Changes in TGF-β1 levels in gingiva, crevicular fluid and serum associated with periodontal inflammation in humans and dogs

Transforming growth factor-beta (TGF-β) represents a family of polypeptide growth factors, involved in embryogenesis, inflammation, regulation of immune responses and wound healing. To determine whether TGF-β contributes to the evolution of periodontal disease, we assayed TGF-β levels in gingiva and crevicular fluid of patients with gingivitis and periodontitis. In parallel, TGF-β was quantified m gingival fluid and serum of beagles with experimentally-induced periodontitis. Disease was monitored by several clinical parameters including Plaque Index, Gingival Index, probing depth, and epithelial attachment loss. Gingival tissues were obtained from 9 patients at the time of periodontal surgery, and gingival fluid samples were collected from an additional population of 10 periodontal patients. In 14 beagles, experimental periodontitis was induced and gingival fluids collected 6 months later. Fluid was collected by paper strips and volume measured by Periotron. Additionally, sera was collected before and 9 months after the ligature-induced periodontitis in 7 beagles. The levels of TGF-β₁ were measured by ELISA. In the patients, a significantly higher concentration of TGF-β₁ was observed both in the gingival tissues and fluid samples obtained from the sites with deeper periodontal pockets than in the less involved sites. In beagles, TGF-β₁ levels measured in gingival fluid were elevated in moderate disease, declining in fluid samples obtained from the pockets during more advanced experimental periodontitis. Furthermore, with the progression of experimental periodontitis, a decrease in TGF-β₁ occurred in the sera of the beagle dogs. These data suggest that TGF-β₁ may play a řle in the pathogenesis and diagnosis of periodontal disease, and that its actions can be further explored in an animal model.     

Immunolocalization of platelet-derived growth factor A and B chains and PDGF-α and β receptors in human gingival wounds

Platelet-derived growth factor (PDGF) is a polypeptide growth factor which has been implicated as a major mitogen involved in wound healing. The PDGF appears to promote periodontal regeneration; however, its distribution in gingival tissues is not known and how it participates in gingival wound healing is unclear. Using highly specific antibodies we have studied the distribution of PDGF A and B chains and α- and β-PDGF receptors in healing human gingival wounds. Wounds were created by making a 0.75 mm deep incision in the papilla of healthy human gingiva and biopsies were obtained from the same site after 8 h and 1, 3, 7, 14 and 21 d. Frozen sections were immunostained with affinity purified antibodies. The results showed that both epithelium and fibrin clot manifested positive immunostaining for anti-PDGF-A and B-chain antibodies. Staining was present in unwounded and wounded epithelia, and in the fibrin clot it appeared to be more intense for the PDGF-A chain. Blood vessels in connective tissue were also positive while other areas were largely negative. No significant staining was detectable in healthy tissues for anti-PDGF-α or -β receptor antibodies. However, the wound site began to manifest positive immunostaining for anti-β-receptor antibody after 3 d of healing, became maximal at 7d, and then decreased. Our data indicate, but do not prove, that gingival epithelium may be a source of PDGF A and B chains and that the A chain may have a more prominent role to play during early stages of healing. Expression of PDGF β-receptor appears later at the wound site, indicating that the PDGF B isomer may regulate later wound healing events.     

Expression of BMP-2 and TGF-β1 mRNA during healing of the rabbit mandible

To identify the cell types which produce BMP and TGF-β during fracture healing and to elucidate the interactions between BMP and TGF-β in regulating cell proliferation and differeentiation at various stages, an experimental model of fracture healing in the rabbit mandible was established and the expression of BMP-2 and TGF-β1 mRNA was studied at different healing stages by in situ hybridization. The results showed that undifferentiated mesenchymal cells, differentiating osteoblasts and chondroblasts, had higher levels of BMP-2 mRNA at the stage of intramembranous bone formation and early chondrogenesis, while the level of TGF-β1 mRNA expression was closely associated with the active synthetic stage of osteoblasts and chondrocytes. These obserbvations suggest that both BMP and TGF-β are involved in the regulation of fracture healing, BMP may play an important role in bone induction and early chondrogenesis, while TGF-β regulates the proliferation and active synthetic ability of chondrocytes and osteoblasts.     

