Ali Moshiri

Biological properties and therapeutic activities of honey in wound healing: A narrative review and meta-analysis

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.

Platelet-rich plasma for bone healing and regeneration.

ABSTRACT 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.

Tendon and Ligament Tissue Engineering, Healing and Regenerative Medicine

Tendons transmit forces from muscle to bone and provide the joint function and ligaments transmit forces from bone to bone and provide joint stability. Tendon and ligament injuries have high incidence and management of tendon and ligament injuries is technically demanding because the healing response of these soft connective tissues is low. In addition, number of the available options to be considered as tissue replacement for large defects is low and healing of tendon and ligaments is faced to significant limitations. Among the available options, autografts are still gold standard but all the auto- allo and xenografts have their own limitations. Tissue engineering is a newer option but it is still primitive to be applicable extensively, in clinical setting. Tissue engineering could be divided into four categories including scaffolds, healing promotive factors, stem cells and gene therapy. To be able to have a good judgment regarding the management of tendon and ligament injuries, it is crucial to have a basic knowledge of tendon and ligament healing and regeneration. In this review, we discussed various types of tendon and ligament injuries and their incidence, and introduced the available and future options in managing large and massive tendon and ligament injuries. We specifically discussed the tissue engineering and it’s advantageous and disadvantageous. To give a better clarification for the readers, we described different phases and cascades of tendon and ligament healing, modeling and remodeling, host-graft interaction after implantation of the graft and various types of prosthetic implants and finally provided some suggestions for the future investigations.

Novel application of Theranekron® enhanced the structural and functional performance of the tenotomized tendon in rabbits.

The effects of Tarantula cubensis extract (TC; Theranekron®) on the experimentally induced rupture of the superficial digital flexor tendon (SDFT) 28 days post-injury (DPI) was studied in rabbits. Forty mature White New Zealand male rabbits were randomly divided into two groups. TC was repeatedly injected subcutaneously over the lesion 3, 7 and 10 days after tenotomy and surgical anastomosis. Clinical and ultrasonographic evaluations were conducted at weekly intervals. The animals were euthanized 28 DPI and the tendons were investigated for macroscopic, histopathologic, ultrastructural, biomechanical and percent dry weight parameters. Treatment reduced signs of acute inflammation and strongly ameliorated clinical symptoms, structural organization and biomechanical properties (p < 0.05). Apparently, TC is effective in restoring the clinical, morphological and biomechanical properties of the injured SDFT in rabbits and may be valuable in human and veterinary medicine.

Comparative study on the role of gelatin, chitosan and their combination as tissue engineered scaffolds on healing and regeneration of critical sized bone defects: an in vivo study.

Gelatin and chitosan are natural polymers that have extensively been used in tissue engineering applications. The present study aimed to evaluate the effectiveness of chitosan and gelatin or combination of the two biopolymers (chitosan–gelatin) as bone scaffold on bone regeneration process in an experimentally induced critical sized radial bone defect model in rats. Fifty radial bone defects were bilaterally created in 25 Wistar rats. The defects were randomly filled with chitosan, gelatin and chitosan–gelatin and autograft or left empty without any treatment (n = 10 in each group). The animals were examined by radiology and clinical evaluation before euthanasia. After 8 weeks, the rats were euthanized and their harvested healing bone samples were evaluated by radiology, CT-scan, biomechanical testing, gross pathology, histopathology, histomorphometry and scanning electron microscopy. Gelatin was biocompatible and biodegradable in vivo and showed superior biodegradation and biocompatibility when compared with chitosan and chitosan–gelatin scaffolds. Implantation of both the gelatin and chitosan–gelatin scaffolds in bone defects significantly increased new bone formation and mechanical properties compared with the untreated defects (P < 0.05). Combination of the gelatin and chitosan considerably increased structural and functional properties of the healing bones when compared to chitosan scaffold (P < 0.05). However, no significant differences were observed between the gelatin and gelatin–chitosan groups in these regards (P > 0.05). In conclusion, application of the gelatin alone or its combination with chitosan had beneficial effects on bone regeneration and could be considered as good options for bone tissue engineering strategies. However, chitosan alone was not able to promote considerable new bone formation in the experimentally induced critical-size radial bone defects.

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

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.

Chemical crosslinking of biopolymeric scaffolds: Current knowledge and future directions of crosslinked engineered bone scaffolds

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.

