Bacterial Nanocellulose Hydrogels Designed as Bioartificial Medical Implants 187
regeneration. of. soft. tissue. that. are. designed. to. ensure. mechanical. stability.
ment.and.migration.of.cells.from.the.target.tissue.into.the.implant,.and.inclusion.of.differentiation.factors.promoting.tissue.maturation.and.integration.
To.fulfill.the.requirements.that.are.suitable.to.overcome.problems.associated.
with.implants.for.cartilage.regeneration,.recent.investigations.have.been.aimed.
at.developing.either.implants.containing.primary.cells.for.. tissue.engineering.
approaches.(Andersson.et.al..2010;.Svensson.et.al..2005).or.cell-free.solutions.
(Endres.et.al..2011)..The.primary.aim.of.cell-free.grafts.is.to.overcome.the.disadvantages.of.established.cell-containing.implants.used.for.matrix-associated.
autologous. chondrocyte. transplantation. (MACT),. such. as. multiple. surgical.
procedures. for. cell. harvesting. and. implantation,. injury. to. healthy. cartilage.
regions,. high. costs. (in. vitro. expansion),. and. potential. cell. dedifferentiation.
or. hypertrophy.. In. our. own. research,. the. cell-free. implants. are. therefore.
focused.on.generating.flat.BNC.scaffolds.with.cell-recruiting.factors.to.attract.
cartilage.cells.and/or.progenitor.cells.into.the.inlays.and.thereby.induce.the.
in.situ.formation.of.repair.tissue.for.improved.integration..Figure 9.4.shows.
the.principle.of.cartilage.repair.by.use.of.such.a.bio. active.implant.
Using. suitable. bioreactor. development. and. postprocessing. techniques,.
the.production.of.standardized.BNC.inlays.with.specific.shape.designs.was.
established.on.a.laboratory.scale.to.produce.cartilage.regeneration.materials..
By.modifying.the.pore.size.of.the.BNC,.a.colonization.of.the.implants.with.
cartilage.cells.was.accomplished.(bovine.model).(Ahrem.et.al..2010)..In.vitro.
studies.resulted.in.the.identification.of.bioactive.substances.able.to.stimulate.
directed.migration.(chemotaxis).and.proliferation.of.cartilage.cells..The.biocompatibility.of.the.BNC.implant.materials.was.confirmed.by.extensive.in.
vitro.and.in.vivo.(sheep).experiments,.including.documentation.of.the.first.
stages.of.cartilage.regeneration.in.the.in.vitro.tests..Prerequisites.of.a.universally.applicable.BNC.network.are.a.permanent,.scaffold-forming.stability.
and.quick.and.homogeneous.seeding.with.chondrocytes.in.order.to.promote.
the.regeneration.of.cartilage.tissue.
Present. prototypes. of. BNC. implants. consist. of. a. wide-meshed. phase.
and. a. narrow-meshed. phase,. both. firmly. connected. (Klemm. et. al.. 2009)..
Colonization.of.this.BNC.and.transmigration.was.investigated.using.isolated.
human.and.bovine.cartilage.cells.and.the.transwell.system..Colonization.of.
the. wide-meshed. BNC. phase. with. the. isolated. chondrocytes. was. already.
observed. after. 24. h. of. the. cultivation. process,. and. chondrocyte. migration.
into.deeper.layers.of.the.BNC.network.was.confirmed.histologically..These.
layers.showed.a.wide-meshed.network.with.pore.sizes.well.adapted.to.the.
size. of. the. chondrocytes.. In. addition,. cartilage. defects. in. bovine. cartilage.
discs.were.filled.with.preformed.BNC.implants.to.investigate.the.cell.migration. in. vitro.. After. 4–8. weeks. of. culture,. early. stages. of. cartilage. matrix.
regeneration. were. observed. in. the. defect-filling. BNC. network.. The. integrity. of. the. cartilage. was. preserved. despite. extended. culture. periods. and.
immunohistochemical. evidence. for. the. deposition. of. intact. aggrecan,. and.