Gellan gum-based bi-polymeric hydrogel scaffolds loaded with Rosuvastatin calcium: A useful tool for tendon tissue regeneration.

Statins have been long used in tissue engineering, besides their marketed hypolipidemic benefits. The aim of this research was to sustain the release of rosuvastatin calcium from bi-polymeric hydrogel scaffolds. A bi-polymer blend technique was used to enhance the mechanical properties of the fabricated hydrogels. Briefly, hydrogels were prepared via crosslinking gellan gum as the main polymer together with a secondary polymer in the presence of Ca2+. The fabricated hydrogels were assessed in terms of % swelling capacity, hydrolytic degradation and % drug released to determine the most efficient carrier system. The selected hydrogel exhibited a swelling capacity of 131.45±1.49 % following 3 weeks in an aqueous environment with a % weight loss of 15.73±1.86 % after 4 weeks post-equilibrium in aqueous medium. The results ensure a proper window for adequate drug diffusion and nutrient exchange. Sustained release was attained where 94.61±2.77 % of rosuvastatin was released at the 4-week mark. Later, FT-IR and DSC, were carried out and suggested the successful crosslinking and formation of new matrix. SEM images demonstrated the porous surface of the hydrogel while a Young's modulus of 888.558±73.549 kPa indicated the suitability of the hydrogel for soft tissue engineering. In-vivo testing involved implanting the selected hydrogel at precisely surgical cuts in the Achilles tendon of male Wistar Albino rats. Upon visual and microscopic evaluation, enhanced rates of fibrous tissue formation, vascularization and collagen expression were clearly noticed in the treatment group.

Injectable systems of chitosan in situ forming composite gel incorporating linezolid-loaded biodegradable nanoparticles for long-term treatment of bone infections.

The objective of the current study was to create an efficient, minimally invasive combined system comprising in situ forming hydrogel loaded with both spray-dried polymeric nanoparticles encapsulating linezolid and nanohydroxyapatite for local injection to bones or their close vicinity. The developed system was designed for a dual function namely releasing the drug in a sustained manner for long-term treatment of bone infections and supporting bone proliferation and new tissues generation. To achieve these objectives, two release sustainment systems for linezolid were optimized namely a composite in situ forming chitosan hydrogel and spray-dried PLGA/PLA solid nanoparticles. The composite, in situ forming hydrogel of chitosan was prepared using two different gelling agents namely glycerophosphate (GP) and sodium bicarbonate (NaHCO3) at 3 different concentrations each. The spray-dried linezolid-loaded PLGA/PLA nanoparticles were developed using a water-soluble carrier (PVP K30) and a lipid soluble one (cetyl alcohol) along with 3 types of DL-lactide and/or DL-lactide-co-glycolide copolymer using nano-spray-drying technique. Finally, the optimized spray-dried linezolid nanoparticles were incorporated into the optimized composite hydrogel containing nanohydroxy apatite (nHA). The combined hydrogel/nanoparticle systems displayed reasonable injectability with excellent gelation time at 37 °C. The optimum formulae sustained the release of linezolid for 7-10 days, which reveals its ability to reduce the frequency of injection during the course of treatment of bones infections and increase the patients' compliance. They succeeded to alleviate the bone infections and the associated clinical, biochemical, radiological, and histopathological changes within 2-4 weeks of injection. As to the state of art in this study and to the best of our knowledge, no such complete and systematic study on this type of combined in situ forming hydrogel loaded with spray-dried nanoparticles of linezolid is available yet in literatures.

Polymeric nanocomposite hydrogel scaffold for jawbone regeneration: The role of rosuvastatin calcium-loaded silica nanoparticles.

