Dissolving Hyaluronic Acid-Based Microneedles to Transdermally Deliver Eugenol Combined with Photothermal Therapy for Acne Vulgaris Treatment.

A microneedle transdermal drug delivery system simultaneously avoids systemic toxicity of oral administration and low efficiency of traditional transdermal administration, which is of great significance for acne vulgaris therapy. Herein, eugenol-loaded hyaluronic acid-based dissolving microneedles (E@P-EO-HA MNs) with antibacterial and anti-inflammatory activities are developed for acne vulgaris therapy via eugenol transdermal delivery integrated with photothermal therapy. E@P-EO-HA MNs are pyramid-shaped with a sharp tip and a hollow cavity structure, which possess sufficient mechanical strength to penetrate the stratum corneum of the skin and achieve transdermal delivery, in addition to excellent in vivo biocompatibility. Significantly, E@P-EO-HA MNs show effective photothermal therapy to destroy sebaceous glands and achieve antibacterial activity against deep-seated Propionibacterium acnes (P. acnes) under near-infrared-light irradiation. Moreover, cavity-loaded eugenol is released from rapidly dissolved microneedle bodies to play a sustained antibacterial and anti-inflammatory therapy on the P. acnes infectious wound. E@P-EO-HA MNs based on a synergistic therapeutic strategy combining photothermal therapy and eugenol transdermal administration can significantly alleviate inflammatory response and ultimately facilitate the repair of acne vulgaris. Overall, E@P-EO-HA MNs are expected to be clinically applied as a functional minimally invasive transdermal delivery strategy for superficial skin diseases therapy in skin tissue engineering.

Emulsion template fabricated gelatin-based scaffold functionalized by dialdehyde starch complex with antibacterial antioxidant properties for accelerated wound healing.

Gelatin and starch are considered as promising sustainable materials for their abundant production and good biodegradability. Efforts have been made to explore their medical application. Herein, scaffolds based on gelatin and starch with a preferred microstructure and antibacterial antioxidant property were fabricated by the emulsion template method. The dialdehyde starch was firstly combined with silver nanoparticles and curcumin to carry out the efficient hybrid antibacterial agent. Then, the gelatin microsphere of appropriate size was prepared by emulsification and gathered by the above agent to obtain gelatin-based scaffolds. The prepared scaffolds showed porous microstructures with high porosity of over 74 % and the preferred pore sizes of ∼65 µm, which is conducive to skin regeneration. Moreover, the scaffolds possessed a good swelling ability of over 640 %, good degradability of over 18 days, excellent blood compatibility, and cell compatibility. The promising antibacterial and antioxidant properties came from the hybrid antibacterial agent were affirmed. As expected, the gelatin-based scaffolds fabricated by the emulsion template method with a preferred microstructure can facilitate more adhered fibroblasts. In summary, gelatin-based scaffolds functionalized by starch-based complex expanded the application of abundant sustainable materials in the biomedical field, especially as antibacterial antioxidant wound dressings.

Antibacterial Conductive Collagen-Based Hydrogels for Accelerated Full-Thickness Wound Healing.

Antibacterial conductive hydrogels have been extensively utilized in tissue repair and regeneration on account of their unique electrochemical performances and advantages of anti-pathogenic bacterial infection. Here, multi-functional collagen-based hydrogels (CHLY) with adhesivity, conductivity, and antibacterial and antioxidant activities were developed by introducing cysteine-modified ε-poly(l-lysine) (ε-PL-SH) and in situ-polymerized polypyrrole (PPy) nanoparticles to induce full-thickness wound healing. CHLY hydrogels have a low swelling ratio, good compressive strength, and viscoelasticity due to chemical crosslinking, chelation, physical interaction, and nano-reinforcements in the matrix network of hydrogels. CHLY hydrogels possess excellent tissue adhesion ability, low cytotoxicity, enhanced cell migration ability, and good blood coagulation performance without causing hemolysis. Interestingly, the chemical conjugation of ε-PL-SH in the hydrogel matrix gives hydrogels an inherently robust and broad-spectrum antibacterial activity, while the introduction of PPy endows hydrogels with superior free radical scavenging capacity and good electroactivity. Significantly, CHLY hydrogels have advantages in alleviating persistent inflammatory response as well as promoting angiogenesis, epidermis regeneration, and orderly collagen deposition at the wound sites through their multi-functional synergies, thus effectively accelerating full-thickness wound healing and improving wound healing quality. Overall, our developed multi-functional collagen-based hydrogel dressing demonstrates promising application prospects in the field of tissue engineering to induce skin regeneration.

