珊瑚羟基磷灰石与异体脱细胞真皮基质联合修复牙根尖周组织缺损

doi:10.3969/j.issn.2095-4344.2014.34.006

中国组织工程研究 ›› 2014, Vol. 18 ›› Issue (34): 5441-5448.doi: 10.3969/j.issn.2095-4344.2014.34.006

• 组织工程口腔材料 tissue-engineered oral materials • 上一篇下一篇

珊瑚羟基磷灰石与异体脱细胞真皮基质联合修复牙根尖周组织缺损

徐隽¹，王进涛²，李刚¹，史芳川²，钟良军²

¹新疆医科大学第一附属医院口腔医学中心牙周粘膜科，新疆维吾尔自治区乌鲁木齐市 830054；²杭州师范大学附属医院口腔科，浙江省杭州市 310015

修回日期:2014-06-05 出版日期:2014-08-20 发布日期:2014-08-20
通讯作者: 钟良军，博士，教授，主任医师，杭州师范大学附属医院口腔科，浙江省杭州市 310015
作者简介:徐隽，女，1974年生，新疆维吾尔自治区乌鲁木齐市人，汉族，2009年新疆医科大学毕业，硕士，讲师，主治医师，主要从事口腔内科学方面的研究。
基金资助:
新疆维吾尔自治区科技支疆项目(201091144)

Acellular dermal matrix allograft combined with coralline hydroxyapatite repair periapical tissue defects

Xu Jun¹, Wang Jin-tao², Li Gang¹, Shi Fang-chuan², Zhong Liang-jun²

¹ Periodontal & Mucosal Department, Center of Stomatology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China; ²Department of Stomatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, Zhejiang Province, China

Revised:2014-06-05 Online:2014-08-20 Published:2014-08-20
Contact: Zhong Liang-jun, M.D., Professor, Chief physician, Department of Stomatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, Zhejiang Province, China
About author:Xu Jun, Master, Lecturer, Attending physician, Periodontal & Mucosal Department, Center of Stomatology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
Supported by:
a grant from Xinjiang Uygur Autonomous Region, No. 201091144

摘要/Abstract

摘要：

背景：慢性根尖周炎症导致根尖周骨质破坏及缺损并不少见，若不能及时消除炎症终止骨吸收和牙龈组织的破坏，修复根尖周组织缺损，最终将导致牙丧失。脱细胞真皮基质和珊瑚羟基磷灰石在动物实验中常用于修复牙周损伤。

目的：评价异体脱细胞真皮基质与珊瑚羟基磷灰石两种材料联合修复根尖周组织缺损的临床疗效。

方法：选择76例慢性根尖周炎患者作为研究对象，患者等分为实验组和对照组。实验组患者采用异体脱细胞基质与珊瑚羟基磷灰石联合修复根尖周组织缺损；对照组患者不植入任何材料。2组患者均行根尖切除及根尖倒充。修复后1周及6，12个月复诊，通过临床症状和 X 射线片检查评价修复效果。

结果与结论：修复1个月后，实验组患者异体脱细胞真皮基质全部存活，因修整瘘管口周围炎性的肉芽组织导致的牙龈组织缺损已经愈合。在修复12个月后，实验组患者的修复有效率明显高于对照组(P < 0.05)。实验组患者修复6个月后骨缺损区阴影基本消失，珊瑚羟基磷灰石颗粒间的透射影减小，出现有一定致密度的影像，提示有新骨长入；12个月后珊瑚羟基磷灰石颗粒密度已接近正常的骨组织密度，与正常骨组织之间有密度移行改变，逐渐与牙槽骨形成骨融合。异体脱细胞基质与珊瑚羟基磷灰石的生物相容性良好。提示异体脱细胞真皮基质与珊瑚羟基磷灰石联合修复根尖周组织缺损具有良好的临床疗效。

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

全文链接：

关键词: 生物材料, 口腔生物材料, 脱细胞真皮基质移植, 珊瑚羟基磷灰石, 根尖周组织缺损, 根尖切除, 根尖倒充, 慢性根尖周炎, 组织再生

Abstract:

BACKGROUND: Chronic periapical periodontitis often causes periapical tissue defects and ultimately leads to the loss of teeth if the inflammation is not promptly cleared to terminate bone resorption and destruction of gingival tissue. Acellular dermal matrix allograft and coralline hydroxyapatite are the common materials to repair periodontal injury.

OBJECTIVE: To evaluate clinical efficacy of acellular dermal matrix allograft combined with coralline hydroxyapatite in repairing periapical tissue defects.

METHODS: A total of 76 patients of chronic apical periodontitis were randomly divided into two groups, with

38 cases in each group. In the experimental group, periapical tissue defects were treated with acellular dermal matrix allograft and coralline hydroxyapatite. In the control group, tissue defects were not treated. All the involved patients underwent apicectomy and retrograde filling. Clinical parameters and radiographic film were recorded at 1 week, 6 months and 3 years follow-up visits to evaluate the repairing effects.

