Evaluation of Demineralized Bone Matrix Particles Delivered by Alginate Hydrogel for a Bone Graft Substitute: An Animal Experimental Study.

BACKGROUND Our objective was to explore a synthetic alginate hydrogel delivery system for the delivery of demineralized bone matrix (DBM) particles for bone graft substitutes. MATERIAL AND METHODS The physiochemical properties of surface morphology, porosity measurements, in vitro degradation, equilibrium swelling, and mechanical testing of combined DBM powder and alginate in amounts of 0 mg/1 mL, 25 mg/1 mL, 50 mg/1 mL, and 100 mg/1 mL were detected. In vitro cell culture and in vivo studies using Sprague-Dawley rats were performed to evaluate the biocompatibility and osteoinductivity of DBM-alginate (ADBM) composites. RESULTS DBM particles were uniformly scattered in all composites, and macro-scale pores were omnipresent. All composites showed a similar low degradation rate, with approximately 85% of weight remaining after 15 days. As the concentration of DBM particles in composites increased, degradation in collagenase and elastic modulus increased and the pore area and swelling ratio significantly decreased. No cytotoxicity of ADBM or alginate on mesenchymal stem cells (MSCs) was observed. Cell cultivation with ADBM showed greater osteogenic potential, evidenced by the upregulation of alkaline phosphatase and alizarin red staining activity and the mRNA expression level of marker genes RUNX2, OCN, OPN, and collagen I compared with the cells grown in alginate. Evaluation of ectopic bone formation revealed the osteoinductivity of the ADBM composites was significantly greater than that of DBM particles. Osteoinduction of the composites was demonstrated by a cranial defect model study. CONCLUSIONS The delivery of DBM particles using a synthetic alginate hydrogel carrier may be a promising approach in bone tissue engineering for bone defects.

3D cone beam computed tomography reconstruction images in diagnosis of ameloblastomas of lower jaw: A case report and mini review.

Cone beam computed tomography (CBCT) has obvious advantages over regular radiography in diagnosis of complex diseases. Objective of this study is to report a case of a mandibular jaw ameloblastoma recurring cyst, which represents a benign tumor of odontogenic epithelium, using CBCT imaging technology. CBCT examination of the patient suffering with recurrent lower jaw cyst (relapsing four years after surgery) showed a decrease in irregular bone density and appearance of a honeycomb pattern (3.5 cm×2.5 cm×1.8 cm) in the right lower jaw. This suggests that the lesion is more likely to be an ameloblastoma. Preoperative tissue biopsy and pathological examination of surgical sample confirmed the diagnosis. Surgical resection of the diseased tissue and autogenous bone grafting in the mandible was performed. Postoperative CBCT examination showed that the bone defect healed well, without recurrence of the tumor 22 months postoperatively. In conclusion, the rotated 3D CBCT images clearly displays the exact size, location, borders and internal changes of the tumor in the jaw cyst itself and the adjacent tissues. Thus, the dental CBCT allows clinicians to better evaluate lesions, leading to better treatment outcomes.

Targeting Inflammatory Lesions Facilitated by Galactosylation Modified Delivery System Eudragit/Gal-PLGA@Honokiol for the treatment of Ulcerative Colitis.

Honokiol (HNK) is one of the bioactive ingredients from the well-known Chinese herbal medicine Magnolia officinalis, and its research interests is rising for its extensive pharmacological activities, including novel therapeutic effect on ulcerative colitis (UC). However, further application of HNK is largely limited by its unique physicochemical properties, such as poor water solubility, low bioavailability, as well as unsatisfied targeting efficacy for inflammatory lesions. In this study, we constructed galactosylation modified PLGA nanoparticles delivery system for efficient target delivery of HNK to the colitic lesions, which could lay a research foundation for the deep development of HNK for the treatment of UC. D-galactose was grafted by chemical coupling reactions with PLGA to prepare Gal-PLGA, which was used as a carrier for HNK (Gal-PLGA@HNK nanoparticles (NPs)). To improve the colon targeting efficiency by oral administration of the NPs, Eudragit S100 was used for wrapping on the surface of Gal-PLGA@HNK NPs (E/Gal-PLGA@HNK NPs). Our results showed that the encapsulation efficiency and drug loading capacity of E/Gal-PLGA@HNK NPs were 90.72 ± 0.54% and 8.41 ± 0.02%, respectively. Its average particle size was 242.24 ± 8.42 nm, with a PDI value of 0.135 ± 0.06 and zeta-potential of -16.83 ± 1.89 mV. The release rate of HNK from E/Gal-PLGA@HNK NPs was significantly decreased when compared with that of free HNK in simulated gastric and intestinal fluids, which displayed a slow-releasing property. It was also found that the cellular uptake of E/Gal-PLGA@HNK NPs was significantly increased when compared with that of free HNK in RAW264.7 cells, which was facilitated by D-galactose grafting on the PLGA carrier. Additionally, our results showed that E/Gal-PLGA@HNK NPs significantly improved colonic atrophy, body weight loss, as well as reducing disease activity index (DAI) score and pro-inflammatory cytokine levels in UC mice induced by DSS. Besides, the retention time of E/Gal-PLGA@HNK NPs in the colon was significantly increased when compared with that of other preparations, suggesting that these NPs could prolong the interaction between HNK and the injured colon. Taken together, the efficiency for target delivery of HNK to the inflammatory lesions was significantly improved by galactosylation modification on the PLGA carrier, which provided great benefits for the alleviation of colonic inflammation and injury in mice.

