Mechanical adaptability of sea cucumber Cuvierian tubules involves a mutable collagenous tissue.

Despite their soft body and slow motion, sea cucumbers present a low predation rate, reflecting the presence of efficient defence systems. For instance, members of the family Holothuriidae rely on Cuvierian tubules for their defence. These tubules are normally stored in the posterior coelomic cavity of the animal, but when the sea cucumber is threatened by a potential predator, they are expelled through the cloacal aperture, elongate, become sticky and entangle and immobilise the predator in a matter of seconds. The mechanical properties (extensibility, tensile strength, stiffness and toughness) of quiescent (i.e. in the body cavity) and elongated (i.e. after expulsion) Cuvierian tubules were investigated in the species Holothuria forskali using traction tests. Important mechanical differences were measured between the two types of tubules, reflecting adaptability to their operating mode: to ease elongation, quiescent tubules present a low resistance to extension, while elongated tubules present a high toughness to resist tractions generated by the predator. We demonstrate that a mutable collagenous tissue (MCT) is involved in the functioning of these organs: (1) some mechanical properties of Cuvierian tubules are modified by incubation in a cell-disrupting solution; (2) the connective tissue layer encloses juxtaligamental-like cells, a cell type present in all MCTs; and (3) tensilin, a MCT stiffening protein, was localised inside these cells. Cuvierian tubules thus appear to enclose a new type of MCT which shows irreversible stiffening.

Bone response to collagenized xenografts of porcine origin (mp3(®) ) and a bovine bone mineral grafting (4BONE(™) XBM) grafts in tibia defects: experimental study in rabbits.

OBJECTIVES: This study aimed to carry out the evaluation of bone response of new bone formation to two different xenografts (bovine and porcine) biomaterials inserted in rabbit tibiae. MATERIALS AND METHODS: The study used a total of 20 male New Zealand albino rabbits. They received a total of 40 grafts in the proximal metaphyseal areas of both tibiae. Two biomaterials were evaluated: 20 porcine xenografts, as a bone granulate (OsteoBiol(®) MP3(®) ; Tecnoss srl, Giaveno, Italy), were placed in the proximal metaphyseal area of the right tibia, 20 anorganic bovine bone mineral grafting (4BONE(™) XBM, MIS Implants Inc., BARLEV, Israel) were placed in the left tibia. Following graft insertion, the animals were sacrificed in two groups of 10 animals, after 1 and 4 months, respectively. For each group, biomaterials were analyzed: newly formed bone, residual graft materials and the connective tissue. Histomorphometric, EDX analysis and element mapping were performed at 1 and 4 months after graft insertion. RESULTS: At 4 months after treatment, the bone defects displayed radiological images that showed complete repair of osseous defects. Histomorphometric evaluation showed that for the porcine xenograft, the study averages for newly formed bone represented 84.23 ± 2.9%, while bovine matrix was 79.34 ± 2.1%. For residual graft material, the porcine biomaterial had 11.23 ± 1.7% and the bovine graft 31.56 ± 2.3%. Finally, the connective tissue for MP3 was 10.33 ± 1.8%, while for the 4BONE(™) XBM we obtained 14.34 ± 2.9%. Element analysis revealed higher percentages of Ca (54 ± 9%) and P (35 ± 6%) in the group B than group A and control group (P < 0.05). CONCLUSIONS: Defects of a critical size in a rabbit tibia model can be sealed using a bovine porous biphasic calcium phosphate and MP3 material; this supports new bone formation, creates a bridge between borders, and facilitates bone ingrowth in both biomaterials. Furthermore, this study observed partial dissolution of the mineral phase of four bone graft and complete resorption of porcine MP3 biomaterial and its incorporation into the surrounding bone. Depending on clinical needs, each biomaterial could be useful in daily clinical practice.

Radula formation in two species of Conoidea (Gastropoda).

