Injectable bioactive poly(propylene fumarate) and polycaprolactone based click chemistry bone cement for spinal fusion in rabbits.

Degenerative spinal pathology is a widespread medical issue, and spine fusion surgeries are frequently performed. In this study, we fabricated an injectable bioactive click chemistry polymer cement for use in spinal fusion and bone regrowth. Taking advantages of the bioorthogonal click reaction, this cement can be crosslinked by itself eliminating the addition of a toxic initiator or catalyst, nor any external energy sources like UV light or heat. Furthermore, nano-hydroxyapatite (nHA) and microspheres carrying recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human vascular endothelial growth factor (rhVEGF) were used to make the cement bioactive for vascular induction and osteointegration. After implantation into a rabbit posterolateral spinal fusion (PLF) model, the cement showed excellent induction of new bone formation and bridging bone, achieving results comparable to autograft control. This is largely due to the osteogenic properties of nano-hydroxyapatite (nHA) and the released rhBMP-2 and rhVEGF growth factors. Since the availability of autograft sources is limited in clinical settings, this injectable bioactive click chemistry cement may be a promising alternative for spine fusion applications in addressing various spinal conditions.

Bioactive Moldable Click Chemistry Polymer Cement with Nano-Hydroxyapatite and Growth Factor-Enhanced Posterolateral Spinal Fusion in a Rabbit Model.

Spinal injuries or diseases necessitate effective fusion solutions, and common clinical approaches involve autografts, allografts, and various bone matrix products, each with limitations. To address these challenges, we developed an innovative moldable click chemistry polymer cement that can be shaped by hand and self-cross-linked in situ for spinal fusion. This self-cross-linking cement, enabled by the bioorthogonal click reaction, excludes the need for toxic initiators or external energy sources. The bioactivity of the cement was promoted by incorporating nanohydroxyapatite and microspheres loaded with recombinant human bone morphogenetic protein-2 and vascular endothelial growth factor, fostering vascular induction and osteointegration. The release kinetics of growth factors, mechanical properties of the cement, and the ability of the scaffold to support in vitro cell proliferation and differentiation were evaluated. In a rabbit posterolateral spinal fusion model, the moldable cement exhibited remarkable induction of bone regeneration and effective bridging of spine vertebral bodies. This bioactive moldable click polymer cement therefore presents a promising biomaterial for spinal fusion augmentation, offering advantages in safety, ease of application, and enhanced bone regrowth.

3D Stem Cell Spheroids with 2D Hetero-Nanostructures for In Vivo Osteogenic and Immunologic Modulated Bone Repair.

3D stem cell spheroids have immense potential for various tissue engineering applications. However, current spheroid fabrication techniques encounter cell viability issues due to limited oxygen access for cells trapped within the core, as well as nonspecific differentiation issues due to the complicated environment following transplantation. In this study, functional 3D spheroids are developed using mesenchymal stem cells with 2D hetero-nanostructures (HNSs) composed of single-stranded DNA (ssDNA) binding carbon nanotubes (sdCNTs) and gelatin-bind black phosphorus nanosheets (gBPNSs). An osteogenic molecule, dexamethasone (DEX), is further loaded to fabricate an sdCNTgBP-DEX HNS. This approach aims to establish a multifunctional cell-inductive 3D spheroid with improved oxygen transportation through hollow nanotubes, stimulated stem cell growth by phosphate ions supplied from BP oxidation, in situ immunoregulation, and osteogenesis induction by DEX molecules after implantation. Initial transplantation of the 3D spheroids in rat calvarial bone defect shows in vivo macrophage shifts to an M2 phenotype, leading to a pro-healing microenvironment for regeneration. Prolonged implantation demonstrates outstanding in vivo neovascularization, osteointegration, and new bone regeneration. Therefore, these engineered 3D spheroids hold great promise for bone repair as they allow for stem cell delivery and provide immunoregulative and osteogenic signals within an all-in-one construct.

3D-printed scaffolds with 2D hetero-nanostructures and immunomodulatory cytokines provide pro-healing microenvironment for enhanced bone regeneration.

