Injectable Composite Hydrogels Research Articles

Injectable composite hydrogels embedded with gallium-based liquid metal particles for solid breast cancer treatment via chemo-photothermal combination

Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy. Eutectic gallium–indium LM particles were first stabilized with 1,2-Distearoyl-sn‑glycero-3-phosphoethanolamine (DSPE) lipids. They were then incorporated into an interpenetrating hydrogel network composed of thiolated gelatin conjugated with 6-mercaptopurine (MP) chemodrug and poly(ethylene glycol)-diacrylate. The resulted composite hydrogel exhibited sufficient capability to induce MDA-MB-231 breast cancer cell death through a multi-step mechanism: (1) hyperthermic cancer cell death due to temperature elevation by near-infrared laser irradiation via LM particles, (2) leakage of glutathione (GSH) and cleavage of disulfide bonds due to destruction of cancer cells. As a consequence, additional chemotherapy was facilitated by GSH, leading to accelerated release of MP within the tumor microenvironment. The effectiveness of our composite hydrogel system was evaluated both in vitro and in vivo, demonstrating significant tumor suppression and killing. These results demonstrate the potential of this injectable composite hydrogel for spatiotemporal cancer treatment. In conclusion, integration of PTT and chemotherapy within our hydrogel platform offers enhanced therapeutic efficacy, suggesting promising prospects for future clinical applications. Statement of significanceOur research pioneers a breakthrough in cancer treatments by developing an injectable hydrogel platform incorporating liquid metal (LM) particle-mediated photothermal therapy and 6-mercaptopurine (MP)-based chemotherapy. The combination of gallium-based LM and MP achieves synergistic anticancer effects, and our injectable composite hydrogel acts as a localized reservoir for specific delivery of both therapeutic agents. This platform induces a multi-step anticancer mechanism, combining NIR-mediated hyperthermic tumor death and drug release triggered by released glutathione from damaged cancer populations. The synergistic efficacy validated in vitro and in vivo studies highlights significant tumor suppression. This injectable composite hydrogel with synergistic therapeutic efficacy holds immense promise for biomaterial-mediated spatiotemporal treatment of solid tumors, offering a potent targeted therapy for triple negative breast cancers.

Hydroxypropyl chitosan/ε-poly-l-lysine based injectable and self-healing hydrogels with antimicrobial and hemostatic activity for wound repair

The biggest obstacle to treating wound healing continues to be the production of simple, inexpensive wound dressings that satisfy the demands associated with full process of repair at the same time. Herein, a series of injectable composite hydrogels were successfully prepared by a one-pot method by utilizing the Schiff base reaction as well as hydrogen bonding forces between hydroxypropyl chitosan (HCS), ε-poly-l-lysine (EPL), and 2,3,4-trihydroxybenzaldehyde (TBA), and multiple cross-links formed by the reversible coordination between iron (III) and pyrogallol moieties. Notably, hydrogel exhibits excellent physicochemical properties, including injectability, self-healing, water retention, and adhesion, which enable to fill irregular wounds for a long period, providing a suitable moist environment for wound healing. Interestingly, the excellent hemostatic properties of the hydrogel can quickly stop bleeding and avoid the serious sequelae of massive blood loss in acute trauma. Moreover, the powerful antimicrobial and antioxidant properties also protect against bacterial infections and reduce inflammation at the wound site, thus promoting healing at all stages of the wound. The study of biohydrogel with multifunctional integration of wound treatment and smart medical treatment is clarified by this line of research.

Combining decellularized adipose tissue with decellularized adventitia extravascular matrix or small intestinal submucosa matrix for the construction of vascularized tissue-engineered adipose

