Supramolecular Adhesive Hydrogels for Tissue Engineering Applications.

Tissue engineering is a promising and revolutionary strategy to treat patients who suffer the loss or failure of an organ or tissue, with the aim to restore the dysfunctional tissues and enhance life expectancy. Supramolecular adhesive hydrogels are emerging as appealing materials for tissue engineering applications owing to their favorable attributes such as tailorable structure, inherent flexibility, excellent biocompatibility, near-physiological environment, dynamic mechanical strength, and particularly attractive self-adhesiveness. In this review, the key design principles and various supramolecular strategies to construct adhesive hydrogels are comprehensively summarized. Thereafter, the recent research progress regarding their tissue engineering applications, including primarily dermal tissue repair, muscle tissue repair, bone tissue repair, neural tissue repair, vascular tissue repair, oral tissue repair, corneal tissue repair, cardiac tissue repair, fetal membrane repair, hepatic tissue repair, and gastric tissue repair, is systematically highlighted. Finally, the scientific challenges and the remaining opportunities are underlined to show a full picture of the supramolecular adhesive hydrogels. This review is expected to offer comparative views and critical insights to inspire more advanced studies on supramolecular adhesive hydrogels and pave the way for different fields even beyond tissue engineering applications.

Hydrogel Composites with Different Dimensional Nanoparticles for Bone Regeneration.

The treatment of large segmental bone defects and complex types of fractures caused by trauma, inflammation, or tumor resection is still a challenge in the field of orthopedics. Various natural or synthetic biological materials used in clinical applications cannot fully replicate the structure and performance of raw bone. This highlights how to endow materials with multiple functions and biological properties, which is a problem that needs to be solved in practical applications. Hydrogels with outstanding biocompatibility, for their casting into any shape, size, or form, are suitable for different forms of bone defects. Therefore, they have been used in regenerative medicine more widely. In this review, versatile hydrogels are compounded with nanoparticles of different dimensions, and many desirable features of these materials in bone regeneration are introduced, including drug delivery, cell factor vehicle, cell scaffolds, which have potential in bone regeneration applications. The combination of hydrogels and nanoparticles of different dimensions encourages better filling of bone defect areas and has higher adaptability. This is due to the minimally invasive properties of the material and ability to match irregular defects. These biological characteristics make composite hydrogels with different dimensional nanoparticles become one of the most attractive options for bone regeneration materials.

A Novel Temperature-Dependent Hydrogel Emulsion with Sol/Gel Reversible Phase Transition Behavior Based on Polystyrene-co-poly(N-isopropylacrylamide)/Poly(N-isopropylacrylamide) Core-Shell Nanoparticle.

As a kind of temperature-responsive hydrogel, polystyrene-co-poly(N-isopropylacrylamide)/poly(N-isopropylacrylamide) (PS-co-PNIPAM/PNIPAM) core-shell nanoparticles prepared by two-step copolymerization are widely studied and used because of their specific structures and properties. Unlike most reports about the steady stability of PS-co-PNIPAM/PNIPAM core-shell nanoparticle hydrogel emulsion, in this work, the PS-co-PNIPAM/PNIPAM core-shell nanoparticle hydrogel emulsion (symbolized as PS/PNIPAM hydrogel emulsion), which is prepared after the second step of synthesis and without washing out a large number of PNIPAM polymer segments, shows a reversible temperature-dependent sol-gel transition characteristic during the temperature range of 34-80 °C. The PS/PNIPAM hydrogel emulsion is a normal solution at room temperature, and it changes from a sol to a gel statue when the temperature approaches up to low critical solution temperature (LCST). As the temperature continues to increase, the gel (core-shell nanoparticles as the crosslinkers and the linear PNIPAM chain as the 3D gel network) of the PS/PNIPAM hydrogel emulsion gradually shrinks and drains linearly. Compared with most crosslinked hydrogels, the hydrogel here can be arbitrarily changed in shape according to use needs, which is convenient for use, transportation, and storage. Here a new route is provided for the preparation of a PS/PNIPAM core-shell hydrogel nanoparticle system, as well as a new supramolecular crosslinking sol-gel system for application in biomedical materials, sensors, biological separation, drug release, macromolecular adsorption, and purification.

