Naghieh Saman, Lindberg Gabriella, Tamaddon Maryam, Liu Chaozong
Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, SK S7N 5A9, Canada.
Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, Department of Orthopaedic Surgery, University of Otago Christchurch, Christchurch 8011, New Zealand.
Bioengineering (Basel). 2021 Sep 10;8(9):123. doi: 10.3390/bioengineering8090123.
Biofabrication has emerged as an attractive strategy to personalise medical care and provide new treatments for common organ damage or diseases. While it has made impactful headway in e.g., skin grafting, drug testing and cancer research purposes, its application to treat musculoskeletal tissue disorders in a clinical setting remains scarce. Albeit with several in vitro breakthroughs over the past decade, standard musculoskeletal treatments are still limited to palliative care or surgical interventions with limited long-term effects and biological functionality. To better understand this lack of translation, it is important to study connections between basic science challenges and developments with translational hurdles and evolving frameworks for this fully disruptive technology that is biofabrication. This review paper thus looks closely at the processing stage of biofabrication, specifically at the bioinks suitable for musculoskeletal tissue fabrication and their trends of usage. This includes underlying composite bioink strategies to address the shortfalls of sole biomaterials. We also review recent advances made to overcome long-standing challenges in the field of biofabrication, namely bioprinting of low-viscosity bioinks, controlled delivery of growth factors, and the fabrication of spatially graded biological and structural scaffolds to help biofabricate more clinically relevant constructs. We further explore the clinical application of biofabricated musculoskeletal structures, regulatory pathways, and challenges for clinical translation, while identifying the opportunities that currently lie closest to clinical translation. In this article, we consider the next era of biofabrication and the overarching challenges that need to be addressed to reach clinical relevance.
生物制造已成为一种颇具吸引力的策略，可实现个性化医疗，并为常见器官损伤或疾病提供新的治疗方法。尽管它在例如皮肤移植、药物测试和癌症研究等方面取得了显著进展，但其在临床环境中治疗肌肉骨骼组织疾病的应用仍然很少。尽管在过去十年中有多项体外研究取得突破，但标准的肌肉骨骼治疗方法仍仅限于姑息治疗或手术干预，长期效果和生物学功能有限。为了更好地理解这种转化不足的情况，研究基础科学挑战与发展之间的联系，以及这种完全颠覆性技术——生物制造的转化障碍和不断发展的框架非常重要。因此，这篇综述文章密切关注生物制造的加工阶段，特别是适用于肌肉骨骼组织制造的生物墨水及其使用趋势。这包括解决单一生物材料不足的潜在复合生物墨水策略。我们还回顾了为克服生物制造领域长期存在的挑战所取得的最新进展，即低粘度生物墨水的生物打印、生长因子的可控递送，以及空间梯度生物和结构支架的制造，以帮助生物制造更具临床相关性的构建体。我们进一步探讨了生物制造的肌肉骨骼结构的临床应用、监管途径以及临床转化面临的挑战，同时确定目前最接近临床转化的机会。在本文中，我们考虑了生物制造的下一个时代以及实现临床相关性需要解决的总体挑战。