The radula is the basic feeding structure in gastropod molluscs and exhibits great morphological diversity that reflects the exceptional anatomical and ecological diversity occurring in these animals. This uniquely molluscan structure is formed in the blind end of the radular sac by specialized cells (membranoblasts and odontoblasts). Secretion type, and the number and shape of the odontoblasts that form each tooth characterize the mode of radula formation. These characteristics vary in different groups of gastropods. Elucidation of this diversity is key to identifying the main patterns of radula formation in Gastropoda. Of particular interest would be a phylogenetically closely related group that is characterized by high variability of the radula. One such group is the large monophyletic superfamily Conoidea, the radula of which is highly variable and may consist of the radular membrane with five teeth per row, or the radular membrane with only two or three teeth per row, or even just two harpoon-like teeth per row without a radular membrane. We studied the radulae of two species of Conoidea (Clavus maestratii Kilburn, Fedosov & Kantor, 2014 [Drilliidae] and, Lophiotoma acuta (Perry, 1811) [Turridae]) using light and electron microscopy. Based on these data and previous studies, we identify the general patterns of the radula formation for all Conoidea: the dorsolateral position of two groups of odontoblasts, uniform size, and shape of odontoblasts, folding of the radula in the radular sac regardless of the radula configuration. The morphology of the subradular epithelium is most likely adaptive to the radula type.

Architecture of connective tissue regenerated by enamel matrix derivative around hydroxyapatite implanted into tooth extraction sockets in the rat maxilla.

We investigated the architecture of periodontal ligament regenerated by an enamel matrix derivative (EMD, Emdogain®) coating on the surface of hydroxyapatite (EMD-HA). Immediately after extraction of the maxillary first molar in rats, HA alone or EMD-HA was implanted into the socket. At 5 days, and 2 and 4 weeks after implantation, the specimens were examined by light and transmission electron microscopy, and immunohistochemistry for periostin and matrix metalloproteinase (MMP)-13. Histological observations revealed a large number of fibroblasts and well-developed blood capillaries in the fibrous connective tissue surrounding EMD-HA at 5 days. Ultrastructural analysis showed a distinct difference in the architecture of the fibrous connective tissue. As compared with the poorly constructed architecture of HA, EMD-HA had an orderly alignment of fibroblasts and bundled collagen fibers, with some fibroblasts in the cytoplasm showing collagen fiber phagocytosis. Periostin immunoreactivity was observed in the fibrous connective tissue around EMD-HA at each time point, but was not seen in HA at 5 days and 2 weeks. MMP-13 immunoreactivity was intensely localized in fibroblasts at 5 days and 2 weeks in EMD-HA. The present results indicate that EMD may greatly contribute to a well-developed architecture accompanied by orderly alignment of fibroblasts and bundled collagen fibers, through accelerated induction of periostin, maintenance of fibrillogenesis, and degradation of collagen fibers by extracellular proteinase and phagocytosis.

TRPV2 expression in rat oral mucosa.

The oral mucosa is a highly specialised, stratified epithelium that confers protection from infection and physical, chemical and thermal stimuli. The non-keratinised junctional epithelium surrounds each tooth like a collar and is easily attacked by foreign substances from the oral sulcus. We found that TRPV2, a temperature-gated channel, is highly expressed in junctional epithelial cells, but not in oral sulcular epithelial cells or oral epithelial cells. Dual or triple immunolabelling with immunocompetent cell markers also revealed TRPV2 expression in Langerhans cells and in dendritic cells and macrophages. Electron microscopy disclosed TRPV2 immunoreactivity in the unmyelinated and thinly myelinated axons within the connective tissue underlying the epithelium. TRPV2 labelling was also observed in venule endothelial cells. The electron-dense immunoreaction in junctional epithelial cells, macrophages and neural axons occurred on the plasma membrane, on invaginations of the plasma membrane and in vesicular structures. Because TRPV2 has been shown to respond to temperature, hypotonicity and mechanical stimuli, gingival cells expressing TRPV2 may act as sensor cells, detecting changes in the physical and chemical environment, and may play a role in subsequent defence mechanisms.

Hierarchical structure in polymeric materials.

The diversity of monomers available for synthesis of high polymers makes it possible to prepare a wide variety of long-chain macromolecular compounds. It is instructive to consider a hierarchical organization of structure in polymers at four successive levels--the molecular, nano-, micro-, and macrolevels--and to examine how interactions at and between these various levels of structure have important and often quite specific influences. Examples are drawn from semicrystalline polymers with flexible chains, liquid-crystalline polymers composed of rigid macromolecules, and amorphous polymers. Structural hierarchies in biocomposite systems are also discussed, particularly in soft connective tissues such as tendon and intervertebral disk.

Biomechanical properties of synthetic and biologic graft materials following long-term implantation in the rabbit abdomen and vagina.

