Hierarchical evolution of bone biomimicry and osteo-coagulo-immunomodulation induced by the size of biological hydroxyapatite

doi:10.7518/hxkq.2024.2024315

Abstract

Abstract:

Biological hydroxyapatite (BHA) is widely used in the treatment of clinical bone defects due to its good biocompatibility and osteoconductivity. The clinical application of mateiral size is based on the principle of bone defect area adaptation, which contributes to diversity of BHA sizes. However, different sizes correspond to different hierarchical levels of bone biomimicry. As the size changes, the bone biomimicry hierarchy evolves accordingly and influences the process of bone repair and regeneration through osteo-coagulo-immunomodulation, leading to unstable bone graft outcomes. Therefore, this paper reviews the size effect of clinical BHA, analyzes the multilevel structure of natural bone, proposes the evolution of bone biomimetic hierarchy triggered by the size of BHA, and further analyzes the size-media-ted osteo-coagulo-immunomodulation. Based on the hierarchical levels of bone and its osteo-coagulo-immunomodulation effect, we provide a new understanding of the biological principle of the size effect of biomaterials and a theoretical basis for the basic research and clinical application of different size BHA materials.

Key words: biological hydroxyapatite, biomimetic hierarchical evolution, osteo-coagulo-immunomodulation, material size effect

CLC Number:

R318.08

Xu Jieyun, Zhao Yuan, Liu Haozhou, Yin Jingyuan, Chen Zetao. Hierarchical evolution of bone biomimicry and osteo-coagulo-immunomodulation induced by the size of biological hydroxyapatite[J]. West China Journal of Stomatology, 2024, 42(6): 706-715.

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References 55

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品牌名称	产地	材料来源	颗粒尺寸
Bio-Oss^?	美国	牛骨	0.25~1 mm；1~2 mm
THE Graft?	中国	猪骨	0.25~1 mm；1~2 mm
Gen-Os^?	英国	猪骨或马骨	0.25~1 mm
Cerabone^?	瑞士	牛骨	0.5~1 mm；1~2 mm
Endobon^?	法国	牛骨	0.5~1 mm；1~2 mm
OsteoGraf^?	美国	牛骨	0.25~0.42 mm；0.42~1 mm
SYMBIOS^?	美国	海藻	0.2~1 mm；1~2 mm
Bio Osteo^?	中国	牛骨	0.25~1 mm；0.4~1 mm；1~2 mm
Adbone^?	葡萄牙	异种骨	0.1~0.5 mm；1~2 mm
BioBase a-pore^?	德国	牛骨	0.25~0.5 mm；0.5~1.4 mm；1.4~3.2 mm
Genoss^?	韩国	猪骨	0.2~0.5 mm；0.5~1 mm；1~2 mm
ChronOS^?	美国	异种骨	0.5~0.7 mm；0.7~1.4 mm；1.4~2.8 mm
BioResorb^?	德国	异种骨	0.2~0.5 mm；0.5~1 mm；1~2 mm
Frios Algipore^?	美国	海藻	0.3~0.5 mm；0.5~1 mm

分级	名称	结构特征	基本结构尺寸
一级	骨骼基本成分	单纯BHA晶体或胶原纤维	BHA晶体长30~50 nm，宽20~25 nm，厚1.5~4 nm
二级	骨骼基础结构	BHA晶体和矿化胶原纤维组成	胶原纤维尺寸0.1 μm左右
三级	纤维阵列	Ⅰ型胶原蛋白组成的三维螺旋结构的纤维阵列	阵列结构尺寸处于小于一个微米到数个微米之间
四级	阵列模式	纤维阵列组成阵列模式，分为平行/扇形模式	板层骨和平行纤维骨尺寸约为1 μm
五级	超结构	分为有序骨中的单向胶原纤维束和无序骨中的骨陷窝-骨小管网络	纤维束直径1~3 μm，相邻纤维束相距67 nm
六级	骨组织	构成骨骼的组织包括编织骨、平行纤维骨和板层骨	骨组织直径10 μm左右，板层间厚度3~7 μm
七级	组织结构基序	4种类型，环形板层基序、板层束、骨单位和纤维层状骨	哈弗系统由直径100~200 μm的圆柱状结构和30~40 μm的中央管形成
八级	组织	密质骨或松质骨	密质骨尺寸约1 mm，松质骨直径0.1~3.5 mm
九级	组织	密质骨和松质骨	密质骨、松质骨尺寸都为毫米级别

尺寸	骨仿生层级
<0.2 mm	仅保留生物骨的第一至第六级结构，其比表面积和纳米至微米级微孔比例最高
0.2~1 mm	保留生物骨的第一至第七级结构和部分第八级结构（尺寸小于等于1 mm松质骨结构），其比表面积和微孔占比居中
>1 mm	保留生物骨的第一至第七级结构和大部分第八级结构（尺寸大于1 mm的松质骨结构），其比表面积和微孔占比最低

尺寸	层级	结构	骨凝血免疫调控潜能
<0.2 mm	一级	钙磷灰石晶体	其晶体、堆积面和离子活性影响凝血系统的活性
	二级	微孔/网孔	提供吸附位点，增加凝血启动信号和官能团暴露，促进凝血因子与周围物质进行离子交换
	三级	单层骨小梁结构	增加血小板分散活性、凝血因子吸附面积，材料支架无法提供稳定的空间支持
0.2~1 mm	四级	单层大孔结构	提供血凝块基本支架，确保血凝块与材料机械嵌合，促进血管生长及细胞渗透，提升骨再生能力
>1 mm	五级	多层多孔结构	促进血浆蛋白循环，为成骨细胞黏附、增殖提供环境

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