Structural and functional modulation of early healing of full-thickness superficial digital flexor tendon rupture in rabbits by repeated subcutaneous administration of exogenous human recombinant basic fibroblast growth factor
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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- "Each of these can be used alone (monotherapy) or designed in combination with other components as poly-therapy  . One of the most important features that a tissue engineered bio-implant should exhibit is osteoinductivity usually provided by growth factors   . Osteoinduction is the process of differentiation of the mesenchymal stem cells (MSCs) into osteoprogenitor cells and ultimately into osteoblasts to form new bone  . "
ABSTRACT: Healing and regeneration of large bone defects leading to non-unions is a great concern in orthopedic surgery. Since auto- and allografts have limitations, bone tissue engineering and regenerative medicine (TERM) has attempted to solve this issue. In TERM, healing promotive factors are necessary to regulate the several important events during healing. An ideal treatment strategy should provide osteoconduction, osteoinduction, osteogenesis, and osteointegration of the graft or biomaterials within the healing bone. Since many materials have osteoconductive properties, only a few biomaterials have osteoinductive properties which are important for osteogenesis and osteointegration. Bone morphogenetic proteins (BMPs) are potent inductors of the osteogenic and angiogenic activities during bone repair. The BMPs can regulate the production and activity of some growth factors which are necessary for the osteogenesis. Since the introduction of BMP, it has added a valuable tool to the surgeon’s possibilities and is most commonly used in bone defects. Despite significant evidences suggesting their potential benefit on bone healing, there are some evidences showing their side effects such as ectopic bone formation, osteolysis and problems related to cost effectiveness. Bone tissue engineering may create a local environment, using the delivery systems, which enables BMPs to carry out their activities and to lower cost and complication rate associated with BMPs. This review represented the most important concepts and evidences regarding the role of BMPs on bone healing and regeneration from basic to clinical application. The major advantages and disadvantages of such biologic compounds together with the BMPs substitutes are also discussed. VC 2014 BioFactors, 00(00):000–000, 2014BioFactors 09/2014; 40(5):459–481. DOI:10.1002/biof.1177 · 3.00 Impact Factor
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- "This multifunctional, 146 amino acid polypeptide has been shown to affect the proliferation, chemotaxis, and differentiation of mesoderm-derived cells  . Recent studies have identified it as a potential stimulator of angiogenesis, and this protein has been intensively studied in the wound healing processes of various animals   . Moreover, other proteins involved in the regulation of angiogenesis, such as vascular endothelial growth factor- A (VEGF-A), have been shown to play important roles in the remodeling of tendons and in their degenerative diseases . "
ABSTRACT: Physical exercise and massage are regarded as key factors in regulating tendon structure. However, information on the mechanism through which massage influences the structure and biology of a tendon is scarce. In this study, we attempted to define the impact of these two activities on rat tendons by using morphological and molecular techniques, determining the expression of VEGF-A, FGF-2, and CD34 in the tendons of rats subjected to 10 weeks of physical exercise (running) with massage of varied duration. The group of rats that was trained and massaged during the entire study was characterized by the highest expression of these markers, compared to the rats subjected to massage before training and to the control group subjected to physical exercises only. The greatest significant differences, compared to the control, were noted in the expression of all the studied markers at mRNA level, and in the case of VEGF-A, at protein level, in the third and fifth weeks of the experiment. The results of this study could point to the synergistic impact of simultaneous massage and physical exercise on the expression of angiogenesis markers in rat tendons.BioMed Research International 05/2014; 2014:878095. DOI:10.1155/2014/878095 · 2.71 Impact Factor
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- "There are many orthopaedic experimental studies which involve the hind legs of rabbits in order to study nerve lesions , bone defects   or tendon injuries  . Interestingly, some researchers decide to use only one hind leg for treatment, while the second hind leg serves as an internal reference     . In contrast, "
ABSTRACT: Considering the 3Rs principle in animal experiments, there is a demand to perform research experiments with the fewest number of animals possible while warranting the welfare of the animals. Orthopaedic experimental studies involving operations on the hind legs of rabbits are either performed on one hind leg with the second hind leg serving as control or on both hind legs simultaneously (control: rabbits with no operations at all). The Achilles tendon of rabbits was transected and sutured, and the two-dimensional motion pattern of animals having only one leg operated was compared to rabbits having both hind legs operated (control: non-treated animals). Step length, maximum ankle angle, minimum ankle angle and the resulting range of motion of both hind legs were determined weekly over a time span from 3 weeks to 12 weeks post-operation. The results were fitted by a linear mixed effects model including time dependency. Moreover, all tendon specimen were analysed histologically. Tenocyte and tenoblast density, tenocyte and tenoblast nuclei width, inflammation level and collagen fibre alignment were determined. Statistically significant differences in the motion pattern were found when one-leg treated and two-leg treated animals were compared. However, the absolute differences were on average less than 20%. Histologically, 1-leg treated animals had tendon tissue with higher cell density, but lower inflammation and less ondulated collagen fibres compared to 2-leg treated animals; the nuclei width was the same for both groups. With regard to welfare, all animals were fine during the experiments. While comparative studies should be performed with one-leg treated animals due to interaction effects, for proof-of-principle studies, operating two legs per animal may be justified as the welfare of the animals is warranted. This is a great benefit in the sense of the 3Rs because up to 50% of animals can be spared.Injury 07/2013; 18. DOI:10.1016/j.injury.2013.05.014 · 2.46 Impact Factor