirmed by FTIR and 1H NMR. Both HBC and HBC-RGD hydrogel had desired thermosensitivity, biocompatibility and enzymatic degradability in vitro. Compared with HBC hydrogel, HBC-RGD hydrogel was more beneficial for the adhesion and proliferation of BMSCs. Furthermore, the BMSCs incorporated HBC-RGD (BMSCs/HBC-RGD) hydrogel could inhibit the proliferation of keloid fibroblasts (Kfs) and suppress the nodular collagenous fibers of keloid tissue. These results suggested that the HBC-RGD hydrogel could be applied as a potential 3D hydrogel scaffold for cell culture, and BMSCs/HBC-RGD hydrogel was potential to be applied for keloid therapy with subcutaneous in-situ injection in the future.

Optimization of the preparation conditions of thermo-sensitive chitosan hydrogel in heterogeneous reaction using response surface methodology.

A thermo-sensitive hydroxybutyl chitosan (HBC) hydrogel was prepared by using 1,2­butene oxide as an etherification modifying agent. To obtain the maximum yield of HBC, response surface methodology (RSM) was applied to optimize its preparation conditions. Key factors were chosen firstly by Plackett-Burman design (PBD) experiments, such as the concentration of NaOH, the ratio of isopropanol to water and reaction temperature. Steepest ascent experiments were employed to reach the top region of the response and determine the appropriate levels of three key factors. A three-level-three-variable Box-Behnken design (BBD) was used to further optimize the synthesis parameters. The results indicated that when the concentration of NaOH and the ratio of isopropyl alcohol to water were 40.65% and 2.68:1 at reaction temperature of 59 °C, respectively, the yield of HBC production was 5.897 ±â€¯0.112 g and close to the predicted value (6.002 g), which demonstrated that the effectiveness of BBD model and the controllability for the yield of HBC in the heterogeneous reaction system.

Reinforcement of thermoplastic chitosan hydrogel using chitin whiskers optimized with response surface methodology.

To strengthen the mechanical strength of thermo-sensitive hydroxybutyl chitosan (HBC) hydrogel, chitin whiskers were used as sticker to fabricate reinforced HBC (HBCW) hydrogel by using response surface methodology. Unlike the intrinsic network of HBC hydrogel, HBCW hydrogel showed a laminar shape with firm structure. The preparation condition was optimized by three-factor-three-level Box-Behnken design. The maximum mechanical strength (1011.11 Pa) was achieved at 50 °C, when the concentrations of HBC and chitin whiskers were 5.1 wt% and 2.0 wt%, respectively. The effects of temperature, pH value and NaCl concentration on mechanical strength of HBCW hydrogels were investigated via the oscillatory stress sweeps. The results showed that HBCW hydrogel could reach the maximum stiffness (∼1126 Pa) at 37 °C pH 12.0. Low pH and high salty ions could decrease the stability of hydrogel, while chitin whiskers could increase the stress tolerance and related ruptured strain of HBCW hydrogels.

The promising indicators of the thermal and mechanical properties of collagen from bass and tilapia: synergistic effects of hydroxyproline and cysteine.

Collagen has been widely documented as one of the most promising and competitive biomaterials for tissue engineering and medical applications. However, the properties of collagen differ from one source to another. In the present study, type I collagen (COL-I) was extracted and purified from the skins of Japanese sea bass (Lateolabrax japonicus) and Nile tilapia (Oreochromis niloticus). Ultraviolet (UV) spectroscopy, Fourier transform infrared spectroscopy (FTIR) and SDS-PAGE were performed to characterize both COL-Is. The denaturing temperature of bass collagen (BC) was observed to be 27.2 °C, and 35.3 °C for tilapia collagen (TC). The content of hydroxyproline was 13.4% in TC, which was similar to that in porcine collagen (PC, 13.6%) and higher than that in BC (10.3%), while the content of cysteine in TC (0.87%) was significantly higher than that in PC (0.04%) and BC (0.35%). After incubation at different temperatures for 9 h, more degraded collagen bands appeared in the BC hydrogel (BCH) group than in the TC hydrogel (TCH) group, indicating that TCH exhibited better thermal stability than BCH. The thermal stabilities of TCH and PC hydrogel (PCH) were similar. The compressive stress of TCH was up to 0.099 MPa, while it was 0.047 MPa for BCH and 0.003 MPa for PCH. These results demonstrated that the content of amino acids (especially hydroxyproline and cysteine) has a synergistic effect on the thermal and mechanical properties of BCH, TCH and PCH, which would be an indicator of the thermal and mechanical properties of collagen hydrogels in future studies.

