口腔颌面部外伤、肿瘤等常造成口腔颌面部软组织缺损,目前传统的修复方法仍以自体组织移植为主.近年来,组织工程的兴起为口腔颌面软组织缺损的修复提供了新的选择.组织工程的3个基本要素为种子细胞、支架、生长因子,其中支架在组织工程领域内应用最为广泛.本文总结归纳目前国内外常用于口腔颌面软组织缺损修复的组织工程支架材料及其应用现状,以期为相关研究的设计与临床应用提供参考.

背景:吲哚菁绿作为高效的光热转换剂可用于口腔鳞状细胞癌的光热治疗,但其具有水不稳定和光降解等缺点,利用载体负载吲哚菁绿提高其稳定性,对探索口腔鳞状细胞癌的光热治疗研究具有重要意义.目的:制备聚乳酸-羟基乙酸共聚物负载吲哚菁绿的微球,延缓吲哚菁绿光降解,提高其光热稳定性.方法:①采用乳液-溶剂蒸发法制备聚乳酸-羟基乙酸共聚物负载吲哚菁绿的微球,对其形貌、粒径分布、表面电荷、载药量和包封率进行表征.②将游离吲哚菁绿溶液与吲哚菁绿微球悬液在不同质量浓度下(0.6,0.8,1.0,1.2 g/L)经近红外光辐照5 min,考察溶液温度变化;将游离吲哚菁绿溶液与吲哚菁绿微球悬液在1.0 g/L质量浓度下未避光放置0,3,6,9 d,观察近红外光辐照5 min内的温度变化;将游离吲哚菁绿溶液与吲哚菁绿微球悬液在1.0 g/L质量浓度下进行4个开-关激光光照循环,考察溶液温度变化.③将舌鳞癌细胞系SCC-25接种于48孔板内,分8组培养:对照组、空白微球组、1.0 g/L游离吲哚菁绿组、1.0 g/L吲哚菁绿微球组、近红外光照组、空白微球+近红外光照组、1.0 g/L游离吲哚菁绿+近红外光照组和1.0 g/L吲哚菁绿微球+近红外光照组.处理12 h后,采用CCK-8法检测细胞活力.结果 与结论:①吲哚菁绿微球表面光滑,平均粒径为(2.54±0.29)μm,Zeta电位为-(20.2±1.58)mV,包封率和载药率分别为(69.24±1.29)％和(4.87±0.15)％;②游离吲哚菁绿与吲哚菁绿微球具有相似的光热转换能力,但增加激光辐照次数或未避光存放后,游离吲哚菁绿的光热转换能力较吲哚菁绿微球明显降低;③1.0 g/L游离吲哚菁绿+近红外光照组和1.0 g/L吲哚菁绿微球+近红外光照组的SCC-25细胞皱缩呈球型,该两组的细胞活力低于对照组(P<0.001);④结果表明,吲哚菁绿微球具有高效的光热转换效率,明显延缓了吲哚菁绿的光漂白和光降解.

The most prevalent oral and maxillofacial cancer is oral squamous cell carcinoma (OSCC). Patient survival is compromised by relapse due to post-operative tumor remnants and significant mucosal defects. Photothermal therapy (PTT) is used to ablate local malignancies, but the capacity of tumor cells to resist it is correlated with the overexpression of heat shock protein 70 (HSP70). In this work, PTT and tissue engineering scaffold were rationally integrated to construct a Ti3C2 MXene, collagen, silk fibroin and quercetin composite scaffold (M-CSQ scaffold), a 3D printed biomaterial that simultaneously kill OSCC cells and promote the regeneration of the mucosal defects. The M-CSQ scaffolds were prepared by cryogenic 3D printing and freeze-drying techniques with sufficient pores that allow an abundant cell migration and provide a proliferation space. Ti3C2 MXene has excellent photothermal conversion ability and stability. Quercetin targeted HSP70 to decrease its expression in OSCC cells, consequently weakening their resistance to high temperature and enhancing the effect of PTT. The M-CSQ scaffold effectively killed OSCC cells in vitro and inhibited tumor growth in vivo. In addition, the M-CSQ scaffold provided adhesion sites for Sprague-Dawley rat (SD rat) buccal mucosal fibroblasts and promoted the repair of buccal mucosal wounds.

