明膠/氫氧基磷灰石微粒搭載基質細胞衍生因子於齒槽骨再生之研究

Abstract

牙周炎是在牙科常見的嚴重炎症，會逐漸損害軟組織並破壞支持牙齒的牙槽骨。由於牙齒的可修復性有限，這種類型的骨丟失自然是不可逆的，組織工程學的進步為牙科植入物或人工替代物提供有效再生齒槽骨缺損的策略，骨再生可以通過三種不同的機制完成：成骨，骨誘導和骨傳導，所有植入材料均發揮這三種作用機理中的一種或多種。在眾多的移植物方面，使用最為廣泛的移植物為同種異體移植物，然而，同種異體移植物通常僅具有骨傳導性，因此，開發具有骨誘導作用的新型同種異體移植物用於牙槽骨再生是必要的。在這項研究中，明膠/羥基磷灰石微球（GHM-S）用於嵌入基質細胞衍生的因子-1 (SDF-1)，這是一種具有良好特徵的趨化因子，可用於吸引幹細胞，是促進齒槽骨再生的潛在候選者。本研究透過FTIR及XRD發現合成的羥磷灰石類似於天然骨組織的羥磷灰石，通過TGA分析測量了GHM-S微球的有機和無機成分，證實了GHM-S微球的組成與天然骨組織相似，SDF-1可以用控制釋放的方式從GHM-S微球中釋放，從而在培養環境中形成濃度梯度以吸引幹細胞遷移，在基因表達和蛋白質表達的結果也顯示幹細胞可以分化或發育為成骨細胞，最後，在具有牙槽骨缺損的大鼠模型中評估了體內的骨形成，並且根據電腦斷層影像和組織學檢查證實了GHM-S可促進齒槽骨的再生。我們的研究結果表明，GHM-S是一種可行且有效的齒槽骨填補材料。

Periodontitis is a severe inflammatory condition of the periodontium that progressively damages the soft tissue and destroys the teeth supporting. This type of bone loss is naturally irreversible due to the limited reparability of teeth. Advances in tissue engineering have provided the means for the effective regeneration of osseous defects with suitable dental implants or tissue-engineered constructs. Bone regeneration can be accomplished through three different mechanisms: osteogenesis, osteoinduction, and osteoconduction. All grafting materials exert one or more of these three mechanisms of action. However, alloplastic grafts are typically only osteoconductive. Therefore, the development of a novel alloplastic graft with osteoinduction for alveolar bone regeneration is necessary. In this study, gelatin/hydroxyapatite microsphere (GHM-S) was used to embed stromal cell-derived factor-1 (SDF-1), a well-characterized chemokine for attracting stem cells and thus a strong candidate for promoting regeneration. Our finding showed that synthesized hydroxyapatite was similar to the natural bone tissue. The organic and inorganic components of the GHM-S was measured by TGA analysis, which confirmed that part of the GHM-S was similar to the natural bone tissue. SDF-1 could be released in a controlled manner from the GHM-S to form a concentration gradient in a culture environment to attract the stem cell migration. Gene expression and protein level indicated that stem cells is able to differentiate or develop into preosteoblasts. The in vivo bone formation was assessed in rats with alveolar bone defects and significant augmentation of bone by GHM-S was by micro-CT imaging and histological examination. The findings in this study demonstrated that the GHM-S is a feasible approach for alveolar bone regeneration.