DOI: 10.5281/zenodo.16921023
title: Dataset of "Fibrin Scaffolds for Angiogenesis in Soft Tissue Models: a Systematic Review"

description: This repository contains the raw data used for the systematic review on "Fibrin Scaffolds for Angiogenesis in Soft Tissue Models" by C.V. Fuenteslópez, S. Bahcevanci, V. Patrulea and H. Ye.

The protocol for this systematic review was registered with PROSPERO [registration number: CRD42025612994] [1] and with OSF [ID: nvfdj] [2]. It was also documented as a project in OSF [3]. [1] https://www.crd.york.ac.uk/PROSPERO/view/CRD42025612994 [2] https://osf.io/nvfdj [3] https://osf.io/ctz8x/

The data included in this repository was used to create the figures and tables featured in the main text and supplementary materials of the systematic review mentioned above. The following terms were repeatedly used: Y - yes; N - no; NS - not stated or not reported; N/A - not applicable. This includes:

Figure 1 ‐ PRISMA Flow Diagram of the Study Selection Process, summarising the number of records identified, screened, excluded, and included at each stage of the systematic review. The diagram provides a detailed account of study progression through the phases of identification, eligibility assessment, and final inclusion.

Figure 2 ‐ Overview of the Corpus of Included Articles in the Systematic Review (n = 81), depicting (A) number of publications by year; (B) number of articles where the main aim of the study either included or not endothelial formation or migration processes; (C) distribution of soft tissue types studied; and (D) classification of studies by type, including in vitro, in vivo, ex vivo, and clinical studies.

Figure 3 ‐ ‐ Impact of Scaffold Formulation on Angiogenic Outcomes, illustrating the relationships between scaffold formulation parameters (fibrin origin, source, combination with other materials, cross‐linker, coagulant, and cell pre‐embedding) and the resulting successful endothelial formation and migration processes, by number of scaffolds. The impact of the scaffold formulation is split into: (A) tube‐like structures, (B) networks, or (C) endothelial cell migration. Data was aggregated from the included studies, showing the frequency of each parameter and its association with successful angiogenic outcomes. N: No; NS: Not Specified; Y: Yes. Please refer to the Supplementary Materials (Tables S3, S4, S5, S6, S7 and S8) for further details.

Figure 4 ‐ Endothelial and Non‐Endothelial Cell Lines Used, by number of scaffolds in which they were used. (A) Endothelial cells by type, species, and specific cell line name. (B) Non‐endothelial cell lines used by source, species, and specific cell line name. Figure 5 ‐ In Vivo Models Used, by taxa, species, and sex, showing the number of times a model was used in the corpus.

Figure 6 ‐ Tissue Engineering Scaffolds Successfully Supporting Endothelial Formation or Migration Pro‐ cesses, Categorised by Type of Manufactured Object. Further insights are provided into scaffold or construct design based on (A) the successful use of acellular versus cell‐embedded models, and (B) the associated features of manufactured objects, as reported in the studies. Colours indicate the number of studies in which each manufactured object was reported as successful. Only features mentioned in at least three studies are shown here; Figure S4 presents all features regardless of the number of studies citing them.

Figure 7 ‐ Assays used to Evaluate Endothelial Formation or Migration Processes. (A) Type of data used to evaluate endothelial formation and migration processes, shown by number of studies using quantitative, qualitative or combined data types. (B) Assays used to evaluate the success of endothelial formation or migration processes, grouped by number of studies in which they were employed. Assays were classified into eight general categories based on the evaluation method.

Figure 8 ‐ Fibrin Tissue Engineering Scaffolds for Muscle Research. (A) Number of studies categorised by study and muscle type. (B) In vivo models used. (C) Endothelial and non‐endothelial cell lines used, classified by species of origin and type. (D) Types of manufactured objects tested with or without pre‐embedded cells and their reported association with the outcomes of endothelial formation or migration processes. For each manufactured object, the number of successful, unsuccessful, and unspecified outcomes is shown.

