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
- 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.
- 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.
- Clinical Trial Type and Status: No exclusions are made based on type (i.e., interventional or observational), recruitment status, or publication status.
- 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.
- Application of bioprinted construct: Clinical trials are included if bioprinted constructs are used for implantation into study participants, or as preclinical in vitro models.
Information sources
Information sources are either primary registries (where clinical trials are directly registered) or databases (which extract clinical trial data from multiple registries). Our protocol searches five databases and two primary registries.
Databases:
- International Clinical Trials Registry Platform (ICTRP) (https://trialsearch.who.int/Default.aspx)
- ScanMedicine (https://scanmedicine.com/)
- Cochrane Central Register of Controlled Trials (CENTRAL) (https://www.cochranelibrary.com/central)
- NIH Clinical Center (NIHCC) (https://clinicalstudies.info.nih.gov/)
- Health Canada Clinical Trial Database (HCCTD) (https://health-products.canada.ca/ctdb-bdec/)
Primary registries:
- ClinicalTrials.gov (CTGOV) (https://clinicaltrials.gov/)
- Philippine Health Research Registry (PHRR) (https://registry.healthresearch.ph/index.php/registry?view=main&layout=result)
Search
Search terms: bioprint*, bioprint, bioprinted, bioprinting
Information sources: ICTRP, ScanMedicine, CENTRAL, NIHCC, HCCTD, CTGOV, PHRR
General search strategy: Enter search term/s into search field and save all results to a reference manager such as Zotero. For sources that accept wildcards (ICTRP, ScanMedicine, and CENTRAL), search “bioprint*” only. Otherwise, search the three other terms individually.
Below are specific search strategies following the format “Information source - Search field: Search term”:
- ICTRP, ScanMedicine - Standard search: bioprint*
- CENTRAL - All Text: bioprint*
- NIHCC - Keyword: bioprint, bioprinted, bioprinting (search each term individually)
- HCCTD - Protocol title: bioprint, bioprinted, bioprinting (search each term individually)
- CTGOV - Other terms: bioprint, bioprinted, bioprinting (search each term individually)
- PHRR - Standard search: bioprint, bioprinted, bioprinting (search each term individually)
Selection of sources of evidence
Two reviewers must independently screen sources of evidence (i.e., dual independent review). We recommend using Rayyan (https://www.rayyan.ai/) (Ouzzani et al., 2016) for this step as follows:
- Import results from Zotero to Rayyan.
- Deduplicate results using the “Detect duplicates” feature.
- Make an inclusion or exclusion decision for each result based on the eligibility criteria described above.
- Compare inclusion decisions between reviewers and consolidate a final inclusion list.
Use the PRISMA flow diagram to summarize results of this step (Tricco et al., 2018).
Data charting process
One or more authors must chart data for each included trial as follows:
- Navigate to the page containing details on the individual clinical trial.
- Retrieve contents of each field identified in the Data Items section below and enter them into a spreadsheet (e.g., Microsoft Excel).
- Once completed, a second author reviews the charted data to check for errors.
Data items
Items relating to logistical information:
- Trial ID: a unique identifier assigned to a clinical trial by a registry or database
- Title: the scientific title of the study
- Responsible party: research investigators and/or sponsors
- Date first posted
- Date last updated
- Country (conducted by): country of research investigators and/or sponsors
- Country (conducted where): country in which the clinical trial is being conducted
- Recruitment status: Not yet recruiting, Recruiting, Active, not recruiting, Withdrawn, Terminated, etc.
- Status of results: No Results Posted, Results Submitted, or Results Posted
Items relating to scientific design:
- Study type: observational or interventional
- Phase: 1, 2, 3, 4, or not applicable
- Description: summary of study
- Objectives
- Types of intervention: control versus experimental group conditions
- General criteria of participants: characteristic information about the participant such as age, medical condition, etc.
- Outcome measures: desired results of the study
- Type of cell: identity of cells used in bioprinting, and whether they are autologous or not
- Bioink: scaffold or matrix used in bioprinting, where cells will be embedded
- Bioprinting application: implantation or model
Synthesis of results
Data will be synthesized narratively, focusing on trends in past and present clinical trials including year of registration, country of origin, recruitment status, and bioprinting application. Figures and tables will be created based on charted data to support the discussion.