The applications of the plasma matrix in the treatments of dental pulp and periapical diseases / 口腔疾病防治

@#The plasma matrix is a kind of autologous blood conduct. It has been widely used in maxillofacial tissue regeneration, skin cosmetology and some other fields. Recently, to preserve the dental pulp as well as the teeth, pulp regeneration therapy and apical surgery have become increasingly important as well as the applications of bioactive materials. As a kind of autologous bioactive material, the plasma matrix has some natural advantages as it is easy to obtain and malleable. The plasma matrix can be used in the following cases: ①pulp revascularization of young permanent teeth with open apical foramina that cannot stimulate apical bleeding; ② apical barrier surgery with bone defects and large area perforation repair with bone defects or root sidewall repair surgery; ③ apical surgeries of teeth with large area of apical lesions, with or without periodontal diseases. The plasma matrix is a product derived from our blood, and there are no obvious contraindications for its use. Several systematic reviews have shown that the plasma matrix can effectively promote the regenerative repair of dental pulp in patients with periapical diseases. However, the applications of plasma matrix are different because its characteristics are affected by different preparation methods. In addition, there is still a lack of long-term clinical researches on the plasma matrix, and the histological evidences are difficult to obtain, so a large number of in vitro and in vivo experimental studies are still needed. This article will describe the applications of different kinds of plasma matrix for dental pulp regeneration and bone tissue regeneration in apical surgeries to provide references for clinicians in indication selection and prognosis evaluation.

Progress in Application of Concentrated Growth Factor in Oral Tissue Regeneration / 中国医学科学院学报

Tissue regeneration is an important engineering method for the treatment of oral soft and hard tissue defects.Growth factors,as one of the three elements of tissue regeneration,are a necessary condition for tissue regeneration.Concentrated growth factor(CGF)is a new generation of blood extract prepared by changing the centrifugal speed on the basis of the preparation of platelet-rich plasma(PRP)and platelet-rich fibrin(PRF).It contains abundant growth factors and a fibrin matrix with a three-dimensional network structure,being capable of activating angiogenesis and promoting tissue regeneration and healing.CGF has been widely used in the repair and regeneration of oral soft and hard tissues.This paper introduces the preparation and composition of CGF and reviews the application of CGF in oral implantation and the regeneration of oral bone tissue,periodontal tissue,and dental pulp tissue.

Advances in the study on cytokines related to dental pulp regeneration / 口腔医学

@#With the development of molecular biology, biomaterials and tissue engineering, regenerative treatment of pulpal and periradicular diseases is facing new opportunities. At present, a large number of studies on dental pulp regeneration reveal that cytokines are essential for promoting migration, proliferation and osteogenic differentiation of dental pulp stem cells. In this paper, we review several kinds of cytokines related to dental pulp regeneration, and analyze their roles and regulatory mechanisms in dental pulp regeneration.

Efficacy of concentrated growth factor in the reduction of complications after bone augmentation during surgery for odontogenic maxillary cyst / 中国基层医药

Objective:To investigate the efficacy of concentrated growth factor (CGF) in the reduction of pain and swelling after bone augmentation during surgery for odontogenic maxillary cyst.Methods:Sixteen patients with odontogenic maxillary cysts who underwent bone augmentation during surgery between June 2018 and December 2019 were included in this study. They were randomly divided into two groups ( n = 8/group). In the observation group, CGF and bone substitutes were mixed and covered with biofilm. In the control group, bone powder was used to fill the bone cavity, and artificial biofilm was applied. Postoperative swelling, pain, and scar hyperplasia were compared between the two groups. Pain was rated according to visual analogue score. Swelling was divided into three grades according to the level of swelling. Scar was compared according to vancouver scar scale. Statistical analysis was performed using SPSS 20.0 software. Results:The percentage of grade 1-3 swelling in the observation group were 62.5% (5/8), 37.5% (3/8) and 0.0% (0/8), respectively, and they were 50.0% (4/8), 37.5% (3/8), 12.5%(1/8), respectively ( Z = -1.71, P > 0.05). There was significant difference in the duration of swelling between observation and control groups [(3.8 ± 0.9) days vs. (5.8 ± 1.4) days, t = 6.88, P < 0.05]. At 3, 7 and 14 days after surgery, visual analogue score was (2.21 ± 0.25) points, (3.75 ± 0.22) points and (0.57 ± 0.13) points in the observation group and it was (3.76 ± 0.18) points, (2.38 ± 0.26) points, and (2.38 ± 0.26) points in the control group ( t = 14.23, t = 11.29, t = 17.61, all P < 0.001). At 1, 2 and 4 weeks after surgery, vancouver scar scale score was (4.26 ± 0.26) points, (1.22 ± 0.13) points and (2.47 ± 0.11) points in the observation group, and it was (6.35 ± 0.27) points, (4.47 ± 0.73) points and (2.77 ± 0.21) points in the control group ( t = 15.77, t = 2.67, t = 3.58, P < 0.001). Conclusion:CGF can promote postoperative bone defect repair and wound healing and reduce postoperative swelling, pain and scar.