Scaffold-Based Poly(Vinylidene Fluoride) and Its Copolymers: Materials, Fabrication Methods, Applications, and Perspectives.

Tissue engineering involves implanting grafts into damaged tissue sites to guide and stimulate the formation of new tissue, which is an important strategy in the field of tissue defect treatment. Scaffolds prepared in vitro meet this requirement and are able to provide a biochemical microenvironment for cell growth, adhesion, and tissue formation. Scaffolds made of piezoelectric materials can apply electrical stimulation to the tissue without an external power source, speeding up the tissue repair process. Among piezoelectric polymers, poly(vinylidene fluoride) (PVDF) and its copolymers have the largest piezoelectric coefficients and are widely used in biomedical fields, including implanted sensors, drug delivery, and tissue repair. This paper provides a comprehensive overview of PVDF and its copolymers and fillers for manufacturing scaffolds as well as the roles in improving piezoelectric output, bioactivity, and mechanical properties. Then, common fabrication methods are outlined such as 3D printing, electrospinning, solvent casting, and phase separation. In addition, the applications and mechanisms of scaffold-based PVDF in tissue engineering are introduced, such as bone, nerve, muscle, skin, and blood vessel. Finally, challenges, perspectives, and strategies of scaffold-based PVDF and its copolymers in the future are discussed.

Electrodeposition of chitosan-glucose oxidase biocomposite onto Pt-Pb nanoparticles modified stainless steel needle electrode for amperometric glucose biosensor.

A glucose biosensor was fabricated by electrodepositing chitosan (CS)-glucose oxidase(GOD) biocomposite onto the stainless steel needle electrode (SSN electrode) modified by Pt-Pb nanoparticles (Pt-Pb/SSN electrode). Firstly, Pt-Pb nanoparticles were deposited onto the SSN electrode and then CS-GOD biocomposite was co-electrodeposited onto the Pt-Pb/SSN electrode in a mixed solution containing p-benzoquinone (p-BQ), CS and GOD. The electrochemical results showed that the Pt-Pb nanoparticles can accelerate the electron transfer and improve the effective surface area of the SSN electrode. As a result, the detection range of the proposed biosensor was from 0.03 to 9 mM with a current sensitivity of 0.4485 µA/mM and a response time of 15 s. The Michaelis constant value was calculated to be 4.9837 mM. The cell test results indicated that the electrodes have a low cytotoxicity. This work provided a suitable technology for the fabrication of the needle-type glucose biosensor.

Preparation and evaluation of an injectable curcumin loaded chitosan/hydroxyapatite cement.

Curcumin (Cur) is an active ingredient of Curcuma longa. Cur has many pharmacological effects, such as anti-inflammation, anti-oxidation, anticoagulation, hypolipidemic, anti-angiogenesis and anti-cancer. An injectable curcumin loaded chitosan/hydroxyapatite bone cement (Cur-CS/HA) was prepared as a bone scaffold and drug delivery. Tween 20, a nonionic surfactant, was incorporated into the cement to improve the solubility of curcumin. Four types of Cur-CS/HA (Group0, Group1, Group5 and Group10) were prepared with different Tween 20 ratios (0, 1, 5 and 10%, respectively). The samples were characterized by infrared spectroscopy (IR), X-ray diffraction (XRD) and scanning electron microscope (SEM). Compression tests were carried out to evaluate the strength of the scaffolds. In addition, the inhibition assay was carried out on MG63 cells with the extracts of drug loaded materials. The results showed that Cur had an effect on the setting time (p < 0.05). Cur reduced the compressive strength of the CS/HA cement (p < 0.05). The release studies showed that Tween 20 could effectively improve the solubility of curcumin. When the Tween 20 content in cement increased from 0 to 10%, the cumulative release (30 d) of Cur increased from 5.5 to 10.6%. Moreover, the cement had good injectability, good anti-collapsibility and good biocompatibility to meet the clinical requirements. The result of inhibition assay showed that Cur-CS/HA could inhibit the proliferation of MG63 cells. Tween 20 incorporated Cur-CS/HA had great potential to use as a drug-loaded artificial bone material.

