Assessing the landscape of clinical trials involving bioprinting: a scoping review protocol

Bioprinting is a tissue engineering method with promising clinical applications. This scoping review protocol aims to assess the past and present landscape of clinical trials involving bioprinting. In this protocol, the term “bioprint” and its variants will be searched in �ve clinical trial databases and two primary registries. Results will then undergo dual independent review to determine the �nal inclusion list. Finally, data will be synthesized narratively. Our protocol is designed to maximize search coverage while minimizing search time by utilizing databases covering multiple international primary registries. Ultimately, we aim to provide a framework for monitoring developments and identifying speci�c research questions within the rapidly evolving �eld of clinical bioprinting over time.


Introduction
Bioprinting is de ned as the printing of live cells in a three-dimensional structure (Gilbert et al., 2018).In this technique, cells are mixed into a bioink and deposited using an automated system called a bioprinter.
Bioprinting allows researchers to create reproducible, high-throughput, and patient-speci c constructs, making it a promising alternative to manual tissue engineering methods.Medical applications of bioprinting include fabricating tissues for patient implantation or constructing preclinical models for in vitro drug screening (Ding et al., 2023).Despite these advances however, to the best of our knowledge there has been no effort to consolidate studies that utilize bioprinting at the clinical trial stage.

Objectives
The main objective of this scoping review protocol is to systematically assess the landscape of clinical trials implementing bioprinting for implantation or modeling purposes.Speci cally, our review aims to map trends in past and present clinical trials including year of registration, country of origin, recruitment status, and bioprinting application.It also aims to identify opportunities for more targeted inquiries into clinical bioprinting in the future.

Procedure
This protocol adheres to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) outlined by Tricco et al. (2018).

Eligibility criteria
1. Publication Type: Only clinical trials are included in this review.Trials may be registered in a clinical trial registry, or unregistered but described in a publication.
2. Location, Date, and Language: Clinical trials may be from any location and date range.However, they must be available in English or translated into English.Solution: Indicate "Maybe" as the inclusion decision and contact the responsible party (for clinical trials)

Clinical Trial
or corresponding author (for publications describing clinical trials) via email for further information.If no response is received after one week, send a follow-up email.If no response is received one week after the follow-up, exclude the study and indicate the reason as "Full record not retrieved".
Step: Selection of sources of evidence ("4.Compare inclusion decisions between reviewers and consolidate a nal inclusion list.

")
Problem: There is a con ict of inclusion decisions between reviewers (e.g., one reviewer indicated "Exclude" while the other indicated "Include").
Possible reason: Eligibility criteria was interpreted differently, information was interpreted differently, or information was overlooked.
Solution: Hold a discussion between reviewers, or all authors, to reach a consensus regarding the nal inclusion decision.
Step: Data charting ("2.Retrieve contents of each eld identi ed in the Data Items section below and enter them into a spreadsheet.") Problem: One or more data items cannot be identi ed from the available information.
Possible reason: full is unavailable, or the full record is not su cient to chart the data item/s.
Solution: Contact the responsible party (for clinical trials) or corresponding author (for publications describing clinical trials) via email for further information.If no response is received after one week, send a follow-up email.If no response is received one week after the follow-up, enter "Data unavailable" into the data charting sheet.

Time Taken Anticipated Results
We expect protocol to comprehensively identify clinical trials involving bioprinting worldwide.Results will describe and interpret trends in the number of trials per year, country, recruitment status, bioprinting application, and other characteristics.The ndings of this protocol may aid in developing more targeted research questions focused on bioprinting at the clinical trial stage.
Type and Status: No exclusions are made based on type (i.e., interventional or observational), recruitment status, or publication status.4.Bioprinting method: Only clinical trials that explicitly mention the term "bioprint" in the title or study design are included.Trials that explicitly mention printing acellular constructs are excluded, regardless of whether cells are grafted into the construct afterwards.5.Application of bioprinted construct: Clinical trials are included if bioprinted constructs are used for implantation into study participants, or as preclinical in vitro models.The full record is unavailable, or the full record is not su cient to determine if the source ts inclusion criteria.