RESULTS AND CONCLUSION: After 1 month of treatment, all acellular dermal matrix allografts survived, and the defect of gingival tissues that caused by repairing fistula had been healed. After 3 years, the repairing efficiency in the experimental group was significantly higher than that in the control group (P < 0.05). The bone defect disappeared in the experimental group at 6 months, the transmission of coralline hydroxyapatite particles was decreased, and there were some fuzzy images of compact density. This suggested that new bone was growing. The density of coralline hydroxyapatite particle got closed to normal bone tissue after 3 years, and there were transitional changes of density between coralline hydroxyapatite with normal bone. Coralline hydroxyapatite particle gradually fused with alveolar bone. Acellular dermal matrix allograft and coralline hydroxyapatite have good biological compatibility. In repairing periapical tissue defects, the application of acellular dermal matrix allograft combined with coralline hydroxyapatite is effective in clinical practice.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

全文链接：

Key words: hydroxyapatites, periapical periodontitis, periodontitis, periodontium

中图分类号:

R318

徐隽，王进涛，李刚，史芳川，钟良军. 珊瑚羟基磷灰石与异体脱细胞真皮基质联合修复牙根尖周组织缺损[J]. 中国组织工程研究, 2014, 18(34): 5441-5448.

Xu Jun, Wang Jin-tao, Li Gang, Shi Fang-chuan, Zhong Liang-jun. Acellular dermal matrix allograft combined with coralline hydroxyapatite repair periapical tissue defects[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(34): 5441-5448.

图/表（结果） 2

Quantitative analysis of subjects

All patients in both groups were included in following analysis.

Clinical observation of periapical tissue defects repaired with different methods

The complaints of patients, the degree of pain when percussed the crown vertically or laterally and the swelling degree of the mucous membranes was observed.

The wounds were all primary healing. One week after operation, no significant discomfort was observed in patients. At 1 month, all acellular dermal matrix allografts survived, moreover, the defect of gingival tissues that caused by repairing fistula had been healed. As shown in Table 1, there was no significant difference between two groups in 3 years postoperative therapy (P > 0.05).

As shown in Table 2, the rate of efficiency was 95% in the experimental group, and 79% in the control group, there was a significant difference between two groups in 3 years postoperative therapy (χ²=4.15, P < 0.05).

There was no significant difference in the teeth, gender, age and style of lesions in 3 years postoperative therapy in the experimental group (Tables 3-6).

Analysis of radiographic films of periapical tissue defects repaired with different methods

Due to the large range of bone destruction, we shot periapical films to observe the tiny changes in periodontal tissue and compare the curative effect. As shown in radiographic films, we can see that there was a large scope of bone defect area before operation. The scope in Figure 2A was about 1.8 cm × 1.4 cm. The bone defect disappeared 6 months after operation, the transmission of coralline hydroxyapatite particles decreased, and, there were some fuzzy images of compact density. It suggested that new bone was growing. The density of coralline hydroxyapatite particle was similar to normal bone tissue after 3 years (Figure 2), and there were transitional changes of density between coralline hydroxyapatite with normal bone, which suggested that it began to combine with the alveolar bone.

Biocompatibility of different methods for repairing periapical tissue defects

Acellular dermal matrix allograft is derived from the human or animal skin tissue, and is treated through physical and chemical treatment. The treatment may remove all the components that may cause immune rejection after implantation, and maintain three-dimensional scaffold structure of original tissue. As the cytoskeleton, it can induce tissue formation, and can be recognized as autologous tissue after implanted into the human body, subsequently neovascularization and fibroblast ingrowth occur, which guide the orderly growth of the cells along its collagen framework to supplement, repair and even reconstruct the tissues. Acellular dermal matrix allograft has no toxicity, no antigenicity, and good biocompatibility. After implantation, acellular dermal matrix allograft induces fewer inflammatory reactions than the mucosa transplantation. Due to excellent biocompatibility, acellular dermal matrix allograft has been widely used as a scaffold for the construction of artificial composite materials and the repair of maxillofacial mucosal defect. No immune response of the host is found. The results of this study revealed no abnormalities.