A radial 3D polycaprolactone nanofiber scaffold modified by biomineralization and silk fibroin coating promote bone regeneration in vivo.

The treatment and repair of large bone defects remains a major therapeutic challenge in the clinical setting. Nanofiber scaffolds fabricated via the electrospinning technique have been developed as a universal method for bone regeneration due to their suitable properties. However, traditional two-dimensional (2D) nanofiber mats are usually too dense, which may prevent cell infiltration and growth, thereby restricting their application. Herein, a three-dimensional (3D) polycaprolactone nanofiber scaffold was developed, modified by biomineralization and silk fibroin coating. The scaffold possessed a parallel array of nanofiber surfaces, mimicking the parallel structure of fibrils in natural bone tissue. Furthermore, the fabricated radially or laterally interconnected macrochannels were investigated to elucidate the effect of the scaffold structure on bone regeneration. In vitro studies revealed that the scaffolds could guide cell arrangement and that the radially aligned scaffold demonstrated a stronger ability to promote cell proliferation. In vivo results showed that the radially aligned scaffold could guide tissue arrangement and remodeling and support a significantly faster regeneration rate of bone tissue. Therefore, 3D-mineralized polycaprolactone nanofiber scaffolds with radially interconnected macrochannels and aligned nanofibers are expected to be used in tissue engineering, including in the repair of bone defects, cartilage or other composite tissues.

Effects of microsurgical repair treatment on the clinical efficacy, complications, and flap follow-up scores of patients with exposed steel plates after surgery for foot and ankle fractures.

BACKGROUND: Treatment of exposed steel plates after surgery for foot and ankle fractures is complicated. This study aims to analyze the effects of microsurgical repair treatment on the clinical efficacy, complications, and flap follow-up scores of patients with exposed steel plates following foot and ankle fracture surgery. METHODS: Eighty-two patients with exposure of steel plates after surgical treatment for foot and ankle fractures in our hospital from March 2017 to March 2018 were included in this study. The patients were divided into a study group (43 patients who received microsurgical repair) and a control group (39 patients who received conventional repair surgery). We compared the clinical efficacy, complication rate, flap followup score, recovery of ankle-hindfoot function and ankle function before treatment and at 3 and 6 months after treatment, and patient satisfaction between the two groups. RESULTS: The clinical effectiveness rate in the study group was 95.35%, which was higher than the control group (76.92%) (P<0.05). The flap appearance, texture, and elasticity scores in the study group were higher than those in the control group (P<0.05). After treatment, the American Orthopedic Foot and Ankle Society (AOFAS) score and Baird ankle score increased significantly in both groups, and reached a peak at 6 months after treatment. The peak scores of the study group were considerably higher than those of the control group at each period after treatment (P<0.05). The incidence of complications in the study group (6.98%) was lower than the control group (25.64%) (P<0.05). Patient satisfaction was higher in the study group (97.67%) than the control group (79.49%) (P<0.05). CONCLUSIONS: Microsurgical repair of exposed steel plates after surgery for foot and ankle fractures has a significant clinical effect. It can improve the flap follow-up scores, accelerate healing of the ankle, improve aesthetics, and reduce the incidence of complications. It is therefore worthy of widespread use in clinics.

Strategies for improving the functionality of an affinity bioreactor.