As the most prevalent malignant tumor of the oral and maxillofacial regions, squamous cell carcinoma (SCC) has relatively high recurrence and low survival rates. Currently, the most common treatment strategies are surgery and chemoradiotherapy. However, incomplete removal of the tumor can allow residual tumor cells to regrow and metastasis, resulting in treatment failure. Although postoperative adjuvant radiotherapy or chemotherapy can reduce recurrence, serious adverse reactions significantly compromise patients' quality of life. Large soft tissue defects after surgery are also difficult to heal. Therefore, therapies that eliminate residual tumor cells and promote tissue regeneration post-surgery are urgently needed. Indocyanine green (ICG) can convert absorbed light into heat to ablate tumor cells. Three-dimensional (3D) scaffolds are efficient drug carriers and support cell migration and proliferation. Here, we fabricated collagen/silk fibroin encapsulated ICG (I-CS) scaffolds by combining 3D printing with freeze-drying methods. The I-CS scaffolds delayed ICG decomposition and clearance, allowing the scaffolds to be used repeatedly for photothermal therapy (PTT). With the laser positioned at 4 cm from the 1.0 I-CS scaffold and irradiation for 10 min (1.0 W/cm2), temperatures above 50 °C were achieved, which effectively killed SCC-25 cells in vitro and suppressed tumor growth in vivo. Moreover, the I-CS scaffolds supported attachment and proliferation of rat buccal mucosa fibroblasts (RBMFs) and promoted the repair of buccal mucosal wounds in rats. These results suggested that I-CS scaffolds may be useful in preventing local recurrence and support regeneration of large soft tissue defects after oral SCC surgery.

Oral cancer is one of the most common tumours in the world threatening human life and health. The 5-years survival rate of patients with oral cancer has not been improved significantly for many years. The existing clinical diagnostic methods rarely achieve early diagnosis due to deficiencies such as lack of sensitivity. Most of the patients have progressed to the advanced stages when oral cancer is detected. Unfortunately, the traditional treatment methods are usually ineffective at this stage. Therefore, there is an urgent need for more effective and precise techniques for early diagnosis and effective treatment of oral cancer. In recent decades, nanomedicine has been a novel diagnostic and therapeutic platform for various diseases, especially cancer. The synthesis and application of various nanoagents have emerged at the right moment. Among them, polymer nanoagents have unique advantages, such as good stability, high biosafety and high drug loading, showing great potential in the early accurate diagnosis and treatment of tumours. In this review, we focus on the application of advanced polymeric nanoagents in both the diagnosis and treatment of oral cancer. Then, the future therapy strategies and trends for polymeric nanoagents applied to oral cancer are discussed, with the hope that more advanced nanomedical technology will be applied to oral cancer research and promote the development of stomatology.

癌症严重威胁着人类健康,甚至危及生命.如何修复癌症术后组织缺损,同时预防残余癌细胞复发成为临床上的重大挑战.将光热试剂与三维支架结合制备光热功能化支架,支架植入术后创面,一方面接受近红外激光照射产生的光热效应消融残余癌细胞,另一方面,支架可刺激缺损周围组织细胞再生.对光热功能化支架在骨肉瘤、皮肤黑色素瘤以及乳腺癌中的应用归纳总结,分析不同支架材料在不同癌症治疗中的优势,可为其他肿瘤的治疗提供新思路.

