The importance of factorial design in tissue engineering and biomaterials science: Optimisation of cell seeding efficiency on dermal scaffolds as a case study

Abstract

This article presents a case study to show the usefulness and importance of using factorial design in tissue engineering and biomaterials science. We used a full factorial experimental design (2 × 2 × 2 × 3) to solve a routine query in every biomaterial research project: the optimisation of cell seeding efficiency for pre-clinical in vitro cell studies, the importance of which is often overlooked. In addition, tissue-engineered scaffolds can be cellularised with relevant cell type(s) to form implantable tissue constructs, where the cell seeding method must be reliable and robust. Our results show the complex relationship between cells and scaffolds and suggest that the optimum seeding conditions for each material may be different due to different material properties, and therefore, should be investigated for individual scaffolds. Our factorial experimental design can be easily translated to other cell types and three-dimensional biomaterials, where multiple interacting variables can be thoroughly investigated for better understanding of cell–biomaterial interactions.

A new approach to the production of a biovital skin graft based on human acellular dermal matrix produced in‐house, in vitro revitalized internally by human fibroblasts and keratinocytes on the surface

“…SEM examination was performed in order to determine the influence of the enzymes used in removing cells from human dermis on the ECM structure of the examined matrices. The SEM study is a recognized, useful research tool (Amos, Leventhal, Louise Chu, & Karnovsky, ; Levin, Sharma, Lilian Hook, & García‐Gareta, ; Matuska & McFetridge, ; Solomonov et al, ). The execution of the examination of the ECM nanostructure in the ADM study groups in comparison to the native ADM‐1 control group demonstrated that only the surface structure of ADM‐2 (24 H/0.05% trypsin) and ADM‐6 (24 H/0.05% trypsin and 4 H/2.4 U/ml dispase II) did not differ significantly from the ADM‐1 control group.…”

Fabrication of electrospun poly(lactic acid) nanoporous membrane loaded with niobium pentoxide nanoparticles as a potential scaffold for biomaterial applications

“…The positive control group consisted of DMEM/10% FBS and NIH/3T3 (density of 2 × 10 4 cells) placed on the surface of the well without membranes. The 96‐well plate was incubated at 37°C, pH 7.2, under humidified 5% CO 2 and 95% O 2 for 24 and 48 hr, as previously described (Chiono et al, ; Levin, Sharma, Hook, & García‐Gareta, ; Santana et al, ).…”

Emerging Trends in Information‐Driven Engineering of Complex Biological Systems

“…This and similar approaches have recently been implemented to identify polymers that are resistant to bacterial attachment, [57] optimize delivery of proteins for cardiac repair, [58] design zwitterionic polymer brushes for stem cell growth, [59] optimize seeding efficiencies for dermal scaffolds, [60] and predict cardiac reprogramming outcomes on biomaterials. At each of these stage iterations, computational and statistical modeling can be implemented to maximize efficiency.…”

“…At each of these stage iterations, computational and statistical modeling can be implemented to maximize efficiency. This and similar approaches have recently been implemented to identify polymers that are resistant to bacterial attachment, [57] optimize delivery of proteins for cardiac repair, [58] design zwitterionic polymer brushes for stem cell growth, [59] optimize seeding efficiencies for dermal scaffolds, [60] and predict cardiac reprogramming outcomes on biomaterials. [61] While these approaches are promising for demystifying the relationship between biological components and synthetic substrates, a number of challenges plague this area of research.…”