Bone tissue scaffolds made from either natural or synthetic polymers are employed to promote bone healing. However, lack of sufficient or poor mechanical properties such as low integrity and ...stability reduces their medical applications. Crosslinking, defined as induction of chemical or physical links among polymer chains, is a simple method generally used to modify mechanical, biological and degradation properties of hydrogels. Although crosslinking through chemical reactions improves the mechanical properties of bone substitutes, most of the reagents used for this aim demonstrate undesirable effects and may exert toxic reactions. Glutaraldehyde is a widely-used chemical crosslinker with unique ability to crosslink a wide variety of biomaterials; however, many contradictory views have been recently raised on its cytotoxic effects. By keeping this limit in mind, green chemicals or natural crosslinking agents have been shown to provide desired improvements in mechanical properties of bone scaffolds. Therefore, developing more efficient crosslinking materials and methods are desirable to obtain crosslinked scaffolds with perfect properties in bone tissue engineering from different biopolymers such as collagen, gelatin, cellulose, chitosan, alginate, etc. In this review, we focused on developed or developing modalities used to improve mechanical properties of various bone scaffolds and matrices based on common crosslinking reagents.
Statins are known for their beneficial effects on cardiovascular diseases. Besides the lipid-lowering properties, statins exert their anabolic effects on the bone by differentiating mesenchymal cells ...to osteoblasts via upregulating BMP-2 and protecting osteoblasts from apoptosis. In addition, statins have been suggested to be anti-osteoclastic by reducing the osteoclast differentiation and activity. Several in vivo and clinical studies have confirmed the beneficial effects of statins in the treatment of osteoporosis and fracture injuries. However, controversial results exist showing statins may have no benefit and in some instances, they may retard bone repair. Different factors such as type, route of administration, dose and dosage of statins, and the injury model seem to be involved for such controversies. In the present study, the most important issues regarding statins have been reviewed to find out how statins may be beneficial and statin therapy can be improved for treating osteoporosis and fracture injuries. The lipophilic statins particularly simvastatin and atorvastatin are the most investigated statins with beneficial results on bone healing and turnover. Most of the in vivo and clinical studies performed systemic route of administration for treating osteoporosis, with much higher clinical doses than the lipid lowering therapy, which increases the statin related side and out of target effects. In contrast, most of the in vivo studies that used statins for fracture repair have applied local delivery methods with much lower doses via tissue engineering approaches. However, local delivery of statins and statin therapy for fracture repair both have low application in the clinical setting and such methods are still under in vivo investigation. Future clinical trials are needed to elucidate how delivery systems and tissue engineering technologies are able to improve the outcome of statin therapy.
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Healing and regeneration of bone injuries, particularly those that are associated with large bone defects, are a complicated process. There is growing interest in the application of osteoinductive ...and osteogenic growth factors and mesenchymal stem cells (MSCs) in order to significantly improve bone repair and regeneration. MSCs are multipotent stromal stem cells that can be harvested from many different sources and differentiated into a variety of cell types, such as preosteogenic chondroblasts and osteoblasts. The effectiveness of MSC therapy is dependent on several factors, including the differentiating state of the MSCs at the time of application, the method of their delivery, the concentration of MSCs per injection, the vehicle used, and the nature and extent of injury, for example. Tissue engineering and regenerative medicine, together with genetic engineering and gene therapy, are advanced options that may have the potential to improve the outcome of cell therapy. Although several in vitro and in vivo investigations have suggested the potential roles of MSCs in bone repair and regeneration, the mechanism of MSC therapy in bone repair has not been fully elucidated, the efficacy of MSC therapy has not been strongly proven in clinical trials, and several controversies exist, making it difficult to draw conclusions from the results. In this review, we update the recent advances in the mechanisms of MSC action and the delivery approaches in bone regenerative medicine. We will also review the most recent clinical trials to find out how MSCs may be beneficial for treating bone defects.
