Pluronic F127-Lipoic Acid Adhesive Nanohydrogel Combining with Ce3+/Tannic Acid/Ulinastatin Nanoparticles for Promoting Wound Healing.

Developing strong anti-inflammatory wound dressings is of great significance for protecting inflammatory cutaneous wounds and promoting wound healing. The present study develops a nanocomposite Pluronic F127 (F127)-based hydrogel dressing with injectable, tissue adhesive, and anti-inflammatory performance. Briefly, Ce3+/tannic acid/ulinastatin nanoparticles (Ce3+/TA/UTI NPs) are fabricated. Meanwhile, α-lipoic acid is bonded to the ends of F127 to prepare F127-lipoic acid (F127LA) and its nanomicelles. Due to the gradual viscosity change instead of mutation during phase transition, the mixed Ce3+/TA/UTI NPs and F127LA nanomicelles show well-performed injectability at 37 °C and can form a semisolid composite nanohydrogel that can tightly attach to the skin at 37 °C. Furthermore, ultraviolet (UV) irradiation without a photoinitiator transforms the semisolid hydrogel into a solid hydrogel with well-performed elasticity and toughness. The UV-cured composite nanohydrogel acts as a bioadhesive that can firmly adhere to tissues. Due to the limited swelling property, the hydrogel can firmly adhere to tissues in a wet environment, which can seal wounds and provide a reliable physical barrier for the wounds. Ce3+/TA/UTI NPs in the hydrogel exhibit lipopolysaccharide (LPS)-scavenging ability and reactive oxygen species (ROS)-scavenging ability and significantly reduce the expression of inflammatory factors in wounds at the early stage, accelerating LPS-induced wound healing.

In Situ Forming Cellulose Nanofibril-Reinforced Hyaluronic Acid Hydrogel for Cartilage Regeneration.

Hyaluronic acid (HA) based hydrogels are one of most functional natural biomaterials in the field of cartilage tissue engineering (CTE). Even with the promising advantages of HA hydrogels, the complicated mechanical properties of the native cartilage have not been realized, and fabricating HA hydrogels with excellent mechanical properties to make them practical in CTE still remains a current challenge. Here, a strategy that integrates hydrogels and nanomaterials is shown to form a HA hydrogel with sufficient mechanical loading for cartilage tissue production and recombination. Cellulose nanofibrils (CNFs) are promising nanomaterial candidates as they possess high mechanical strength and excellent biocompatibility. In this study, we developed methacrylate-functionalized CNFs that are able to photo-crosslink with methacrylated HA to fabricate HA/CNF nanocomposite hydrogels. The present composite hydrogels with a compressive modulus of 0.46 ± 0.05 MPa showed adequate compressive strength (0.198 ± 0.009 MPa) and restorability, which can be expected to employ as a stress-bearing tissue such as articular cartilage. Besides, this nanocomposite hydrogel could provide a good microenvironment for bone marrow mesenchymal stem cell proliferation, as well as chondrogenic differentiation, and exhibit prominent repair effect in the full-thickness cartilage defect model of SD rats. These results suggest that the HA/CNF nanocomposite hydrogel creates a new possibility for fabricating a scaffold in CTE.

Injectable Maltodextrin-Based Micelle/Hydrogel Composites for Simvastatin-Controlled Release.

Injectable hydrogels have shown great potential in bone tissue engineering. Simvastatin (SIM), a common hypolipidemic drug, has been suggested as a potential agent to promote bone regeneration. However, due to its hydrophobic nature, the compatibility between SIM and hydrogels is rather poor, thereby greatly affecting the drug release behavior, the mechanical properties, and dimensional stability of the hydrogels. Herein, we presented a novel design to entrap SIM in an injectable maltodextrin-based micelle/hydrogel composite system. Maltodextrin-based micelles were prepared to solubilize and encapsulate SIM. The SIM-loaded aldehyde-modified micelles were anchored to the hydrogel network and served as a cross-linker to realize improved mechanical strength of hydrogel, controlled release, and osteogenic capability of SIM. In all, this study demonstrated a strategy to incorporate drug loaded carriers into hydrogels for drug delivery and tissue engineering applications.