Human periodontal ligament and gingival fibroblast response to TGF-β1 stimulation

Abstract. The purpose of this study was to measure the time-sequence response of RNA and protein synthesis to transforming growth factor-β1 (TGF-β1) by human periodontal ligament (HPDLF) and gingival (HGF) fibroblasts in culture. HPDLF and HGF were cultured from explants of healthy gingival tissue and freshly extracted teeth. Cultures of 8×10⁴ cells/ml were exposed to medium containing ³H-uridine and ³⁵S-methionine with TGF-β1 at concentrations from 10^-9 M to 10^-21 M, or control medium, for up to 60 hours in order to assess RNA and protein synthesis. Protein concentrations of comparable cultures were also assayed colorimetrically. Results were reported as specific activity (CPM/μMg protein). The results indicate that 10^-9 M TGF-β1 treated cultures showed a significant increase in RNA synthesis by HPDLF and HGF over time, as compared to the control cultures. HPDLF showed a significant increase in protein synthesis over time while that by HGF was not significant as compared to the control cultures. Lower concentrations of TGF-β1 demonstraled no significant differences from control. Results suggest that the effects of TGF-β1 on HPDLF and HGF are both time and dose dependent, with 10^-9 M TGF-β1 providing the best response of those concentrations tested. These findings support the concept that TGF-β1 may play a role in periodontal regeneration due to its ability to promote fibroblast RNA and protein synthesis. The results also demonstrate that although these two cells types appear morphologically similar, they exhibit distinct biological responses to growth factors such as TGF-β1.     

Progesterone metabolism by rat oral mucosa. III. Participation of granulation tissue and fibroblasts

The metabolism of progesterone by rat granulation tissue was studied. Experimental granulation tissue was produced by implanting viscose-cellulose sponges beneath the dorsal skin of female and male rats for 21 days. The granuloma capsules and fibroblasts in the sponges were homogenized, and mitochondrial, microsomal and soluble fractions were prepared with differential centrifugation. The subcellular Preparations were incubated with 4-¹⁴C-progesterone and NADPH for 30 min at PH 7.4 and 37°C. The metabolites were identified with column and multiple thinlayer chromatography and radioautography and quantitated with liquid scintillation counting. The granulation tissue and fibroblasts showed much less activity in metabolizing progesterone than the gingival tissue of either sex. As reported earlier, gingival tissues contain Δ⁴-5α- and,Δ⁴-5β-steroid hydrogenases and 3α-, 3β-, 20α- and 20β-hydroxysteroid dehydrogenases. The granulation tissue and fibroblasts lack 3 β-hydroxysteroid dehydrogenase activity. In addition, the fibroblasts show no 20 β-hydroxysteroid dehydrogenase activity. The enhanced metabolism of progesterone during gingival inflammation is thus probably not due to the formation of granulation tissue.     

Histological evaluation of rabbit gingival wound healing transplanted with human amniotic membrane

Human amniotic membrane has been used as a material to accelerate wound healing and reconstruct damaged organs. The aim of the present study was to assess histologically human amniotic membrane transplantation on rabbit's gingival wound. Three- to 4-month-old male rabbits were divided into 2 groups, i.e., control (group I) and amniotic membrane-transplanted animals (group II). Buccal gingival wounds were created by a punch-biopsy instrument and covered by a 5-layered human amniotic membrane for group II or left uncovered for group I. Gingival biopsies were taken at days 1, 3, 5, 7 and 10, processed for paraffin sections and stained with haematoxylin-eosin or von Gieson. Thickness of epithelial layer, the number of polymorphonuclear cells (PMN), fibroblasts and new blood vessels as well as density of collagen fibres were assessed. The results showed that the number of fibroblasts and new blood vessels, but not PMN, from group II was higher than that from group I (P < 0.05). Similarly, the epithelial thickness and density of collagen fibres from group II were significantly higher than those from group I (P < 0.05). The results of the present study indicate that amniotic membrane transplantation may induce rapid epithelialization and both granulation tissue and collagen formation but suppress inflammation, suggesting that amniotic membrane transplantation may promote rapid gingival wound healing in rabbits compared to secondary healing.     