Polystyrene@poly(ar-vinylbenzyl)trimethylammonium-co-acrylic acid core/shell pH-responsive nanoparticles for active targeting and imaging of cancer cell based on aggregation induced emission.

Doubly charged pH-responsive core/shell hydrogel nanoparticles with green fluorescence were prepared and were shown to be viable bioprobes for active targeting tumor tissue and imaging of cancer cells. Via emulsionfree copolymerization hydrogel nanoparticles as VANPs were prepared, the core of which was polystyrene (Ps) and the shell was comprised of strongly positive electrolyte (ar-vinylbenzyl)trimethylammonium (VBTAC) with weak negative electrolyte acrylic acid (AA). Through conventional amidation, the shell was conjugated with cell-specific folic acid (FA), denoted as VANPs-FA. Then, negatively charged sulfonated 9,10-distyrylanthracene derivatives (SDSA) based on aggregation induced emission (AIE), was binding tightly to positively charged VBTAC of VANPs-FA shell. The prepared double charged fluorescent core/shell hydrogel nanoparticles abbreviated as VANPs-FS, showed excitation/emission wavelengths at ~420/528 nm. Dynamic light scattering (DLS) measurements were performed to determine the size and surficial zeta potential of VANPs-FS. Under proper ratio of VBTAC to AA, the VANPs-FS was stable (~ 64.63 nm, -20.2 mV) at high pH (> 7), started to aggregate (~ 683.0 nm, -3.2 mV) at pH around 6, and can redispers at low pH (< 5). The MTT analysis proved that VANPs-FS had good biocompatibility and low cytotoxicity. The targeting effectiveness of VANPs-FS was confirmed by confocal laser scanning microscopy (CLSM). Graphical abstract Detailed synthetic route of VANPs-FS (top) and schematic cancer tumor-target aggregation of pH-sensitive VANPs-FS with enhanced retention and rapid cancer cell imaging (bottom).

UCNP-based Photoluminescent Nanomedicines for Targeted Imaging and Theranostics of Cancer.

Theranostic approach is currently among the fastest growing trends in cancer treatment. It implies the creation of multifunctional agents for simultaneous precise diagnosis and targeted impact on tumor cells. A new type of theranostic complexes was created based on NaYF4: Yb,Tm upconversion nanoparticles coated with polyethylene glycol and functionalized with the HER2-specific recombinant targeted toxin DARPin-LoPE. The obtained agents bind to HER2-overexpressing human breast adenocarcinoma cells and demonstrate selective cytotoxicity against this type of cancer cells. Using fluorescent human breast adenocarcinoma xenograft models, the possibility of intravital visualization of the UCNP-based complexes biodistribution and accumulation in tumor was demonstrated.

Liposomal paclitaxel versus docetaxel in induction chemotherapy using Taxanes, cisplatin and 5-fluorouracil for locally advanced nasopharyngeal carcinoma.