Adipose tissue is an endocrine organ. It serves many important functions, such as energy storage, hormones secretion, and providing insulation, cushioning and aesthetics to the body etc. Adipose tissue engineering offers a promising treatment for soft tissue defects. Early adipose tissue production and long-term survival are closely associated with angiogenesis. Decellularized matrix has a natural ECM (extracellular matrix) component, good biocompatibility, and low immunogenicity. Therefore, in this study, the injectable composite hydrogels were developed to construct vascularized tissue-engineered adipose by using the pro-angiogenic effects of aortic adventitia extravascular matrix (Adv) or small intestinal submucosa (SIS), and the pro-adipogenic effects of decellularized adipose tissue (DAT). The composite hydrogels were cross-linked by genipin. The adipogenic and angiogenic abilities of composite hydrogels were investigated in vitro, and in a rat dorsal subcutaneous implant model. The results showed that DAT and SIS or Adv 1:1 composite hydrogel promoted the migration and tube formation of endothelial cells. Furthermore, DAT and SIS or Adv 1:1 composite hydrogel enhanced adipogenic differentiation of adipose-derived mesenchymal stem cells (ASCs) through activation of PPARγ and C/EBPα. The in vivo studies further demonstrated that DAT with SIS or Adv in a 1:1 ratio also significantly promoted adipogenesis and angiogenesis. In addition, DAT with SIS or Adv in a 1:1 ratio hydrogel recruited macrophage population with enhanced M2-type macrophage polarization, suggesting a positive effect of inflammatory response on angiogenesis. In conclusion, these data suggest that the composite hydrogels of DAT with SIS or Adv in 1:1 ratio have apparent pro-adiogenic and angiogenic abilities, thus providing a promising cell-free tissue engineering biomaterial with broad clinical applications. Statement of significanceDecellularized adipose tissue (DAT) has emerged as an important biomaterial in adipose tissue regeneration. Early adipose tissue production and long-term survival is tightly related to the angiogenesis. The revascularization of the DAT is a key issue that needs to be solved in adipose regeneration. In this study, the injectable composite hydrogels were developed by using DAT with Adv (aortic adventitia extravascular matrix) or SIS (small intestinal submucosa) in different ratio. We demonstrated that the combination of DAT with SIS or Adv in 1:1 ratio effectively improved the proliferation of adipose stem cells and endothelial cells, and promoted greater adipose regeneration and tissue vascularization as compared to the DAT scaffold. This study provides the potential biomaterial for clinical soft tissue regeneration.

Hyaluronic acid-based injectable nanocomposite hydrogels with photo-thermal antibacterial properties for infected chronic diabetic wound healing

A hydrogel wound dressing with a single functionality fails to meet the requirements for successful clinical treatment of chronic diabetic wounds that generally possess complicated microenvironments. A multifunctional hydrogel is thus highly desirable for improved clinical treatment. For this purpose, we reported herein construction of an injectable nanocomposite hydrogel with self-healing and photo-thermal properties as an antibacterial adhesive via dynamic Michael addition reaction and electrostatic interactions among three building moieties, i.e., catechol and thiol-modified hyaluronic acid (HA-CA and HA-SH), poly(hexamethylene guanidine) (PHMG), and black phosphorus nanosheets (BPs). An optimized hydrogel formulation eliminated over 99.99 % of bacteria (E. coli and S. aureus) and exhibited a free radical scavenging capability >70 % as well as photo-thermal properties in addition to viscoelastic characteristics, degradation properties in vitro, good adhesion and self-adaptation capacity. Wound healing experiments in vivo further confirmed the better performance of the developed hydrogels than that of a commercially available dressing (Tegaderm™) in promoting the healing of infected chronic wounds by preventing wound infection, decreasing inflammation, supporting collagen deposition, facilitating angiogenesis, and improving granulation tissues formation in the wound sites. Overall, the HA-based injectable composite hydrogels developed herein represent promising multifunctional wound dressings for infected diabetic wound repair.

Injectable composite hydrogels encapsulating gelatin methacryloyl/chitosan microspheres as ARPE-19 cell transplantation carriers.

Retinal pigment epithelial (RPE) cell transplantation is being explored as a feasible approach for treating age-related macular degeneration. The low aggregation ability of RPE cell suspensions or microtissues after transplantation has limited cell utilisation. Therefore, alternative transplantation strategies should be explored to induce cell aggregation and maintain cell viability. Herein, we propose a composite hydrogel that encapsulates gelatin methacryloyl (GelMA)/chitosan microspheres (GCMSs) as ARPE-19 cell transplantation carriers. The diameter of the GCMS was adjusted by tuning the parameters of the microfluidic devices, yielding a cell-adhering platform that induced uniform cell spreading. The live/dead assay and immunofluorescence results showed that ARPE-19 cells adhered and spread uniformly around the microspheres. Moreover, the hydrogel sheets were used to provide an aggregated protective shell, and the ARPE-19 cells on the microspheres encapsulated within these hydrogel sheets remained viable post-injection and produced fewer reactive oxygen species after cyclic stretching. Furthermore, we found that the composite hydrogel was biodegradable and biocompatible in vivo. Therefore, GCMSs provide an injectable microcarrier for ARPE-19 cells, and the hydrogel provides an aggregated protective shell in this novel platform, which has considerable potential for an alternative injectable and highly aggregated RPE cell transplantation strategy design.