Dual-drug loaded polysaccharide-based self-healing hydrogels with multifunctionality for promoting diabetic wound healing.

Diabetic chronic wound healing still faces huge clinical challenge. The arrangement and coordination of healing processes are disordered in diabetic wound caused by the persistent inflammatory response, microbial infection, impaired angiogenesis, resulting in the delayed and even non-healing wounds. Here, the dual-drug loaded nanocomposite polysaccharide-based self-healing hydrogels (OCM@P) with multifunctionality were developed to promote diabetic wound healing. Curcumin (Cur) loaded mesoporous polydopamine nanoparticles (MPDA@Cur NPs) and metformin (Met) were introduced into the polymer matrix formed by the dynamic imine bonds and electrostatic interactions between carboxymethyl chitosan and oxidized hyaluronic acid to fabricate OCM@P hydrogels. OCM@P hydrogels show homogeneous and interconnected porous microstructure, which possess good tissue adhesiveness, enhanced compression strength, great anti-fatigue behavior, excellent self-recovery capacity, low cytotoxicity, rapid hemostatic ability and robust broad-spectrum antibacterial activity. Interestingly, OCM@P hydrogels exhibit rapid release of Met and long-term sustained release of Cur, thereby to effectively scavenge extracellular and intracellular free radicals. Significantly, OCM@P hydrogels remarkably promote re-epithelization, granulation tissue formation, collagen deposition and arrangement, angiogenesis as well as wound contraction in diabetic wound healing. Overall, the multifunctional synergy of OCM@P hydrogels greatly contributes to accelerating diabetic wound healing, which demonstrate promising application as scaffolds in regenerative medicine.

Antibacterial Collagen-Based Nanocomposite Dressings for Promoting Infected Wound Healing.

Pathogenic bacterial infection is the most frequent wound complication, which has become a major clinical and healthcare challenge in wound management worldwide, leading to impaired healing processes, the risk of amputation, and even death. Here, collagen-based nanocomposite dressings (APZC) with broad-spectrum antibacterial activity are developed to promote the infected full-thickness wound healing. Short rod-like shaped ZnO NPs are synthesized and then coated with polydopamine (PDA) to obtain PDA coated ZnO NPs (PDA@ZnO NPs). Afterward, PDA@ZnO NPs are conjugated on the backbone of a collagen chain, and the obtained collagen-PDA@ZnO NPs conjugate is crosslinked by dialdehyde sodium alginate to fabricate APZC dressings. PDA@ZnO NPs show well dispersibility and are uniformly incorporated into the collagen matrix. APZC dressings have interconnected microporous structure and great physicochemical properties, besides good blood coagulation performance and well cytocompatibility. APZC dressings demonstrate long-lasting and excellently broad-spectrum antimicrobial activity, which can relieve the inflammatory reaction by killing pathogenic bacteria and induce the generation of blood vessels and the orderly deposition of collagen in the wound site, thus promoting infected full-thickness wound healing without obvious scar formation. Overall, the functionalized collagen-based nanocomposite dressings have great potential in the clinical treatment against bacteria-associated wound infection.

Gelatin/alginate-based microspheres with sphere-in-capsule structure for spatiotemporal manipulative drug release in gastrointestinal tract.