Chitosan-Based Thermo/pH Double Sensitive Hydrogel for Controlled Drug Delivery.

A series of thermo/pH sensitive N-succinyl hydroxybutyl chitosan (NSHBC) hydrogels with different substitution degrees of succinyl are prepared for drug delivery. Rheology analysis shows that the gelation temperature of NSHBC hydrogels is 3.8 °C higher than that of hydroxybutyl chitosan (HBC) hydrogels. A model drug bovine serum albumin (BSA) is successfully loaded and released. NSHBC hydrogels show excellent pH sensitivity drug release behaviors. After incubation for 24 h, 93.7% of BSA is released from NSHBC hydrogels in phosphate buffer saline (PBS) (pH 7.4), which is significantly greater than that of 24.6% at pH 3.0. In contrast, the release rate of BSA from HBC is about 70.0% at pH 3.0 and 7.4. Thus, these novel hydrogels have the prominent merits of high adaptability to soluble drugs and pH sensitivity triggered release, indicating that NSHBC hydrogels have promising applications in oral drug delivery.

Tough chitosan hydrogel based on purified regeneration and alkaline solvent as biomaterials for tissue engineering applications.

The chitosan based on purified regeneration could be dissolved in 6wt% aqueous NaOH without freeze-thawing cycles and acetylation processing, and such a solution system was effective and different from other dissolving methods Upon heating, a tough hydrogel was constructed from the chitosan (purified regeneration) alkaline solution. The results of XRD, TEM, SEM and rheology analysis proved that chitosan easily aggregated in the solution and formed a nanofibers network to gelate at elevated temperature and concentration. The merely chitosan hydrogel had a uniform network structure and its (5wt%) compressive fracture stress could reach 0.2MPa. Furthermore, the hydrogels exhibited excellent biodegradability, blood compatibility and cellular compatibility. Therefore, the tough chitosan hydrogels may have a wide range of applications in biomedicine.

The influence of solvent formulations on thermosensitive hydroxybutyl chitosan hydrogel as a potential delivery matrix for cell therapy.

Many cell delivery matrices have been developed due to the low transplantation efficiency of cell therapy. In the present study, thermosensitive hydroxybutyl chitosan (HBC) hydrogels were prepared with different formulations' solvent (Dulbecco's modified eagle's medium/phosphate buffered saline [DMEM/PBS], 0:100, 30:70, 50:50, 70:30, 100:0 [v/v]). Their gelation temperature was raised with DMEM ratio increase (from 9.5°C to 20.9°C). Pore sizes of HBC hydrogels treated with high ionic strength solutions became smaller. HUVECs cultured with HBC hydrogels exhibited proliferation in high DMEM ratio groups, and the optimal solvent formulation was DMEM/PBS 70:30 (v/v). Upon exposure to PBS, HUVECs encapsulated in HBC hydrogels could survive better than that when seeded on the surface of HBC hydrogels. These results demonstrated that HBC hydrogel could be a potential cell delivery matrix for cell therapy applications, especially when DMEM proportion in solvent formulations was higher than 50% (DMEM/PBS>50:50 [v/v]).

Thermo-responsive hydroxybutyl chitosan hydrogel as artery intervention embolic agent for hemorrhage control.

This work targeted to investigate the potential of thermo-responsive hydroxybutyl chitosan (HBC) hydrogel using as an embolic material for occlusion of selective blood vessels. HBC hydrogel was prepared via an etherification reaction between chitosan (CS) and 1, 2-butene oxide. The hydroxybutyl groups were introduced into CS backbone, which endowed HBC hydrogel with properties of porous structure, favorable hydrophilia and rapid sol-gel interconvertibility. The gelation temperatures and gelation time respectively decreased from 30.7°C to 11.5°C and 79.60±3.19s to 7.70±1.42s at 37°C, with HBC solutions viscoelasticity increased from 3.0% to 7.0%. HBC hydrogel exhibited noncytotoxic to mouse embryo fibroblasts (MEFs) and excellent hemocompatibility with red blood cells (RBCs). After injection HBC solution into rat renal arteries, HBC solution transformed into hydrogel and attached onto blood vessel inner wall tightly, giving immediate blood vessels embolization. Meanwhile, RBCs could aggregate around HBC hydrogel to form moderate coagulation, which was beneficial to avoid hydrogel migration with blood flow. Above results suggested that HBC hydrogel could be applied as a promising embolic agent for hemorrage in the interventional vascular embolization field.