Biglycan在牙周损伤愈合中的免疫化学定位和表达

目的：研究biglycan在牙周组织损伤愈合过程中的免疫化学定位。方法：损伤成年鼠磨牙周围的牙周组织,跟踪28d,对biglycan和Ⅰ型、Ⅲ型胶原在愈合过程中的免疫组织化学分布进行分析。结果：biglycan在结缔组织中的免疫组织化学分布与Ⅰ型胶原相似。在牙周损伤愈合早期,biglycan在损伤区炎性细胞和移行的牙龈上皮细胞有强烈表达。愈合中期,biglycan广泛表达于肉芽组织成纤维细胞及其基质。愈合晚期,biglycan在新骨成骨细胞中表达明显。结论：biglycan在牙周组织损伤区中的细胞内特征性表达,预示其在牙周损伤愈合过程中起着不可忽视的作用。     

The expression of plasminogen activator system in a rat model of periodontal wound healing

BACKGROUND: The plasminogen activator system has been proposed to play a role in proteolytic degradation of extracellular matrices in tissue remodeling, including wound healing. The aim of this study was to elucidate the presence of components of the plasminogen activator system during different stages of periodontal wound healing. METHODS: Periodontal wounds were created around the molars of adult rats and healing was followed for 28 days. Immunohistochemical analyses of the healing tissues and an analysis of the periodontal wound healing fluid by ELISA were carried out for the detection of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and 2 plasminogen activator inhibitors (PAI-1 and PAI-2). RESULTS: During the early stages (days 1 to 3) of periodontal wound healing, PAI-1 and PAI-2 were found to be closely associated with the deposition of a fibrin clot in the gingival sulcus. These components were strongly associated with the infiltrating inflammatory cells around the fibrin clot. During days 3 to 7, u-PA, PAI-1, and PAI-2 were associated with cells (particularly monocytes/macrophages, fibroblasts, and endothelial cells) in the newly formed granulation tissue. During days 7 to 14, a new attachment apparatus was formed during which PAI-1, PAI-2, and u-PA were localized in both periodontal ligament fibroblasts (PDL) and epithelial cells at sites where these cells were attaching to the root surface. In the periodontal wound healing fluid, the concentration for t-PA increased and peaked during the first week. PAI-2 had a similar expression to t-PA, but at a lower level over the entire wound-healing period. CONCLUSIONS: These findings indicate that the plasminogen activator system is involved in the entire process of periodontal wound healing, in particular with the formation of fibrin matrix on the root surface and its replacement by granulation tissue, as well as the subsequent formation of the attachment of soft tissue to the root surface during the later stages of wound repair.     

Differential expression and distribution of syndecan-1 and -2 in periodontal wound healing of the rat

Cell-surface proteoglycans participate in several biological functions including interactions with adhesion molecules, growth factors and a variety of other effector molecules. Accordingly, these molecules play a central role in various aspects of cell-cell and cell-matrix interactions. To investigate the expression and distribution of the cell surface proteoglycans, syndecan-1 and -2, during periodontal wound healing, immunohistochemical analyses were carried out using monoclonal antibodies against syndecan-1, or -2 core proteins. Both syndecan-1 and -2 were expressed and distributed differentially at various stages of early inflammatory cell infiltration, granulation tissue formation, and tissue remodeling in periodontal wound healing. Expression of syndecan-1 was noted in inflammatory cells within and around the fibrin clots during the earliest stages of inflammatory cells infiltration. During granulation tissue formation it was noted in fibroblast-like cells and newly formed blood vessels. Syndecan-1 was not seen in newly formed bone or cementum matrix at any of the time periods studied. Syndecan-1 expression was generally less during the late stages of wound healing but was markedly expressed in cells that were close to the repairing junctional epithelium. In contrast, syndecan-2 expression and distribution was not evident at the early stages of inflammatory cell infiltration. During the formation of granulation tissue and subsequent tissue remodeling, syndecan-2 was expressed extracellularly in the newly formed fibrils which were oriented toward the root surface. Syndecan-2 was found to be significantly expressed on cells that were close to the root surface and within the matrix of repaired cementum covering root dentin as well as at the alveolar bone edge. These findings indicate that syndecan-1 and -2 may have distinctive functions during wound healing of the periodontium. The appearance of syndecan-1 may involve both cell-cell and cell-matrix interactions, while syndecan-2 showed a predilection to associate with cell-matrix interactions during hard tissue formation.     