Microsphere with sphere-in-capsule structure is a multi-drugs delivery system to achieve the purpose of combination therapy. In this paper, we have prepared gelatin/alginate-based microspheres with sphere-in-capsule structure by a relatively fast, simple, and easily large-scale industrialized emulsification method for spatiotemporal manipulative drug release in gastrointestinal tract. Calcium alginate microspheres encapsulated with bovine serum albumin (BSA) were first prepared as inner microspheres, and then inner microspheres and ranitidine hydrochloride (RH) were co-encapsulated by gelatin microspheres to form double-layer microspheres with sphere-in-capsule structure. The size and distribution of microspheres can be easily controlled by emulsifying conditions. The microspheres with sphere-in-capsule structure displayed desirable encapsulation efficiency of BSA (61.52 %) and RH (56.07 %). The in vitro simulated drug release showed the spatiotemporal release feature of microspheres with sphere-in-capsule structure. In the specific simulated fluid, the release behavior and cumulative release of RH (sustainedly released 95 % in simulated gastric fluid) and BSA (rapidly released 73 % in simulated intestinal fluid) were different. The drug release mechanisms were analyzed to determine RH and BSA's release behavior. Overall, the microspheres with sphere-in-capsule structure have the potential application of spatiotemporal manipulative drug delivery in the gastrointestinal tract.

Multifunctional ß-Cyclodextrin-Poly(ethylene glycol)-Cholesterol Nanomicelle for Anticancer Drug Delivery.

Nanoparticle drug delivery systems have drawn considerable attention worldwide due to their unique characteristics and advantages in anticancer drug delivery. Herein, the curcumin (Cur) loaded nanomicelles with two-stage drug release behavior were developed. ß-Cyclodextrin (ß-CD) and cholesterol were conjugated onto both ends of the poly(ethylene glycol) (PEG) chain to obtain an amphiphilic ß-CD-PEG-Chol. The Cur was loaded into the cavities of ß-CD and nanomicelle when the ß-CD-PEG-Chol self-assembled to the Cur@ß-CD-PEG-Chol nanomicelles (Cur@CPC NMs). These Cur@CPC NMs are spherical particles with a particle size of 120.9 nm. The Cur drug loading capacity of Cur@CPC NMs are 61.6 ± 6.9 mg/g. The release behavior of Cur from Cur@CPC NMs conformed to a two-stage mode of "burst-release followed by sustained-release". The prepared Cur@CPC NMs possess high storage stability and excellent hemocompatibility. Moreover, these Cur@CPC NMs exhibit satisfactory antioxidant activity and anticancer activity, resulting in significant reduction in intracellular H2O2-induced ROS and a nearly 50% lethality rate of HepG-2 cells. Meanwhile, the Cur@CPC NMs show good anti-inflammatory activity, by which the secretion of inflammatory factors of IL-6 and TNF-α are inhibited. Overall, the developed Cur@CPC NMs show application prospects in anticancer drug delivery systems.

Matrix metalloproteinase-responsive collagen-oxidized hyaluronic acid injectable hydrogels for osteoarthritic therapy.

Drug delivery system and intra-articular injection have been clinically applied to prolong drug residence time and reduce side effects in the treatment of osteoarthrosis. Herein, injectable hydrogels with sustained-dexamethasone sodium phosphate (DSP) release behavior in response to matrix metalloproteinase (MMP) were developed for osteoarthritic therapy. Hyaluronic acid undergoes specific oxidation in the present of sodium periodate to prepare oxidized hyaluronic acid (OHA). Then the DSP-loaded collagen-based hydrogels (Col-OHA) were developed by the Schiff's base crosslinking between OHA and Type I collagen besides the self-assembly of collagen induced by OHA. The results indicate that the collagen self-assembly into collagen fibrils makes great contribution for shortening gelation time of Col-OHA hydrogels. Col-OHA hydrogels possess interconnected porous microstructure, good injectability, excellent self-healing performance, strong mechanical property, low swelling ability, good blood compatibility and no cytotoxicity. Significantly, Col-OHA hydrogels show highly sensitive and significantly substantially sustained release of DSP in response to MMP. DSP-loaded Col-OHA hydrogel possesses significant inhibition for the production of inflammatory cytokines in the joint synovium, which can effectively relieve the symptoms of osteoarthritis continuously. Col-OHA hydrogel has no obvious effect on liver and kidney functions. Overall, the Col-OHA hydrogels with excellent biocompatibility are the promising drug-loading system for the intra-articular injection therapy of osteoarthrosis.