Figure 9 ‐ Risk of Bias and Quality Assessment of In Vivo Muscle Models. (A) Risk of bias (RoB) was evaluated using SYRCLE’s RoB tool. All ten items were assessed: (1) Was the allocation sequence generated and applied properly? (2) Were the groups similar at baseline or were they adjusted for confounding factors in the analysis? (3) Was the allocation adequately concealed? (4) Were the animals randomly housed during the experiment? (5) Were the carers and/or investigators blinded to the knowledge of which intervention each animal received during the experiment? (6) Were the animals randomly selected for outcome assessment? (7) Was the outcome researcher blinded? (8) Were incomplete outcome data adequately addressed? (9) Are the study reports free of selective reporting of results? (10) Was the study apparently free of other problems that could result in a high RoB? (B) Methodological quality was assessed using a modified CAMARADES checklist [39]. The eight items evaluated were: (1) Sample size calculation, (2) Random allocation to treatment or control, (3) Blinded assessment of out‐ come, (4) Use of an appropriate animal model, (5) Use of anaesthetic without significant intrinsic neuroprotective activity, (6) Compliance with animal welfare regulations, (7) Peer‐reviewed publication, and (8) Statement of potential conflicts of interest.

Figure S1: Visual representation of the number of records found in each database when independently searching for each of the four search query components: “Soft Tissue”, “Microvascular Structures and/or Network”, “Tissue Engineering Scaffolds”, and “Fibrin”. (A) PubMed, (B) Scopus, and (C) OVID. The full search query used for each database can be found in Appendix I. Each ring represents 200,000 records.

Figure S2: Screening Decisions, as agreed by the reviewers after independent binary classification of the study based on the inclusion and exclusion criteria. Two rounds of screening were conducted to evaluate the relevance of each record based on (A) title and abstract, and (B) full-text review. Two full-text articles could not be retrieved, so were excluded.

Figure S3: Aggregated Success Rates of Fibrin Scaffold Design Parameters. Success rates were calculated as the proportion of successful scaffolds relative to the total number of successful and unsuccessful scaffolds. Scaffolds with no reported outcome or lacking the specified formulation element were excluded. The heatmap is colour-coded in five tiers: green (80-100% success rate), blue (60-80%), yellow (40-60%), orange (20-40%), and black (0-20%). The aggregated success rates associated with the following scaffold design parameters: fibrinogen source, fibrinogen origin, combination with other materials (including the type of material), type of crosslinker, use of a coagulant, and cell pre‐embedding. Success rates are reported for three specific outcomes: (a) tube formation, (b) network formation, and (c) endothelial cell migration. GF/P/AA/E: Growth Factors, Peptides, Amino Acids & Enzymes. NS: Not specified.

Figure S4: Materials Used in Combination with Fibrin, Coagulants, and Crosslinkers. (A) Number of publications using each category of material. (B) Median number of different materials used per scaffold within each category. Error bars indicate the range.

Figure S5: Features Associated with the Manufactured Objects Used in the Corpus, as described in the studies.

Table S1: Articles excluded during the 2nd screening round (full-text screening), by reason for exclusion.

Table S2: Studies Included in the Corpus (n = 81), with their corresponding bibliographical data.

Table S3: Fibrinogen, Coagulant, and Crosslinker Formulations Used in the Corpus, by article, outlining the concentration used at the reported formulation step, as well as the type of coagulant or crosslinker chosen. NS: Not Specified; N: Not Reported; N/A: Non-Applicable.

Table S4: Polymers, both natural and synthetic, used in the fibrin scaffolds by frequency of use in the studies included in the corpus.

Table S5: Growth Factors, Peptides, Amino Acids and Enzymes used in the fibrin scaffolds by frequency of use in the studies included in the corpus

Table S6: Cell Media & Solutions used in the fibrin scaffolds by frequency of use in the studies included in the corpus

Table S7: Chemicals used in the fibrin scaffolds by frequency of use in the studies included in the corpus

Table S8: Other materials used in the fibrin scaffolds by frequency of use in the studies included in the corpus

Table S9: Composition of Modified Cell Media Used for Fibrin Scaffolds, by the number of scaffolds in which a given combination was used.