Sr-HA-graft-Poly(γ-benzyl-l-glutamate) Nanocomposite Microcarriers: Controllable Sr2+ Release for Accelerating Osteogenenisis and Bony Nonunion Repair.

The microcarrier system offers an attractive method for cellular amplification and phenotype enhancement in the field of bone tissue engineering. However, it remains a challenge to fabricate porous microcarriers with osteoinductive activity for speedy and high-quality osseointegration in regeneration of serious complication of bone fracture, like nonunion. Here, we present a facile method for the first time manufacture microcarriers with osteogenic effects and properties based on well controlled and long-term Sr2+ release. At first, strontium-substituted hydroxyapatite was prepared (Sr-HA) and a novel Sr-HA-graft-poly(γ-benzyl-l-glutamate) (Sr-HA-PBLG) nanocomposite was synthesized. Then, the microcarriers with highly interconnected macropores were fabricated by a double emulsion method, which allowed cells to adhere and proliferate and secrete extracellular matrix. Besides, the microcarriers with a relatively uniform diameter of 271.5 ± 45.0 µm are feasible for injection. The Sr-HA-PBLG microcarriers efficiently promoted osteogenic gene expression in vitro. With injection of the Sr-HA-PBLG microcarriers loading adipose derived stem cells (ADSCs) into the nonunion sites, bone regeneration was observed at 8 weeks after injection in a mice model.

Self-Healing Supramolecular Self-Assembled Hydrogels Based on Poly(L-glutamic acid).

Self-healing polymeric hydrogels have the capability to recover their structures and functionalities upon injury, which are extremely attractive in emerging biomedical applications. This research reports a new kind of self-healing polypeptide hydrogels based on self-assembly between cholesterol (Chol)-modified triblock poly(L-glutamic acid)-block-poly(ethylene glycol)-block-poly(L-glutamic acid) ((PLGA-b-PEG-b-PLGA)-g-Chol) and ß-cyclodextrin (ß-CD)-modified poly(L-glutamic acid) (PLGA-g-ß-CD). The hydrogel formation relied on the host and guest linkage between ß-CD and Chol. This study demonstrates the influences of polymer concentration and ß-CD/Chol molar ratio on viscoelastic behavior of the hydrogels. The results showed that storage modulus was highest at polymer concentration of 15% w/v and ß-CD/Chol molar ratio of 1:1. The effect of the PLGA molecular weight in (PLGA-b-PEG-b-PLGA)-g-Chol on viscoelastic behavior, mechanical properties and in vitro degradation of the supramolecular hydrogels was also studied. The hydrogels showed outstanding self-healing capability and good cytocompatibility. The multilayer structure was constructed using hydrogels with self-healing ability. The developed hydrogels provide a fascinating glimpse for the applications in tissue engineering.

Injectable in situ self-cross-linking hydrogels based on poly(L-glutamic acid) and alginate for cartilage tissue engineering.

Injectable hydrogels as an important biomaterial class have been widely used in regenerative medicine. A series of injectable poly(l-glutamic acid)/alginate (PLGA/ALG) hydrogels were fabricated by self-cross-linking of hydrazide-modified poly(l-glutamic acid) (PLGA-ADH) and aldehyde-modified alginate (ALG-CHO). Both the degree of PLGA modification and the oxidation degree of ALG-CHO could be adjusted by the amount of activators and sodium periodate, respectively. The effect of the solid content of the hydrogels and oxidation degree of ALG-CHO on the gelation time, equilibrium swelling, mechanical properties, microscopic morphology, and in vitro degradation of the hydrogels was examined. Encapsulation of rabbit chondrocytes within hydrogels showed viability of the entrapped cells and good biocompatibility of the injectable hydrogels. A preliminary study exhibited injectability and rapid in vivo gel formation, as well as mechanical stability, cell ingrowth, and ectopic cartilage formation. The injectable PLGA/ALG hydrogels demonstrated attractive properties for future application in a variety of pharmaceutical delivery and tissue engineering, especially in cartilage tissue engineering.

The prevention effect of poly (L-glutamic acid)/chitosan on spinal epidural fibrosis and peridural adhesion in the post-laminectomy rabbit model.