Graphene Oxide/Chitosan Injectable Composite Hydrogel for Controlled Release of Doxorubicin: An Approach for Enhanced Intratumoral Delivery

Intratumoral (IT) injection of chemotherapeutics into needle-accessible solid tumors can directly localize the anticancer drug in the tumor site, thus increasing its local bioavailability and reducing its undesirable effects compared to systemic administration. In this study, graphene oxide (GO)-based chitosan/β-glycerophosphate (CS/GP) thermosensitive injectable composite hydrogels (CH) were prepared and optimized for the localized controlled delivery of doxorubicin (DOX). A quality-by-design (QbD) approach was used to study the individual and combined effects of several formulation variables to produce optimal DOX-loaded GO/CS/GP CH with predetermined characteristics, including gelation time, injectability, porosity, and swelling capacity. The surface morphology of the optimal formulation (DOX/opt CH), chemical interaction between its ingredients and in vitro release of DOX in comparison to GO-free CS/GP CH were investigated. Cell viability and cellular uptake after treatment with DOX/opt CH were studied on MCF 7, MDB-MB-231 and FaDu cell lines. The statistical analysis of the measured responses revealed significant effects of the concentration of GO, the concentration of CS, and the CS:GP ratio on the physicochemical characteristics of the prepared GO/CS/GP CH. The optimization process showed that DOX-loaded GO/CS/GP CH prepared using 0.1% GO and 1.7% CS at a CS: GO ratio of 3:1 (v/v) had the highest desirability value. DOX/opt CH showed a porous microstructure and chemical compatibility between its ingredients. The incorporation of GO resulted in an increase in the ability of the CH matrices to control DOX release in vitro. Finally, cellular characterization showed a time-dependent increase in cytotoxicity and cellular uptake of DOX after treatment with DOX/opt CH. The proposed DOX/opt CH might be considered a promising injectable platform to control the release and increase the local bioavailability of chemotherapeutics in the treatment of solid tumors.

Hydroxyapatite-Integrated, Heparin- and Glycerol-Functionalized Chitosan-Based Injectable Hydrogels with Improved Mechanical and Proangiogenic Performance.

The investigation of natural bioactive injectable composites to induce angiogenesis during bone regeneration has been a part of recent minimally invasive regenerative medicine strategies. Our previous study involved the development of in situ-forming injectable composite hydrogels (Chitosan/Hydroxyapatite/Heparin) for bone regeneration. These hydrogels offered facile rheology, injectability, and gelation at 37 °C, as well as promising pro-angiogenic abilities. In the current study, these hydrogels were modified using glycerol as an additive and a pre-sterile production strategy to enhance their mechanical strength. These modifications allowed a further pH increment during neutralisation with maintained solution homogeneity. The synergetic effect of the pH increment and further hydrogen bonding due to the added glycerol improved the strength of the hydrogels substantially. SEM analyses showed highly cross-linked hydrogels (from high-pH solutions) with a hierarchical interlocking pore morphology. Hydrogel solutions showed more elastic flow properties and incipient gelation times decreased to just 2 to 3 min at 37 °C. Toluidine blue assay and SEM analyses showed that heparin formed a coating at the top layer of the hydrogels which contributed anionic bioactive surface features. The chick chorioallantoic membrane (CAM) assay confirmed significant enhancement of angiogenesis with chitosan-matrixed hydrogels comprising hydroxyapatite and small quantities of heparin (33 µg/mL) compared to basic chitosan hydrogels.

Ultrashort Peptides and Hyaluronic Acid-Based Injectable Composite Hydrogels for Sustained Drug Release and Chronic Diabetic Wound Healing.

Peptide hydrogels are widely used for biomedical applications owing to their good biocompatibility and unique advantages in terms of amino acid-based structures and functions. However, the exploration of the peptide/saccharide composite hydrogels as potential biomaterials for chronic diabetic wound healing is still limited. Herein, hyaluronic acid (HA) was incorporated into diphenylalanine (FF) conjugated with different aromatic moieties by a one-pot reaction. Our results showed that the dipeptide derivatives modified by benzene (B), naphthalene (N), and pyrene (P) self-assembled into composite hydrogels with uniform distribution and good mechanical properties in the presence of HA. The obtained N-FF/HA composite hydrogel exhibited greatly improved self-healing properties via injection syringe needle operation and good biocompatibility on human skin fibroblast (HSF) cells. Besides, the structure of thinner nanofibers and honeycomb networks inside the composite hydrogel allowed for a longer sustained release of curcumin, a hydrophobic drug for anti-inflammation and wound healing. The curcumin-loaded N-FF/HA composite hydrogels could promote chronic wound healing in the streptozotocin-induced type I diabetic mouse model. The results suggested that our developed saccharide-peptide hydrogels could serve as very promising synthetic biomaterials for applications in both drug delivery and wound healing in the future.

