Human stem cell decorated nanocellulose threads for biomedical applications

Abstract

Upon surgery, local inflammatory reactions and postoperative infections cause complications, morbidity, and mortality. Delivery of human adipose mesenchymal stem cells (hASC) into the wounds is an efficient and safe means to reduce inflammation and promote wound healing. However, administration of stem cells by injection often results in low cell retention, and the cells deposit in other organs, reducing the efficiency of the therapy. Thus, it is essential to improve cell delivery to the target area using carriers to which the cells have a high affinity. Moreover, the application of hASC in surgery has typically relied on animal-origin components, which may induce immune reactions or even transmit infections due to pathogens. To solve these issues, we first show that native cellulose nanofibers (nanofibrillated cellulose, NFC) extracted from plants allow preparation of glutaraldehyde cross-linked threads (NFC-X) with high mechanical strength even under the wet cell culture or surgery conditions, characteristically challenging for cellulosic materials. Secondly, using a xenogeneic free protocol for isolation and maintenance of hASC, we demonstrate that cells adhere, migrate and proliferate on the NFC-X, even without surface modifiers. Cross-linked threads were not found to induce toxicity on the cells and, importantly, hASC attached on NFC-X maintained their undifferentiated state and preserved their bioactivity. After intradermal suturing with the hASC decorated NFC-X threads in an ex vivo experiment, cells remained attached to the multifilament sutures without displaying morphological changes or reducing their metabolic activity. Finally, as NFC-X optionally allows facile surface tailoring if needed, we anticipate that stem-cell-decorated NFC-X opens a versatile generic platform as a surgical bionanomaterial for fighting postoperative inflammation and chronic wound healing problems.

Advanced Materials through Assembly of Nanocelluloses

“…Recent results in this respect include the use of poly(vinyl alcohol) to spin CNC‐loaded fibers, which yielded a remarkable high strength (880 MPa) (Figure d) . Moreover, crosslinking with glutaraldehyde promoted sufficient wet strength for CNF fibers to generate surgery threads and, upon careful removal of the unreacted crosslinkers, even allowed stem cell growth for improved wound healing (Figure e) . Finally, interfacial polyelectrolyte complex spinning with chitosan toward multicomponent CNF fibers has been demonstrated, producing fibers that can allow crimping (Figure f) …”

“…Therein hASC‐loaded CNF‐based surgery‐threads could be feasible due to their biocompatibility, taken that the strength under moist conditions could be improved. Drastically improved wet strength was indeed achieved by glutaraldehyde crosslinking, still allowing hASC attachment on CNF in the undifferentiated state and preserved bioactivity, after glutaraldehyde was carefully removed (Figure b) . Also BC‐based CNCs show potential in biomedical and pharmaceutical applications, e.g., as injectable nanogels .…”

Interfacial Polyelectrolyte Complex Spinning of Cellulose Nanofibrils for Advanced Bicomponent Fibers

“…Fibers based on CNF or TOCN have aroused particular interest in the nanocellulose research community, due to the inherent suitability of cellulose to form strong fibers. [15][16][17][18][19][20][21][22] Especially, wet-spinning of CNF into a nonsolvent (i.e. coagulation bath such as ethanol or acetone) has been widely explored and exploited.…”

Hydrogel films and coatings by swelling-induced gelation

“…The quality of their interactions with biological tissues or entrapped cells is central to the performance of these systems. Although considerable advances have been made in synthesis (6) and processing (7) to tailor these interactions, the toxicity of by-products and the degradation caused by harsh processing conditions remain key issues (8), which can be overcome (9) but are often addressed at the cost of difficult synthesis or multistep processes. There is a great interest for simple, versatile, and in vivo-friendly methods to fabricate and modify hydrogels.…”