Biofabrication Strategies for Musculoskeletal Disorders: Evolution towards Clinical Applications

Abstract

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.

Early-Phase Clinical Trials of Bio-Artificial Organ Technology: A Systematic Review of Ethical Issues

“…Thirdly, besides the medical risks of transplanting allogeneic donor cell (cells taken from another human being), for example developing immunological problems, use of these cells also raises relational issues ( 20 , 27 , 30 , 38 , 41 , 43 , 63 , 71 , 72 ). Relational issues include questions such as: Who is the owner of the human cells once it is separated from the body ( 30 , 38 , 41 , 43 )?…”

“…Thirdly, besides the medical risks of transplanting allogeneic donor cell (cells taken from another human being), for example developing immunological problems, use of these cells also raises relational issues ( 20 , 27 , 30 , 38 , 41 , 43 , 63 , 71 , 72 ). Relational issues include questions such as: Who is the owner of the human cells once it is separated from the body ( 30 , 38 , 41 , 43 )? ; Can cells from the human body be subjected to laws regarding property rights ( 38 , 43 )?, and; To what extent can the donor’s privacy and confidentiality be ensured by adopting additional measures (e.g., pseudonymisation) ( 20 , 27 , 30 , 38 , 41 , 43 , 63 , 71 , 72 ).…”

“…Relational issues include questions such as: Who is the owner of the human cells once it is separated from the body ( 30 , 38 , 41 , 43 )? ; Can cells from the human body be subjected to laws regarding property rights ( 38 , 43 )?, and; To what extent can the donor’s privacy and confidentiality be ensured by adopting additional measures (e.g., pseudonymisation) ( 20 , 27 , 30 , 38 , 41 , 43 , 63 , 71 , 72 ). Removing the donor’s personal information is often not desirable, because subsequent research may necessitate ongoing access to the information about the cell donor’s health status requiring personal data of the donor (e.g., their name and/or address) ( 20 , 52 ).…”

“…Researchers should obtain an adequate informed consent from donors to respect their autonomy (12,20,22,27,28,34,38,43,45,52,57,63,67,(72)(73)(74)(75)(76), and give them some degree of insight and perhaps control over the use of donated materials by informing them about the types of incidental findings they wish to receive, future commercial applications, individualized research and therapeutic uses (12,20,27,38,43,52,72,76), for instance by maintaining an ongoing dialogue with the donors (76). Moreover, to safeguard the health of the recipient over the years, it may be necessary to periodically obtain records on the medical and family history of the cell donor to monitor potential health risks, such as long-term immunological or tumorigenic reactions (12,19,20,22,27,28,32,34,35,39,41,49,(51)(52)(53).…”

Meniscus regeneration by 3D printing technologies: Current advances and future perspectives

“…Thus, they do not act as an inert carrier, but they constitute the microenvironment which will significantly affect cells behavior within the 3D structure and the leading agent responsible for 3D structure integrity. 121 – 123 …”