Advances in Pickering emulsions stabilized by protein particles: Toward particle fabrication, interaction and arrangement.

With the increasing global demand for clean-label and sustainable emulsifiers that are suitable for use in agrochemicals, personal care and food industry, protein-based particles are becoming promising emulsion stabilizer in food industry owing to their considerable surface activity, biodegradability and excellent nutritional value. Accumulating evidence implies that, relative to classical rigid inorganic particles, protein colloidal particles perform more as soft particles to stabilize emulsions. A brief historical introduction to Pickering emulsions provides a conceptual framework firstly. Then, the conformational properties and methods of fabrication and modification of protein-based particles are introduced in more detail. In addition, the particle shape, interfacial arrangement and interaction are also discussed. Finally, novel application of these materials and future perspectives concerning the interfacial conformation, rheology and industrial production of protein-based Pickering particles are considered. In summary, thermal and solvent-induced aggregation are found to be the principal fabrication methods of protein-based Pickering particles. Through the complexation or covalent interaction with polysaccharides, proteins and phenolics, protein particles exhibit improved solubility, emulsification effectiveness and bioactive functionalities. According to different shapes, protein-based Pickering particles can be categorized into elongated and linear particles, spherical particles, plate-shaped particles, and fractal aggregates, which have different interfacial adsorption energy. Overall, the embedding arrangement, interfacial rheology and large-scale production of protein particles are challenges as well as opportunities that coexist in further studies.

131I-Labeled Silk Fibroin Microspheres for Radioembolic Therapy of Rat Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) is a promising technology in hepatocellular carcinoma (HCC) therapy, which utilizes radionuclide-labeled microspheres to achieve arterial embolization and internal irradiation. However, the therapeutic effect of liver cancer can be affected by low radionuclide labeling rate and stability, as well as poor biocompatibility, and non-biodegradability of microspheres. Here, 131I-labeled silk fibroin microspheres (131I-SFMs) were developed as radioembolization material for effective TARE therapy against HCC. Silk fibroin rich in 10.03% of tyrosine was extracted from silkworm cocoons and then emulsified and genipin-crosslinked to prepare SFMs. SFMs show a good settlement rate, biodegradability, hemocompatibility, and low cytotoxicity. Afterward, 131I-SFMs were obtained by radiolabeling 131I onto the SFMs through the chloramine-T method. 131I-SFMs possess a high 131I labeling rate of over 84% and good radioactive stability and are thus conducive to internal radiotherapy. Significantly, 131I-SFMs with diameters around 11 µm were successfully radioembolized at the hepatic artery. 131I-SFMs were diffused in the liver, indicating the favorable biodistribution and biosafety in vivo. Based on the combination of embolization and local radiotherapy, the administration of 131I-SFMs shows a favorable inhibitive effect against the progression of HCC. Overall, the newly developed 131I-SFMs as radioembolization microspheres provide a promising application for effective TARE therapy against liver cancer.

Antibacterial dialdehyde sodium alginate/ε-polylysine microspheres for fruit preservation.

Food security is an important global public health issue, which will not only endanger consumers' life and health, but also cause serious food waste. Herein, antibacterial dialdehyde sodium alginate/ε-polylysine microspheres (DSA-PL MPs) were developed to effectively prolong the shelf life of fruit. DSA was prepared by periodate oxidation of sodium alginate. Then the PL was conjugated onto DSA backbone via the Schiff's base reaction to synthesize DSA-PL conjugates, followed by the emulsification and Ca2+ ions crosslinking to obtain DSA-PL MPs. The results indicate that DSA-PL MPs show smooth spherical particle, relatively narrow size distribution and good dispersity. In vitro degradation rate of DSA-PL MPs is higher in acetate buffer (pH = 5.0) than that in PBS buffer (pH = 7.4), showing acid-sensitive degradation property. Significantly, DSA-PL MPs possess strong broad-spectrum antibacterial activity, which can effectively extend the shelf life of fruit. Overall, DSA-PL MPs possess promising application as antibacterial agents for fruit preservation.