参考文献

[1] Tronstad L, Barnett F, Cervone F. Periapical bacterial plaque in teeth refractory to endodontic treatment. Endod Dent Traumatol. 1990;6(2):73-77.
[2] Sen BH, Piskin B, Demirci T. Observation of bacteria and fungi in infected root canals and dentinal tubules by SEM. Endod Dent Traumatol. 1995;11(1):6-9.
[3] Ng YL, Mann V, Gulabivala K. Tooth survival following non-surgical root canal treatment: a systematic review of the literature. Int Endod J. 2010;43(3):171-189.
[4] Tsesis I, Rosen E, Tamse A, et al. Effect of guided tissue regeneration on the outcome of surgical endodontic treatment: a systematic review and meta-analysis. J Endod. 2011;37(8):1039-1045.
[5] Goyal B, Tewari S, Duhan J, et al. Comparative evaluation of platelet-rich plasma and guided tissue regeneration membrane in the healing of apicomarginal defects: a clinical study. J Endod. 2011;37(6):773-780.
[6] Kovác J, Kovác D. Histopathology and etiopathogenesis of chronic apical periodontitis--periapical granuloma. Epidemiol Mikrobiol Imunol. 2011;60(2):77-86.
[7] Nair PN. Pathogenesis of apical periodontitis and the causes of endodontic failures. Crit Rev Oral Biol Med. 2004; 15(6):348-381.
[8] Kawaguchi H, Kurihara H. Clinical trial of periodontal tissue regeneration. Nihon Rinsho. 2008;66(5):948-954.
[9] Ng YL, Mann V, Gulabivala K. A prospective study of the factors affecting outcomes of non-surgical root canal treatment: part 2: tooth survival. Int Endod J. 2011;44(7): 610-625.
[10] Ma J, Al-Ashaw AJ, Shen Y, et al. Efficacy of ProTaper Universal Rotary Retreatment system for gutta-percha removal from oval root canals: a micro-computed tomography study. J Endod. 2012;38(11):1516-1520.
[11] García CC, Sempere FV, Diago MP, et al. The post-endodontic periapical lesion: histologic and etiopathogenic aspects. Med Oral Patol Oral Cir Bucal. 2007;12(8):E585-590.
[12] Maddalone M, Gagliani M. Periapical endodontic surgery: a 3-year follow-up study. Int Endod J. 2003;36(3):193-198.
[13] von Arx T. Apical surgery: A review of current techniques and outcome. Saudi Dent J. 2011;23(1):9-15.
[14] Lindeboom JA. Apical endodontic surgery. Ned Tijdschr Tandheelkd. 2004;111(4):146-151.
[15] Pawar AM, Kokate SR, Shah RA. Management of a large periapical lesion using Biodentine(™) as retrograde restoration with eighteen months evident follow up. J Conserv Dent. 2013;16(6):573-575.
[16] Bashutski JD, Wang HL. Periodontal and endodontic regeneration. J Endod. 2009;35(3):321-328.
[17] Kinaia BM, Chogle SM, Kinaia AM, et al. Regenerative therapy: a periodontal-endodontic perspective. Dent Clin North Am. 2012;56(3): 537-547.
[18] Pecora G, De Leonardis D, Ibrahim N, et al. The use of calcium sulphate in the surgical treatment of a 'through and through' periradicular lesion. Int Endod J. 2001;34(3): 189-197.
[19] Lin L, Chen MY, Ricucci D, et al. Guided tissue regeneration in periapical surgery. J Endod. 2010;36(4): 618-625.
[20] Naylor J, Mines P, Anderson A, et al. The use of guided tissue regeneration techniques among endodontists: a web-based survey. J Endod. 2011;37(11):1495-1498.
[21] Tobón SI, Arismendi JA, Marín ML, et al. Comparison between a conventional technique and two bone regeneration techniques in periradicular surgery. Int Endod J. 2002;35(7):635-641.
[22] von Arx T, Cochran DL. Rationale for the application of the GTR principle using a barrier membrane in endodontic surgery: a proposal of classification and literature review. Int J Periodontics Restorative Dent. 2001;21(2):127-139.
[23] Taschieri S, Corbella S, Tsesis I, et al. Effect of guided tissue regeneration on the outcome of surgical endodontic treatment of through-and-through lesions: a retrospective study at 4-year follow-up. Oral Maxillofac Surg. 2011; 15(3): 153-159.
[24] Marín-Botero ML, Domínguez-Mejía JS, Arismendi-Echavarría JA, et al. Healing response of apicomarginal defects to two guided tissue regeneration techniques in periradicular surgery: a double-blind, randomized-clinical trial. Int Endod J. 2006;39(5):368-377.
[25] Sánchez-Torres A, Sánchez-Garcés MA, Gay-Escoda C. Materials and prognostic factors of bone regeneration in periapical surgery: A systematic review. Med Oral Patol Oral Cir Bucal. 2014. in press.
[26] Baran ET, Tuzlakoglu K, Salgado AJ, et al. Multichannel mould processing of 3D structures from microporous coralline hydroxyapatite granules and chitosan support materials for guided tissue regeneration/engineering. J Mater Sci Mater Med. 2004;15(2):161-165.
[27] Swetha M, Sahithi K, Moorthi A, et al. Biocomposites containing natural polymers and hydroxyapatite for bone tissue engineering. Int J Biol Macromol. 2010;47(1):1-4.
[28] Zhang L, Tang P, Zhang W, et al. Effect of chitosan as a dispersant on collagen-hydroxyapatite composite matrices. Tissue Eng Part C Methods. 2010;16(1):71-79.
[29] Venkatesan J, Kim SK. Chitosan composites for bone tissue engineering--an overview. Mar Drugs. 2010;8(8):2252-2266.
[30] Chen L, Hu J, Shen X, et al. Synthesis and characterization of chitosan-multiwalled carbon nanotubes/hydroxyapatite nanocomposites for bone tissue engineering. J Mater Sci Mater Med. 2013;24(8):1843-1851.
[31] Pighinelli L, Kucharska M. Chitosan-hydroxyapatite composites. Carbohydr Polym. 2013;93(1):256-262.
[32] Zigdon H, Horwitz J. Using acellular dermal matrix (ADM) allograft in periodontal surgery--a literature review and case reports. Refuat Hapeh Vehashinayim. 2006;24(3):19-29, 92.
[33] Tal H. Subgingival acellular dermal matrix allograft for the treatment of gingival recession: a case report. J Periodontol. 1999;70(9):1118-1124.
[34] de Souza SL, Novaes AB Jr, Grisi DC, et al. Comparative clinical study of a subepithelial connective tissue graft and acellular dermal matrix graft for the treatment of gingival recessions: six- to 12-month changes. J Int Acad Periodontol. 2008;10(3):87-94.
[35] Rahmani ME, Lades MA. Comparative clinical evaluation of acellular dermal matrix allograft and connective tissue graft for the treatment of gingival recession. J Contemp Dent Pract. 2006;7(2):63-70.