The Effect of Platelet‐Rich Plasma on Healing of Palatal Donor Site following Connective Tissue Harvesting: A Pilot Study in Dogs

Background: Peri‐implant plastic surgery includes soft tissue enhancement by connective tissue grafting. The palatal donor site provides peri‐implant keratinized mucosa and soft tissue height. Platelet‐rich plasma (PRP) contains growth factors that may enhance early healing. Purpose: The present animal study investigated the effect of PRP on wound healing of palatal donor site after connective tissue harvesting. Materials and Methods: In 12 mongrel dogs, bilateral palatal connective tissues of 10 × 15 mm were harvested. At test site, PRP was applied into the wound, and the contralateral site served as control. The healing was evaluated clinically and histologically at 1 week, 2 weeks, and 4 weeks after surgeries. Exact binomial probability and Wilcoxon signed‐rank test were used to compare the clinical and histologic measurements. Results: No statistically significant differences between PRP and control sites were measured with regard to clinical healing (p = 1.000) and histologic variables, including inflammatory cells (p = .750), collagen fibers (p = .375), and granulation tissue (p = .500) at any time interval. Conclusion: The addition of PRP to palatal mucosal wound sites did not accelerate wound healing.     

Interleukin 1, interleukin 6 and transforming growth factor-β production by human gingival mononuclear cells following stimulation with Porphyromonas gingivalis and Fusobacterium nucleatum

Gingival mononuclear cell production of interleukin 1 (IL-1), interleukin 6 (IL-6) and transforming growth factor-β(TGF-β) after stimulation with the putative periodontopathic bacteria, Porphyromonas gingivalis and Fusobacterium nucleatum was investigated. Using an ELISA method, gingival mononuclear cells extracted from 18 adult periodontitis subjects were found to be producing IL-1. However, IL-1 activity could only be detected in 5 out of these 18 cases when tested using a thymocyte proliferation bio-assay, suggesting the presence of IL-1 inhibitors. Depletion of monocytes from peripheral blood cultures resulted in a significant decrease in IL-1 activity following P. gingivalis stimulation while there was no effect in the level of IL-1 activity following stimulation with F. nucleatum. This suggests that P. gingivalis and F. nucleatum stimulate different cell types to produce IL-1. Like IL-1. IL-6 production by gingival mononuclear cells was significantly greater than that produced by the control peripheral blood mononuclear cells. Following P. gingivalis and F. nucleatum stimulation, higher levels of IL-6 could be detected; however, both organisms stimulated similar levels. Intracytoplasmic immunofluorescence staining demonstrated a lower percent TGF-β⁺ cells in bacterial stimulated peripheral blood mononuclear cell cultures compared with cells in medium alone. In the gingival mononuclear cell cultures, the percentage TGF-β⁺ cells peaked at day 1 in F. nucleatum -stimulated, whereas in P. gingivalis -stimulated cultures the peak TGF-β⁺ cells occurred at day 3, again suggesting stimulation of different cell subsets. These results ilustrate that different periodontopathic bacteria may stimulate different cell types to produce cytokines which may have synergistic or antagonistic effects.     

Periodontal wound healing/regeneration following implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) in an absorbable collagen sponge carrier into one-wall intrabony defects in dogs: a dose-range study

Aim: Recombinant human growth/differentiation factor-5 (rhGDF-5) is being evaluated as a candidate therapy in support of periodontal regeneration. The objective of this study was to evaluate cementum and alveolar bone formation, and aberrant healing events following surgical implantation of rhGDF-5 in an absorbable collagen sponge (ACS) carrier using an established periodontal defect model.
Materials and Methods: Bilateral 4 × 5 mm (width × depth), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular second and fourth pre-molar teeth in 15 Beagle dogs. Five animals received 1  μ g/defect and five animals 20  μ g/defect rhGDF-5 in unilateral defect sites. Contralateral sites received treatments reported elsewhere. Five animals received rhGDF-5/ACS with 0 (buffer control) and 100  μ g/defect rhGDF-5 in contralateral defect sites. The animals were euthanized at 8 weeks post-surgery for histologic and histometric evaluation.
Results: Surgical implantation of rhGDF-5 stimulated significant periodontal regeneration. Cementum formation was significantly enhanced in sites implanted with rhGDF-5 (1 and 100  μ g) compared with control ( p <0.05). Similarly, bone formation height was significantly greater in sites receiving rhGDF-5 (1 and 100  μ g) compared with control ( p <0.05). There were no significant or remarkable differences in bone and cementum formation within the selected dose interval (1, 20 and 100  μ g rhGDF-5). None of the control or the rhGDF-5 sites exhibited root resorption, ankylosis, or other aberrant tissue reactions.
Conclusion: Surgical implantation of rhGDF-5/ACS may be used safely to support periodontal wound healing/regeneration in intrabony periodontal defects without complications.     