BACKGROUND: We wished to evaluate the efficacy and safety of liposomal paclitaxel and docetaxel for induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC). METHODS: A total of 1498 patients with newly-diagnosed NPC between 2009 and 2017 treated with IC plus concurrent chemotherapy were included in our observational study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and grade-3-4 toxicities were compared between groups using propensity score matching (PSM). RESULTS: In total, 767 patients were eligible for this study, with 104 (13.6%) and 663 (86.4%) receiving a liposomal paclitaxel-based and docetaxel-based taxanes, cisplatin and 5-fluorouracil (TPF) regimen, respectively. PSM identified 103 patients in the liposomal-paclitaxel group and 287 patients in the docetaxel group. There was no significant difference at 3 years for OS (92.2% vs. 93.9%, P = 0.942), PFS (82.6% vs. 81.7%, P = 0.394), LRFS (94.7% vs. 93.3%, P = 0.981) or DMFS (84.6% vs. 87.4%, P = 0.371) between the two groups after PSM. Significant interactions were not observed between the effect of chemotherapy regimen and sex, age, T stage, N stage, overall stage, or Epstein-Barr virus DNA level in the subgroup multivariate analysis. The prevalence of grade-3-4 leukopenia and neutropenia in the liposomal-paclitaxel group was significantly lower than that of the docetaxel group (P < 0.05 for all). CONCLUSIONS: Compared with docetaxel, liposomal paclitaxel has identical anti-tumor efficacy, but causes fewer and milder adverse reactions in IC for NPC.

Pretreatment quality of life as a predictor of survival for patients with nasopharyngeal carcinoma treated with IMRT.

BACKGROUND: To evaluate the prognostic significance of pretreatment quality of life for patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy. METHODS: We performed a prospective, longitudinal study on 554 newly diagnosed patients with NPC from April 2011 to January 2015. A total of 501 consecutive NPC patients were included. Patients were asked to complete the EORTC QLQ-C30 (version 3.0) and QLQ-H&N35 questionnaires before treatment. RESULTS: Global health status among QLQ-C30 correlates with EBV DNA(P = 0.019). In addition, pretreatment appetite loss was significantly correlated with EBV DNA(P = 0.02). Pretreatment teeth, opening mouth, feeding tube was significantly correlated with EBV DNA, with P value of 0.003, < 0.0001, and 0.031, respectively. In multivariate analysis, pretreatment cognitive functioning of QLQ-C30 was significantly associated with LRFS, with HR of 0.971(95%CI 0.951-0.990), P = 0.004. Among scales of QLQ-H&N35 for multivariate analysis, pretreatment teeth (P = 0.026) and felt ill (P = 0.012) was significantly associated with PFS, with HR of 0.984 (95%CI 0.971-.998) and 1.004 (95%CI 1.001-1.007), respectively. Felt ill of QLQ-H&N35 was significantly associated with DMFS, with HR of 1.004(95%CI 1.000-1.007), P = 0.043. There is no QoL scale significantly associated with OS after multivariate analysis. CONCLUSIONS: In conclusion, our analysis confirms that pretreatment teeth and felt ill was significantly associated with PFS in NPC patients treated with IMRT. In addition, the posttreatment EBV DNA was significantly associated with OS.

Advancing Spinal Cord Injury Bioimaging and Repair with Multifunctional Gold Nanodots Tracking.

High levels of reactive oxygen species (ROS) are known to play a critical role in the secondary cascade of spinal cord injury (SCI). The scavenging of ROS has emerged as a promising approach for alleviating acute SCI. Moreover, identifying the precise location of the SCI site remains challenging. Enhancing the visualization of the spinal cord and improving the ability to distinguish the lesion site are crucial for accurate and safe treatment. Therefore, there is an urgent clinical need to develop a biomaterial that integrates diagnosis and treatment for SCI. Herein, ultra-small-sized gold nanodots (AuNDs) were designed for dual-mode imaging-guided precision treatment of SCI. The designed AuNDs demonstrate two important functions. First, they effectively scavenge ROS, inhibit oxidative stress, reduce the infiltration of inflammatory cells, and prevent apoptosis. This leads to a significant improvement in SCI repair and promotes a functional recovery after injury. Second, leveraging their excellent dual-mode imaging capabilities, the AuNDs enable rapid and accurate identification of SCI sites. The high contrast observed between the injured and adjacent uninjured areas highlights the tremendous potential of AuNDs for SCI detection. Overall, by integrating ROS scavenging and dual-mode imaging in a single biomaterial, our work on functionalized AuNDs provides a promising strategy for the clinical diagnosis and treatment of SCI.

