PMID- 36837169 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230228 IS - 1996-1944 (Print) IS - 1996-1944 (Electronic) IS - 1996-1944 (Linking) VI - 16 IP - 4 DP - 2023 Feb 12 TI - Towards a Material-by-Design Approach to Electrospun Scaffolds for Tissue Engineering Based on Statistical Design of Experiments (DOE). LID - 10.3390/ma16041539 [doi] LID - 1539 AB - Electrospinning bears great potential for the manufacturing of scaffolds for tissue engineering, consisting of a porous mesh of ultrafine fibers that effectively mimic the extracellular matrix (ECM) and aid in directing stem cell fate. However, for engineering purposes, there is a need to develop material-by-design approaches based on predictive models. In this methodological study, a rational methodology based on statistical design of experiments (DOE) is discussed in detail, yielding heuristic models that capture the linkage between process parameters (Xs) of the electrospinning and scaffold properties (Ys). Five scaffolds made of polycaprolactone are produced according to a 2(2)-factorial combinatorial scheme where two Xs, i.e., flow rate and applied voltage, are varied between two given levels plus a center point. The scaffolds were characterized to measure a set of properties (Ys), i.e., fiber diameter distribution, porosity, wettability, Young's modulus, and cell adhesion on murine myoblast C1C12 cells. Simple engineering DOE models were obtained for all Ys. Each Y, for example, the biological response, can be used as a driver for the design process, using the process-property model of interest for accurate interpolation within the design domain, enabling a material-by-design strategy and speeding up the product development cycle. The implications are also illustrated in the context of the design of multilayer scaffolds with microstructural gradients and controlled properties of each layer. The possibility of obtaining statistical models correlating between diverse output properties of the scaffolds is highlighted. Noteworthy, the featured DOE approach can be potentially merged with artificial intelligence tools to manage complexity and it is applicable to several fields including 3D printing. FAU - Carotenuto, Felicia AU - Carotenuto F AUID- ORCID: 0000-0002-0142-6690 AD - Dipartimento di Scienze Cliniche e Medicina Traslazionale, Universita degli Studi di Roma "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy. AD - CIMER-Centro di Ricerca Interdipartimentale di Medicina Rigenerativa, Universita degli Studi di Roma "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy. FAU - Fiaschini, Noemi AU - Fiaschini N AUID- ORCID: 0000-0003-1094-7743 AD - Nanofaber S.r.l., Via Anguillarese 301, 00123 Rome, Italy. FAU - Di Nardo, Paolo AU - Di Nardo P AD - Dipartimento di Scienze Cliniche e Medicina Traslazionale, Universita degli Studi di Roma "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy. AD - CIMER-Centro di Ricerca Interdipartimentale di Medicina Rigenerativa, Universita degli Studi di Roma "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy. FAU - Rinaldi, Antonio AU - Rinaldi A AUID- ORCID: 0000-0002-3087-2649 AD - SSPT-PROMAS-MATPRO Laboratory, ENEA-Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Via Anguillarese 301, 00123 Rome, Italy. LA - eng PT - Journal Article DEP - 20230212 PL - Switzerland TA - Materials (Basel) JT - Materials (Basel, Switzerland) JID - 101555929 PMC - PMC9961090 OTO - NOTNLM OT - ECM OT - biomaterials OT - electrospinning OT - material genome initiative OT - polycaprolactone OT - rational design COIS- The authors declare no conflict of interest. EDAT- 2023/02/26 06:00 MHDA- 2023/02/26 06:01 PMCR- 2023/02/12 CRDT- 2023/02/25 03:26 PHST- 2022/12/30 00:00 [received] PHST- 2023/02/02 00:00 [revised] PHST- 2023/02/09 00:00 [accepted] PHST- 2023/02/25 03:26 [entrez] PHST- 2023/02/26 06:00 [pubmed] PHST- 2023/02/26 06:01 [medline] PHST- 2023/02/12 00:00 [pmc-release] AID - ma16041539 [pii] AID - materials-16-01539 [pii] AID - 10.3390/ma16041539 [doi] PST - epublish SO - Materials (Basel). 2023 Feb 12;16(4):1539. doi: 10.3390/ma16041539.