The synthesis of 5α - dihydrotestosterone from androgens by human gingival tissues and fibroblasts in culture in response to TGIF-β and PDGF

The effects of TGF-β and PDGF on the metabolic conversion of 14C-testosterone by human gingival tissue (HGT) from 5 subjects was investigated. The metabolic conversions in response to TGF-β and PDGF were also studied in 4-6 cell-lines of cultured gingival fibroblasts, using 14C-testosterone and 14C-4-androstenedi one as substrates. Duplicate incubations of HGT were performed in Eagle's MEM + 10% FCS and optimal stimulatory concentrations of TGF-β/PDGF for 24 h. Similar incubations were performed in duplicate with cell-lines of cultured gingival fibroblasts, TGF-β PDGF, 14C-testosterone/14C-4-androstenedione in Eagle's MEM + 10% FCS. The radioactive metabolites were extracted, separated and quantified. With HGT, TGF-β and PDGF caused 2.5/12-fold increases in DHT synthesis (p< 0.1; Wilcoxon signed rank test) and 3.4/12-fold increases in 4-androstenedione formation (p<0.1) from 14C-testosterone. PDGF increased DHT and testosterone synthesis from 14C-4-androstenedione by 3-fold in gingivae (p<0.1). With cell-lines, average values of duplicate incubations showed 2.8/2-fold increases in DHT synthesis from 14C-testosterone in response to TGF-β/PDGF (p<0.1; p<0.2) and 2.4/2-fold increases in 4-androstenedione synthesis (p<0.1; p<0.2). With 14C-4-androstenedione as substrate, TGF-β/PDGF caused 1.611.9fold increases in DHT synthesis compared with controls (p<0.05; p<0.1) and 1.711.5-fold increases in testosterone formation from this substrate (p<0.05; p<0.1). Due to the strong implications of TGF-β/PDGF and anabolic androgens on matrix repair, significant increases in DHT synthesis from 2 androgenic substrates in response to TGF-β and PDGF are of particular relevance to inflammatory repair processes.     

SDF-1在拔牙创软组织愈合过程中的表达及分布

目的:观察拔牙创软组织内基质细胞衍生因子l(SDF-1)的表达及分布,为促进拔牙创愈合提供新思路。方法:Wistar雄性大鼠30只,随机分为10组,每组3只,分别拔除左侧下颌第一磨牙。于拔牙后1、2、4、7、10 d分别采用免疫组织化学染色和RT-PCR技术观察SDF-1在创缘软组织内的分布及表达变化情况。采用SPSS12.0软件包对数据进行统计学分析。结果:免疫组织化学染色显示,拔牙早期创口周围牙龈组织内SDF-1表达增强,染色部位主要分布于牙龈上皮的棘层及基底层细胞胞质与细胞间。越靠近基底层细胞,染色越明显。拔牙后4 d,阳性染色部位主要位于基底细胞层,新生肉芽组织内可见新生血管的内皮细胞和增殖活跃的成纤维细胞阳性表达。拔牙后7 d,牙龈上皮细胞层染色变得均匀,固有层可见少量阳性染色的新生血管内皮细胞及成纤维细胞;拔牙后10 d,牙龈上皮染色特点基本与正常牙龈相似。实时定量PCR检测结果表明,SDF-1mRNA的表达水平在拔牙后1 d达到最高（P<0.01）,第2天开始下降(P<0.05),拔牙后4 d出现第2次峰值（P<0.01）,7 d后其表达水平仍高于对照组(P<0.05),10 d时恢复正常水平(P>0.05)。结论:SDF-1参与拔牙创软组织的早期愈合过程,可能对拔牙创的愈合起着一定的促进作用。     