Mussel-inspired antimicrobial hydrogel with cellulose nanocrystals/tannic acid modified silver nanoparticles for enhanced calvarial bone regeneration.

Bacterial infection is a serious challenge in the treatment of open bone defects, and reliance on antibiotic therapy may contribute to the emergence of drug-resistant bacteria. To solve this problem, this study developed a mineralized hydrogel (PVA-Ag-PHA) with excellent antibacterial properties and osteogenic capabilities. Silver nanoparticles (CNC/TA@AgNPs) were greenly synthesized using natural macromolecular cellulose nanocrystals (CNC) and plant polyphenolic tannins (TA) as stabilizers and reducing agents respectively, and then introduced into polyvinyl alcohol (PVA) and polydopamine-modified hydroxyapatite (PDA@HAP) hydrogel. The experimental results indicate that the PVA-Ag-PHA hydrogel, benefiting from the excellent antibacterial properties of CNC/TA@AgNPs, can not only eliminate Staphylococcus aureus and Escherichia coli, but also maintain a sustained sterile environment. At the same time, the HAP modified by PDA is uniformly dispersed within the hydrogel, thus releasing and maintaining stable concentrations of Ca2+ and PO43- ions in the local environment. The porous structure of the hydrogel with excellent biocompatibility creates a suitable bioactive environment that facilitates cell adhesion and bone regeneration. The experimental results in the rat critical-sized calvarial defect model indicate that the PVA-Ag-PHA hydrogel can effectively accelerate the bone healing process. Thus, this mussel-inspired hydrogel with antibacterial properties provides a feasible solution for the repair of open bone defects, demonstrating the considerable potential for diverse applications in bone repair.

Characterization of Chitosan-Gallic Acid Graft Copolymer for Periodontal Dressing Hydrogel Application.

The postoperative periodontal wound is in a complex physiological environment; the bacteria accumulation, the saliva stimulation, and the food residues retention will aggravate the wound deterioration. Commercial periodontal dressings have been widely used for postoperative periodontal treatment, and there still exists some problems, such as poor biocompatibility, weak adhesion, insufficient antibacterial, and anti-inflammatory properties. In this study, a chitosan-gallic acid graft copolymer (CS-GA) is synthesized as a potential periodontal dressing hydrogel. CS-GA possesses high swelling rate, adjustable degradability, self-healing ability, biocompatibility, strong adhesion ability, high mechanical properties and toughness. Furthermore, CS-GA has good scavenging ability for ·OH, O2 - , and 1 O2. And CS-GA has good inhibition effect on different bacterial through bacterial membranes damage. CS-GA can stop bleeding in a short time and adsorb erythrocytes to form physical blood clots to enhance the hemostatic performance. In addition, CS-GA can reduce inflammatory factors expressions, increase collagen fibers deposition, and neovascularization to promote wounds healing, which makes it as a potential periodontal dressing for postoperative tissue restoration.

Paclitaxel liposome, cisplatin and 5-fluorouracil-based induction chemotherapy followed by de-escalated intensity-modulated radiotherapy with concurrent cisplatin in stage IVA-IVB childhood nasopharyngeal carcinoma in endemic area: a phase II, single-arm trial.