Fine property-tuning through Ca content control in a facile synthesis of glasses-based self-setting injectable hydrogel

Self-setting injectable composite hydrogels are promising materials in tissue engineering. In this study a facile synthetic approach was designed based on traditional sol–gel method to produce particulate calcium aluminosilicate-type glasses, which were then formulated with potassium alginate to form a self-setting injectable hydrogel. In order to control the setting-time and mechanical properties of the composite materials, a series of samples were produced with different starting chemical composition. The change in chemical composition and morphology of the glass particles in response to varying initial Ca2+ content were further elucidated by a combination of EM, XRF and NMR spectroscopy, revealing that the binary aluminosilicate glass was preferably formed when low Ca content (<20%) was used in the formulation. At higher Ca content (>30%), calcium aluminosilicates were predominantly formed due to the change in the type of zeolite precursor formed during the low temperature nucleation process in the sol–gel approach. It was also found the hardening times of the alginate gels was positively correlated to the mole ratio of Ca/Al due to high acid resistance of high coordination number Al species. For hydrogels made with glass particle additions, the mechanical strengths were also positively correlated with the Ca/Al ratio for all formulations.

Degradable photothermal bioactive glass composite hydrogel for the sequential treatment of tumor-related bone defects: From anti-tumor to repairing bone defects

To treat tumor-related irregular bone defects, the implanted biomaterials after surgery should combine the functions of both tumor therapy and bone regeneration. To address the requirement, double crosslinking injectable composite hydrogels based on Furan-Sodium Alginate/bis-maleimide-Polyethylene Glycol/Copper doped Bioactive Glass-ceramic Microspheres (SA/PEG-CuBGM) were prepared using Diels–Alder (DA) reaction and ionic crosslinking. The prepared composite hydrogel showed excellent photothermal effects and killed most tumor cells in vitro and inhibited tumor growth in mice at the early implantation stage. The photothermal effects were derived from the oxide formed by doping copper ions in bioactive glass, and the photothermal temperature could be controlled by the CuBGM concentration and power densities of near infrared (NIR). Next, the photothermal agent concentration decreased rapidly with the degradation of the material. Additionally, the Ca, Si and Cu released from CuBGM improved the capability to stimulate the osteogenic differentiation of mBMSCs by upregulating bone-related gene expression, significantly promoting new bone formation in a femoral defect model of rats. Therefore, as the sequential progress of photothermal treatment and osteogenesis promotion is realized, the SA/PEG-CuBGM composite hydrogel will demonstrate considerable potential to aid the development and application of implanted biomaterials to tumor-related bone defects.

Remarkable bactericidal traits of a metal-ceramic composite coating elated by hierarchically structured surface.

SummaryA ceramic-based coating with a hierarchical surface structure was synthesized via solid-state reaction enabled by a double cathode glow discharge technique. This innovative coating comprises two distinct layers, specifically an outer layer with a well-aligned micro-pillar array and a dense inner layer. Both are composed of a face-centered cubic Cu(Co,Ni,Fe) solid solution phase together with a spinel-type Fe(Al,Cr)2O4 oxide. This coating exhibits superhydrophobicity and, yet, a very strong adhesion to water, i.e., the so-called “rose petal effect”. This coating also exhibits highly efficient antibacterial ability against both Staphylococcus aureus and Escherichia coli bacteria under both dark and visible light conditions. The excellent antibacterial property originates from the synergistic effects through the release of Cu ions coupled with photothermal activity upon light activation.

Injectable chitosan/gelatin/bioactive glass nanocomposite hydrogels for potential bone regeneration: In vitro and in vivo analyses.