OBJECTIVE: We sought to evaluate the effects of anatomic location and ovariectomy on biomechanical properties of synthetic and biologic graft materials after long-term implantation. STUDY DESIGN: A total of 35 rabbits underwent ovariectomy or sham laparotomy and were implanted with polypropylene (PP) mesh (n = 17) or cross-linked porcine dermis (PS) (n = 18) in the vagina and abdomen. Grafts were harvested 9 months later and underwent mechanical properties testing. RESULTS: After implantation, PS was similar in strength (P = .52) but was twice as stiff as PP (P = .04) and had a maximal elongation only half that of PP (P < .001). Degradation of PS was associated with decreased ultimate tensile strength (P = .03) and elastic modulus (P = .046). Vaginal PP grafts shrunk more (P < .001) and were less stiff than abdominal PP grafts (P = .049) but were not different in strength (P = .19). Ovariectomy had no effect (P > .05). CONCLUSION: Cross-linked PS undergoes long-term degradation resulting in compromised biomechanical properties and thus is likely inferior to lightweight PP meshes for pelvic organ prolapse and incontinence procedures.

Protection of saphenous vein graft from arterial pressure: an experimental study.

BACKGROUND: Reoperations for bypass surgery increase the need for new grafts. We investigated early changes in both the normal human saphenous vein and in ectatic varicose veins externally supported by PTFE (polytetrafluoroethylene) graft and exposed to arterial pressure in an IN VITRO non-pulsatile flow model. MATERIAL AND METHODS: A total of 24 saphenous vein pieces (11 of them normal, the other 13 with varicosities) with a length of 6 centimeters were divided into equal parts; half of these parts were wrapped in PTFE grafts. All vein parts were placed in a perfusion circuit. Tissue biopsies were obtained from the vein segments. Light and electron microscopy examinations were performed, and endothelial continuity, elastic laminate continuity, medial connective tissue uniformity, medial smooth muscle uniformity, and adventitial connective tissue uniformity parameters were identified. RESULTS: All parameters in the PTFE protected vein groups were better. The fewest morphological changes among all four groups were detected in the vein walls from normal veins with PTFE protection. There was no significant difference in endothelial continuity and adventitial connective tissue uniformity between the normal vein group and the varicose vein group with PTFE protection. CONCLUSIONS: It is suggested that supporting vein grafts externally with PTFE sufficiently protects the vein walls against damage from exposure to arterial pressure. If varicose veins are used as arterial grafts, supporting them with PTFE may be useful because of the good protection of endothelial and medial connective tissues, resulting in similar parameters to those of normal vein walls.

Remodeling of the rat gingiva induced by CO2 laser coagulation mode.

BACKGROUND AND OBJECTIVES: This study was conducted to clarify the morphologic characteristics and subsequent repair process of coagulation necrosis produced by pulsed CO(2) laser irradiation with relatively low fluence, and thereby to evaluate the clinical efficacy of this irradiation mode. STUDY DESIGN/MATERIALS AND METHODS: Wounding of rat gingiva to produce coagulation necrosis was done with a CO(2) laser with a fluence of 326 J/cm(2). The structural characteristics of the wound and subsequent repair process were examined by means of histology, immunohistochemistry, and electron microscopy. RESULTS: At 6 hours after irradiation, the cells in the laser wound appeared histologically intact but had lost the immunoreactivity to antibodies against Hsp47 and exhibited various ultrastructural signs of cell death. This wound area was lined by Hsp70-positive cells. At 1-day post-irradiation, the uptake of BrdU rapidly increased in the adjacent epithelium and connective tissue. The re-epithelization commenced at 1 day and was completed by 7 days. The necrotic tissue gradually became integrated within the newly formed connective tissue and the original contour of the gingiva was retained during the repair process. The repair process of the laser-induced wound progressed more rapidly than that of a scalpel-made wound. CONCLUSIONS: The present study suggests that the coagulation necrosis produced by the low fluence pulsed CO(2) laser does not disturb the repair process but promotes its steady progress and subsequent tissue remodeling. This laser mode will pave the way for more conservative and minimally invasive surgery for treating a wide variety of oral soft tissue disorders.

Long-term evaluation of porous PEGT/PBT implants for soft tissue augmentation.

