Chitosan (CS) is a carbohydrate biopolymer, which has been known as a biological material in promoting the healing process of soft and hard connective tissues. It is biocompatible, biodegradable, ...bioactive, non-toxic, non-expensive and non-immunogenic, with antibacterial capability. Additionally, the capacity of forming complexes with other anionic biomaterials and molecules offers CS the characteristics to be used in biomedical applications. Therefore, this natural polysaccharide has widely been used as a wound dressing and in bone and cartilage regeneration because of these considerable properties. However, some studies have showed limited value in application of CS in tissue regeneration. It has been used alone or in combination with other biopolymers, bioceramics, or promotive growth factors to enhance regeneration of the soft and hard connective tissues. This study has reviewed various forms of CS including hydrogels, sponges, films, and nanofiber membranes. The role of CS alone or in combined form with other materials has also been reviewed in healing and regeneration of the cutaneous, cartilage and bone wounds. In addition, the present study has attempted to clarify the controversies and conflicts regarding effectiveness of CS in the healing process.
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.
Bone Injury and Fracture Healing Biology Oryan, Ahmad; Monazzah, Somayeh; Bigham-Sadegh, Amin
Biomedical and environmental sciences,
2015, January 2015, 2015-Jan, 20150101, Letnik:
28, Številka:
1
Journal Article
Recenzirano
Bones are organs of the skeletal system, providing shape, mechanical support, and protection to the body and facilitating the movement. In addition, bones contribute to the mineral homeostasis of the ...body and have recently been found to participate in endocrine regulation of energy metabolism. The well-known limitations associated with clinical use of autografts and allografts continue to drive efforts to develop bone graft substitutes, using the principles of biomaterials and tissue engineering. Under some stressful and continuous compressive conditions, the ability of the bone tissue to tolerate strength decreases. Whenever these forces overcome the toleration of the bone tissue, bone fracture occurs. years
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.
Fracture healing is a complex physiological process, which involves a well‐orchestrated series of biological events. Repair of large bone defects resulting from trauma, tumours, osteitis, delayed ...unions, non‐unions, osteotomies, arthrodesis and multifragmentary fractures is a current challenge of surgeons and investigators. Different therapeutic modalities have been developed to enhance the healing response and fill the bone defects. Different types of growth factors, stem cells, natural grafts (autografts, allografts or xenografts) and biologic‐ and synthetic‐based tissue‐engineered scaffolds are some of the examples. Nevertheless, these organic and synthetic materials and therapeutic agents have some significant limitations, and there are still no well‐approved treatment modalities to meet all the expected requirements. Bone tissue engineering is a newer option than the traditional grafts and may overcome many limitations of the bone graft. To select an appropriate treatment strategy in achieving a successful and secure healing, more information concerning injuries of bones, their healing process and knowledge of the factors involved are required.
The main goals of this work are to present different treatment modalities of the fractured bones and to explain how fractures normally heal and what factors interfere with fracture healing. This study provides an overview of the processes of fracture healing and discusses the current therapeutic strategies that have been claimed to be effective in accelerating fracture healing.
Accelerative effect of topical administration of DEO on infected wound healing; (A) DEO by up-regulating the FGF-2 and VEGF expression enhances the angiogenesis and fibroblasts distribution, ...respectively. That in turn enhances the vascularization and cellularity at early stages of the healing process. On day 8 after wound induction (B) the DEO by up-regulating the ERα expression increases the bcl-2 mRNA level and protein biosynthesis, which reduces the p53 expression and biosynthesis. All these alterations result in accelerated fibroblast proliferation that finally elevates the collagen biosynthesis as well as dermal maturation. The elevated bcl-2 expression enhances the epithelial cells proliferation and ultimately shortens the re-epithelialization.
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•DEO, exerted antibacterial impact against MRS.•DEO, shortened inflammation and promoted cellularity.•DEO significantly up-regulated VGEF and FGF-2 expression.•DEO ameliorated bcl-2, p53 and caspase III expression.•DEO provoked angiogenesis by enhancing ERα expression.
Medicinal plants are conventionally used for wound healing, but their action mechanisms are still unknown. The present study evaluated the effect of topical administration of ointment containing dill (Anethum graveolens) essential oil (DEO) in the management of apoptosis and cell proliferation during MRSA-infected experimentally induced wound healing process in BALB/c mice model. The GC-FID and GC-MS techniques were used to analyze chemical composition of the essential oil. The mice were randomly divided into four treatment groups including negative control (sham), 2% and 4% DEO and mupirocin®-treated animals. The full-thickness excisional wounds were inoculated by 5 × 107 colony-forming units of MRSA. In order to assess the effect of different concentrations of DEO on wounds infection, wound area, bacterial count, histopathological, immunohistochemical and RT-PCR analysis were evaluated. The GC-MS analysis identified α-phellandrene (47.3%), p-cymene (18.5%) and carvone (14.1%) as the main compounds of the essential oil tested here. Administration of DEO prevented bacterial growth and also reduced wound area in comparison to the control group. Topical administration of DEO significantly reduced the inflammatory phase and accelerated re-epithelialization, angiogenesis, fibroblast and collagen deposition. Moreover, the DEO-treated animals exhibited higher expressions of Bcl-2, p53 caspase-3, VEGF and FGF-2 in comparison to the control and mupirocin®-treated groups (P < 0.05). Topical administration of DEO decreases the inflammatory phase by increasing p53 and caspases-3 expression. It triggers the proliferative phase by up-regulation of the Bcl-2, VEGF and FGF-2 expression and also up-regulates the collagen biosynthesis by enhancing the ERα expression level. Thus, ointment prepared from dill essential oil, in Iran, with its major compounds such as α-phellandrene, p-cymene and carvone can be used as an agent for accelerating the infected wound healing.
Osteoconductive biomaterials were used to find the most reliable materials in bone healing. Our focus was on the bone healing capacity of the stem cell–loaded and unloaded PLA/PCL/HA scaffolds. The ...3D scaffold of PLA/PCL/HA was characterized by scanning electron microscopy (SEM), rheology, X-ray diffraction (XRD), and Fourier transform-infrared (FT-IR) spectroscopy. Bone marrow stem cells (BMSCs) have multipotential differentiation into osteoblasts. Forty Wistar male rats were used to organize four experimental groups: control, autograft, scaffold, and BMSCs-loaded scaffold groups. qRT-PCR showed that the BMSCs-loaded scaffold had a higher expression level of CD31 and osteogenic markers compared with the control group (
P
< 0.05). Radiology and computed tomography (CT) scan evaluations showed significant improvement in the BMSCs-loaded scaffold compared with the control group (
P
< 0.001). Biomechanical estimation demonstrated significantly higher stress (
P
< 0.01), stiffness (
P
< 0.001), and ultimate load (
P
< 0.01) in the autograft and BMSCs-loaded scaffold groups compared with the untreated group and higher strain was seen in the control group than the other groups (
P
< 0.01). Histomorphometric and immunohistochemical (IHC) investigations showed significantly improved regeneration scores in the autograft and BMSCs-loaded scaffold groups compared with the control group (
P
< 0.05). Also, there was a significant difference between the scaffold and control groups in all tests (
P
< 0.05). The results depicted that our novel approach will allow to develop PLA/PCL/HA 3D scaffold in bone healing via BMSC loading.
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