The Evaluation of Bone Regeneration Following Socket Preservation with Concentrated Growth Factor (CGF) and Poly Lactic-Co-Glycolic Acid (PLGA) Scaffold in Rabbits

ABSTRACT@#Various grafting materials are utilised to facilitate regeneration. There is currently a paradigm shift towards applying poly lactic-co-glycolic acid (PLGA), which is regarded as an excellent scaffold for tissue engineering. Concentrated growth factor (CGF) has also been reported to promote wound healing. Nevertheless, the role of PLGA microspheres as a substitute for bone graft material with CGF in bone regeneration remains unclear. This study was designed to evaluate the effect of CGF with PLGA on bone formation and the expression of alkaline phosphatase (ALP) following socket preservation. PLGA microspheres were prepared using double solvent evaporation method and observed under scanning electron microscopy (SEM). A 6 mL of rabbit’s blood was collected from the marginal ear vein and centrifuged to obtain CGF. Blood was also collected for ALP assessment from 24 New Zealand White (NZW) male rabbits subjected to the first upper left premolar extraction. Sockets were filled with CGF, PLGA, CGF+PLGA or left empty and observed with microscopic computed tomography (micro-CT) at four weeks and eight weeks. The SEM image revealed a spherical shape with interconnected pores on the surface of the PLGA particles. Repeated measures ANOVA were used to evaluate the effect of time and treatment (p < 0.05) with significant differences in bone width, height, volume, volume fraction and expression of ALP was observed with CGF+PLGA. Both CGF and PLGA have the potential as the alternative grafting materials and this study could serve as an ideal benchmark for future investigations on the role of CGF+PLGA in bone regeneration enhancement.

Clinical and histological evaluations of the effects of concentrated growth factor combined with deproteinated bovine bone mineral in site preservation / 口腔疾病防治

Objective@#To evaluate the osteogenic effect of concentrated growth factor (CGF) combined with deproteinated bovine bone mineral (DBBM) in site preservation using clinical and histomorphometric observations.@*Methods @#A total of 26 patients who needed extraction of affected teeth and received staged implantation after site preservation were selected. The patients were randomly divided into the DBBM group (Bio-Oss was implanted simultaneously after extraction) and CGF+DBBM group (CGF+Bio-Oss was implanted simultaneously after extraction), with 13 patients in each group, and both groups were covered with Bio-Gide collagen membrane. Cone beam computed tomography (CBCT) was performed preoperatively and 6 months later to measure the changes in alveolar bone height and width, and the bone specimens were drilled 6 months after site preservation during implant surgery for histological analyses.@*Results@# CBCT showed that the height and width of alveolar bone were absorbed 6 months after site preservation in the CGF+DBBM and DBBM groups, and the reduction in alveolar ridge width in the CGF+DBBM group was statistically less than the DBBM group (P <0.05). The histomorphometry results showed that the percentage of new bone in the CGF+DBBM and DBBM groups were 35.30% ± 3.56% and 26.38% ± 5.04%, respectively, and the amount of new bone in the CGF+DBBM group was statistically higher than the DBBM group (P<0.05). @*Conclusion @#CGF combined with DBBM is superior to DBBM in maintaining the alveolar bone volume and shape in site preservation, which creates favorable conditions for implant restoration.

Concentrated growth factors in the repair of a full-thickness condylar cartilage defect in a rabbit / 中国组织工程研究