[36] Novaes AB Jr, de Barros RR. Acellular dermal matrix allograft. The results of controlled randomized clinical studies. J Int Acad Periodontol. 2008;10(4):123-129.
[37] Moslemi N, Mousavi Jazi M, Haghighati F, et al. Acellular dermal matrix allograft versus subepithelial connective tissue graft in treatment of gingival recessions: a 5-year randomized clinical study. J Clin Periodontol. 2011; 38(12): 1122-1129.
[38] Fotek PD, Neiva RF, Wang HL. Comparison of dermal matrix and polytetrafluoroethylene membrane for socket bone augmentation: a clinical and histologic study. J Periodontol. 2009;80(5):776-785.
[39] Froum S, Cho SC, Elian N, et al. Extraction sockets and implantation of hydroxyapatites with membrane barriers: a histologic study. Implant Dent. 2004;13(2):153-164.
[40] Terino EO. Alloderm acellular dermal graft: applications in aesthetic soft-tissue augmentation. Clin Plast Surg. 2001; 28(1):83-99.
[41] Barros RR, Novaes AB, Grisi MF, et al. A 6-month comparative clinical study of a conventional and a new surgical approach for root coverage with acellular dermal matrix. J Periodontol. 2004;75(10):1350-1356.
[42] Sclafani AP, Romo T 3rd, Jacono AA, et al. Evaluation of acellular dermal graft (AlloDerm) sheet for soft tissue augmentation: a 1-year follow-up of clinical observations and histological findings. Arch Facial Plast Surg. 2001;3(2): 101-103.
[43] Orstavik D, Kerekes K, Eriksen HM. The periapical index: a scoring system for radiographic assessment of apical periodontitis. Endod Dent Traumatol. 1986;2(1):20-34.
[44] Friedman S, Abitbol S, Lawrence HP. Treatment outcome in endodontics: the Toronto Study. Phase 1: initial treatment. J Endod. 2003;29(12):787-793.
[45] Lin L, Chen MY, Ricucci D, et al. Guided tissue regeneration in periapical surgery. J Endod. 2010;36(4): 618-625.
[46] Moreira-Gonzalez A, Jackson IT, Miyawaki T, et al. Augmentation of the craniomaxillofacial region using porous hydroxyapatite granules. Plast Reconstr Surg. 2003;111(6):1808-1817.
[47] Damien E, Revell PA. Coralline hydroxyapatite bone graft substitute: A review of experimental studies and biomedical applications. J Appl Biomater Biomech. 2004;2(2):65-73.
[48] Ducheyne P, Qiu Q. Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials. 1999;20(23-24):2287-2303.
[49] Luo ZB, Zhang QB, Zhang ZQ, et al. Performance of coralline hydroxyapatite in sinus floor augmentation: a retrospective study. Clin Oral Investig. 2013;17(9): 2003-2010.
[50] Fu K, Xu Q, Czernuszka J, et al. Characterization of a biodegradable coralline hydroxyapatite/calcium carbonate composite and its clinical implementation. Biomed Mater. 2013;8(6):065007.
[51] Markel DC, Guthrie ST, Wu B, et al. Characterization of the inflammatory response to four commercial bone graft substitutes using a murine biocompatibility model. J Inflamm Res. 2012;5:13-18.
[52] Moslemi N, Mousavi Jazi M, Haghighati F, et al. Acellular dermal matrix allograft versus subepithelial connective tissue graft in treatment of gingival recessions: a 5-year randomized clinical study. J Clin Periodontol. 2011;38(12): 1122-1129.
[53] Thombre V, Koudale SB, Bhongade ML. Comparative evaluation of the effectiveness of coronally positioned flap with or without acellular dermal matrix allograft in the treatment of multiple marginal gingival recession defects. Int J Periodontics Restorative Dent. 2013;33(3):e88-94.
[54] Wagshall E, Lewis Z, Babich SB, et al. Acellular dermal matrix allograft in the treatment of mucogingival defects in children: illustrative case report. ASDC J Dent Child. 2002; 69(1):39-43, 11.
[55] Batista EL Jr, Batista FC. Managing soft tissue fenestrations in bone grafting surgery with an acellular dermal matrix: a case report. Int J Oral Maxillofac Implants. 2001;16(6):875-879.
[56] Koudale SB, Charde PA, Bhongade ML. A comparative clinical evaluation of acellular dermal matrix allograft and sub-epithelial connective tissue graft for the treatment of multiple gingival recessions. J Indian Soc Periodontol. 2012; 16(3):411-416.
[57] Zuolo ML, Ferreira MO, Gutmann JL. Prognosis in periradicular surgery: a clinical prospective study. Int Endod J. 2000;33(2):91-98.
[58] Luczyszyn SM, Papalexiou V, Novaes AB Jr, et al. Acellular dermal matrix and hydroxyapatite in prevention of ridge deformities after tooth extraction. Implant Dent. 2005;14(2): 176-184.
[59] Sàndor GK, Kainulainen VT, Queiroz JO, et al. Preservation of ridge dimensions following grafting with coral granules of 48 post-traumatic and post-extraction dento-alveolar defects. Dent Traumatol. 2003;19(4):221-227.
[60] Fowler EB, Breault LG. Ridge augmentation with a folded acellular dermal matrix allograft: a case report. J Contemp Dent Pract. 2001;2(3):31-40.
[61] Sadat Mansouri S, Ayoubian N, Eslami Manouchehri M. A comparative 6-month clinical study of acellular dermal matrix allograft and subepithelial connective tissue graft for root coverage. J Dent (Tehran). 2010;7(3):156-164.
[62] Artzi Z, Wasersprung N, Weinreb M, et al. Effect of guided tissue regeneration on newly formed bone and cementum in periapical tissue healing after endodontic surgery: an in vivo study in the cat. J Endod. 2012;38(2):163-169.
[63] Steele MH, Seagle MB. Palatal fistula repair using acellular dermal matrix: the University of Florida experience. Ann Plast Surg. 2006;56(1):50-53.
[64] de Souza SL, Novaes AB Jr, Grisi DC, et al. Comparative clinical study of a subepithelial connective tissue graft and acellular dermal matrix graft for the treatment of gingival recessions: six- to 12-month changes. J Int Acad Periodontol. 2008;10(3):87-94.
[65] Thomas LJ, Emmadi P, Thyagarajan R, et al. A comparative clinical study of the efficacy of subepithelial connective tissue graft and acellular dermal matrix graft in root coverage: 6-month follow-up observation. J Indian Soc Periodontol. 2013;17(4):478-483.