Porous PEGT/PBT implants with different physico-chemical characteristics were evaluated to identify its potential as biodegradable and biofunctional soft tissue filler. Implants (50 x 10 x 5 mm3) were implanted subcutaneously in mini-pigs and tissue response, tissue volume generated and its consistency were assessed quantitatively with a 52 weeks follow-up. The absence of wound edema, skin irritation, and chronic inflammation demonstrated biocompatibility of all implants evaluated. The hydrophobic implants induced the mildest foreign body response, generated highest amount of connective tissue and demonstrated a decrease in copolymer MW of 34-37% compared to 90% decrease of the hydrophilic implants. The rate and extent of copolymer fragmentation seems to be the determining factor of success of soft tissue augmentation using porous PEGT/PBT copolymer implants.

Histological study of expanded polytetrafluoroethylene (Gore-Tex) implanted in the human nose.

In rhinoplasty, various materials are used for nasal augmentation. Among these, expanded polytetrafluoroethylene (Gore-Tex) is commonly used because of its supposed high biocompatibility. However, most studies regarding histological changes associated with its implantation have been carried out in animal models, and very few data are available from long-term human studies. We used light and electron microscopy to investigate the histological changes associated with expanded polytetrafluoroethylene in nasal augmentation in 30 patients. Histologically, connective tissue ingrowth was observed in all specimens. However, the degree of foreign body reaction and collagen deposition varied from specimen to specimen and had no apparent relationship with duration. Neovascularization was observed in specimens with durations longer than 12 months, and degenerative calcification was observed in a 36-month-duration specimen. Unlike the findings in previous reports, differences among individual responses, degenerative changes, and partially calcified lesions were observed in the expanded polytetrafluoroethylene. Based on this study, expanded polytetrafluoroethylene is a biocompatible material, but further long-term studies are necessary to address histological changes associated with the implantation of the material in the human nose.

Morphological analysis of the connective tissue reaction in linear hypertrophic scars treated with intralesional steroid or silicone-gel sheeting. A light and electron microscopic study.

The linear hypertrophic scar has become the most common type of pathologic scarring. Silicone-gel sheeting is the first line therapy while intralesional steroid is the second. A light and electron microscopic analysis was carried out to reveal differences in tissue reaction following the two different treatments. Two groups of 12 patients each were treated for 4 months. For the first group, diluted Triamcinolone acetonide was injected until an inactive state was achieved. The other group of patients was treated with silicone-gel sheeting. The scars were examined every two weeks and their appearance documented. After reaching the expected therapeutic response, inactive scars were removed. The excised scars were evaluated through light microscopic histopathology and electron microscopy. The light and electron microscopic observations revealed marked differences following treatments. The activity of fibroblasts and the numbers of collagen fibers forming bundles decreased and the orientation of the collagen fibers was more variable in the treated scars. The amount of elastic fibers increased after both steroid and silicone-gel sheeting treatment. Vascularization was also slightly changed, with more capillaries and fewer pre-capillary arteries detected in the treated scars. Both treatments resulted in the same decrease in score but steroid treatment was more rapid in onset. We suggest that the two different treatments work through different mechanisms, although the final functional outcome is similar.

New insights into the cellular makeup and progenitor potential of palatal connective tissues.

The present study investigated the regenerative potential of connective tissues harvested from two palatal areas widely used as donor sites for muco-gingival surgical approaches. Connective tissue grafts (CTGs) were obtained by de-epithelialisation of a free gingival graft (deCTG) and by a split flap approach from a previous donor site (reCTG). Two types of mesenchymal stem cell (MSCs) were isolated and were named de-epithelialised MSCs (deMSCs) and re-entry MSCs (reMSCs). The cells were characterised and cellular functionality was investigated. CTGs were evaluated using immunohistochemical and ultrastructural approaches. No significant differences were observed regarding the frequency of colony-forming unit- fibroblasts, migration potential, and population doubling time between the two cell lines (p > 0.05). Both cell lines showed positivity for CD105, CD73, CD90, and CD44 and negative expression for CD34/45, CD14, CD79a, and HLA-DR. MSCs from both cell lines successfully differentiated into osteogenic, adipogenic, and chondrogenic lineages. Cells expressing antigens characteristic of CD34+ stromal cells (CD34+, αSMA-, CD31-) were traced in both CTGs. Ultrastructural analysis highlighted the presence of putative progenitors, namely fibroblasts,-in the pericapillary regions and in remote regions of the lamina propria- and pericytes-surrounding the capillaries. This study provides supplementary arguments for the use of CTG grafts in clinical practice due to the presence of putative progenitor cell. However, results were inconclusive regarding clinical decision-making to determine optimal harvesting area. Prior harvesting in the donor area did not appear to alter the regenerative capabilities of the connective tissue.