Objectives: To study the effect of mechanical overload stimulation on proliferation, differentiation and mineralization of osteoblast and the underlying mechanisms. Methods: MC3T3-E1 cells were divided into overload group and control group. Four-point bending loading device was used to exert mechanical overload stimulation on MC3T3-E1 cells for a certain time. The proliferation of osteoblasts was detected by MTT colorimetric assay. Real-time PCR and Western Blot were used to detect the transcription and expression of osteoblast marker genes and proteins. The specific fluorescent dyes were used to label the actin filament and the nucleus, and the changes of cytoskeleton were observed under laser scanning confocal microscope. The mineralization of osteoblasts was evaluated by the number of calcium nodules formed by alizarin red staining. Results: Compared with the control group, the mechanical overload group significantly inhibited the proliferation of osteoblasts ( p <0.05). Real-time PCR and Western Blot showed that the expression of osteoblast differentiation marker gene and protein was inhibited by mechanical overload stimulation. Under laser confocal microscopy, the overload group cell shrinkage deformation was observed, also the microfilament arrangement disorder, the skeleton arrangement loose, the direction difference and the skeleton breakage, but the nucleus does not have obvious change. Alizarin red staining showed that mechanical overload inhibited the formation of calcium nodules in osteoblasts. The expression of β-catenin protein in Wnt signaling pathway was inhibited by overload mechanical stimulation under immunofluorescence microscopy. Conclusion: Mechanical overload stimulation reduces the expression of Runx 2 by affecting the classical Wnt/β-catenin signaling pathway, thus it was inhibited osteoblast proliferation, differentiation and mineralization.

Oral squamous cell carcinoma is one of the most common malignant tumours in the oral and maxillofacial regions and is highly malignant and prone to recur despite the development of various effective treatments, including surgery and chemoradiotherapy. Actually, it is difficult to ensure the complete elimination of tumour cells, and maxillofacial bone defects caused by surgery are hard to heal by themselves. In addition, chemoradiotherapy can bring serious side-effects. Therefore, it is imperative to develop a postoperative therapy to kill residual squamous cancer cells and repair bone defects without any side-effects. Here, we prepared a 3D scaffold by a 3D printing technique and freeze-drying method, which contained collagen, silk and hydroxyapatite (CSH) and was functionalized with MXene nanosheets (M-CSH). The considerable photothermal effect with long-term stability can significantly kill squamous CAL-27 cancer cells in vitro and inhibit tumour growth in vivo, increasing the probability of the M-CSH scaffold being applied in the photothermal therapy of oral squamous cell carcinoma. Moreover, the cell proliferation- and osteogenic-related protein expression of mouse embryonic osteogenic precursors (MC3T3-E1) indicated excellent biocompatibility and osteogenic activity of M-CSH scaffolds. The good compression modulus (52.8362.25 kPa) and in vivo bone formation performance made it possible to be used as reconstructive materials for bone defects. This scaffold is likely promising in future tissue engineering, especially for the multifunctional treatment of maxillofacial tumours.

The three-dimensional (3D) printing technology combined with bone tissue engineering has become one of the major methods for mandibular reconstruction. However, the key factor retarding mandible reconstruction is the barrier of understanding and achieving the complex 3D gridwork formed by the trabeculae. This study innovatively constructed a low-temperature 3D printing silk fibroin/collagen/hydroxyapatite (SF/COL/HA) composite scaffold with a stable structure and remarkable biocompatibility. We designed three kinds of six-layer scaffolds with mixed fiber cross-angle structures (FCAS) of [0°/90°/0°/90°/0°/90°], [0°/45°/90°/135°/180°/225°] and [0°/30°/60°/90°/120°/150°]. Material properties of these scaffolds such as porosity, water absorption rate, X-ray diffraction, Fourier transform infrared spectroscopy, and compression performance were detected. Then, the MC3T3-E1 cells were seeded on these scaffolds and the adhesion, proliferation, and differentiation were investigated. To be more convincing, the same experiments were performed on another polycaprolactone/hydroxyapatite scaffold. The results suggested that the changes of FCAS affected the mechanical properties of 3D printed scaffolds and performance of seeded cells. Besides, the 90° FCAS significantly enhanced the compressive modulus in two groups and were more conducive to the cell proliferation and osteogenesis, which provided evidence for exploring the influence of FCAS on the properties of scaffolds and the application of two composite scaffolds in tissue regeneration.