The present work describes in vitro and in vivo behaviors of thermosensitive composite hydrogels based on polymers/bioactive glass nanoparticles. Assays in SBF (simulated body fluid) solution showed that loss of hydrogel mass in vitro was decreased by 4.3% when bioactive glass nanoparticles (nBG) were incorporated, and confirmed the bioactivity of nBG containing hydrogels. In vitro assays demonstrated the cytocompatibility of the hydrogels with encapsulated rat bone marrow mesenchymal stem cells (BMSC). Crystal violet assays showed a 27% increase in cell viability when these cells were seeded in hydrogels containing nBG. In vivo biocompatibility was examined by injecting hydrogels into the dorsum of Swiss rats. The results indicated that the prepared hydrogels were nontoxic upon subcutaneous injection, and could be candidates for a safe in situ gel-forming system. Injection of the hydrogels into a rat tibial defect allowed preliminary evaluation of the hydrogels' regenerative potential. Micro Computed Tomography analysis suggested that more new tissue was formed in the defects treated with the hydrogels. Taken together, our data suggest that the developed injectable composite hydrogels possess properties which make them suitable candidates for use as temporary injectable matrices for bone regeneration.

Adhesive Hemostatic Conducting Injectable Composite Hydrogels with Sustained Drug Release and Photothermal Antibacterial Activity to Promote Full-Thickness Skin Regeneration During Wound Healing.

Developing injectable nanocomposite conductive hydrogel dressings with multifunctions including adhesiveness, antibacterial, and radical scavenging ability and good mechanical property to enhance full-thickness skin wound regeneration is highly desirable in clinical application. Herein, a series of adhesive hemostatic antioxidant conductive photothermal antibacterial hydrogels based on hyaluronic acid-graft-dopamine and reduced graphene oxide (rGO) using a H2 O2 /HPR (horseradish peroxidase) system are prepared for wound dressing. These hydrogels exhibit high swelling, degradability, tunable rheological property, and similar or superior mechanical properties to human skin. The polydopamine endowed antioxidant activity, tissue adhesiveness and hemostatic ability, self-healing ability, conductivity, and NIR irradiation enhanced in vivo antibacterial behavior of the hydrogels are investigated. Moreover, drug release and zone of inhibition tests confirm sustained drug release capacity of the hydrogels. Furthermore, the hydrogel dressings significantly enhance vascularization by upregulating growth factor expression of CD31 and improve the granulation tissue thickness and collagen deposition, all of which promote wound closure and contribute to a better therapeutic effect than the commercial Tegaderm films group in a mouse full-thickness wounds model. In summary, these adhesive hemostatic antioxidative conductive hydrogels with sustained drug release property to promote complete skin regeneration are an excellent wound dressing for full-thickness skin repair.

Black Phosphorus Hydrogels: Conceptually Novel Black Phosphorus/Cellulose Hydrogels as Promising Photothermal Agents for Effective Cancer Therapy (Adv. Healthcare Mater. 7/2018)

In article number 1701510, Liping Liu, Han Zhang, and co-workers demonstrate that green and injectable composite hydrogels based on cellulose and Black Phosphorus (BP) nanosheets (BPNSs) are of great efficiency for photothermal therapy (PTT) against cancer. The cellulose/BPNS-based hydrogel possesses 3D networks with irregular micrometer-sized pores and thin, strong cellulose-formed walls and exhibits an excellent photothermal response, enhanced stability, and good flexibility.

Conceptually Novel Black Phosphorus/Cellulose Hydrogels as Promising Photothermal Agents for Effective Cancer Therapy.

Black phosphorus (BP) has recently emerged as an intriguing photothermal agent in photothermal therapy (PTT) against cancer by virtue of its high photothermal efficiency, biocompatibility, and biodegradability. However, naked BP is intrinsically characterized by easy oxidation (or natural degradation) and sedimentation inside the tumor microenvironment, leading to a short-term therapeutic and inhomogeneous photothermal effect. Development of BP-based nanocomposites for PTT against cancer therefore remains challenging. The present work demonstrates that green and injectable composite hydrogels based on cellulose and BP nanosheets (BPNSs) are of great efficiency for PTT against cancer. The resultant cellulose/BPNS-based hydrogel possesses 3D networks with irregular micrometer-sized pores and thin, strong cellulose-formed walls and exhibits an excellent photothermal response, enhanced stability, and good flexibility. Importantly, this hydrogel nanoplatform is totally harmless and biocompatible both in vivo and in vitro. This work may facilitate the development of BP-polymer-based photothermal agents in the form of hydrogels for biomedical-related clinic applications.

Alginate-aker injectable composite hydrogels promoted irregular bone regeneration through stem cell recruitment and osteogenic differentiation.