PURPOSE: Spinal epidural fibrosis and adhesion are implicated as one of the key factors of failed back surgery syndrome, which may cause dura mater compression or peridural tethering, resulting in persistent backache and leg pain. Various materials or drugs have been used to inhibit formation of epidural fibrosis and reduce the compressive effect on neural structures. Nevertheless, the effects are not satisfied. In this study, we investigated the prevention effect of poly (L-glutamic acid)/chitosan (PLGA/CS) barrier on epidural fibrosis developing post-laminectomy in a rabbit model. METHODS: Sixteen rabbits were divided randomly into two equal groups: group A (experimental group, n = 8) and group B (non-treatment group, n = 8). In both groups, total L5-6 laminectomy was performed; further both ligamentum flavum and epidural fat were removed gently. In experimental group, the laminectomy sites were treated with PLGA/CS barriers, while no additional treatment was received in non-treatment group. At 1, 12 and 24 weeks post-surgery, the animals were subjected to magnetic resonance imaging (MRI) evaluation. Following last MRI examination, all rabbits were sacrificed and their spinal columns were totally removed for further macroscopic and histological evaluation. RESULTS: MRI showed that rabbits treated with PLGA/CS barrier at 12 and 24 weeks post-surgery had less epidural fibrosis or scar tissue, peridural adhesion, foreign body reaction and low pressure of spinal cord in comparison with the non-treatment group. In consistence with the radiographic results, macroscopic analysis and histological examination showed that the amount of scar tissue and the extent of epidural adhesion decreased significantly in experimental groups. Concerning the fibroblast density evaluated, the scores were significantly lower in experimental group compared with those in non-treatment group. CONCLUSION: The results of our study demonstrate that PLGA/CS barrier is effective in inhibiting epidural fibrosis and peridural adhesions in post-laminectomy rabbit model.

Oxygen-Generating Hydrogels as Oxygenation Therapy for Accelerated Chronic Wound Healing.

Hypoxia in chronic wounds impairs the activities of reparative cells, resulting in tissue necrosis, bacterial infections, decreased angiogenesis, and delayed wound healing. To achieve effective oxygenation therapy and restore oxygen homeostasis, oxygen-generating hydrogels based on different oxygen sources have been developed to release dissolved oxygen in the wound bed, which not only alleviate hypoxia, but also accelerate chronic wound healing. This review first discusses the vital role of oxygen and hypoxia in the wound healing process. The advancements in oxygen-generating hydrogels, which produce oxygen through the decomposition of hydrogen peroxide, metal peroxides, glucose-activated cascade reactions, and photosynthesis of algae microorganisms for chronic wound healing, are discussed and summarized. The therapeutic effects and challenges of using oxygen-generating hydrogels for the clinical treatment of chronic wounds are concluded and prospected.

Tranexamic acid-loaded catechol-modified hyaluronic acid/carboxymethyl chitosan double cross-linked porous gel micropowders for rapid hemostasis and wound healing.

Acquiring rapid and effective hemostasis remains a critical clinical challenge. Current researches focus on concentrating blood components to speed up the hemostatic while ignore the effect of anti-fibrinolysis in promoting blood coagulation. Herein, we designed a novel tranexamic acid (TA)-loaded physicochemical double cross-linked multifunctional catechol-modified hyaluronic acid-dopamine/carboxymethyl chitosan porous gel micropowders (TA&Fe3+@HA-DA/CMCS PGMs) for rapid hemostasis and wound healing. TA&Fe3+@HA-DA/CMCS PGMs exhibited high water absorption rate (505.9 ± 62.1 %) and rapid hemostasis (79 ± 4 s) in vivo. Catechol groups, Fe3+ and the protonated amino groups of CMCS induced bacterial death. Moreover, TA&Fe3+@HA-DA/CMCS PGMs displayed sufficient adhesion to a variety of wet rat tissues. TA&Fe3+@HA-DA/CMCS PGMs on various bleeding wounds, including rat liver injury and tail severed models showed excellent hemostasis performance. The TA&Fe3+@HA-DA/CMCS PGMs could promote the healing of full-thickness skin wounds on the backs of rats. The advantages of TA&Fe3+@HA-DA/CMCS PGMs including rapid hemostasis, effective wound healing, good tissue adhesion, antibacterial properties and ease of use make it potentially valuable in clinical application.