引言

Chronic periapical periodontitis is one of the common stomatological diseases, in which chronic periapical periodontitis (with fistula- shaped) often undermines periapical bone tissue and forms fistula. The cause of apical periodontitis emerges from a pulpal inflammation that exceeds to a necrotic pulp which gives opportunity for bacteria from the oral environment to enter the pulp chamber and the root canal. This colonization inside the tooth results in a leakage of bacterial products, toxins, and/or bacteria's through the apical foramen, thus causing an inflammatory reaction in the periapical tissue^[1-2]. Endodontic treatment attempts to eliminate bacterial infection in the radicular duct. According to a meta-analysis carried out by Ng et al^[3], the probability of success of this treatment ranges from 86% to 93% in a period of 2-10 years following root canal treatment. Despite a correct endodontic treatment or retreatment, in some cases periapical pathology persists. Therefore, periapical surgery may be considered as the last therapeutic option before tooth extraction^[4-5]. If it can not be cured in time to eliminate bone resorption and destruction of gingival tissue, it will eventually lead to tooth loss^[6-7]. The ultimate goal of periapical therapy is to achieve the periapical tissue repair and regeneration, new attachment formation and bone remodeling^[8], not only emphasizes the elimination of inflammation to prevent recurrence

of infection, but also restores the normal structures and functions of periapical tissue. The outcomes of non-surgical root canal treatment are usually good^[9], but sometimes root canal therapy^[10] alone is very difficult to heal those cases with larger periapical alveolar bone destruction^[11], longer time sinus, periapical tissue damage and the scope of periapical bone defect ≥ 10 mm × 10 mm^[12]. In these cases, oral periapical surgery is often needed^[13-15].

Guided tissue regeneration using barrier membranes and/or bone grafts has been successfully applied in different surgical techniques in oral surgery (such as periodontal surgery, implantology), just like in periapical surgery to enhance new tissue formation in the defect created by the lesion and by the surgical technique^[16-20]. The regeneration techniques in periapical surgery can accelerate periapical healing and allow healing in compromised clinical situations like large periapical lesions (> 1 cm), through-and-through lesions^[21-23], and lesions with a periodontal component as apicomarginal lesions^[24]. Guided tissue regeneration is an adjunct technique to periapical surgery that can use a wide variety of techniques and materials^[25]. Baran et al ^[26] reported that cylindrical hydroxyapatite microgranules were oriented along channel direction within multi-channel mould space and aligned particles were supported with fibers and a chitosan membrane. The positive replica of mould channels was clasp fixed to produce thicker scaffolds. The inclusion of nanoparticles of hydroxyapatite (one of the most widely used bioceramic materials) into the biopolymer matrix improves the mechanical properties and incorporates the nanotopographic features that mimic the nanostructure of bone^[27-31]. The acellular dermal matrix allograft is widely used in periodontal surgery^[32], and may be a possible substitute to free autogenous connective tissue grafts and/or bioabsorbable barrier membranes^[33]. acellular dermal matrix allograft is also a substitute for palatal donor tissue in root coverage procedures and gingival recessions^[34-35]. Novaes et al ^[36] reported that sites treated with the combination of allograft plus resorbable hydroxyapatite showed significantly greater ridge thickness preservation at 6 months when compared to sites treated with allograft alone^[37-39].

Thus, the aim of the present study is to report the clinical and radiographic results in the treatment of periapical tissue defects with acellular dermal matrix allograft combined with coralline hydroxyapatite.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程
全文链接：

材料方法

Design

A non-randomized controlled trial.

Time and setting

All patients were recruited from the Department of Periodontal & Mucosal Disease, Center of Stomatology, the First Affiliated Hospital of Xinjiang Medical University, China. The recruitment and active treatment period ranged from January 2009 to January 2011.

Subjects

Inclusion criteria

(1) No systemic disease, good oral hygiene and compliance, clinical examination and radiographic diagnosis of chronic periapical periodontitis; (2) Root canal overfilling with clinical symptoms or periapical lesions not healed; (3) Periapical bone destroyed after post and core crowns were repaired; (4) Periapical cyst or periapical granuloma with extensive periapical bone destruction; (5) Bits for the upper and lower teeth suffering from anterior and premolar; (6) Periapical bone destruction area was ≥ 10 mm × 10 mm.