Gravity spun polycaprolactone fibres for soft tissue engineering: interaction with fibroblasts and myoblasts in cell culture.

Poly(epsilon-caprolactone) (PCL) fibres were produced by wet spinning from solutions in acetone under low shear (gravity flow) conditions. As-spun PCL fibres exhibited a mean strength and stiffness of 7.9 MPa and 0.1 GPa, respectively and a rough, porous surface morphology. Cold drawing to an extension of 500% resulted in increases in fibre strength (43 MPa) and stiffness (0.3 GPa) and development of an oriented, fibrillar surface texture. The proliferation rate of Swiss 3T3 mouse fibroblasts and C2C12 mouse myoblasts on as-spun, 500% cold-drawn and gelatin-modified PCL fibres was determined in cell culture to provide a basic measure of the biocompatibility of the fibres. Proliferation of both cell types was consistently higher on gelatin-coated fibres relative to as-spun fibres at time points below 7 days. Fibroblast growth rates on cold-drawn PCL fibres exceeded those on as-spun fibres but myoblast proliferation was similar on both substrates. After 1 day in culture, both cell types had spread and coalesced on the fibres to form a cell layer, which conformed closely to the underlying topography. The high fibre compliance combined with a potential for modifying the fibre surface chemistry with cell adhesion molecules and the surface architecture by cold drawing to enhance proliferation of fibroblasts and myoblasts, recommends further investigation of gravity-spun PCL fibres for 3-D scaffold production in soft tissue engineering.

Collagen deposition around polypropylene tapes implanted in the rectus fascia of female rats.

OBJECTIVE: Implantation of the mesh induces a foreign-body reaction followed by the development of connective tissue that may alter tape property. The aim of our study was to evaluate the deposition of collagen in the vicinity of monofilament tension-free vaginal tape (TVT; Ethicon Inc., Johnson & Johnson) and multifilament intravaginal slingplasty (IVS; Tyco Healthcare) polypropylene tapes implanted in female rats. METHODS: The samples of the meshes (10 mg each) were implanted in the rectus fascia of 14 Wistar female rats and removed after 42 days. Collagen was extracted with 0.5 M acetic acid and subsequently with pepsin (1 mg/ml in 0.5 M acetic acid). Collagen concentration was measured using Sircol Collagen Assay (Biocolor Ltd.) and normalised for milligrams of tape weight. For histological examination, tape samples were stained with haematoxylin and eosin or with silver for type III collagen. RESULTS: The total amount of collagen extracted did not differ significantly between TVT and IVS samples. For both tapes, extraction with acetic acid yielded a higher amount of collagen (about 70%) than extraction with pepsin. On histological examination, less densely packed bundles of collagen fibres and a slightly more intense inflammatory reaction were observed with TVT compared with IVS mesh. CONCLUSION: The total amount of collagen deposited around the polypropylene mesh implanted in female rats was similar for TVT and IVS meshes, but differences were noted in the arrangement of the collagen fibres and the intensity of the inflammatory reaction.

Arrangement of Peri-implant Connective Tissue Fibers Around Platform-Switching Implants with Conical Abutments and Its Relationship to the Underlying Bone: A Human Histologic Study.

The objective of this study was to clarify and evaluate the orientation of the collagen fibers around platform-switching (PS) implants with conical abutments in humans after 8 weeks of healing, and to determine how this orientation would help stabilize the soft tissue and prevent bone resorption. On PS implants, circular orientation of collagen fiber was observed as the main arrangement in a cross-sectional view. The circular collagen fibers might be the key factor in stabilizing the soft tissues around the rehabilitation, inhibiting apical migration of the soft tissues and, in turn, protecting the underlying bone.

Ultrastructural evaluation of gingival connective tissue in hereditary gingival fibromatosis.

