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Currently, despite decades of trial and error, peripheral nerve injury is an impenetrable clinical dilemma. Any proven effective pharmacologic agent leads to a decisive leap forward to the clinical management of neuropathies. This study investigated the effects of tacrolimus and erythropoietin on sciatic nerve regeneration. Twenty-three mice were randomly assigned to tacrolimus, erythropoietin, tacrolimus + erythropoietin, control, and sham groups following sciatic nerve crush via hemostatic forceps. Medications were administered for 28 consecutive days. The sham group received neither crush injury nor medication. Histopathologic, immunohistochemical, and walking track analyses were performed. In the erythropoietin group, axonal swelling was significantly reduced and the average axonal number significantly recovered up to 75% of normal nerve compared to other groups. Marked immunoreactivity to GFAP and S-100 protein was present in the tacrolimus group. Nevertheless, at least moderate GFAP and S-100 expressions were observed in all of the groups. Functional recovery was superior in the tacrolimus group after 14 days, although a complete return to near-normal function was achieved in all groups after 28 days, regardless of the medication used. Our data supported the neurotrophic effects of tacrolimus and erythropoietin; however, not enough data was gathered to confirm their synergistic effects. Whether these results are extensible to clinical scenarios requires further detailed investigations. [ABSTRACT FROM AUTHOR]

Objective(s): Polyethylenimine (PEI) is one of the most-extensively investigated cationic polymers for gene and drug delivery. Recently, great attention has been directed to design of carriers for co-delivery of nucleic acids and small molecules. These delivery systems are able to overcome the limitations of gene or drug delivery alone. The aim of this study is to prepare a targeted nano-carrier for co-delivery of doxorubicin (Dox) and gene using polyethylenimine. Materials and Methods: In order to prepare the ligand-containing polymer conjugates, succinic anhydride was conjugated onto the hydroxyl group of Dox through an ester bond following the protection of Dox amines by Fmoc. Drug-polymer conjugates were then coupled with L-DOPA in order to prepare the targeted nanocarriers to the cells through Large Amino Acid Transporter-1 (LAT-1). The PEI derivatives were characterized using 1H-NMR. The toxicity of conjugated polymer, Dox and PEI was assessed on HepG2 and A375 cell lines with different expression level of LAT-1 transporters using MTT assay. Results: The chemical structure of PEI conjugate was confirmed by 1H-NMR. The cytotoxicity measurement demonstrated a cell line-dependent toxicity profile at the concentrations tested in this study. It was shown that there was no significant difference in cell-induced toxicity between conjugated polymer and its parent form in A375 cell line while the cytotoxicity of conjugated polymer was significantly lower than the parent PEI in HepG2 cells. Conclusion: These results provide promising evidence for further evaluation of PEI conjugate for co-delivery of drug and gene via LAT-1 transporters. [ABSTRACT FROM AUTHOR]

Bone is a complex, constantly changing organ comprised of mineralized hard tissue. This important structural component of vertebrate's body serves a variety of functions. Healthy bone system is essential for lifelong execution of these functions. Millions of people worldwide suffer from bone defects due to various reasons, including trauma, tumor, bone diseases, congenital defects, and aging. These defects are increasingly becoming the majority of the clinical cases in orthopedics. For all the aforementioned cases in which the normal process of bone regeneration is either impaired or simply insufficient, there are currently a number of treatment methods available which can be used either alone or in combination for the enhancement of bone healing and regeneration. Accordingly, bone repair has been the focus of many research activities related to clinical therapies. The traditional bone repair procedure widely used in current era involves the use of bone-grafting methods such as autografts, allografts, and xenografts; however, these methods are associated with number of limitations. Therefore, to overcome these problems, tissue engineering as a new and developing option had been introduced recently. In order to provide ideal bone substitutes, a wide range of biomaterials and synthetic bone substitutes are available depending on the goal, each has advantages and disadvantages. The combined use of different bone substitutes together with healing promotive factors, stem cells, gene therapy, and more recently, three-dimensional printing of tissue-engineered constructs may open new insights in bone regeneration in near future. In this review, we describe developments and recognized properties of some of the most utilized materials in bone regenerative medicine heretofore. It may be concluded that presently strong requirements are still to be met in the repair and regeneration of bone defects. [ABSTRACT FROM AUTHOR]

Today marine-derived biologic scaffolds are popular due to their biocompatibility and high regenerative potential. Previous studies prepared hydroxyapatite from cuttlebone, the internal shell of cuttlefish; However, its biocompatibility and bioactivity has not been fully studied especially in-vivo. The aim of this study was to evaluate cuttlebone-derived hydroxyapatite in-vivo potential and possible synergistic effect of platelet rich plasma with this scaffold in promoting bone healing. Hydroxyapatite was prepared from cuttlebone (Sepia officinalis) via hydrothermal transformation. The conversion and microstructure of prepared material was assessed by scanning electron microscopy (SEM) and x-ray diffraction (XRD) analysis. Fifteen male white New Zealand rabbits were randomly divided to 6 groups each containing 5 limbs. In order to reduce sample size right and left pelvic limbs of rabbits were used as separate groups. Full thickness bi-cortical defects were created bilaterally in proximal tibia. The defect was left untreated in negative control group. In experimental group I to V the defect was filled with platelet rich plasma, raw cuttlebone, raw cuttlebone combined with platelet rich plasma, cuttlebone derived hydroxyapatite and cuttlebone derived hydroxyapatite combined with platelet rich plasma, respectively. Histopathological evaluation was performed on specimens received on day 56. Bone healing was assessed according to union, spongiosa, cortex and bone marrow indices. Our results demonstrated that Group I was superior to negative control group in defined indices. Groups IV and V showed preferable outcomes regarding to union and cortex indices in comparison to groups II and III. Also acceptable degree of spongiosa formation was observed in all groups. Cuttlebone derived hydroxyapatite could be an appropriate biomaterial to stimulate bone formation and enhance bone regeneration. Furthermore platelet rich plasma was successful in advancement of bone marrow formation. [ABSTRACT FROM AUTHOR]