Exclusion criteria

(1) Side plate of teeth lip (buccal) completely lost; (2) Root canal perforation; (3) Too little periodontal support; (4) Systemic disease or poor compliance.

We chose 76 periapical periodontitis patients, aged 20-56 years, for the treatment. All the patients with chronic apical periodontitis were randomly and equally divided into two groups: 38 patients in experimental group and 38 in control group. In the experimental group, there were 21 males and 17 females, the average age was (37.79±9.19) years. Tissue defects were packed with acellular dermal matrix allograft and coralline hydroxyapatite. In the control group, there were 23 males and 15 females, the average age was (37.53±9.81) years. Tissue defects were void. All patients in both groups had signed written consent upon received vocal and written information explaining the purpose and the possible risks/side-effects of the treatment. The study protocol had previously been approved by the Science Ethics Committee for the district of The First Affiliated Hospital of Xinjiang Medical University in China.

Materials

Acellular dermal matrix allograft

It is soft, leather-like, white, smooth surface membrane, and the other side is rougher than former. The patch can induce growth characteristics of epithelial cells, and dermis is induced rapid vascular post-implantation and there is ingrowth of neovascularization and fibroblasts. Furthermore, acellular dermal matrix allograft and the host tissue can reconstruct soft tissue in the absence of infiltration of inflammatory cells^[40-41]. Moreover, the inflammatory response induced much lower than mucosa transplantation after acellular dermal matrix allograft implanted into the body^[42]. Acellular dermal matrix allograft was provided by Beijing Qingyuan Weiye Biotissue Engineering Technology Co., Ltd., Beijing, China.

Coralline hydroxyapatite

It is derived from natural coral, which has a good biocompatibility and bone conductivity of porous bioceramics. The specifications is 0.4-1.0 mm in diameter and weighs 0.25 g/0.5 g. Coralline hydroxyapatite was provided by Beijing Yihua Kejiang Business Co., Ltd., Beijing, China.

Methods

Repair of teeth defects

In order to avoid the confounding brought by different operators, all the surgical procedures were executed by the same dentist.

Surgical steps: (1) In order to expose damaged bone tissue and protect the gingival tissue as much as possible, we injected articaine hydrochloride adrenal into lip (buccal) side of gingiva and made arc incision. (2) The edge of alveolar bone was polished as smooth as possible while repairing it. (3) Periapical inflammatory granulation tissue was cleared away, as well as that around fistula, and then washed the wound thoroughly and stopped bleeding. All teeth of the experimental group and the control group used apicoectomy and retrograde filling. (4) Then bone defect was filled with coralline hydroxyapatite and it should be compressed. Coralline hydroxyapatite should be filled for 2/3-3/4 of the concave bone loss zone and it was necessary to slightly lower than the surrounding bone. (5) Repairing medical organizations patch to cover the coralline hydroxyapatite and bone defect and 2-3 mm beyond the edge of bone defect, which prevented coralline hydroxyapatite from leaking out of the defect after its contraction in the experimental group. Contrarily, in the control group tissue defects were void. (6) Gingival flap was sutured tightly and oral hygiene should keep good after operation. Appropriate antibiotics and rinse were needed to prevent infection, and suture should be removed 10 days after operation (Figure 1).

Postoperative evaluation

All patients in both groups were screened with conventional radiographic film to observe the survivable situation, healing time, biocompatibility with the surrounding tissue and contraction of the acellular dermal matrix allografts 1 month after operation. Periapical status was measured by periapical index^[43]: I-II class indicates no periapical lesions, > II class indicates periapical lesions.

Operation and radiographic films

Clinical examination and radiographic film were performed after 1 week, 6 months and 3 years follow-up visits to evaluate the effect. The radiographic films before and after surgery, and during follow-up visit were all screened by the experienced technician with the same radiographic machine and film projection methods, at the same time, all radiographic films were evaluated by two experienced dental pulp general practitioners.

Evaluation criteria

Cure: no abnormal chewing, no loose and knocking pain, fistula and apical shadow disappeared; Improvement: normal chewing, fistula and periapical shadow disappeared; Invalidation: masticatory pain, persistent fistula, the same or increase of periapical shadow. Both cure and improvement were regarded as validity^[44].

Main outcome measures

The periapical tissue defects repaired with different methods were observed.

Statistical analysis

SPSS statistical package (Version 12.0, SPSS Inc., Chicago, IL, USA) was used for the data analysis. The baseline age and gender between the experimental group and the control group were evaluated with the t-test, and statistics. Fisher exact probability test was used to compare teeth, gender, age and style of lesions in 3 years postoperative therapy in the experimental group. A value of P < 0.05 was considered statistically significant.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

全文链接：

讨论

Tissue regeneration by using membrane barriers and bone grafting materials in periapical surgery is an example of tissue engineering technology^[45]. Coralline hydroxyapatite is well biocompatible to human bone, and it is non-toxic, safe and stable^[46-47]. When coralline hydroxyapatite is implanted into the periapical bone defects, through the porous and specific surface of bio-derived coral hydroxyapatite, bone cells are chemotactic, proliferate, differentiate and secrete extracellular matrix. Ultimately coralline hydroxyapatite is replaced by a new life bone tissue^[48-50]. It contributes to alveolar bone regeneration and new bone formation, so it could make teeth strong, reduce the local fibrous tissue formation and the chance of infection and promote the healing of periapical changes^[51].

