title: Bioreactor system using noninvasive imaging and mechanical stretch for biomaterial screening.
abstract: Screening of biomaterial and tissue systems in vitro, for guidance of performance in vivo, remains a major requirement in the field of tissue engineering. It is critical to understand how culture stimulation affects both tissue construct maturation and function, with the goal of eliminating resource-intensive trial-and-error screening and better matching specifications for various in vivo needs. In this article a multifunctional and robust bioreactor design that addresses this need is presented. The design enables a range of mechanical inputs, durations, and frequencies to be applied in coordination with noninvasive optical assessments. A variety of biomaterial systems, including micro- and nano-fiber and porous sponge biomaterials, as well as cell-laden tissue engineering constructs were used in validation studies to demonstrate the versatility and utility of this new bioreactor design. The silk-based biomaterials highlighted in these studies offered several unique optical signatures for use in label-free nondestructive imaging that allowed for sequential profiling. Both short- and long-term culture studies were conducted to evaluate several practical scenarios of usage: on a short-term basis, the authors demonstrate that construct cellularity can be monitored by usage of nonpermanent dyes; on a more long-term basis, the authors show that cell ingrowth can be monitored by green-fluorescent protein (GFP)-labeling, and construct integrity probed with concurrent load/displacement data. The ability to nondestructively track cells, biomaterials, and new matrix formation without harvesting designated samples at each time point will lead to less resource-intensive studies and should enhance our understanding and the discovery of biomaterial designs related to functional tissue engineering.
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Kluge
authors.forename: Gary G
authors.initials: GG
authors.lastname: Leisk
authors.forename: Robyn D
authors.initials: RD
authors.lastname: Cardwell
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Fernandes
authors.forename: Michael
authors.initials: M
authors.lastname: House
authors.forename: Andrew
authors.initials: A
authors.lastname: Ward
authors.forename: A Luis
authors.initials: AL
authors.lastname: Dorfmann
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D019149:Bioreactors; D002460:Cell Line; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008422:Materials Testing; D057139:Nanofibers; D013997:Time Factors; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*