Background: Previous studies demonstrated that induction chemotherapy (IC) followed by de-escalated chemoradiotherapy adapted to tumor response was effective in treating childhood nasopharyngeal carcinoma (NPC), but the toxicity profile of this treatment strategy, and whether childhood patients with advanced stages can obtain enough benefits from it requires further investigation. Methods: We conducted a single-center phase II trial (NCT03020329). All participants received 3 cycles of paclitaxel liposome, cisplatin and 5-fluorouracil (TPF)-based IC. Patients who showed complete or partial response received de-escalated radiotherapy of 60 Gy with 3 cycles of concurrent cisplatin, and those who showed stable or progressive disease received standard-dose radiotherapy of 70 Gy with concurrent cisplatin. The primary endpoint was the complete response (CR) rate at the end of concurrent chemoradiotherapy (CCRT). Findings: From November 2016 to March 2021, 44 patients were recruited in the cohort. The CR rate was 80% (35/44, 95% CI, 65-90) of the whole cohort. All patients achieved CR 3 months after CCRT. By the last follow-up, the 3-year progression-free survival and overall survival were 91% (95% CI, 82-99) and 100% respectively. Dry mouth was the most common late toxicity, with an incidence of 41% (18/44), followed by skin fibrosis and hearing impairment. No patient suffered from severe late toxicity and growth retardation. Interpretation: Our results proved the efficacy and safety of TPF regimen followed by de-escalated radiotherapy with concurrent cisplatin in treating stage IVa-b childhood NPC patients. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Reduced-dose radiotherapy for Epstein-Barr virus DNA selected staged III nasopharyngeal carcinoma: A single-arm, phase 2 trial.

BACKGROUND: Radiotherapy-related toxicities of nasopharyngeal carcinoma (NPC) caused by a standard dose of 70 Gy remain a critical issue. Therefore, we assessed whether a radiotherapy dose of 60 Gy was non-inferior to the standard dose in patients with low-risk stage III NPC with a favourable response to induction chemotherapy (IC). PATIENTS AND METHODS: We did a single-arm, single-centre, phase II clinical trial in China. Patients with low-risk (Epstein-Barr virus [EBV] DNA level <4000 copies/ml) stage III NPC were treated with two cycles IC. Patients with complete/partial response and undetectable EBV DNA level were assigned 60 Gy intensity-modulated radiotherapy concurrently with three cycles of cisplatin. The primary end-point was 2-year progression-free survival (PFS). This trial is registered with ClinicalTrials.gov, number NCT03668730. RESULTS: One patient quit because of withdrawal of informed consent after IC. In total, 215 patients completed two cycles of IC, after which 116 (54.0%) and 99 (46.0%) patients were assigned 60 and 70 Gy radiotherapy, respectively. For 215 patients, the 2-year PFS was 90.7% (95% CI, 86.8%-94.6%) with a median follow-up of 43.9 months (interquartile range [IQR], 39.8-46.2). For patients treated with 60 Gy radiotherapy, the 2-year PFS rate was 94.8% (95%CI 90.7%-98.9%) with a median follow-up of 43.9 months (IQR 40.2-46.2). The most common late toxicity was grade 1-2 dry mouth (incidence rate: 54.3%). No grade 3+ long-term adverse event was observed, and most quality-of-life items, domains, and symptom scores returned to baseline by 6 months. CONCLUSION: Reduced-dose radiation (60 Gy) is associated with favourable survival outcomes and limited treatment-related toxicities in patients with low-risk stage III NPC sensitive to IC.

Engineering Multifunctional Hydrogel-Integrated 3D Printed Bioactive Prosthetic Interfaces for Osteoporotic Osseointegration.

3D printed porous titanium alloy implants is an advanced orthopedic material for joint replacement. However, the high risk of aseptic loosening and periprosthetic infection is difficult to avoid, and the declined autophagy of osteoporosis-derived bone marrow mesenchymal stem cells (OP-BMSCs) further severely impairs the osseointegration under the osteoporotic circumstance. It is thus becoming urgently significant to develop orthopedic materials with autophagy regulation and antibacterial bioactivity. In this regard, a novel class of multifunctional hydrogel-integrated 3D printed bioactive prosthetic interfaces is engineered for in situ osseointegration in osteoporosis. The hydrogel is fabricated from the dynamic crosslinking of synthetic polymers, natural polymers, and silver nanowires to deliver autophagy-regulated rapamycin. Therefore, the resultant soft material exhibits antibacterial ability, biocompatibility, degradability, conductive, self-healing, and stimuli-responsive abilities. In vitro experiments demonstrate that the hydrogel-integrated 3D printed bioactive prosthetic interfaces can restore the declined cellular activities of OP-BMSCs by upregulating the autophagy level and show excellent antibacterial activity against S. aureus and MRSA. More remarkably, the multifunctional 3D printed bioactive prosthetic interfaces significantly improve osseointegration and inhibit infection in osteoporotic environment in vivo. This study provides an efficient strategy to develop novel prosthetic interfaces to reduce complications after arthroplasty for patients with osteoporosis.