Tissue adhesive, ROS scavenging and injectable PRP-based 'plasticine' for promoting cartilage repair.

Platelet-rich plasma (PRP) that has various growth factors has been used clinically in cartilage repair. However, the short residence time and release time at the injury site limit its therapeutic effect. The present study fabricated a granular hydrogel that was assembled from gelatin microspheres and tannic acid through their abundant hydrogen bonding. Gelatin microspheres with the gelatin concentration of 10 wt% and the diameter distribution of 1-10 µm were used to assemble by tannic acid to form the granular hydrogel, which exhibited elasticity under low shear strain, but flowability under higher shear strain. The viscosity decreased with the increase in shear rate. Meanwhile, the granular hydrogel exhibited self-healing feature during rheology test. Thus, granular hydrogel carrying PRP not only exhibited well-performed injectability but also performed like a 'plasticine' that possessed good plasticity. The granular hydrogel showed tissue adhesion ability and reactive oxygen species scavenging ability. Granular hydrogel carrying PRP transplanted to full-thickness articular cartilage defects could integrate well with native cartilage, resulting in newly formed cartilage articular fully filled in defects and well-integrated with the native cartilage and subchondral bone. The unique features of the present granular hydrogel, including injectability, plasticity, porous structure, tissue adhesion and reactive oxygen species scavenging provided an ideal PRP carrier toward cartilage tissue engineering.

Naturally biocompatible melanin based iron-complex nanoparticles for pH-responsive magnetic resonance imaging.

The sensitivity and diagnostic accuracy of magnetic resonance imaging mainly depend on the relaxation capacity of contrast agents (CAs) and their accumulated amount at the pathological region. Due to the better biocompatibility and high-spin capacity, Fe-complexes have been studied widely as an alternative to replace popular Gd-based CAs associated with potential biotoxicity. Compared with a variety of Fe complex-based CAs, such as small molecular, macrocyclic, multinuclear complexes, the form of nanoparticle exhibits outstanding longitudinal relaxation, but the clinical transformation was still limited by the inconspicuous difference of contrast between tumor and normal tissue. The enhanced effect of contrast is a positive relation as relaxation of CAs and their concentration in desired region. To specifically improve the amount of CAs accumulated in the tumor, pH-responsive polymer poly(2-ethyl-2-oxazoline) (PEOz) was modified on melanin, a ubiquitous natural pigment providing much active sites for chelating with Fe(III). The Fe(III)-Mel-PEOz we prepared could raise the tumor cell endocytosis efficiency via switching surface charge from anion to cation with the stimuli of the decreasing pH of tumor microenvironment. The change of pH has negligible effect on ther1of Fe(III)-Mel-PEOz, which is always maintained at around 1.0 mM-1s-1at 0.5 T. Moreover, Fe(III)-Mel-PEOz exhibited low cytotoxicity, and satisfactory enhancement of positive contrast effectin vivo. The excellent biocompatibility and stable relaxation demonstrate the high potential of Fe(III)-Mel-PEOz in the diagnosis of tumor.

Thermal-Assisted Laser Fabrication of Broadband Ultralow Reflectance Surface by Combining Marangoni Flow with In Situ Deposition.

Functional surfaces with broadband ultralow optical reflectance have many potential applications in the fields of enhancing solar energy utilization, stray light shielding, infrared stealth, and so on. To fabricate broadband anti-reflection surfaces with low cost, high quality, and more controllability, a strategy of preparing multi-scale structures by thermal-assisted nanosecond laser was proposed. This strategy combines laser ablation with Marangoni flow of molten materials and in situ deposition of nanoparticles. The thermal-assisted strategy increases the depth to width ratio of the anti-reflection structures. The average reflectance of laser-textured TC4 (Ti-6Al-4V) surface is as low as 1.71% in the wavelength range of 200-2250 nm and 7.8% in the 2500-25,000 nm. The ultra-low reflectance surface has a significantly enhanced photothermal conversion performance. Meanwhile, the anti-reflection effect can be extended to the mid-infrared band, which has potential stealth application prospect. This synergetic manufacturing strategy has wide adaptability of materials, which provides new paths for the preparation of broadband ultralow reflectance surface. Moreover, this thermal-assisted laser fabrication strategy is prospective in the preparation of other functional micro-nano structures.