BACKGROUND: Concentrated growth factors can promote the repair of tissue injuries. Its effect on the repair of condylar cartilage injuries is rarely documented. OBJECTIVE: To investigate the effect of concentrated growth factors on the repair of full-thickness condylar cartilage defects in rabbits. METHODS: Concentrated growth factors were prepared by collecting the venous blood of rabbits. A full-thickness cartilage defect penetrating the subchondral cortex was created at both sides of condyle in rabbits. The experimental side was filled with concentrated growth factors, and the control side healed naturally. The histomorphology was examined at 2, 6 and 12 weeks postoperatively. The degree of cartilage repair was evaluated by the modified Pineda cartilage repair scale. The release rate of concentrated growth factors was measured at different observational times. The study protocol was approved by the Experimental Animal Ethics Committee of Peking University Health Science Center (approval No. LA201809). RESULTS AND CONCLUSION: Fillings of fibrous and cartilage-like tissue in the defect were observed on both of the experimental and the control sides at 2 weeks postoperatively. Toluidine blue was stained homogeneously in the experimental side. Intercellular fibrous tissues with interpenetrating and heterogeneous toluidine blue staining appeared in the control side. At 6 and 12 weeks postoperatively, the repaired cartilage was identified in the experimental side. On the contrary, fibroid tissue hyperplasia was found in the control side, where toluidine blue staining showed no heterochromatin. Based on the modified Pineda cartilage repair score, the mean value of the total score in the experimental side was better than that in the control side at 6 and 12 weeks postoperatively. The difference in the mean value of the total score (P 0.05). ELISA tests showed that insulin-like growth factor 1, transforming growth factor β1, basic fibroblast growth factor, and vascular endothelial growth factor could be released continuously for more than 14 days. The release rates of these cytokines were decreased with time. These results indicate that concentrated growth factors can improve the early repair of full-thickness condylar cartilage defects in rabbits to some extent.

Guided bone regeneration using preformed titanium mesh combined with bioabsorbable membranes in aesthetic area / 中国组织工程研究

BACKGROUND: Absorbable and non-absorbable barrier membranes have their own merits and demerits in the guided bone regeneration. OBJECTIVE: To investigate the clinical effect of new preformed titanium mesh combined with different bone augmentation materials in anterior teeth with inadequate bone volume for dental implants. METHODS: Thirty-one patients with single maxillary anterior tooth loss were divided into three groups: Bio-Gide collagen membrane + Bio-oss bone group (C; n=12), titanium mesh + Bio-Gide collagen membrane + Bio-Oss bone group (TC; n=10), titanium mesh + concentrated growth factor + Bio-Gide collagen membrane + Bio-Oss bonegroup (TCC; n=9). Through clinical review, cone-beam CT and histological examination, osteogenic effects of the three treatment methods were compared and statistically analyzed at 0 day and 6 months after operation. The implementation of the study protocol complied with the relevant ethical requirements of Qingdao Stomatological Hospital, and each patient was fully informed of the trial process. RESULTS AND CONCLUSION: In the postoperative review, only two patients in the TC group had wound deformations, and the wound healed about 3 weeks postoperation. Six months after the operation, cone-beam CT results revealed significant differences in bone height between the TCC and TC groups and the C group (P < 0.05), as well as in bone width at the mark points of 2, 4 and 6 mm (P < 0.05). There was no significant difference in bone width between three groups at the mark point of 8 mm (P < 0.05). Hematoxylin-eosin staining of bone tissue around the implant showed that trabecular structure was visible in all three groups, but the structures was more mature and denser in the TCC group and sparser in the C group. These findings indicate that titanium mesh has good space maintenance function, better maintains the stability of bone graft material, and enhances the osteogenesis effect to a certain extent. Concentrated growth factors may promote soft tissue healing.

Evaluation of the effect of concentrated growth factor in guided bone regeneration in maxillary anterior tooth defects / 口腔疾病防治

Objective@#To investigate the clinical effect of concentrated growth factor (CGF) applied in guided bone regeneration (GBR) for severe bone deficiency in the anterior maxilla.@*Methods @#Forty patients with bone defects in the anterior maxilla were chosen to be treated with GBR, 20 patients were treated with CGF applied in GBR as the observation group, and the other 20 patients were treated only with GBR as the control group. The evaluation of wound healing was performed after the operation, and bone augmentation was evaluated half a year after the operation.@*Results@#The first-stage healing rate of soft tissue wounds in the observation group was 100% and 75% in the control group, and the primary healing rate in the observation group was better than that in the control group (P=0.017). The changes in bone width of the observation group were （3.70 ± 0.28） mm, and those of the control group were （2.96 ± 0.16） mm. The bone augmentation in the observation group was higher than that in the control group (P=0.000). @*Conclusion@#CGF applied in GBR has a good effect on bone augmentation for severe bone deficiency in the anterior maxilla.