A smart hydrogel patch with high transparency, adhesiveness and hemostasis for all-round treatment and glucose monitoring of diabetic foot ulcers.

The treatment and management of diabetic foot ulcers (DFUs) is a pretty intractable problem for clinical nursing. Urgently, the "Black Box" status of the healing process prevents surgeons from providing timely analysis for more effective diagnosis and therapy of the wound. Herein, we designed a transparent monitoring system to treat and manage the DFUs with blood oozing and hard-healing, which resolved the problem of blind management for the other conductive patches. This system was prepared from a conductive hydrogel patch with ultra-high transparence (up to 93.6%), adhesiveness and hemostasis, which is engineered by assembling in situ formed poly(tannic acid) (PTA)-doped polypyrrole (PPy) nanofibrils in the poly(acrylamide-acrylated adenine) (P(AM-Aa)) polymer networks. Significantly, the high transparent conductive hydrogel patch can monitor the wound-healing status visually and effectively promote the healing of DFUs by accelerating hemostasis, improving communication between cells, preventing wound infection, facilitating collagen deposition, and promoting angiogenesis. In addition, the versatile hydrogel patch could realize indirect blood glucose monitoring by detecting the glucose levels on wounds, and further sense the movements with different magnitudes of human body timely. This research may provide a novel strategy in the design of chronic wound dressings for monitoring and treating the wounds synergistically.

Deintensified Chemoradiotherapy for Pretreatment Epstein-Barr Virus DNA-Selected Low-Risk Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II Randomized Noninferiority Trial.

PURPOSE: Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS: Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS: Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, -4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION: Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

Dual-emission hydrogel nanoparticles with linear and reversible luminescence-response to pH for intracellular fluorescent probes.

A type of dual-emission probe with highly recognizable luminescence-response to pH has been designed. For the prepared core-shell polymeric hydrogel nanoparticles probe (Eu(DBM)3Phen doped polystyrene (PS)-co-poly(N-isopropylacrylamide)(PNIPAM)/FITC), the red emission of inner encapsulated europium complexes Eu(DBM)3Phen is remained in the hydrophobic PS core and used as a stable reference signal. Comparingly, the green emission of outer electrostatic bonded fluorescent isothiocyanate (FITC) moieties on the hydrophilic PNIPAM shell is adjusted and acted linear and reversible luminescence-response to pH between 5.8 and 7.4 with an exact resolution of 0.1 units. As a remarkable and smart pH probe, the hydrogel nanoparticles show low biological toxicity and prolonged resistance to ions and photobleaching. Also, the probes have successfully discriminated the fluorescent imaging for cytoplasmic matrix based on different pH with minimum biologic background fluorescence. These dual-emission pH-sensitive hydrogel nanoparticles suggest potential applications in clinical medicine, such as cell imaging and disease diagnosis.

Injectable hydrogel-loaded nano-hydroxyapatite that improves bone regeneration and alveolar ridge promotion.

