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替换与修复:用于有效肌肉组织工程的仿生生物打印

Replace and repair: Biomimetic bioprinting for effective muscle engineering.

作者信息

Blake Cooper, Massey Oliver, Boyd-Moss Mitchell, Firipis Kate, Rifai Aaqil, Franks Stephanie, Quigley Anita, Kapsa Robert, Nisbet David R, Williams Richard J

机构信息

Institute of Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia.

Laboratory of Advanced Biomaterials, The Australian National University, Canberra, ACT 2601, Australia.

出版信息

APL Bioeng. 2021 Jul 8;5(3):031502. doi: 10.1063/5.0040764. eCollection 2021 Sep.

Abstract

The debilitating effects of muscle damage, either through ischemic injury or volumetric muscle loss (VML), can have significant impacts on patients, and yet there are few effective treatments. This challenge arises when function is degraded due to significant amounts of skeletal muscle loss, beyond the regenerative ability of endogenous repair mechanisms. Currently available surgical interventions for VML are quite invasive and cannot typically restore function adequately. In response to this, many new bioengineering studies implicate 3D bioprinting as a viable option. Bioprinting for VML repair includes three distinct phases: printing and seeding, growth and maturation, and implantation and application. Although this 3D bioprinting technology has existed for several decades, the advent of more advanced and novel printing techniques has brought us closer to clinical applications. Recent studies have overcome previous limitations in diffusion distance with novel microchannel construct architectures and improved myotubule alignment with highly biomimetic nanostructures. These structures may also enhance angiogenic and nervous ingrowth post-implantation, though further research to improve these parameters has been limited. Inclusion of neural cells has also shown to improve myoblast maturation and development of neuromuscular junctions, bringing us one step closer to functional, implantable skeletal muscle constructs. Given the current state of skeletal muscle 3D bioprinting, the most pressing future avenues of research include furthering our understanding of the physical and biochemical mechanisms of myotube development and expanding our control over macroscopic and microscopic construct structures. Further to this, current investigation needs to be expanded from immunocompromised rodent and murine myoblast models to more clinically applicable human cell lines as we move closer to viable therapeutic implementation.

摘要

肌肉损伤(无论是缺血性损伤还是容积性肌肉损失(VML))的衰弱影响会对患者产生重大影响,然而有效的治疗方法却很少。当由于大量骨骼肌损失导致功能退化,超出内源性修复机制的再生能力时,就会出现这一挑战。目前针对VML的手术干预具有相当大的侵入性,通常无法充分恢复功能。对此,许多新的生物工程研究表明3D生物打印是一种可行的选择。用于VML修复的生物打印包括三个不同阶段:打印与接种、生长与成熟以及植入与应用。尽管这种3D生物打印技术已经存在了几十年,但更先进和新颖的打印技术的出现使我们离临床应用更近了一步。最近的研究通过新颖的微通道构建架构克服了先前在扩散距离方面的限制,并通过高度仿生的纳米结构改善了肌管排列。这些结构还可能增强植入后的血管生成和神经长入,不过改善这些参数的进一步研究有限。加入神经细胞也已显示可改善成肌细胞成熟和神经肌肉接头的发育,使我们离功能性、可植入的骨骼肌构建体又近了一步。鉴于骨骼肌3D生物打印的当前状态,未来最紧迫的研究途径包括进一步了解肌管发育的物理和生化机制,以及扩大我们对宏观和微观构建体结构的控制。除此之外,随着我们向可行的治疗实施迈进,目前的研究需要从免疫受损的啮齿动物和小鼠成肌细胞模型扩展到更适用于临床的人类细胞系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c46/8270648/6229de171225/ABPID9-000005-031502_1-g001.jpg

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