Evaluation of SDF-1 complex with CGF applied to canine dental-pulp-like tissue regeneration / 上海交通大学学报（医学版）

Objective: To evaluate the feasibility of immature permanent teeth pulp regeneration with a new method that utilizes the integration of concentrated growth factor (CGF) as a scaffold and stromal cell-derived factor-1 (SDF-1). Methods: Canine dental pulp cells (DPC) were isolated and cultured in vitro. Then the effects of SDF-1 and CGF were observed on DPC proliferation and differentiation. The pulpless model was established on the beagle’s immature incisors which were divided into four groups: natural pulp (A), empty cannel (B), CGF-filling (C) and SDF-1/CGF-filling (D). After 10 weeks, specimens were checked by imaging examination, RT-PCR and histological observation. Results: CGF extraction (CGFe) induced DPC proliferation while the combination of SDF-1 and CGFe enhanced this effect and also facilitated odontogenic and angiogenic differentiation of DPC. According to imaging examination, the apex growth of all four groups was in varying degrees. RT-PCR indicated the expressions of odontogenesis and angiogenesis related genes in group D were higher than those in group C. Besides, neonatal dentin and dental-pulp-like tissue were observed inside the canal of both group C and D, while only cementum-like tissue existed around root apex of group B. Conclusion:SDF-1 plays an important role in driving the process of pulp-like-tissue regeneration of immature permanent teeth by using CGF as an effective scaffold.

Effects of concentrated growth factors on proliferation and osteogenic differentiation in Beagle adipose-derived stem cells / 中南大学学报(医学版)

Objective:To investigate the effect of concentrated growth factor (CGF) on proliferation and differentiation in Beagle adipose-derived stem cells (ADSCs).Methods:ADSCs were isolated from adipose tissue of healthy Beagles and cultured.The multidirectional differentiation potential of ADSCs was identified.The ADSCs were assigned to a CGF group and a control group.The rate of proliferation was analyzed by CCK-8 assay.The osteogenic differentiation capability was detected by ALP staining after the osteoinduction.Bone formationrelated gene expression was detected by RT-PCR.Results:CGF promoted the proliferation of ADSCs in vitro.ADSCs in the CGF group showed higher level of ALP activity than that in the control group (P＜0.05).CGF stimulated the expression of the genes associated with osteogenesis,such as Col-I and Runx2.Conclusion:CGF can promote the proliferation and osteogenic differentiation in ADSCs in vitro.

Histological characterization of sacco's concentrated growth factors membrane / Caracterización histológica de la membrana de los factores de crecimiento concentrados sacco

Along with the emerging needs of the dental patients, numerous techniques for oral tissue stimulation and regeneration were developed to be employed in the modern implant rehabilitation therapies. The Concentrated Growth Factors (CGF) are a relatively new therapeutic presidium that can be used for this purpose, enhancing the regenerative potential property of blood cells. Although literature presents numerous studies evaluating the CGF for their clinical uses and efficacy, data regarding their biological characteristics are very few. The present study evaluates and describes the CGF structural morphology by means of classical histological methods, using haematoxilin-eosin and azan mallory stains. A three layers organization with a fibrin complex network was noted, with blood corpuscular elements entrapped, especially in the most external layer. These descriptions enrich the knowledge about this new type of membrane, showing the bio-morphological side of the regenerative techniques. These findings will be useful in clinical practice for the choice of the most suitable technique in each implant rehabilitation.

Junto con las nuevas necesidades dentales de los pacientes, se han desarrollado numerosas técnicas para la estimulación y regeneración de los tejidos orales para ser empleadas en las modernas terapias de rehabilitación de implante. Los Factores de Crecimiento Concentrados (FCC) son relativamente una nueva alternativa terapéutica que pueden utilizarse para este propósito, mejorando la propiedad regenerativa potencial de las células de la sangre. A pesar de que la literatura presenta numerosos estudios que evalúan los FCC por sus usos clínicos y su eficacia, los datos relativos a sus características biológicas son muy escasos. El presente estudio evalúa y describe la morfología estructural de los FCC por medio de métodos histológicos tradicionales, utilizando hematoxilina-eosina y tinción de Azan Mallory. Se observó una organización en tres capas con una compleja red de fibrina, con elementos corpusculares de la sangre atrapados, especialmente en la capa más externa. Estas descripciones enriquecen el conocimiento acerca de este nuevo tipo de membrana, que muestra el lado biomorfológico de las técnicas regenerativas. Estos resultados serán de utilidad en la práctica clínica para la elección de la técnica más adecuada en los casos de rehabilitación con implantes.