Bones are subject to different types of damages ranging from simple fatigue to profound defects. In serious cases, the endogenous healing mechanism is not capable of healing the damage or restoring the normal structure and function of the bony tissue. The aim of this research was to achieve a sustained delivery of rosuvastatin and assess its efficacy in healing bone tissue damage. Rosuvastatin was entrapped into silica nanoparticles and the system was loaded into an alginate hydrogel to be implanted in the damaged tissue. Silica nanoparticles were formulated based on a modified Stöber technique and alginate hydrogel was prepared via sprinkling alginate onto silica nanoparticle dispersion followed by addition of CaCl2 to promote crosslinking and hydrogel rigidification. The selected nanoparticle formulation possessed high % drug content (100.22±0.67%), the smallest particle size (221.00±7.30 nm) and a sustained drug release up to 4 weeks (98.72±0.52%). The fabricated hydrogel exhibited a further delay in drug release (81.52±4.81% after 4 weeks). FT-IR indicated the silica nanoparticle formation and hydrogel crosslinking. SEM visualized the porous and dense surface of hydrogel. In-vivo testing on induced bone defects in New Zealand rabbits revealed the enhanced rate of new bone tissue formation, its homogeneity in color as well as similarity in structure to the original tissue.

Dual-Drug Delivery via Zein In Situ Forming Implants Augmented with Titanium-Doped Bioactive Glass for Bone Regeneration: Preparation, In Vitro Characterization, and In Vivo Evaluation.

In situ forming implants (IFIs) are non-surgical approach using biodegradable polymers to treat bone fractures. The study aimed at preparing dual-drug-loaded IFIs to deliver pitavastatin (osteogenic drug) and tedizolid (antibiotic) using zein as the implant matrix via solvent-induced phase inversion method. At first, several investigations were done on pitavastatin-loaded zein IFIs, where three concentrations of zein were used (10, 20, and 30% w/v). IFIs were evaluated for their solidification time, rheological properties, injectability, and in vitro release. IFIs containing bioactive glass nanoparticles were prepared by the addition of non-doped bioactive glass nanoparticles (BGT0; 1, 3, 5, and 10% w/v) or titanium-doped bioactive glass nanoparticles (BGT5; 1% w/v) to the selected concentration of zein (30% w/v) and then evaluated. The optimized dual-medicated implant (D-ZIFI 1) containing pitavastatin, tedizolid, sodium hyaluronate (3% w/v), and BGT5 (1% w/v) was prepared and compared to IFI lacking both sodium hyaluronate and BGT5 (D-ZIFI 2). D-ZIFI 1 and 2 sustained the release profiles of both drugs for 28 days. SEM images proved the interconnected porous structure of D-ZIFI 1 due to sodium hyaluronate. In vivo studies on surgically induced bone defects in Sprague-Dawley rats signified the proper accelerated bone healing ability of D-ZIFI 1 over D-ZIFI 2. Results presented D-ZIFI 1 as a promising, effective, non-surgical approach for bone healing.

Repair of experimentally induced femoral chondral defect in a rabbit model using Lyophilized growth promoting factor extracted from horse blood platelets (L-GFequina).

Lyophilized equine platelet derived growth factors (LGF) is a novel advanced platelet rich protein growth factor. It has been successfully applied in various fields of regenerative medicine to treat a variety of inflammatory and degenerative musculoskeletal conditions. Our study aimed to evaluate the efficacy of intraarticularly injected LGF for the remedy of articular cartilage injury, commonly characterized by progressive pain and loss of joint function in osteoarthritic rabbits. Full-thickness cylindrical cartilage defects were generated in both femoral condylar articular surfaces in twenty rabbits. The left joint of all animals was injected with the adjuvant as a self-control negative, while the right joint was injected by LGF. Four- and eight-weeks post-surgery, the femoral condyles were harvested, and assessed grossly, microscopically and immunohistochemically. Cytokines (TNF-α, IL-1ß, PDGF and TGF-ß1) contents of the chondral defects were quantified by ELISA as well as the gene expression of Col I and Col II via RT-qPCR. The LGF treated defects showed significant higher ICRS (International cartilage repair society) healing scores of cartilaginous regeneration with a significant higher histological healing score on using O'Driscoll histological scoring system. Additionally, LGF significantly lowered the levels of the pro-inflammatory cytokines TNF-α and IL-1ß. It also significantly increased the anabolic and angiogenic growth factors (PDGF and TGF-ß1), and significantly elevated the expression of chondrogenic-related marker genes; Col I and Col II. The current study reveals that LGF improves chondral healing and thus it can be a superior nominee as an adjunctive therapy to positively influence regeneration of chondral defects in osteoarthritic patients.