Nanoparticles/thermosensitive hydrogel reinforced with chitin whiskers as a wound dressing for treating chronic wounds.

Cutaneous chronic wounds are characterized by impaired wound healing which may lead to infection and even amputation. To surmount this problem, we developed a chitin whisker (CW)/carboxymethyl chitosan nanoparticles (CMCS NPs)/thermosensitive hydroxybutyl chitosan (HBC) composite hydrogel (CW/NPs/HBC-HG) as a wound dressing for treating chronic wounds. Upon introduction of CWs, the composite hydrogel exhibited a significant decrease in gelation temperature and enhanced mechanical properties. The storage modulus (G') of the CW/NPs/HBC-HG was 3.6 times that of the NPs/HBC-HG at 37 °C and the ex vivo rat skin test also showed that the mechanical properties were significantly improved. Linezolid, a wide-spectrum antibiotic, was dissolved directly in the water phase of the composite hydrogel, and the antibacterial activity of the composite hydrogel against Escherichia coli and Staphylococcus aureus was up to 99% until 7 days. When recombinant human epidermal growth factor (rhEGF) was encapsulated into the NPs, the CW/NPs/HBC-HG offered prolonged cell proliferation activity up to 5 days. More importantly, the in vivo chronic wound healing model evaluation in diabetic rats revealed that the CW/NPs/HBC-HG dressing promoted wound healing and accelerated reepithelialization, collagen deposition and angiogenesis. These findings demonstrated that CW/NPs/HBC-HG is a promising dressing for chronic wounds.

Chitosan based nanoparticles as protein carriers for efficient oral antigen delivery.

This study aimed to investigate the efficacy of nanoparticles based on chitosan as a vehicle for oral antigen delivery in fish vaccination. Carboxymethyl chitosan/chitosan nanoparticles (CMCS/CS-NPs) loaded extracellular products (ECPs) of Vibrio anguillarum were successfully developed by ionic gelation method. The prepared ECPs-loaded CMCS/CS-NPs were characterized for various parameters including morphology, particle size (312±7.18nm), zeta potential (+17.4±0.38mV), loading efficiency (57.8±2.54%) and stability under the simulated gastrointestinal (GI) tract conditions in turbot. The in vitro profile showed that the cumulative release of ECPs from nanoparticles was higher in pH 7.4 (58%) than in pH 2.0 (37%) and pH 4.5 (29%) after 48h. Fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) was used as model protein antigen and encapsulated in CMCS/CS-NPs for investigating the biodistribution of antigen after oral delivery to turbot in 24h. Oral immunization of ECPs-loaded CMCS/CS-NPs group in turbot showed elevated specific antibody and higher concentrations of lysozyme activity and complement activity in fish serum than ECPs solution. CMCS/CS-NPs loaded with ECPs could enhance both adaptive and innate immune responses than the group treated with ECPs solution and suggested to be a potential antigen delivery system.

A thermosensitive hydroxybutyl chitosan hydrogel as a potential co-delivery matrix for drugs on keloid inhibition.

Keloid is a kind of unique human fibroproliferative dermal disease, and there are still no optimal treatment methods for it. In the present study, a thermosensitive hydroxybutyl chitosan (HBC) hydrogel as a co-delivery matrix for 5-fluorouracil (5-FU) and dexamethasone sodium phosphate (DEXSP) in keloid treatment was developed. The gelation temperature of the HBC hydrogel was observed to be 25.7 °C by rheology analysis. The HBC hydrogel showed sustained drug release capacity (5-FU, 89.3 ± 3.4%; DEXSP, 95.6 ± 3.9%) for drug delivery. The HBC hydrogel was shown to be cytocompatible, while the dual drug-loaded HBC hydrogel could suppress the proliferation of keloid fibroblasts (KFs). The keloid biopsies treated with the dual drug-loaded hydrogel could be inhibited through the efficient suppression of VEGF expression within 7 days. The results suggested that the HBC hydrogel could be applied as a potential co-delivery matrix for drugs in the keloid therapy field.