Injectable, self-healing poly(amino acid)-hydrogel based on phenylboronate ester bond for osteochondral tissue engineering.

A new generation of osteochondral integrated scaffolds is needed for articular osteochondral regeneration, which can not only facilitate the accurate construction of osteochondral scaffolds in a minimally invasive manner but also firmly combine the subchondral bone layer and cartilage layer. Herein, an osteochondral integrated hydrogel scaffold was constructed by the poly(L-glutamic acid) (PLGA) based self-healing hydrogels with phenylboronate ester (PBE) as the dynamic cross-linking. The bone layer self-healing hydrogel (hydrogel O-S) was prepared by physically blending nanohydroxyapatite into the self-healing hydrogel PLGA-PBE-S, which was fabricated by 3-aminophenylboronic acid/glycidyl methacrylate-modified PLGA (PLGA-GMA-PBA) and 3-amino-1,2-propanediol/N-(2-aminoethyl) acrylamide-modified PLGA (PLGA-ADE-AP). The cartilage layer self-healing hydrogel (hydrogel C-S) was prepared by PLGA-GMA-APBA and glucosamine- modified PLGA-ADE-AP (PLGA-ADE-AP-G). Excellent injectability and self-healing profiles of hydrogel O-S and C-S were observed, the self-healing efficiencies were 97.02% ± 1.06% and 99.06% ± 0.57%, respectively. Based on the injectability and spontaneous healing on the interfaces of hydrogel O-S and C-S, the osteochondral hydrogel (hydrogel OC) was conveniently constructed in a minimally invasive manner. In addition,in situphotocrosslinking was used to enhance the mechanical strength and stability of the osteochondral hydrogel. The osteochondral hydrogels exhibited good biodegradability and biocompatibility. The osteogenic differentiation genes BMP-2, ALPL, BGLAP and COL I of adipose-derived stem cells (ASCs) in the bone layer of the osteochondral hydrogel were significantly expressed, and the chondrogenic differentiation genes SOX9, aggrecan and COL II of ASCs in the cartilage layer of the osteochondral hydrogel were obviously upregulated after 14 d of induction. The osteochondral hydrogels could effectively promote repair of osteochondral defects after 3 months post-surgery.

Cardiac organoid: multiple construction approaches and potential applications.

The human cardiac organoid (hCO) is three-dimensional tissue model that is similar to an in vivo organ and has great potential on heart development biology, disease modeling, drug screening and regenerative medicine. However, the construction of hCO presents a unique challenge compared with other organoids such as the lung, small intestine, pancreas, liver. Since heart disease is the dominant cause of death and the treatment of such disease is one of the most unmet medical needs worldwide, developing technologies for the construction and application of hCO is a critical task for the scientific community. In this review, we discuss the current classification and construction methods of hCO. In addition, we describe its applications in drug screening, disease modeling, and regenerative medicine. Finally, we propose the limitations of the cardiac organoid and future research directions. A detailed understanding of hCO will provide ways to improve its construction and expand its applications.

An anti-bacterial porous shape memory self-adaptive stiffened polymer for alveolar bone regeneration after tooth extraction.