Crosslinking effect of dialdehyde cholesterol modified starch nanoparticles on collagen hydrogel.

Crosslinking is frequently used to improve the inherent poor physicochemical properties of collagen. However, local flocculation and irregular crosslinking of collagen would be unavoidably occurred once contacting with crosslinking agents due to widespread complex interactions. Herein, dialdehyde starch-based nanoparticles were developed to crosslink collagen as a new strategy. Starch was conjugated with cholesterol chloroformate before periodate oxidation to obtain dialdehyde cholesterol modified starch (DACS). DACS self-assembled into nanoparticles (DACSNPs) and crosslinked with collagen to fabricate collagen hydrogels (DACSNPs-Col). DACSNPs-Col hydrogels exhibited faster gelation rate, better uniform porous structure, higher mechanical properties and better degradation stability than dialdehyde starch crosslinked hydrogels. Significantly, DACSNPs-Col hydrogels show homogeneous structure, improved mechanical properties, low cytotoxicity, well blood compatibility, high cell adhesion and proliferation. Overall, the oxidized polysaccharide nanoparticles crosslinked collagen hydrogels have homogeneous and compact microstructure and improved physicochemical properties, which show potential application prospect in the field of tissue engineering scaffold.

Mimicking the Composition and Structure of the Osteochondral Tissue to Fabricate a Heterogeneous Three-Layer Scaffold for the Repair of Osteochondral Defects.

Heterogeneous three-layer scaffolds were fabricated by mimicking the biochemical composition and structure of the hyaline cartilage, calcified cartilage, and subchondral bone of the osteochondral tissue for the repair of osteochondral defects. The hyaline cartilage layer was composed of collagen I (50.0 wt %) and sodium hyaluronate (50.0 wt %). The calcified cartilage layer and subchondral bone layer were composed of collagen I, sodium hyaluronate, and nanohydroxyapatite with different proportions. N-Hydroxysuccinimide/N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride was used to mediate the crosslinking reaction of the amine groups of collagen with carboxyl groups of sodium hyaluronate. The hyaline cartilage layer and calcified cartilage layer were designed as dense structures, while the subchondral bone layer was designed as a relatively loose structure by adjusting the crosslinking degree. The scaffolds displayed a uniform and interconnected porous structure and possessed a high porosity over 85%, which were conducive to cellular adhesion and proliferation. The scaffolds could remain at 50-75% after 30 days of degradation owing to crosslinking, providing enough time for the regeneration of the osteochondral tissue. Especially, the hyaline cartilage layer and calcified cartilage layer preferred to induce the proliferation of chondrocytes, while the subchondral bone layer was more conducive to the proliferation of osteoblasts. In conclusion, the heterogeneous multilayer scaffolds could serve as implant materials for osteochondral reconstruction.

pH-Sensitive nanoparticles based on amphiphilic imidazole/cholesterol modified hydroxyethyl starch for tumor chemotherapy.

pH-Responsive nanoparticles (NPs) have emerged as an effective antitumor drug delivery system, promoting the drugs accumulation in the tumor and selectively releasing drugs in tumoral acidic microenvironment. Herein, we developed a new amphiphilic modified hydroxyethyl starch (HES) based pH-sensitive nanocarrier of antitumor drug delivery. HES was first modified by hydrophilic imidazole and hydrophobic cholesterol to obtain an amphiphilic polymer (IHC). Then IHC can self-assemble to encapsulate doxorubicin (DOX) and form doxorubicin-loaded nanoparticles (DOX/IHC NPs), which displayed good stability for one week storage and acidic sensitive long-term sustained release of DOX. As a result, cancer cell endocytosed DOX/IHC NPs could continuously release doxorubicin into cytoplasm and nucleus to effectively kill cancer cells. Additionally, DOX/IHC NPs could be effectively enriched in the tumor tissue, showing enhanced tumor growth inhibition effect compared to free doxorubicin. Overall, our amphiphilic modified HES-based NPs possess a great potential as drug delivery system for cancer chemotherapy.