Crataegus sinaica defatted methanolic extract ameliorated monosodium iodoacetate-induced oxidative stress andinhibited inflammation in a rat model of osteoarthritis.

Background and purpose: Osteoarthritis is a degenerative joint disease without definite treatment. It is characterized by intra-articular inflammation, cartilage degeneration, subchondral bone remodeling, and joint pain. The objective of the current study was to assess the anti-osteoarthritic effect and the possible underlying mechanism of action of Crataegus sinaica extract (CSE). Experimental approach: Intra-articular injection of monosodium iodoacetate in the right knee joint of all rats was done except for the sham group. One week later, the anti-inflammatory efficacy of CSE (100, 200, 300 mg/kg, daily p.o) for 4 successive weeks versus ibuprofen (40 mg/kg, p.o) was assessed. Serum inflammatory cytokines; as well as weekly assessment of knee joint swelling, joint mobility, and motor coordination were done. At the end of the experiment, a histopathological investigation of the affected knee joints and an x-ray investigation were also executed. Findings / Results: CSE significantly decreased joint swelling, pain behaviors, and serum levels of TNF-α, IL6, hyaluronic acid, and CTX-II. The radiographic findings revealed almost normal joint space with normal radiodensity and diameter in CSE-treated rats. As well, the histopathological and immunohistochemical investigations of the knee joints in CSE-treated groups retained the cartilage structure of knee joints. A significant reduction in the percentage of caspase-3-stained chondrocytes and a decrease in TGF-ß1 immuno-positive areas in the synovial lining and sub lining were recorded in CSE-treated rats, compared to the osteoarthritis control group. Conclusion and implications: This study approved the chondroprotective effects of CSE, and its ability to inhibit the pain associated with osteoarthritis.

Manjarix attenuated pain and joint swelling in a rat model of monosodium iodoacetate-induced osteoarthritis.

Osteoarthritis (OA) is a joint disease characterized by degeneration of cartilage, intra-articular inflammation, remodeling of subchondral bone and joint pain. The present study was designed to assess the therapeutic effects and the possible underlying mechanism of action of Manjarix, a herbal combination composed of ginger and turmeric powder extracts, on chemically induced osteoarthritis in rats. An OA model was generated by intra-articular injection of 50 µL (40 mg mL-1) of monosodium iodoacetate (MIA) into the right knee joint of rats. After one week of osteoarthritis induction, a comparison of the anti-inflammatory efficacy of indomethacin at an oral dose of 2 mg kg-1 daily for 4 successive weeks versus five decremental dose levels of Manjarix (1000, 500, 250, 125, and 62.5 mg kg-1) was performed. Serum inflammatory cytokines, interleukin 6, interleukin 8, and tumor necrosis factor alpha; C-telopeptide of type II collagen (CTX-II) and hyaluronic acid (HA) were measured, along with weekly assessment of the knee joint swelling. Pain-like behavior was assessed and knee radiographic and histological examination were performed to understand the extent of pain due to cartilage degradation. Manjarix significantly reduced the knee joint swelling, decreased the serum levels of IL6, TNF-α, CTX-II and HA, and reduced the pathological injury in joints, with no evidence of osteo-reactivity in the radiographic examination. Manjarix also significantly prevented MIA-induced pain behavior. These results demonstrate that Manjarix exhibits chondroprotective effects and can inhibit the OA pain induced by MIA, and thus it can be used as a potential therapeutic product for OA.