Acellular dermal matrix allograft is the film or sheet that mainly used for oral soft tissue injury and hernia repair, and it is a kind of biological material that can be used for human directly^[52-53]. It could completely repair lesions without immune rejection. It has a good biocompatibility with human tissue after decellularization (eliminating cell surface antigen that cause immunologic rejection). Wagshall et al ^[54] is used to replace hard palate mucosa by acellular dermal matrix allograft to repair the children's film gingival defect, which was resumption of the joint membrane and gingiva and restoration of normal blood vessels in 6 months after postoperation therapy. Batista^[55]used acellular dermal matrix allograft to promote the survival of bone graft after repairing gingival fenestration. Acellular dermal matrix allograft was implanted into surface of the submucosal graft bone, then it can protect the bone graft, promote hyperplasia and vascular network formation in the tissue graft, and accelerate reconstructive process of trauma. Koudale^[56] results suggest that acellular dermal matrix allograft may be a useful substitute instead of subepithelial connective tissue graft for root coverage.

For such refractory cases of periapical periodontitis, periapical surgery in this study could promote the healing of periapical lesions through the method of removal of the infection and lesion. Periapical bone defect with fistula-shaped is one of the chronic periapical periodontitis. It can be a result of root canal calcifying, excessive bending, super-filling fillings, broken equipment left in root canals. The fistula would destroy the gingival tissue. It is difficult to induce natural regeneration of periapical bone defects through a simple root canal treatment.

In this study, the efficiency of periapical surgery at post-operative 3 years was 94.7% in the experimental group, which approached to the other research^[57]. Moreover, there was no significant difference in teeth, gender, age and style of lesions in 3 years postoperative therapy in the experimental group. We used acellular dermal matrix allograft combined with coralline hydroxyapatite to repair periapical tissue defects^[58], that is ≥ 10 mm × 10 mm (it could be found that the scope of bone defect during operation was usually greater than the shadow of radiographic films). And the curative effect was very significant.

The bone cavity is bequeathed after operation, which often leads to periapical re-infection during the long time of bone tissue repairing. Coralline hydroxyapatite is a major inorganic component in human body. It has a good chemical stability and biological histocompatibility. When the coralline hydroxyapatite is implanted into the bone cavity, it could eliminate the dead space directly. And more importantly, bone tissue can penetrate into the space inside the particles, which would result in ossification of integration. Furthermore, coralline hydroxyapatite could induce the growth of bone and easily integrate with bone tissue. Sàndor et al ^[59] used coralline hydroxyapatite for clinical bone graft to repair bone defects and found that coralline hydroxyapatite can be a perfect substitute for autogenous bone in long-term and follow-up observation of postoperative therapy. The soft tissue would take precedence over bone growth, occupy the apical bone cavity, and could fail the treatment after periapical surgery. Acellular dermal matrix allograft, such as covering the surface of coralline hydroxyapatite, and guiding tissue regeneration membrane^[60], will prevent junctional epithelium and connective tissue from into bone defects^[61]. At the same time it can play the role as bone leader to provide a set of high-calcium environment for the formation of new bone and accelerate the repair of bone defects^[45].

Different from other types of collagen membrane^[62], acellular dermal matrix allograft only retains in extracellular matrix such as collagen, elastin, glycoproteins^[63]. Its unique three-dimensional structure provides a place for growth and metabolism of the host cells. The host fibroblasts can grow in its structure. Using acellular dermal matrix allograft we could reconstruct the form, structure and function of lesions and this would provide us with a permanent substitute^[64-65].

With the development of new materials and medical technology, the study of repairing therapy of periapical tissue will become more and more important objective and in-depth. The renewal and regeneration of periapical tissue could become more realistic.

The ?ndings of the present study suggest that the improvements in periapical conditions obtained after acellular dermal matrix allograft combined with coralline hydroxyapatite in repairing periapical tissue defects, can be preserved on a long-term basis. Moreover, comparing the tooth therapy efficiency there was no significant difference between teeth, gender, age and style of lesions in 3 years postoperative therapy in the experimental group.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程
全文链接：

文章快阅

延伸阅读

1文章概要：
在临床上，由于牙齿的慢性根尖周炎症所导致的根尖周骨质破坏及缺损并不少见，对根尖周牙槽骨组织破坏较大、窦道存留时间较长且牙龈组织破坏的病例，要寻求合适的组织替代材料用于组织缺损重建以达到彻底消除并修复病变，稳固患牙的最终治疗目标。

实验中根尖周骨缺损是用珊瑚羟基磷灰石与异体脱细胞真皮基质联合进行修复。将两者联合应用，在临床思路，手术效果及术后愈合等方面，较之仅选用骨替代材料进行修复有一定优势。

今后的研究中，应加大样本量并延长观察时间，同时去发现更多更好的修复材料应用于临床。

2实验设计构思介绍：
根尖外科手术不仅需要刮除根尖周的病变组织，而且还要切除病变的根尖，为根尖周病灶的痊愈创造了条件。对根尖周牙槽骨组织破坏较大、窦道存留时间较长且牙龈组织破坏的病例，要寻求合适的组织替代材料用于组织缺损重建以达到彻底消除并修复病变，稳固患牙的最终治疗目标。