Three-dimensional (3D) printing technology is driving forward the progresses of various engineering fields, including tissue engineering. However, the pristine 3D-printed scaffolds usually lack robust functions in stimulating desired activity for varied regeneration applications. In this study, we combined the two-dimensional (2D) hetero-nanostructures and immuno-regulative interleukin-4 (IL-4) cytokines for the functionalization of 3D-printed scaffolds to achieve a pro-healing immuno-microenvironment for optimized bone injury repair. The 2D hetero-nanostructure consists of graphene oxide (GO) layers, for improved cell adhesion, and black phosphorous (BP) nanosheets, for the continuous release of phosphate ions to stimulate cell growth and osteogenesis. In addition, the 2D hetero-nanolayers facilitated the adsorption of large content of immuno-regulative IL-4 cytokines, which modulated the polarization of macrophages into M2 phenotype. After in vivo implantation in rat, the immuno-functioned 3D-scaffolds achieved in vivo osteo-immunomodulation by building a pro-healing immunological microenvironment for better angiogenesis and osteogenesis in the defect area and thus facilitated bone regeneration. These results demonstrated that the immuno-functionalization of 3D-scaffolds with 2D hetero-nanostructures with secondary loading of immuno-regulative cytokines is an encouraging strategy for improving bone regeneration.

Simultaneous Pantalar Dislocation and Bimalleolar Ankle Fracture.

A 17-year-old boy presented with a totally dislocated talus and open bimalleolar ankle fracture dislocation. After thorough debridement and irrigation, the talus and bimalleolar fracture were reduced and fixed. At 21 months after surgery, he could walk using regular shoes without any aid but with moderate pain in the sinus tarsi during activities. No evidence of osteonecrosis or infection was seen in the last radiograph, except for a small degree of narrowing in the talonavicular joint. Reimplantation and fixation of pantalar dislocation seems to have an acceptable outcome.

Phenol-Rich Compounds Sweet Gel: A Statistically More Effective Antibiotic than Cloxacillin Against Pseudomonas Aeruginosa.

OBJECTIVES: The purpose of this study was to obtain a natural antibiotic from Phenol-rich compounds; for the dressing and the treatment of chronic wounds. METHODS: The Phenol-rich compound sweet gel was prepared by blending four natural herbal extracts, Acacia catechu (L.F.), Momia (Shilajit), Castanea sativa, and Ephedra sinica stapf, with combination of a sweet gel medium, including honey, maple saps, Phoenix dactylifera L. (date), pomegranate extract and Azadirachta indica gum as a stabilizer. The combinations were screened by using a well-diffusion assay with cloxacillin as a control. Pseudomonas spp. was tested with our novel antimicrobial compound. The zones of inhibition in agar culture were measured for each individual component and for the compound, and the results were compared with those of the control group which had been treated with cloxacillin. Data were expressed as means ± standard deviations. Quantitative analyses were performed using the paired t-test. RESULTS: The antibiotic effect of the Phenol-rich compound sweet gel was statistically shown to be more significant than that of cloxacillin against Pseudomonas aeruginosa (P < 0.05). CONCLUSION: Our novel approach to fighting the antibiotic resistance of Pseudomonas proved to be successful. The Phenol-rich compound sweet gel was found to be suitable for use as an alternative medicine and bioactive dressing material, for the treatment of patients with various types of wounds, including burns, venous leg ulcers, ulcers of various etiologies, leg ulcers on the feet of diabetic, unhealed graft sampling sites, abscesses, boils, surgical wounds, necrotic process, post-operative and neonatal wound infection, and should be considered as an alternative to the usual methods of cure.

The Concept of Wind in Traditional Chinese Medicine.