Recent studies have unveiled the unique osteogenesis and angiogenesis abilities of akermanite. However, such bioceramics rarely fit well into irregularly shaped bony cavities (such as bone defects and the maxillary sinus). In this study, an injectable hydrogel SAG system containing sodium alginate, akermanite and glutamate was prepared and evaluated in such defects. Cell proliferation experiments showed that except for stoste, the other extracts showed no cytotoxicity at various concentrations. In addition, the gene expression of Runx2 (runt-related transcription factor-2), BMP-2 (bone morphogenetic protein-2), ALP (alkaline phosphatase), and BSP (bone sialoprotein) and the activity of ALP were significantly higher in human bone marrow stromal cells (hBMSCs) cultured with 1/2 hydrogel extracts containing 66.9 ppm calcium ions, 23.8 ppm magnesium ions and 33.5 ppm silicon ions compared to those in hBMSCs cultured with the control medium, which indicated that the hydrogel extracts could stimulate the osteogenic differentiation of hBMSCs. Further experiments revealed that the ERK signaling pathway was engaged in osteogenic differentiation as early as 15 minutes after incubation with the hydrogel extracts. In addition, hBMSCs incubated in half-diluted extracts exhibited an almost doubled migration ability compared with the hBMSCs in the control group. More specifically, compared to the control group, hBMSCs cultured with 1/2 hydrogel extracts showed a 7% increase and a 10-fold increase in the protein and gene levels of CXCR4 (C-X-C chemokine receptor type 4), respectively. In vivo tests demonstrated that the bone formation rate of SAG hydrogels injected alone was similar to that of its counterpart seeded with BMSCs, reaching 24% at three months after operation. Therefore, it could be concluded that SAG hydrogels contribute to bone regeneration by not only promoting osteogenic differentiation but also by enhancing the recruitment of BMSCs to defect sites, making the injectable SAG hydrogels competent for the regeneration of irregular bony cavities.

Injectable Alginate Hydrogel Cross-Linked by Calcium Gluconate-Loaded Porous Microspheres for Cartilage Tissue Engineering.

A great interest has been shown in the injectable scaffolds for cartilage tissue regeneration because it can fill irregularly shaped defects easily through minimally invasive surgical treatments. Herein, we developed a new injectable three-dimensional (3D) alginate hydrogel loaded with biodegradable porous poly(ε-caprolactone)–b-poly(ethylene glycol)–b-poly(ε-caprolactone) microspheres (MPs/Alg) as the calcium gluconate container to cross-link alginate. Suspensions of chondrocytes/alginate and porous microspheres turned into a gel because of the release of calcium gluconate; thus, the injectable composite hydrogels give a 3D scaffold to fit the defects perfectly and integrate the extracellular-matrix-mimicking architecture to efficiently accommodate cartilage cells in situ. Tissue repair in a full-thickness cartilage defect model was controlled at 6, 12, and 18 weeks after the implant by micro-CT and immunohistochemistry to evaluate the healing status. The defect in the MPs/Alg+ cells group achieved an almost complete repair at 18 weeks, and the repaired chondrocytes regained a normal tissue structure. Moreover, the MPs/Alg+ cells-treated group increased the quality of tissue formed, including the accumulated glycosaminoglycan and the uniformly deposited type II collagen. The results point out the promising application of the injectable MPs/Alg-chondrocytes system for cartilage tissue engineering.

Spatiotemporal Programing for the On-Demand Release of Bupivacaine Based on an Injectable Composite Hydrogel

We report a programed drug delivery system that can tailor the release of anesthetic bupivacaine in a spatiotemporally controlled manner. The drug delivery system was developed through the combination of a collagen-based injectable hydrogel and 2 types of poly(lactic-co-glycolic acid) (PLGA) particles. As a rapid-release platform (90% release after 24 h), bupivacaine hydrochloride was incorporated into collagen/poly(γ-glutamic acid) hydrogel, which exhibited gel formation at body temperature. PLGA microparticles (diameter 1-3 μm) containing bupivacaine base showed a very slow release of bupivacaine (95% after 240 h), whereas PLGA nanoparticles (124 ± 30 nm) containing bupivacaine base demonstrated an intermediate release rate (95% after 160 h). By changing the relative composition ratio between the 3 components in these injectable composite hydrogels, the release of bupivacaine could be easily controlled from very rapid (within 1 day) to very delayed (up to 9 days). The experimental results on the release data (cumulative release, time point release, average release rate) were coincident with the release profile generated by computer simulation. These injectable composite hydrogels with systematically tunable mixing ratios are expected to serve as a promising technology for the on-demand release of bupivacaine in pain management.

Injectable composite hydrogels containing mesoporous silica nanoparticles for controlled release of chemotherapeutics

Injectable composite hydrogels containing mesoporous silica nanoparticles for controlled release of chemotherapeutics