Functionalization of an Electroactive Self-Healing Polypyrrole-Grafted Gelatin-Based Hydrogel by Incorporating a Polydopamine@AgNP Nanocomposite.

Hydrogels are considered a promising wound dressing owing to their ability to absorb wound exudates and their moist network structure for skin regeneration. It is of great significance to give added multiple functions to hydrogels for wound healing. In this paper, we present a gelatin-based hydrogel with self-healing ability, conductivity, and antibacterial and antioxidant activities. Dopamine was added into an alkaline solution to polymerize into polydopamine (PDA), which was used to reduce AgNO3 into Ag nanoparticles (AgNPs) to gain a PDA@AgNP composite. Polypyrrole-grafted gelatin (PPyGel) was dissolved in a PDA@AgNP solution and ferric ions were used as a cross-linking agent to form PDA@AgNPs-PPyGel-Fe hydrogels. The as-prepared hydrogels are soft and ductile and exhibit porous structures with pore sizes from 20 to 50 µm. The hydrogels have high water absorption ability, indicating the potential to absorb wound exudates. PPy and Fe3+ endow the hydrogels with slightly higher conductivity than that of skin tissue, indicating the ability to effectively transmit bioelectric signals for skin regeneration. The ionic interactions and hydrogen bonding in hydrogels make them possess self-healing ability, and the self-healing process can be completed in 30 min. PDA confers hydrogels with effective antioxidant activities, while AgNPs endow hydrogels with good antibacterial activities. Moreover, the hydrogels possess good blood compatibility and cytocompatibility. In sum, the developed hydrogel has potential applications as wound dressings.

Oxidized starch cross-linked porous collagen-based hydrogel for spontaneous agglomeration growth of adipose-derived stem cells.

Many strategies have been employed to artificially reconstruct adipose tissue in tissue engineering. The functionalization and survival of reconstructed adipose tissue depend on sufficient angiogenesis. Notably, agglomeration growth of adipose-derived stem cells (ASCs) is beneficial to promoting angiogenesis. Herein, we present a porous collagen-based hydrogel for spontaneous agglomeration growth of ASCs to promote angiogenesis. Oxidized starch with different oxidation degree was prepared and used to cross-link collagen to fabricate the porous hydrogel. The gelation time and pore size of hydrogels can be controlled by adjusting the oxidation degree of starch. Crosslinking enhances the mechanical properties, inhibits the swelling and biodegradation of the hydrogels. The hydrogels possess good blood compatibility and cytocompatibility. Significantly, ASCs tended to adhere to the hydrogels and spontaneously grew into spheres along with time. Effective expression of vascular endothelial growth and fibroblast growth factors were observed. Overall, the hydrogels have application prospects in vascularized adipose tissue engineering.

Functional-modified polyurethanes for rendering surfaces antimicrobial: An overview.

Antimicrobial surfaces and coatings are rapidly emerging as primary components in functional modification of materials and play an important role in addressing the problems associated with biofouling and microbial infection. Polyurethane (PU) consisting of alternating soft and hard segments has been one of the most important coating materials that have been widely applied in many fields due to its versatile properties. This review attempts to provide insight into the recent advances in antimicrobial polyurethane coatings or surfaces. According to different classes of antimicrobial components along with their antimicrobial mechanism, the synthesis pathways are presented systematically herein to afford polyurethane with antimicrobial properties. Also, the challenges and opportunities of antimicrobial PU coatings and surfaces are also discussed. This review will be beneficial to the exploitation and the further studies of antimicrobial polyurethane materials for a variety of applications.

pH-Responsive nanoparticles based on cholesterol/imidazole modified oxidized-starch for targeted anticancer drug delivery.