Abstract For thousands of years, honey has been used for medicinal applications. The beneficial effects of honey, particularly its anti-microbial activity represent it as a useful option for ...management of various wounds. Honey contains major amounts of carbohydrates, lipids, amino acids, proteins, vitamin and minerals that have important roles in wound healing with minimum trauma during redressing. Because bees have different nutritional behavior and collect the nourishments from different and various plants, the produced honeys have different compositions. Thus different types of honey have different medicinal value leading to different effects on wound healing. This review clarifies the mechanisms and therapeutic properties of honey on wound healing. The mechanisms of action of honey in wound healing are majorly due to its hydrogen peroxide, high osmolality, acidity, non-peroxide factors, nitric oxide and phenols. Laboratory studies and clinical trials have shown that honey promotes autolytic debridement, stimulates growth of wound tissues and stimulates anti-inflammatory activities thus accelerates the wound healing processes. Compared with topical agents such as hydrofiber silver or silver sulfadiazine, honey is more effective in elimination of microbial contamination, reduction of wound area, promotion of re-epithelialization. In addition, honey improves the outcome of the wound healing by reducing the incidence and excessive scar formation. Therefore, application of honey can be an effective and economical approach in managing large and complicated wounds.
Introduction: Successful healing of large bone defects (LBDs) is a complicated phenomenon because the body's natural ability often fails to effectively repair the LBDs. New modalities should be ...utilized to increase the quality and accelerate bone healing. Platelet concentrates in different forms can be considered an attractive option for such purpose.
Areas covered: Platelets as a natural source of growth factors, cytokines, and other micro and macromolecules are hypothesized to improve bone healing. This review has covered important concepts regarding platelet-rich plasma (PRP) including mechanisms of action, preparation protocols and their differences, and factors affecting the PRP efficacy during bone healing. In addition, the most recent studies in different levels which evaluated the role of PRP on bone repair has been reviewed and discussed to clarify the controversies and conflicts, and to illustrate a future prospective and directions for orthopedic surgeons to overcome current limitations and difficulties.
Expert opinion: As the efficacy of PRP is dependent on various factors, the outcome of PRP therapy is variable and unpredictable in orthopedic patients. Therefore, it is still too soon to suggest PRP as the first line treatment option in complicated bone injuries such as LBDs and nonunions. However, combination of PRP with natural and synthetic biomaterials can enhance the effectiveness of PRP.
Healing of large tendon defects is challenging. We studied the role of collagen implant with or without polydioxanone (PDS) sheath on the healing of a large Achilles tendon defect model, in rabbits. ...Sixty rabbits were divided into three groups. A 2 cm gap was created in the left Achilles tendon of all rabbits. In the control lesions, no implant was used. The other two groups were reconstructed by collagen and collagen-PDS implants respectively. The animals were clinically examined at weekly intervals and their lesions were observed by ultrasonography. Blood samples were obtained from the animals and were assessed for hematological analysis and determination of serum PDGF level, at 60 days post injury (DPI). The animals were then euthanized and their lesions were assessed for gross and histopathology, scanning electron microscopy, biomechanical testing, dry matter and hydroxyproline content. Another 65 pilot animals were also studied grossly and histopathologically to define the host implant interaction and graft incorporation at serial time points. The treated animals gained significantly better clinical scoring compared to the controls. Treatment with collagen and collagen-PDS implants significantly increased the biomechanical properties of the lesions compared to the control tendons at 60DPI (P<0.05). The tissue engineered implants also reduced peritendinous adhesion, muscle fibrosis and atrophy, and increased ultrasonographical echogenicity and homogenicity, maturation and differentiation of the collagen fibrils and fibers, tissue alignment and volume of the regenerated tissue compared to those of the control lesions (P<0.05). The implants were gradually absorbed and substituted by the new tendon. Implantation of the bioimplants had a significant role in initiating tendon healing and the implants were biocompatible, biodegradable and safe for application in tendon reconstructive surgery. The results of the present study may be valuable in clinical practice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Polymethylmethacrylate (PMMA) is the most commonly used filler material that lacks biological properties and osteoconductivity or osteoinductivity. Platelet gel (PG) is a typical