Effectiveness of tissue engineered chitosan-gelatin composite scaffold loaded with human platelet gel in regeneration of critical sized radial bone defect in rat

&NA; Although many strategies have been utilized to accelerate bone regeneration, an appropriate treatment strategy to regenerate a new bone with optimum morphology and mechanical properties has not been invented as yet. This study investigated the healing potential of a composite scaffold consisting of chitosan (CS), gelatin (Gel) and platelet gel (PG), named CS‐Gel‐PG, on a bilateral critical sized radial bone defect in rat. Eighty radial bone defects were bilaterally created in 40 Sprague‐Dawley rats and were randomly divided into eight groups including untreated, autograft, CS, Gel, CS‐PG, Gel‐PG, CS‐Gel, and CS‐Gel‐PG treated defects. The bone defects were evaluated clinically and radiologically during the study and their bone samples were assessed by gross and histopathology, histomorphometry, CT‐scan, scanning electron microscopy, and biomechanical testing after 8 weeks of bone injury. The autograft and CS‐Gel‐PG groups showed significantly higher new bone formation, density of osseous and cartilaginous tissues, bone volume, and mechanical performance than the defect, CS and Gel‐PG groups (P < 0.05). In addition, bone volume, density of osseous and cartilaginous tissues, and numbers of osteons in the CS‐Gel‐PG group were significantly superior to the CS‐PG, CS‐Gel and Gel groups (P < 0.05). Increased mRNA levels of alkaline phosphatase, runt‐related transcription factor 2, osteocalcin, collagen type 1 and CD31, vascular endothelial growth factor as osteogenic and angiogenic differentiation markers were found with the CS‐Gel‐PG scaffold by quantitative real‐time PCR in vitro after 30 days of culturing on bone marrow‐derived mesenchymal stem cells. In conclusion, the healing potential of CS‐Gel scaffold embedded with PG was comparable to autografting and therefore, it can be offered as an appropriate scaffold in bone tissue engineering and regenerative applications.

Topical Application of Aloe vera Accelerated Wound Healing, Modeling, and Remodeling: An Experimental Study.

ObjectiveTreatment of large wounds is technically demanding and several attempts have been taken to improve wound healing. Aloe vera has been shown to have some beneficial roles on wound healing but its mechanism on various stages of the healing process is not clear. This study was designed to investigate the effect of topical application of A. vera on cutaneous wound healing in rats. MethodsA rectangular 2 × 2-cm cutaneous wound was created in the dorsum back of rats. The animals were randomly divided into 3 groups of control (n = 20), low-dose (n = 20), and high-dose (n = 20) A. vera. The control and treated animals were treated daily with topical application of saline, low-dose (25 mg/mL), and high-dose (50 mg/mL) A. vera gel, up to 10 days, respectively. The wound surface, wound contraction, and epithelialization were monitored. In each group, the animals were euthanized at 10 (n = 5), 20 (n = 5), and 30 (n = 10) days post injury (DPI). At 10, 20, and 30 DPI, the skin samples were used for histopathological and biochemical investigations; and at 30 DPI, the skin samples were also subjected for biomechanical studies. ResultsAloe vera modulated the inflammation, increased wound contraction and epithelialization, decreased scar tissue size, and increased alignment and organization of the regenerated scar tissue. A dose-dependent increase in the tissue level of dry matter, collagen, and glycosaminoglycans’ content was seen in the treated lesions, compared to the controls. The treated lesions also demonstrated greater maximum load, ultimate strength, and modulus of elasticity compared to the control ones (P < 0.05). ConclusionsTopical application of A. vera improved the biochemical, morphological, and biomechanical characteristics of the healing cutaneous wounds in rats. This treatment option may be valuable in clinical practice.

Comparative study on the healing potential of chitosan, polymethylmethacrylate, and demineralized bone matrix in radial bone defects of rat

This study aimed to compare the effectiveness of xenogeneic demineralized bone matrix (DBM), chitosan (CS), and polymethylmethacrylate (PMMA) on the regeneration of the critical-sized radial bone defects in rats after eight weeks. Fifty bilateral radial bone defects were randomly divided into five groups including untreated defects and those treated with autograft, CS scaffold, PMMA, and DBM. The defects were evaluated by diagnostic imaging, histopathology, histomorphometry, scanning electron microscopy, and biomechanical testing. Compared with the defect, CS, and PMMA groups, the autograft and DBM treated defects showed significantly higher new bone formation, bone volume, ultimate mechanical strength, and stiffness, but significantly lower inflammatory cells, fibroblasts, fibrocytes, and strain. Moreover, DBM showed significantly superior biocompatibility, biodegradability, osteoconductivity, and osteoinductivity to the CS scaffold and PMMA. In conclusion, both CS and PMMA alone were non-biocompatible polymers with slow biodegradation which retarded bone regeneration, whereas DBM significantly improved bone healing close to the gold method. However CS was not osteoconductive or osteoinductive alone, it can be combined with other biomaterials and molecules considering the excellent properties of this carbohydrate biopolymer for bone healing and regeneration.