A novel system for expansion and delivery of human keratinocytes for the treatment of severe cutaneous injuries using microcarriers and compressed collagen

Abstract

Cell therapy with autologous or allogeneic keratinocytes applied as a single-cell suspension is well established in clinical practice in the treatment of severe burn injuries to augment epithelial barrier restoration. Yet, the application of cell sprays can lead to significant cell loss owing to lack of adhesion of cell suspension to the wound bed. The development of a robust and controllable method of transplanting cells onto the wound bed is yet to be established. The ability to control adhesion and distribution of cells by using a cell carrier embedded in a biodegradable scaffold could significantly improve the treatment of cutaneous wounds with keratinocyte cell therapy. Several microcarrier-based systems for expanding keratinocytes already exist. A new method for expansion of human keratinocytes in a feeder-free, defined medium system on microcarriers has been developed. The cells retained their basal, proliferative phenotype after rapid expansion in a clinically relevant time-frame. The cell-laden microcarriers were further incorporated into collagen scaffolds fabricated by plastic compression. When cultured in vitro, cells continued to proliferate and migrate along the surface of the collagen scaffold. Using an in vitro wound bed model, cells were observed to form mostly single cell layers and in some areas multiple cell layers within 8 days, while retaining their basal, proliferative phenotype, indicating the suitability of this cell transplantation method to improve epithelial barrier restoration. This advanced cell expansion and delivery method for cutaneous cell therapy provides a flexible tool for use in clinical application. Copyright © 2017 John Wiley & Sons, Ltd.

Cell marbles: A novel cell encapsulation technology by wrapping cell suspension droplets using electrospun nanofibers for developmental engineering

“…The total cell number within each CM is simply controlled by the volume and cell density of the wrapped suspension droplets, while the CM size can be tailored by varying the volume of the liquid core from 3 µl to 15 µl. Robust and accurate control of cell release and delivery is crucial for the success of cell transplantation (Martin et al, 2017). Our research has demonstrated that the CMs were mechanically strong enough to be handled as 'soft solids', thus accurate delivery was achieved by transferring the CMs into very distinct culture systems using sterilised forceps.…”

Sprayed cultured autologous keratinocytes in the treatment of severe burns: a retrospective matched cohort study

“…Our culture time was somehow longer than what have been reported before (12 -21 days) [9,28,29,32]. Alternatives to the classical CAK, tissue-engineered products that combine keratinocytes with other cell types, micro barriers, or scaffolds could be considered [22,31,[33][34][35][36][37].…”

Silk/Fibroin Microcarriers for Mesenchymal Stem Cell Delivery: Optimization of Cell Seeding by the Design of Experiment

“…Moreover, the use of fibroin as a support for cell growth was considered a suitable approach for MSCs culture to provide not only a good cellular expansion but also a good maintenance of cell proliferation and differentiation capability [54,55,56,57,58]. Finally, microcarriers were defined as a suitable cell delivery system since they can be directly injected locally, ensuring the maintenance of cells at the target site while minimizing patients’ discomfort [25,59,60].…”