The regeneration of alveolar bone after tooth extraction is critical for the placement of dental implants. Developing a rigid porous scaffold with defect shape adaptability is of great importance but challenging for alveolar bone regeneration. Herein, we design and synthesize a biocompatible poly(l-glutamic acid)-g-poly(ε-caprolactone) (PLGA-g-PCL) porous shape memory (SM) polymer. The PLGA-g-PCL is then copolymerized with acryloyl chloride grafted poly(ω-pentadecalactone) (PPDLDA) having a higher phase transition temperature than shape recovery temperature to maintain stiffness after shape recovery to resist chewing force. The hybrid polydopamine/silver/hydroxyapatite (PDA/Ag/HA) is coated to the surface of (PLGA-g-PCL)-PPDL scaffold to afford the anti-bacterial activity. The porous SM scaffold can be deformed into a compact size and administered into the socket cavity in a minimally invasive mode, and recover its original shape with a high stiffness at body temperature, fitting well in the socket defect. The SM scaffold exhibits robust antibacterial activity against Staphylococcus aureus (S. aureus). The porous microstructure and cytocompatibility of PLGA allow for the ingrowth and proliferation of stem cells, thus facilitating osteogenic differentiation. The micro-CT and histological analyses demonstrate that the scaffold boosts efficient new bone regeneration in the socket of rabbit mandibular first premolar. This porous shape memory self-adaptive stiffened polymer opens up a new avenue for alveolar bone regeneration.

Nanofiber Composite Microchannel-Containing Injectable Hydrogels for Cartilage Tissue Regeneration.

Articular cartilage tissue is incapable of self-repair and therapies for cartilage defects are still lacking. Injectable hydrogels have drawn much attention in the field of cartilage regeneration. Herein, the novel design of nanofiber composite microchannel-containing hydrogels inspired by the tunnel-piled structure of subway tunnels is proposed. Based on the aldehydized polyethylene glycol/carboxymethyl chitosan (APA/CMCS) hydrogels, thermosensitive gelatin microrods (GMs) are used as a pore-forming agent, and coaxial electrospinning polylactic acid/gelatin fibers (PGFs) loaded with kartogenin (KGN) are used as a reinforcing agent and a drug delivery system to construct the nanofiber composite microchannel-containing injectable hydrogels (APA/CMCS/KGN@PGF/GM hydrogels). The in situ formation, micromorphology and porosity, swelling and degradation, mechanical properties, self-healing behavior, as well as drug release of the nanofiber composite microchannel-containing hydrogels are investigated. The hydrogel exhibits good self-healing ability, and the introduction of PGF nanofibers can significantly improve the mechanical properties. The drug delivery system can realize sustained release of KGN to match the process of cartilage repair. The microchannel structure effectively promotes bone marrow mesenchymal stem cell (BMSC) proliferation and ingrowth within the hydrogels. In vitro and animal experiments indicate that the APA/CMCS/KGN@PGF/GM hydrogels can enhance the chondrogenesis of BMSCs and promote neocartilage formation in the rabbit cartilage defect model.

A tumor-targeting and ROS-responsive iron-based T1 magnetic resonance imaging contrast agent for highly specific tumor imaging.

T1 contrast agents (CAs) exhibit outstanding capacity in enhancing the magnetic resonance imaging (MRI) contrast between tumor tissues and normal tissues for generating bright images. However, the clinical application of representative gadolinium(III) chelate-based T1 CAs is limited due to their potential toxicity and low specificity for pathological tissues. To obtain MRI CAs with a combination of low toxicity and high tumor specificity, herein, we report a reactive oxygen species (ROS)-responsive T1 CA (GA-Fe(II)-PEG-FA), which was constructed by chelating Fe(II) with gallic acid (GA), and modified with tumor-targeted folic acid (FA). The resultant CA could accumulate in tumor tissues via the affinity between FA and their receptors on the tumor cell membrane. It realized the switch from Fe(II) to Fe(III), and further enhancing the longitudinal relaxation rate (r1) under the stimuli of ROS in the tumor microenvironment. The r1 of GA-Fe(II)-PEG-FA on a 0.5 T nuclear magnetic resonance analyzer increased to 2.20 mM-1 s-1 under ROS stimuli and was 5 times greater than the r1 (0.42 mM-1 s-1) before oxidation. The cell and in vivo experiments demonstrated that GA-Fe(II)-PEG-FA exhibited good biocompatibility and significant targeting specificity to tumor cells and tumor tissues. Furthermore, in vivo MRI studies demonstrated that the enhanced T1 contrast effect against tumors could be achieved after injecting the CA for 3 h, indicating that GA-Fe(II)-PEG-FA has the potential as an ideal tumor MRI CA to increase the contrast and improve the diagnostic precision.

Hyaluronic acid-g-lipoic acid granular gel for promoting diabetic wound healing.