Various nanoparticles have been developed for tumor-targeted drug delivery. However, nanoparticles with effective targeting and intelligent release capacity are still deficient. Herein, we present new pH-responsive and neutral charged nanoparticles for tumor-targeted anticancer drug delivery. Oxidized starch was synthesized and simultaneously modified by cholesterol and imidazole to obtain amphiphilic cholesterol/imidazole modified oxidized-starch (Cho-Imi-OS). Cho-Imi-OS easily self-assembled into nanoparticles by dialysis. Curcumin was selected as model drug to be encapsulated into the hydrophobic core of nanoparticles. The results showed that curcumin would effectively accumulate in cancer cells by encapsulating into the nanoparticles owing to the nano-sized structure and near neutral charged property of nanoparticles. Curcumin was released faster at pH 5.5 than that at pH 7.4 from the curcumin-loaded nanoparticles (Cur-NPs), indicating the pH-triggered release capacity of Cur-NPs after endocytosis by endosomes since the pH is low to 5.0∼6.0 in endosomes. Naturally, Cur-NPs showed significantly strong inhibitory effect on cancer cells.

Controlling the Pore Structure of Collagen Sponge by Adjusting the Cross-Linking Degree for Construction of Heterogeneous Double-Layer Bone Barrier Membranes.

Guided bone regeneration (GBR) has been regarded as a valuable way to effectively induce bone remodeling. The key factor of GBR is to place a barrier membrane between the soft tissue and bone defect, preventing the untimely intrusion of fibroblasts and permitting the prior settlement of internal osteoblasts. Notably, heterogeneous double-layer GBR membranes with a compact upper layer and a loose lower layer exhibit enhanced effectiveness in blocking fibroblasts and promoting the growth of osteoblasts. Herein, we present porous and interconnected collagen-based sponges with controllable pore size for the fabrication of absorbable GBR membranes with a heterogeneous double-layer structure. Dialdehyde carboxymethyl cellulose was used to fix collagen-based sponges. The pore size of the sponges can be well controlled by adjusting the cross-linking degree, which is decreased with an increase of cross-linking degree. The sponges show enhanced mechanical properties, inhibited swelling ability and biodegradation, good blood compatibility, and good cytocompatibility. The sponges are feasible to form a heterogeneous double-layer structure with a loose lower layer and a compact upper layer. Interestingly, the lower layer with the pore size of 200-300 µm can promote the adhesion, proliferation, and differentiation of osteoblasts MC3T3-E1 cells, while the upper layer with the pore size of 20-50 µm makes a great contribution to the growth of myoblast C2C12 cells. Overall, the collagen-based sponges have the potential to be used to fabricate heterogeneous double-layer bone barrier membranes for bone remodeling.

Green synthesis of κ-carrageenan@Ag submicron-particles with high aqueous stability, robust antibacterial activity and low cytotoxicity.

Silver nanoparticles (AgNPs) are effective antimicrobial reagent, especially for the treatment of multidrug-resistant microorganisms. However, it is difficult to remove the residual harmful reducing agents in AgNPs synthesized by the traditional chemical reduction method. In addition, AgNPs exhibit cytotoxicity when exposed directly to cells for biomedical applications and will rapidly aggregate in aqueous environment. Herein, we develop a new route to synthesize submicron-particles containing AgNPs (κC@Ag MPs) with high aqueous stability, robust antibacterial activity and low cytotoxicity. AgNPs were firstly greenly synthesized using κ-carrageenan as environmental friendly reducing and stabilizing agent under heating in aqueous solution. Then the AgNPs were immobilized in the net of κ-carrageenan by adding KCl to obtain κC@Ag MPs. The results indicated that κC@Ag MPs were quite stable without any agglomeration and precipitation in aqueous solution for more than three months. κC@Ag MPs exhibited robust antibacterial activity against Gram-positive and Gram-negative bacteria, even better than that of pure AgNPs. Notably, κC@Ag MPs maintained the long-lasting retention of antibacterial activity. In addition, κC@Ag MPs possessed well cytocompatibility towards the L02 and L929 cells. Overall, κC@Ag MPs may have prospective application as effective and sustainable antibacterial agent in biomedical fields.