Heparin employed in extracorporeal blood circulation (ECBC) procedures (e.g. open heart operations) often leads to a high incidence of bleeding complications. Protamine employed in heparin neutralization, on the other hand, can cause severe adverse reactions. We previously developed an approach that could prevent both heparin- and protamine-induced toxic side effects concomitantly. This approach consisted of placing a hollow fiber-based bioreactor device containing immobilized protamine (termed a "protamine bioreactor") at the distal end of the ECBC procedure. This protamine bioreactor would remove heparin after heparin served its anticoagulant purpose in the ECBC device, thereby eliminating heparin-induced bleeding risks. In addition, this protamine bioreactor would prevent protamine from entering the patients, thereby aborting any protamine-induced toxic effects. Both in vitro and in vivo studies have successfully demonstrated the feasibility of this approach. Despite promises, early findings also revealed two shortcomings that must be overcome for the protamine bioreactor to be applied clinically. The first drawback was that the cyanate ester linkages, involved in conjugating protamine to the bioreactor device, were unstable and prone to hydrolysis, resulting in the leakage of a significant amount of protamine into circulation during application of the protamine bioreactor. The second deficiency was that the capacity of the protamine bioreactor in heparin removal was rather low, owing to the limited surface area of the hollow fibers for protamine immobilization and subsequently heparin adsorption. In this paper, we present novel strategies to overcome these two limitations. A new conjugation method based on the use of 4-(oxyacetyl)phenoxyacetic acid (OAPA) as the activating reagent was employed to yield stable linkages, via the abundant arginine residues of protamine, onto the hollow fibers. Results showed that while the amount of protamine immobilized on each gram of fibers was relatively comparable between the OAPA and the previous CNBr activation methods (7.45 mg/g versus 7.69 mg/g fibers), there was virtually no detectable leaching of immobilized protamine from the bioreactor by the OAPA method, comparing to 35% leaching of protamine by the previous CNBr method following 72 h of storage of the bioreactor in PBS buffer at 37 degrees C. To improve the capacity and functionality of the protamine bioreactor, two novel approaches were adopted. Long chain and high molecular weight poly-lysine was linked to the hollow fibers, prior to protamine coupling, to create multiple layers of immobilized protamine for subsequent heparin adsorption. In addition, a poly(ethylene glycol) (PEG) chain was inserted between protamine and the hollow fibers to yield a three-dimensional, free dynamic motion for immobilized protamine. Preliminary observations indicated that a four- to five-fold enhancement in heparin adsorption was attained by utilizing each of these new approaches. Aside from their current use, these new strategies can also be employed generically to improve the functionality of any affinity-type bioreactor. Indeed, efforts have been made recently in utilizing these approaches to develop a clinically usable GPIIb/IIIa bioreactor for the treatment of immune thrombocytopenic purpura (ITP)-an autoimmune disease.

Poly(glutamic acid) poly(ethylene glycol) hydrogels prepared by photoinduced polymerization: Synthesis, characterization, and preliminary release studies of protein drugs.

A class of new biodegradable hydrogels based on poly(ethylene glycol) methacrylate-graft-poly(glutamic acid) and poly(ethylene glycol) dimethacrylate was synthesized by photoinduced polymerization. Because all the polymeric constituents were highly hydrophilic, crosslinking could be performed in aqueous solutions. This type of crosslinked hydrogel was prepared by modifying a select number of acidic side-groups on poly(glutamic acid) with poly(ethylene glycol) methacrylate. These modified chains were then crosslinked in the presence of poly(ethylene glycol) dimethacrylate under a photoinduced polymerization at a wavelength of 365 nm. Swelling experiments were conducted to study the crosslinking density, pH-responsive behavior, and degradation of the hydrogel. Results showed that the degree of swelling of this type of hydrogels increased as the crosslinker concentration (or density) was reduced. Because of the presence of acidic side chains on poly(glutamic acid), swelling behavior was found to be pH-responsive, increasing at high pH in response to the increase in the amount of ionized acidic side chains. The degradation rate of these hydrogels also varied with pH. More rapid degradation was observed under stronger alkaline conditions because of the hydrolysis of the ester bonds between the crosslinker and the polymer backbone. Practically useful degradation rates could be achieved for such hydrogels under physiological conditions. Drug release rates from these hydrogels were found to be proportional to the protein molecular weight and the crosslinker density; increasing at lower protein molecular weight or crosslinker density. The preliminary findings presented in this article suggest that this class of biodegradable hydrogels could be an attractive avenue for drug delivery applications. The specific photoinduced crosslinking chemistry used would permit hydrogels to be synthesized in existence of the entrapped macromolecular drugs including peptides, proteins, and cells. In addition, the rapid feature of this polymerization procedure along with the ability to perform hydrogel synthesis and drug loading in an aqueous environment would offer great advantages in retaining drug activity during hydrogel synthesis.