Diabetic patients are prone to developing chronic inflammation after trauma and have persistent nonhealing wounds. Reactive oxygen species (ROS) and recurrent bacterial infections at the site of long-term wounds also further delay skin wound healing and tissue regeneration. In this study, a granular gel (which exhibits ROS scavenging and antibacterial properties) is fabricated based on hyaluronic acid-g-lipoic acid (HA-LA). Briefly, HA-LA is synthesized to fabricate HA-LA microgels, which are further assembled by Ag+ via its coordination effect with disulfide in dithiolane to form a granular gel. The extrudable bulk granular gel possesses a shear-thinning feature and is immediately restored to a solid state after extrusion, and this can be easily applied to the whole wound area. Therefore, the grafted LA not only allows for the construction of the granular gel but also removes excess ROS from the microenvironment. Additionally, the presence of Ag+ realizes the assembly of microgels and has antibacterial effects. In vivo experiments show that the HA-LA granular gel eliminates excessive ROS at the wound site and up-regulates the secretion of reparative growth factors, thus, accelerating common and diabetic wound healing significantly. Therefore, the ROS-scavenging granular gel that can be applied to the wound surface with chronic inflammation demonstrates strong clinical utility.

Injectable, In Situ Self-cross-linking, Self-healing Poly(l-glutamic acid)/Polyethylene Glycol Hydrogels for Cartilage Tissue Engineering.

Injectable hydrogels have drawn much attention in the field of tissue engineering because of advantages such as simple operation, strong plasticity, and good biocompatibility and biodegradability. Herein, we propose the novel design of injectable hydrogels via a Schiff base cross-linking reaction between adipic dihydrazide (ADH)-modified poly(l-glutamic acid) (PLGA-ADH) and benzaldehyde-terminated poly(ethylene glycol) (PEG-CHO). The effects of the mass fraction and the molar ratio of -CHO/-NH2 on the gelation time, mechanical properties, equilibrium swelling, and in vitro degradation of the hydrogels were examined. The PLGA/PEG hydrogels cross-linked by dynamic Schiff base linkages exhibited good self-healing ability. Additionally, the PLGA/PEG hydrogels had good biocompatibility with bone marrow-derived mesenchymal stem cells (BMSCs) and could effectively support BMSC proliferation and deposition of glycosaminoglycans and upregulate the expression of cartilage-specific genes. In a rat cartilage defect model, PLGA/PEG hydrogels significantly promoted new cartilage formation. The results suggest the prospect of the PLGA/PEG hydrogels in cartilage tissue engineering.

Injectable macro-porous chitosan/polyethylene glycol-silicotungstic acid double-network hydrogels based on "smashed gels recombination" strategy for cartilage tissue engineering.

The lack of interconnected macro-porous structure of most injectable hydrogels lead to poor cell and tissue infiltration. Herein, we present the fabrication of injectable macro-porous hydrogels based on "smashed gels recombination" strategy. Chitosan/polyethylene glycol-silicotungstic acid (CS/PEG-SiW) double-network hydrogels were prepared via dual dynamic interactions. The bulk CS/PEG-SiW hydrogels were then smashed into micro-hydrogels with average sizes ranging from 47.6 to 63.8 µm by mechanical fragmentation. The CS/PEG-SiW micro-hydrogels could be continuously injected and rapidly recombined into a stable porous hydrogel based on the dual dynamic interactions between micro-hydrogels. The average pore size of the recombined porous CS/PEG-SiW hydrogels ranged from 52 to 184 µm. The storage modulus, compress modulus and maximum compressive strain of the recombined porous CS/PEG-SiW1.0 hydrogels reached about 47.2 %, 28.2 % and 127.6 % of the values for their corresponding bulk hydrogels, respectively. The recombined porous hydrogels were cytocompatible and could effectively support proliferation and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In a rat cartilage defect model, recombined porous CS/PEG-SiW hydrogels could promote cartilage regeneration. Hematoxylin and eosin (H&E), Safranin-O/Fast green and immunohistochemical staining confirmed the accumulation of glycosaminoglycans (GAG) and type II collagen (Col II) in regenerated cartilage.