OBJECTIVE: To describe the ultrastructural features of hereditary gingival fibromatosis (HGF) in affected family members and compare microscopic findings with normal gingival (NG) tissue. STUDY DESIGN: Gingival tissue samples from nine patients with HGF from five unrelated families were evaluated by transmission electron microscopy. Nine NG tissue samples were used for comparison. RESULTS: Areas containing collagen fibrils forming loops and folds were observed in both groups, whereas oxytalan fibers were frequently identified in the HGF group. The diameter of collagen fibrils and the interfibrillar space among them were more uniform in the NG group than in the HGF group. Fibroblasts were the most common cells found in both the HGF and NG groups and exhibited enlarged, rough endoplasmic reticulum, mitochondria with well-preserved crests, conspicuous nucleoli, and euchromatic chromatin. Other cells, such as mast cells, plasma cells, and macrophages, were also observed. CONCLUSIONS: HGF tissues had ultrastructural characteristics that were very similar to those of NG tissues. Oxytalan fibers were observed more frequently in the HGF samples than in the NG samples. Other studies of HGF in patients from different families should be performed to better understand the pathogenesis of this hereditary condition.

A survey of clearing techniques for 3D imaging of tissues with special reference to connective tissue.

For 3-dimensional (3D) imaging of a tissue, 3 methodological steps are essential and their successful application depends on specific characteristics of the type of tissue. The steps are 1° clearing of the opaque tissue to render it transparent for microscopy, 2° fluorescence labeling of the tissues and 3° 3D imaging. In the past decades, new methodologies were introduced for the clearing steps with their specific advantages and disadvantages. Most clearing techniques have been applied to the central nervous system and other organs that contain relatively low amounts of connective tissue including extracellular matrix. However, tissues that contain large amounts of extracellular matrix such as dermis in skin or gingiva are difficult to clear. The present survey lists methodologies that are available for clearing of tissues for 3D imaging. We report here that the BABB method using a mixture of benzyl alcohol and benzyl benzoate and iDISCO using dibenzylether (DBE) are the most successful methods for clearing connective tissue-rich gingiva and dermis of skin for 3D histochemistry and imaging of fluorescence using light-sheet microscopy.

Ultrastructure and composition of basement membranes in the tooth.

The tooth, the hardest organ in the body, is known to be formed through highly elaborate, unique processes of differentiation and development. Basement membranes play critical roles in fundamentally important biological processes such as growth and differentiation, and for better understanding of the mechanism of development and maintenance of the tooth, specializations of tooth basement membranes are reviewed in detail in relation to their roles. The basement membrane at such diverse locations in the tooth as the inner enamel epithelium, maturation-stage ameloblasts, and junctional epithelium at the dentogingival border are specialized in their own highly unique ways for anchoring, firm binding, or mediation in the transport of substances. Thus, the role of basement membranes in the developing and mature tooth is manifold and for these roles individual basement membranes are specialized in their own specific ways which are rare or not seen in nondental tissues, and these specializations are essential for successful development and maintenance of the tooth.

A rat model of radiation injury in the mandibular area.

BACKGROUND: Radiation technology focuses on delivering the radiation as precisely as possible to the tumor, nonetheless both acute and long-term damage to surrounding normal tissue may develop. Injuries to the surrounding normal tissue after radiotherapy of head and neck cancer are difficult to manage. An animal model is needed to elucidate good treatment modalities. The aim of this study was to establish a rat model where a certain radiation dose gives reproducible tissue reactions in the mandibular area corresponding to injuries obtained in humans. METHOD: The left mandible of male Sprague Dawley rats was irradiated by external radiotherapy (single fraction 15 Gy, total dose 75 Gy) every second week five times. Endpoint was six weeks after last radiation treatment, and the test group was compared to non-irradiated controls. Morphological alterations of the soft tissues, bone and tooth formation, as well as alterations of salivation, vascularity and collagen content were assessed. An unpaired, non-parametric Mann-Whitney test was used to compare the statistical differences between the groups. RESULTS: Analysis of the soft tissues and mandible within the radiation field revealed severe unilateral alopecia and dermatitis of the skin, extensive inflammation of the submandibular gland with loss of serous secretory cells, hyperkeratinization and dense connective fiber bundles of the gingival tissue, and disturbed tooth development with necrosis of the pulp. Production of saliva and the vascularity of the soft tissues were significantly reduced. Furthermore, the collagen fibril diameter was larger and the collagen network denser compared to non-irradiated control rats. CONCLUSION: We have established an animal model of radiation injury demonstrating physiological and histological changes corresponding to human radiation injuries, which can be used for future therapeutic evaluations.