3国内外同类研究水平的介绍：
:临床上常见因炎症而导致的根尖周骨缺损，目前解决方法包括：自体骨移植、异体骨移植及人工骨替代材料修复骨缺损。其中，自体骨移植存在供骨来源有限、移植骨的远期吸收、供骨区损伤、疼痛和出血等，患者往往不愿接受；异体骨移植存在潜在的抗原性和传播疾病的风险；而人工骨替代材料因其来源充足、可标准化生产及避免不必要的疾病传播等优点成为众多学者的研究方向。
国内外学者采用羟基磷灰石，骨无机材料以及可吸收生物膜等进行根尖周及牙周组织缺损的修复。

4与其他同类研究的比较：
当珊瑚羟基磷灰石植入骨腔中，直接可消除死腔，更主要的是骨组织可直接长入颗粒间隙内，产生骨化溶合，不被机体排斥，对骨的生长有诱导作用，并易与骨组织形成整合。而根尖手术后软组织会优先于骨质生长而占据根尖骨腔导致治疗失败，珊瑚羟基磷灰石表面如覆盖异体脱细胞异体真皮基质作为组织引导再生膜，将防止结合上皮及结缔组织长入骨缺损区，同时具有骨引导作用，能为新骨的形成提供一个钙磷高集的环境，加快骨缺损修复。作者认为将两者联合应用，在临床思路，手术效果及术后愈合等方面，较之仅选用骨替代材料进行修复还是有一定优势的。

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

全文链接：

珊瑚羟基磷灰石与异体脱细胞真皮基质联合修复牙根尖周组织缺损

Acellular dermal matrix allograft combined with coralline hydroxyapatite repair periapical tissue defects

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

图/表（结果） 2

参考文献

相关文章 15

引言

材料方法

讨论

文章快阅

延伸阅读

编辑推荐

Metrics

本文评价

[1]	李黎, 马力. 磁性壳聚糖微球固定化乳糖酶及其酶学性质[J]. 中国组织工程研究, 2021, 25(4): 576-581.
[2]	刘鋆, 杨龙, 王伟宇, 周玉虎, 吴颖, 卢涛, 舒莉萍, 马敏先, 叶川. 聚3-羟基丁酸酯4-羟基丁酸酯/聚乙二醇/氧化石墨烯组织工程支架的制备和性能评价[J]. 中国组织工程研究, 2021, 25(22): 3466-3472.
[3]	周安琪, 唐渝菲, 吴秉峰, 向琳. 骨膜组织工程设计：共性与个性的结合[J]. 中国组织工程研究, 2021, 25(22): 3551-3557.
[4]	郎丽敏, 何生, 姜增誉, 胡奕奕, 张智星, 梁敏茜. 导电复合材料在心肌梗死组织工程治疗领域的应用进展[J]. 中国组织工程研究, 2021, 25(22): 3584-3590.
[5]	解健, 苏俭生. 静电纺丝取向纳米纤维作为组织工程生物支架的优势与特征[J]. 中国组织工程研究, 2021, 25(16): 2575-2581.
[6]	纪琦, 喻正文, 张剑. 3D打印金属基生物材料工艺和临床应用的问题与趋势[J]. 中国组织工程研究, 2021, 25(16): 2597-2604.
[7]	宋涯含, 吴云霞, 范道洋. 基于VOSviewer生物医学领域3D打印的知识图谱分析[J]. 中国组织工程研究, 2021, 25(15): 2385-2393.
[8]	钱楠楠, 张潜, 杨睿, 敖俊, 章涛. 间充质干细胞治疗脊髓损伤：细胞治疗及联合新药和生物材料[J]. 中国组织工程研究, 2021, 25(13): 2114-2120.
[9]	罗雅馨, 毕浩然, 陈晓旭, 杨琨. 细胞外基质与组织的再生与修复[J]. 中国组织工程研究, 2021, 25(11): 1785-1790.
[10]	贾巍, 张满栋, 陈维毅, 王晨艳, 郭媛. 股骨假体材料对人工膝关节置换性能的影响[J]. 中国组织工程研究, 2021, 25(10): 1477-1481.
[11]	王倩, 李璐, 舒静媛, 董志恒, 靳友士, 王青山. 氧化锆基纳米羟基磷灰石功能梯度生物材料的微观形貌和物相分析[J]. 中国组织工程研究, 2021, 25(10): 1517-1521.
[12]	杨亚楠, 李峻峰, 王立, 刘恒全, 赖雪飞. 柠檬酸钙：一种有趣的有机钙生物医用材料[J]. 中国组织工程研究, 2021, 25(10): 1609-1615.
[13]	樊雪敏, 方善宝, 陈志兴, 莫水学. 纳米粘土锂皂石的研究现状与应用前景[J]. 中国组织工程研究, 2021, 25(10): 1622-1627.
[14]	王刚, 李东辉, 白志明. 长段输尿管损伤替代治疗的方法、材料及修复重建的演变历程[J]. 中国组织工程研究, 2020, 24(8): 1299-1305.
[15]	任春梅, 刘玉芳, 许诺, 邵苗苗, 何建亚, 李晓杰. 非编码RNAs在人牙髓干细胞中的调控作用及机制 [J]. 中国组织工程研究, 2020, 24(7): 1130-1137.