In stomatology, the promotion of alveolar bone regeneration while preventing the reduction of ridge absorption remains a challenge. In this work, we designed and prepared bio-mimetic polysaccharide hydrogels that are multi-functional in terms of being injectable, promote self-healing, degradable, porous structure, et al. After introducing nano-hydroxyapatite particles, the composite scaffold of hydrogel/hydroxyapatite (GH) stent was obtained. When GH material was injected into the mandibular incisors of rats following tooth extraction, the new bone area was enhanced more than 50%, while the alveolar ridge was promoted in excess of 60% after 4 weeks. What's more, the wound soft tissue was healed within 1 week. Overall, our results indicate that this optimized GH stent has the potential to both maintain dimensional alveolar ridge, as well as to promote soft tissue healing. Moreover, using the hydroxyapatite-containing hydrogel platform has the potential to promote bone and soft tissue regeneration.

Enhanced osteogenic healing process of rat tooth sockets using a novel simvastatin-loaded injectable microsphere-hydrogel system.

PURPOSE: To evaluate the effects of simvastatin in a new injectable microsphere hydrogel system on bone healing process of tooth sockets. MATERIALS AND METHODS: Simvastatin was loaded in poly (lactic-co-glycolic acid) (PLGA) microspheres using an emulsion process, and the drug-loaded PLGA microspheres were further entrapped in a gelatin hydrogel to form an injectable microsphere-hydrogel system. Simvastatin-free hydrogel and blank microspheres hydrogel were used as controls. A rat tooth extraction socket model was generated, and the simvastatin-loaded microsphere-hydrogel composite was injected in the defect area of a tooth socket. At 1, 2, 5, and 8 weeks after the surgery, all the animals were sacrificed and the mandibles were harvested. The samples were examined using X-ray, hematoxylin and eosin staining, and histological evaluations. RESULTS: Five weeks after the surgery, significantly more bone tissue was formed in the simvastatin-loaded hydrogel group than in the simvastatin-free hydrogel group and the blank microspheres hydrogel group as control (p < 0.05). CONCLUSION: The injectable simvastatin-loaded microsphere hydrogel promoted new bone formation in the tooth extraction socket after 5 weeks, and has a promising potential for bone repair and regeneration.

One-step synthesis of photoluminescent carbon dots with excitation-independent emission for selective bioimaging and gene delivery.

Photoluminescent carbon dots (C-dots), as new members of the quantum sized carbon analogues have attracted significant attention due to their unique size, less toxicity, good compatibility and relatively easy surface modification. In this work, we report a simple, low-cost and one-step hydrothermal carbonization approach to synthesize the positively charged C-dots using PEI and FA. From the photoluminescence (PL) measurements, the as-prepared C-dots exhibit good stability and intense PL with the high quantum yield (QY) at Ca. 42%. Significantly, The as-prepared C-dots integrate the advantages of C-dots and PEI: the presence of C-dots can effectively decrease the cytotoxicity of PEI, the C-dots can be applied in biological system for selective imaging of folate receptor (FR)-positive cancerous cells from normal cells, while the cationic PEI with positive charges can make them link to plasmid DNA and efficiently transfect the therapeutic plasmid into cells. Therefore, the as-prepared with the facile synthesis method can be a promising photoluminescent probe for cancer diagnosis and gene therapy.

Surface PEGylation of intraocular lens for PCO prevention: An in vivo evaluation.

Posterior capsular opacification (PCO) is a common complication in cataract surgery. The development of PCO is attributed to the combination of adhesion, migration, proliferation, and transdifferentiation of the residual lens epithelial cells (LEC) onto the interface of intraocular lens (IOL) material and lens posterior, in which the initial adhesion is the beginning step and plays important roles. In the present study, hydrophilic polyethylene glycol (PEG) was immobilized onto IOL surface via plasma-aided chemical grafting procedure. The attenuated total reflection - Fourier transform infrared (ATR-FTIR) and contact angle (CA) - measurements indicate the successful surface PEGylation, as well as the excellent hydrophilicity of the surfaces. Compared with pristine IOL, the PEGylation does not influent its optical property, whereas the initial adhesion of LEC is greatly inhibited. In vivo ocular implantation results show that the PEGylated IOL presents good in vivo biocompatibility, and can effectively prevent the PCO development.