磷酸鹽陶瓷組成對於骨誘導作用之研究

The effects of compositions of Phosphate Bioceramics on osteoinduction

陳翰生(Han-Sheng Chen)

指導教授 ： 蔡偉博

國立臺灣大學/工學院/化學工程學研究所/碩士(2013年)

https://doi.org/10.6342/NTU.2013.02210

摘要

骨填補物可以刺激骨組織再生於骨缺陷中，恢復骨組織結構與功能。由於氫氧基磷灰石的組成與性質接近骨組織的無機鹽成分，因此成為人造的骨移植材料的主流。經過臨床實驗證實磷酸鈣生醫陶瓷甚為安全，生物相容性良好，並且有引導骨成長的特性，不過一般認為氫氧基磷灰石缺乏骨誘導作用。然而從若干動物實驗顯示，在植入磷酸鹽陶瓷的骨缺陷處，在復原時有骨誘導作用發生的跡象，不過鮮少有研究對此現象進行研究。我們推測其可能原因為磷酸鹽陶瓷可以吸附骨髓腔中的Bone morphogenetic proteins (BMPs)，或是磷酸鹽陶瓷可以促進間葉幹細胞分泌BMPs，以刺激周圍的間葉幹細胞分化為骨母細胞。
磷酸鈣陶瓷的組成或結構會影響其骨誘導的效果，首先我們想探討磷酸鈣陶瓷在骨髓腔的環境中是否具有骨誘導作用。我們藉由不同組成的磷酸鈣陶瓷來觀察細胞在磷酸鈣陶瓷上的生長及分化狀況。並檢測不同組成的磷酸鈣陶瓷的表面結構及物化性質，推論出陶瓷的結構及組成對於細胞生長和分化的影響，進而找出最適合用於骨移植材料的磷酸鈣陶瓷組成。此外我們也觀察陶瓷加入BMP-2是否能促進細胞進行分化。陶瓷吸附BMP-2的能力愈好則愈容易促進細胞分化。
此研究我們使用五組不同組成的磷酸鈣陶瓷進行實驗，分析了各種材料性質對細胞生長及分化的影響。我們證實了加入磷酸鹽確實使氫氧基磷灰石具有骨誘導，也發現磷酸鹽比例愈高其骨誘導效果愈好。藉由各種實驗結果我們找出最適合骨新生的配方。未來可以此配方生產新型的骨填補材。

關鍵字

氫氧基磷灰石 ； 磷酸鈣陶瓷 ； 骨誘導

並列摘要

Bone grafts are aimed to stimulate osteogenesis in bone defects, and restore the structure and function of bone tissue. Since the atomic composition and mechanical properties of hydroxyapatite (HA) resemble the inorganic portion of bone tissue, HA becomes a popular material for synthetic bone grafts. Clinical evidence reveals that HA bioceramics process excellent biocompatibility and the property of osteoconduction. Although it is generally thought that HA lacks the osteoinduction property, some animal implant experiments reveal that osteoinduction may happen in the surroundings of HA in the bone defects. Nevertheless, such phenomenon is usually ignored in the studies of bone grafts. We suggest that it might be due to the adsorption of BMPs to HA from bone marrow or the stimulation in the secretion of BMPs from mesenchymal stem cells when they are cultured on HA.
The composition or structure of calcium phosphate ceramic will affect its osteoinductive effect. First of all we would like to explore whether calcium phosphate ceramics have osteoinduction in the bone marrow cavity environment. We used different composed of calcium phosphate ceramics to observe the 3A6 mesenchymal stem cells growth and differentiation status. And we detect the surface structure and physical properties of calcium phosphate ceramics to infer the effect of ceramic structure and composition on cell growth and differentiation, and thus we identify the most suitable composed of calcium phosphate ceramics for the bone graft material. In addition, we also observed whether the ceramic added BMP-2 can promote cell differentiation. Ceramic which adsorbed BMP-2 well is more easy to promote cell differentiation.
In this study, we used five different composition of calcium phosphate ceramics to conduct experiments, and we analyzed the effect of various material properties on cell growth and differentiation. We verified that the addition of phosphate does make hydroxyapatite osteoinductive, and has also found that the higher the percentage of phosphate, the effect of osteoinduction is better. With a variety of experimental results, we identify the most suitable composition for bone filling. This formula can be used to product new bone filling material in future.

並列關鍵字

hydroxyapatite ； calcium phosphate ceramics ； osteoinduction

參考文獻

[1] Langer R, Vacanti JP. TISSUE ENGINEERING. Science. 1993;260:920-6.

[2] O'Brien FJ. Biomaterials & scaffolds for tissue engineering. Mater Today. 2011;14:88-95.

[3] Sheridan MH, Shea LD, Peters MC, Mooney DJ. Bioadsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery. J Control Release. 2000;64:91-102.

[4] Ma PX, Choi JW. Biodegradable polymer scaffolds with well-defined interconnected spherical pore network. Tissue Eng. 2001;7:23-33.

[5] Porter JR, Ruckh TT, Popat KC. Bone Tissue Engineering: A Review in Bone Biomimetics and Drug Delivery Strategies. Biotechnol Prog. 2009;25:1539-60.