source of growth ...factors, cytokines and molecules efficient for bone formation and remodeling. The aim of this study was to evaluate bone healing and regeneration of bone defect in rat model by combining PMMA with PG. A total of 50 defects were created in the diaphysis of the radii of 25 male Sprague-Dawley rats. These defects were randomly divided into five groups (n = 10 defects for each group) and treated by autograft, plain PMMA, PG and PMMA-PG or left untreated. The rats were examined clinically and radiologically during the experiment and also after euthanasia at the 8th post-operative week, the healed defects were evaluated by gross morphology, histopathology, histomorphometry, computed tomography, scanning electron microscopy and biomechanical testing. PG could function as efficiently as autograft in promoting bone healing of the radial bones. Additionally, bone formation, and densities of cartilaginous and osseous tissues in the defects treated with autograft, PG and PMMA-PG were more satisfactory than the untreated and PMMA treated defects. Compared with the PMMA-PG implant, more PMMA residuals remained in the defect area and induced more intense inflammatory reaction. In conclusion, addition of PG could improve the bone regenerative properties of PMMA bone cement compared with PMMA alone in vivo. Therefore, the PG-PMMA can be proposed as a promising option to increase regenerative potential of PMMA, particularly when it is used as fixator, filler or adhesive in the dentistry, neurosurgery and bone tissue engineering applications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Melanoma is a dangerous type of skin cancer sometimes treated with radiotherapy. However, it induces damage to the surrounding healthy tissue and possibly further away areas. Therefore, it is ...necessary to give a lower dose to the patient with targeted therapy. In this study, the radio‐sensitising effect of gold‐coated iron oxide nanoparticles on electron beam radiotherapy of a melanoma tumour with magnetic targeting in a mouse model was investigated. Gold‐coated iron oxide nanoparticles were prepared in a steady procedure. The melanoma tumour model was induced in mice. Animals were divided into five groups: (1) normal; (2) melanoma; (3) gold‐coated iron oxide nanoparticles alone; (4) electron beam radiotherapy; (5) electron beam radiotherapy plus gold‐coated iron oxide nanoparticles. The magnet was placed on the tumour site for 2 h. The tumours were then exposed to 6 MeV electron beam radiotherapy for a dose of 8 Gy. Inductively coupled plasma optical emission spectrometry test, hematoxylin and eosin staining, and enzyme‐linked immunosorbent assay blood test were also performed. Gold‐coated iron oxide nanoparticles with magnetic targeting before electron beam radiotherapy reduced the growth of the tumour compared to the control group. Blood tests did not show any significant toxicity. Deposition of nanoparticles was more in the tumour and spleen tissue and to a lesser extent in the liver, kidney, and lung tissues. The synergistic effect of nanoparticles administered by the intraperitoneal route and then concentrated into the tumour area by application of an external permanent magnet, before delivery of the electron beam radiotherapy improved the overall cancer treatment outcome and prevented metal distribution side effects.
The gold‐coated iron oxide nanoparticles were synthesised and characterised. A magnetic field was applied for the physical delivery of synthesised nanoparticles in the melanoma tumour in a mouse model. The radio sensitising effect of the nanoparticles on electron beam radiotherapy of the melanoma tumour was investigated.
Abstract The present study was designed to investigate the effects of basic fibroblast growth factor on the healing of the acute phase of complete superficial digital flexor tendon rupture in ...rabbits. A total of 40 skeletally mature female white New Zealand rabbits were randomly divided into 2 equal groups of injured treated and injured control. After tenotomy and surgical anastomosis, using a modified Kessler and running pattern, the injured legs were placed in casts for 14 days, and basic fibroblast growth factor was injected subcutaneously over the lesion on days 3, 7, and 10 after injury. The injured control rabbits received a normal saline injection in a similar protocol. The rabbits' weight, tendon diameter, clinical signs, radiographs, and ultrasound scans were evaluated weekly. The rabbits were killed 28 days after injury, and the tendons were evaluated at the macroscopic, histopathologic, and ultrastructural levels and for biomechanical and the percentage of dry weight analysis. Treatment significantly reduced the diameter and increased the echogenicity and dry weight content and enhanced the maturation rate of the tenoblasts, fibrillogenesis, collagen fibril diameter, fibrillar density, tensile strength, and stiffness and stress of the injured tendons. Treatment with basic fibroblast growth factor was effective in restoring the morphologic and biomechanical properties of the injured superficial digital flexor tendon and could be valuable in clinical trial studies.
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