Effect of the dental adhesive, 4-META/MMA-TBB resin, on adhesion and keratinization of regenerating oral epithelium

Background and Objective:  The 4-META/MMA-TBB [4-(2-methacryloxyethyl)trimellitic anhydride/methyl methacrylate-tributylborane] resin is widely used as a dental adhesive. It has also been applied in the dressing of gingival wound surfaces following periodontal surgery. However, its effect on the regeneration and/or cell attachment of the oral epithelium remains to be clarified. To evaluate the effect of the resin applied as a wound dressing, we investigated expression of laminin 5, integrin β₄ and cytokeratin 14 in regenerating oral epithelium treated with this resin following gingivectomy from the viewpoint of cell attachment and differentiation.
Material and Methods:  The resin was applied to the entire wound surface in rats after gingival surgery, and regenerating epithelium was examined immediately and at 1, 3, 5, 7 and 14 days later. The resin was removed 2 weeks after application in some animals and tissue further examined at 1, 3, 5 and 7 days later.
Results:  Regenerating epithelium under the resin was not keratinized, but became keratinized immediately after removal of the resin. Laminin 5 and integrin β₄ were immunolocalized in the basal lamina, the internal basal lamina, in marginal cells of the regenerating epithelium and at the resin–regenerating epithelium interface. Cytokeratin 14 localized in the regenerating epithelium underneath the resin, as well as in healthy and regenerated junctional epithelial cells.
Conclusion:  These results suggest that this resin covers the wound surface and that the regenerating epithelium biologically adheres to the resin during the initial process of its regeneration.     

Growth factors in periodontal regeneration

Abstract:  Inflammatory periodontal disease is an almost ubiquitous disorder in the adult population. Cases or sites with moderate to advanced disease often continue to show signs of inflammation after non-surgical approach. Our current understanding of periodontal healing is based on a hypothesis by Melcher who proposed that the cell type that repopulates the exposed root surface at the periodontal repair site will define the nature of the attachment/repair that take place. If mesenchymal cells from periodontal ligament/perivascular region of the bone proliferate and colonize the root surface, regeneration occurs. Growth factors are natural cell products that are released or activated when cell division is needed. This action typically occurs during such events as wound healing or tissue regeneration. Activated platelets at the wound margins release several growth factors such as platelet-derived growth factor (PDGF), transforming growth factor (TGF)-α, epidermal growth factor etc. Cells adjacent to the injured site also are induced to release growth factors such as insulin-like growth factor-I, PDGF, TGF-α and TGF-α within a few hours after injury. In periodontal regeneration, the coronal re-establishment of the periodontal ligament (PDL) is required together with corresponding cementum and supporting alveolar bone. Thus, agents which promote periodontal ligament fibroblast (PLF) proliferation and migration as well as collagen biosynthesis would appear to be mediators for enhancing new PDL formation. When combinations or cocktails of different factors are used, greater repair is achieved than when individual factors are applied.     

Effects of implant geometry, surface properties, and TGF-β1 on peri-implant bone response: an experimental study in goats

Objectives: Despite the high success rates in implantology, the desire to use oral implants in more challenging clinical situations drives the need for continuing refinements in implant design and surface properties. In the present study, the effect of implant geometry on implant bone response was evaluated using two geometrically different implant types, i.e. screw type (St) and push-in type(Pi). Furthermore, the potential beneficial effect of an electrosprayed calcium phosphate (CaP) coating, either or not enriched with the osteoinductive growth factor TGF-β1, on the osteogenic response was examined.
Material and methods: A total of 54 implants, divided into six groups ( n =9), were inserted into the femoral condyles of nine goats. After an implantation period of 12 weeks, retrieved specimens were evaluated histologically and histomorphometrically. Measurements were statistically evaluated using SPSS 14.0 and analyzed using a linear regression model.
Results: With respect to implant design, St-implants showed an overall superior biological healing response compared with Pi-implants. Considering surface properties, the deposition of an electrosprayed CaP (2–3 μm) coating onto implants significantly increased the amount of bone–implant contact for both implant types. Additional enrichment of the CaP coating with the osteoinductive growth factor TGF-β1 did not significantly affect peri-implant bone response.
Conclusions: The results of this study indicate that a substantial improvement of the osteogenic response to titanium implants can be achieved by the deposition of an electrosprayed CaP coating. The enrichment of the coating with 1 μg TGF-β1 has only a marginal effect.     