Cranial defect repair with coralline hydroxyapatite scaffolds in combination with concentrated growth factors in rabbits / 医学研究生学报

Objective Bone defect repair remains a challenge in regenerative medicine, which has triggered a research upsurge on improving the bone repairing effect using heterogeneous bone combined with growth factors.The aim of this study was to evaluate local bone formation following surgical implantation of coralline hydroxyapatite (CHA), a heterogeneous bone, in combination with the concentrated growth factor (CGF).Methods This randomized prospective study included 24 New Zealand rabbits, which were equally divided into a CHA/CGF+CHA, a CHA/CGF+autograft and a CHA+autograft group.A defect 10 mm in diameter was made in the parietal bone of each animal and filled with CHA/CGF, CHA or autograft.At 6 and12 weeks after the operation, we observed the bone formation by micro-CT and histological examination.Results The bone volume (BV) was significantly higher in the CHA/CGF+CHA than in the CHA+autograft group both at 6 weeks ([39.00±7.61] vs [32.12±6.55] mm3, P<0.05) and at 12 weeks after the operation ([49.75±2.36] vs [39.45±7.02] mm3, P<0.05), and so was the bone mineral density (BMD) ([308.30±29.82] vs [256.85±151.25] mg/mL, P<0.05;[389.00±31.87] vs [302.53±127.05] mg/mL, P<0.05).Histological examination showed that the new bone was distributed throughout the CHA scaffold in the CGF/CHA group at 6 weeks, and the new bone was observed only in the periphery region of the CHA scaffold in the CHA group.The bone defects in the CGF/CHA group were fully repaired at 12 weeks, while those in the CHA group were partly repaired with bone and fibrous tissue in the central region of the defects.Conclusion Combination of CHA with CGF could effectively enhance bone healing.CHA/CGF compound artificial bone is an ideal substitute in bone transplantation.

Comparison of Effects of Platelet Rich Fibrin and Concentrated Growth Factor on Schwann Cells / 中国医科大学学报

Objective To compare the effects of platelet rich fibrin(PRF)and concentrated growth factors(CGF)using Schwann cells as a pe?ripheral nerve model. Methods A total of 10 healthy volunteers aged 18 to 55 were randomly selected,and 10 mL venous blood was collected un?der aseptic conditions to prepare PRF and CGF. The cells were randomly divided into three groups,control group,PRF group and CGF group. The cell morphology was observed by inverted phase contrast microscope. The cell proliferation was analyzed by MTT assay. The secretion of nerve growth factor in supernatant was detected by enzyme?linked immunosorbent assay. Cell cycle was detected by flow cytometry. Results There was no significant difference of the morphology of cells in each group as observed under inverted phase contrast microscope. MTT results showed that the absorbance values of PRF group and CGF group were significantly higher than those of the control group(P<0.05). The secretion of nerve growth factor in the supernatant were significantly increased(P<0.05). The number of cells in S+G2M phase was significantly increased(P<0.01),but there was no significant difference between PRF group and CGF group. Conclusion Both PRF and CGF can promote proliferation of Schwann cells and increased the amount of nerve growth factor secretion ,but there is no significant difference between PRF and CGF in terms of improving cell proliferation and promoting nerve growth factor secretion.

Comparison of removal torques of SLActive® implant and blasted, laser-treated titanium implant in rabbit tibia bone healed with concentrated growth factor application

PURPOSE: The purpose of this study was to compare the removal torques of a chemically modified SLActive implant and a blasted, laser-treated (BLT) implant, which were soaked in saline for 2 weeks after their surface modifications. The removal torques of the two implants were measured 4 weeks after their implantation into the bone defect area in rabbit tibias with concentrated growth factor (CGF) application. MATERIALS AND METHODS: To make artificial bone defects in the cortical layers of both tibias, an 8-mm diameter trephine bur was used. Then, prepared CGF was applied to the bony defect of the left tibia, and the bony defect of the right tibia was left unfilled. Four weeks later, the surgical sites of 16 rabbits were re-exposed. For 8 rabbits, the SLActive implants (Straumann, Switzerland) were inserted in the left tibia, and the BLT implants (CSM implant, Daegu, Korea) were inserted in the right tibia. For other rabbits, the BLT implants were inserted in the left tibia, and the SLActive implants were inserted in the right. Four weeks afger the insertion, torque removal was measured from 4 rabbits exterminated via CO2 inhalation. RESULTS: No significant difference was observed between removal torques of the BLT implant and the SLActive implant (P>.05). CONCLUSION: It was found that BLT surface modification exhibited excellent osseointegration. In addition, CGF application did not affect the insertion and removal torque of the implants.