The use of folk medicine has been widely embraced in many developed countries under the name of traditional, complementary and alternative medicine (TCAM) and is now becoming the mainstream in the UK and the rest of Europe, as well as in North America and Australia. Diversity, easy accessibility, broad continuity, relatively low cost, base levels of technological inputs, fewer side effects, and growing economic importance are some of the positive features of folk medicine. In this framework, a critical need exists to introduce the practice of folk medicine into public healthcare if the goal of reformed access to healthcare facilities is to be achieved. The amount of information available to public health practitioners about traditional medicine concepts and the utilization of that information are inadequate and pose many problems for the delivery of primary healthcare globally. Different societies have evolved various forms of indigenous perceptions that are captured under the broad concept of folk medicine, e.g., Persian, Chinese, Grecian, and African folk medicines, which explain the lack of universally accepted definitions of terms. Thus, the exchange of information on the diverse forms of folk medicine needs to be facilitated. Various concepts of Wind are found in books on traditional medicine, and many of those go beyond the boundaries established in old manuscripts and are not easily understood. This study intends to provide information, context, and guidance for the collection of all important information on the different concepts of Wind and for their simplification. This new vision for understanding earlier Chinese medicine will benefit public health specialists, traditional and complementary medicine practitioners, and those who are interested in historical medicine by providing a theoretical basis for the traditional medicines and the acupuncture that is used to eliminate Wind in order to treat various diseases.

In-Vitro, Anti-Bacterial Activities of Aqueous Extracts of Acacia catechu (L.F.)Willd, Castanea sativa, Ephedra sinica stapf and shilajita mumiyo Against Gram Positive and Gram Negative Bacteria.

OBJECTIVE: Evaluations of the in-vitro anti-bacterial activities of aqueous extracts of Acacia catechu (L.F.)Willd, Castanea sativa, Ephedra sinica stapf and Shilajita mumiyo against gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumonia) and gram-negative bacteria (Escherichia coli, klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa) are reasonable since these ethnomedicinal plants have been used in Persian folk medicine for treating skin diseases, venereal diseases, respiratory problems and nervous disorders for ages. METHODS: The well diffusion method (KB testing) with a concentration of 250 µg/disc was used for evaluating the minimal inhibitory concentrations (MIC). Maximum synergistic effects of different combinations of components were also observed. RESULTS: A particular combination of Acacia catechu (L.F.) Willd, Castanea sativa, Ephedra sinica stapf and shilajita mumiyo extracts possesses an outstanding anti-bacterial activity. It's inhibiting effect on microorganisms is significant when compared to the control group (P< 0.05). Staphylococcus aureus was the most sensitive microorganism. The highest antibacterial activity against gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumonia) or gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, Proteus mirabilis and Pseudomonas aeruginosa) was exerted by formula number 2 (Table1). CONCLUSION: The results reveal the presence of antibacterial activities of Acacia catechu, Castanea sativa husk, Ephedra sp. and Mumiyo against gram-positive and gram-negative bacteria. Synergistic effects in a combined formula, especially in formula number 2 (ASLAN(Ⓡ)) can lead to potential sources of new antiseptic agents for treatment of acute or chronic skin ulcers. These results considering the significant antibacterial effect of the present formulation, support ethno-pharmacological uses against diarrheal and venereal diseases and demonstrate use of these plants to treat infectious diseases.

Role of glyco-persica(®) in targeting diabetes type 2: an integrative approach.

OBJECTIVES: The objective of this study was to examine how an integrated approach to type 2 diabetes mellitus treatment could improve glycemic control and immune-potentiating activities adherent to oral hypoglycemic agents along with a botanical compound, among primary care patients. METHODS: In this study, we used the self-control and the group-control methods. Candidates meeting the trial conditions were selected from among volunteers who had taken the test substance for 45 days. During the trial, all groups were on a controlled diet; neither were the original medications nor their dosages changed. RESULTS: The results showed that the botanical compound (Glyco-Persica(®)) significantly reduced the main clinical symptoms in diabetes type 2. In the treatment group, 36 of 52 patients (69.23%) and in the control group 10 of 52 patients (19.23%) showed reduced symptoms, and this difference was statistically significant (P< 0.05). The fasting blood sugar in the treatment group after treatment compared with that before treatment and with that in the control group after treatment was statistically different (P< 0.05). The post-prandial glucose in the treatment group after treatment was significantly different from that before treatment and from that in the control group after treatment (P< 0.05); the post-prandial blood sugar in the treatment group was reduced by 8.98%. CONCLUSIONS: The results revealed that the botanical compound (Glyco-Persica(®)) has significant hypoglycemic properties which affect main clinical symptoms in diabetes type 2. Body weight, blood pressure, heart rate, routine blood, stool and urine tests showed no meaningful negative changes after the course of treatment. There was no significant adverse reaction during the trial.