3D生物打印中骨打印支架材料与血管网络形成的探究

Study on the Formation of Bone Printed Scaffolds and Vascular Networks in 3D Bioprinting

在全球范围内,每年有200多万例骨移植手术用于骨科、神经外科和牙科手术中的骨缺损。目前的治疗方案包括使用人、动物或合成来源的移植物。在这种情况下,自体移植是目前的黄金标准。然而它的数量是有限的,需要创建第二个伤口(供体部位),并且感染、疼痛和发病率的风险也随之提高。近年来,组织工程与3D生物打印的兴起,为治疗患者骨缺损提供一种新思路。3D生物打印是"增材制造"在生物组织工程中应用的分支,能对细胞进行精确控制,并按需实现个性化构建宏观及微观的结构,能在骨再生运用中得到运用。其中成骨细胞支架的建立是3D生物打印的基础,具有适宜骨和软骨生长的水凝胶是支架研究的基础,为此国内外学者进行多种水凝胶支架的开发与研究,发现由多种生物材料混合的水凝胶比单一材料水凝胶更具有优势,如以羟基磷灰石或藻酸盐或透明质酸为主体混合几种或多种生物打印材料,结合所需细胞后最终形成的3D打印骨支架,比传统支架更能够促进骨成长分化。随着打印结构变厚,营养物质和氧气的扩散越来越困难,这在骨组织的重建中尤其如此,需要制造互连且有效的血管网络,因此支架中血管的形成是必不可少的环节。本文主要综述了3D生物打印中骨打印支架材料与血管网络形成的逐步探究进展。

Globally,more than 2 million bone grafts are performed every year for bone defects in orthopedics,neurosurgery,and dental procedures.Current treatment options include the use of grafts of human,animal or synthetic origin.In this case,autograft is the current gold standard.However,its quantity is limited,a second wound(donor site)needs to be created,and the risk of infection,pain,and morbidity increases.In recent years,the rise of tissue engineering and 3D bioprinting has provided a new idea for treating bone defects in patients.3D bioprinting is a branch of the applications of"additive manufacturing"in biological tissue engineering.It can precisely control cells,personalize macro and micro structures as needed,and can be used in bone regeneration applications.The establishment of osteoblast scaffolds is the basis of 3D bioprinting,and hydrogels suitable for the growth of bone and cartilage are the basis of scaffold research.For this reason,domestic and foreign scholars have developed and researcheda variety of hydrogel scaffolds,and they have found that mixed hydrogels with multiple biological materials have more advantages than single-material hydrogels.For example,hydroxyapatite,alginate or hyaluronic acid is used as the main component to mix several or more bioprinting materials,and 3D printed bone scaffold formed after combining the required cells can promote bone growth and differentiation better than traditional scaffolds.As the printed structure becomes thicker,the diffusion of nutrients and oxygen becomes more and more difficult.This is especially true in the reconstruction of bone tissue and it is necessary to create an interconnected and effective vascular network.Therefore,the formation of blood vessels in the stent is indispensable.This article mainly reviews the step-by-step research progress of bone printing scaffold materials and vascular network formation in 3D bioprinting.