In-situ forming chitosan implant-loaded with raloxifene hydrochloride and bioactive glass nanoparticles for treatment of bone injuries: Formulation and biological evaluation in animal model.

In-situ forming implants receive great attention for repairing serious bone injuries. The aim of the present study was to prepare novel chitosan in-situ forming implants (CIFI) loaded with bioactive glass nanoparticles and/or raloxifene hydrochloride (RLX). Incorporating raloxifene hydrochloride (RLX) as a selective estrogen receptor modulator was essential to make use of its anti-resorptive properties. The prepared formulae were tested for their in-vitro gelation time, drug release, injectability, rheological properties, erosion rate and morphological properties. Results revealed that the formulation composed of 1% (w/v) chitosan with 2% (w/v) NaHCO3 and 1% (w/v) bioactive glass nanoparticles (CIFI-BG) possessed the most sustained drug release profile which extended over four months with low burst release effect compared to the same formulation lacking bioactive glass nanoparticles (CIFI). Selected formulations were tested for their ability to enhance bone regeneration in induced puncture in rate tibia. Results declared that these formulations were able to enhance bone regeneration after 12 weeks in comparison to the untreated tibial punctures and that containing bioactive glass could be considered as novel approach for treatment of serious bone injuries which require long term treatment and internal mechanical bone support during healing.

Long lasting in-situ forming implant loaded with raloxifene HCl: An injectable delivery system for treatment of bone injuries.

Bone injury is very serious in elder people or osteoporotic patients. In-situ forming implants (IFI) for bone rebuilding are usually poly-lactic-co-glycolic acid (PLGA)-based, which have a burst release effect. This study aimed to prepare novel liquid lipid-based PLGA-IFI loaded with raloxifene hydrochloride for prolonged non-surgical treatment of bone injuries by applying solvent-induced phase inversion technique. Labrasol® and Maisine® were added to the selected IFI forming long lasting lipid-based IFI (LLL-IFI). The formulations were characterized by analysing their in-vitro drug release, solidification time, injectability, rheological properties, and DSC in addition to their morphological properties. Results revealed that the LLL-IFI composed of 10%w/v PLGA with a lactide to glycolide ratio of 75:25 with ester terminal and 10% Maisine® possessed the most sustained drug release and lowest burst effect, as well as delayed pore formation compared to its counterpart lacking Maisine®. The selected LLL-IFI and PLGA-IFI formulations were tested for their capability to enhance bone regeneration in bone injuries induced in rats. Both formulations succeeded in healing the bones completely with the superiority of LLL-IFI in the formation of well-organized bone structures lacking fibrous tissues. The results suggest that LLL-IFI and PLGA-IFI are innovative approaches for treating critical and non-critical sized bone injuries.

Radiographic and ultrasonographic characteristics of ventral abdominal hernia in pigeons (Columba livia).

Five female egg-laying pigeons presented with painless, reducible, ventral abdominal swellings located between the keel and the pubis, or close to the cloaca. Based on clinical, radiographic, and ultrasonographic examination, these pigeons were diagnosed with ventral abdominal hernia requiring surgical interference. Reduction was successfully performed under general anesthesia. Radiographic and ultrasonographic examinations were beneficial for confirming the diagnosis and visualizing the hernial content for surgical planning. Lateral radiographs were more helpful than ventrodorsal radiographs for identification of the hernial content and its continuation with the abdominal muscles. Ultrasonographic examination offered a non-invasive diagnostic tool that allowed for the differentiation of hernia from other abdominal swellings. In addition, it played a beneficial role in identification of the hernial content and follow up after surgical interference. In conclusion, radiographic and ultrasonographic examinations were beneficial in the diagnosis, surgical planning, and follow up after surgical interference of ventral abdominal hernia in pigeons.