Regulation of fibroblast-induced collagen gel contraction by interleukin-1β

Fibroblasts incorporated within collagen gels induce a cell-mediated contraction of the gel to form a three-dimensional, tissue-like structure by a mechanism thought to mimic wound contraction in vivo . In this study a gel contraction model was used to investigate the ability of fibroblasts derived from adult gingiva, adult skin and fetal skin to organise a collagen matrix. In addition the effects of interleukin-1β (IL-1β) on the contraction process was also investigated. Over the concentration range 5-50 U/ml, IL-1β induced a statistically significant inhibition of gel contraction in all fibroblast cell types ( P <0.05), although fetal fibroblasts appeared least responsive and gingival fibroblasts most responsive to the inhibitory effects of this cytokine. Comparison of gel contraction by the different fibroblast strains indicated that fetal and gingival fibroblasts shared similar contraction kinetics. For the adult skin fibroblasts, three of five strains studied showed significantly diminished levels of gel contraction compared to fetal and gingival cells. This apparent difference in fibroblast phenotype may, at least in part, explain the fetal-like wound healing pattern seen in the oral mucosa.     

Increased expression of integrin α2 and abnormal response to TGF-β1 in hereditary gingival fibromatosis

Objective:  To investigate the possible correlation between integrin α1, α2, and β1 expression and excessive collagen synthesis in fibroblasts from 3 unrelated Chinese families with hereditary gingival fibromatosis (HGF).
Design:  Gingival fibroblasts from three Chinese HGF patients and three healthy subjects were included. The expression of α1, α2, and β1 integrin subunits was examined by immunohistochemistry, quantitative PCR, and flow cytometry. We also investigated the effects of transforming growth factor-β1 (TGF-β1) on the expression of these integrin subunits.
Results:  Our results demonstrate that the expression of α2 was significantly higher in HGF fibroblasts compared with control fibroblasts ( P  < 0.01). No significant differences in the expression of α1 and β1 were detected. Furthermore, TGF-β1 promoted the expression of α1 and α2 in fibroblasts from both HGF patients and controls. However, it had a larger effect on the expression of α2 in HGF fibroblasts than in control cells. In contrast, α1 expression was stimulated more in control fibroblasts.
Conclusion:  The increased expression of integrin α2 and the increased response to TGF-β1 of HGF fibroblasts may be related to the excessive collagen deposition in HGF patients.     

Topical simvastatin gel as a novel therapeutic modality for palatal donor site wound healing following free gingival graft procedure

Objective: Autogenous soft-tissue grafting is a commonly used procedure nowadays in dentistry. However, the prolonged healing time needed for the donor site leads to increase the patient’s pain and discomfort. Statin has been observed to be beneficial in reducing bacterial burden, improving epithelization and wound healing. The aim of this study was to evaluate intra-oral topical application of simvastatin/chitosan gel (10?mg/mL) over the palatal donor site following free gingival graft (FGG) procedure.

Material and methods: Subjects indicated for FGG procedure were divided into four groups. Group I: Simvastatin suspension (S), group II: simvastatin/chitosan gel (SC), group III: chitosan gel (C), group IV: petroleum gel (P). Treatment was applied three times/day for the following 7 days. Wound healing was evaluated at day 3, 7 and 14 post-surgery. A visual analogue scale (VAS) was used to measure the experienced discomfort at 1, 3, 5, 7 and 14 days.

Results: Statistical significant reduction in wound-healing scores was observed after 3 and 7 days for group II compared to other groups (p =?.015). A significant reduction was also observed in VAS score for group II compared to other groups at day 1, 3, 5 and 7.

Conclusion: Topical application of S/C gel could be used as a novel therapeutic modality that improved healing and reduced pain in the palatal donor site following FGG procedure.