- ABSTRACT- "Biological fixation will require re-establishment of the structure-function relationship inherent at the native
soft tissue-to-bone interface on these tissue engineered grafts. To this end, strategic biomimicry must be incorporated into
advanced scaffold design." - ADVANCES- "Significant advances have thus been
made in the development of ligament- [1-7], tendon- [8-13],
cartilage-[14-24] and bone-like [25-34] tissues by combining
cells and biomaterials along with biochemical and/or biophysical
stimulation" - TISSUE TO TISSUE INTERFACE- "Therefore,
the development of integrated musculoskeletal tissue
systems will require not only the re-establishment of the inherent
structure-function relationship of each type of tissue,
but also the concurrent regeneration of the complex tissueto-
tissue interface." - MULTI-PHASE SCAFFOLD-" It is anticipated that the formation of integrated tissue
systems similar to those observed at the junctions between
orthopaedic soft and hard tissues will require a multi-phased
scaffold which supports the growth and differentiation of
multiple cell types." - PROBLEM WITH TENDON ACL RECONST.- "While
tendon-based ACL reconstruction grafts may restore the
physiological range of motion through mechanical fixation,
biological fixation is not achieved. In the absence of an anatomical
interface, the graft-bone junction exhibits poor mechanical
stability [56-58] and this remains the primary cause
of graft failure" - UNDERSTAND MATERIAL PROPERTIES- "In the paradigm for functional tissue engineering outlined
by Butler et al., [37] significant emphasis is placed on understanding
the material properties of the tissue to be replaced,
as well as quantifying the in vivo strains and stresses experienced
by the native tissue under physiological loading." - 3 REGIONS OF TISSUES IN ACL- "three distinct tissue regions are found at the ACL-bone insertion site: ligament, fibrocartilage, and bone. The fibrocartilage
region is further divided into non-mineralized fibrocartilage
and mineralized fibrocartilage regions" - DESIGN MORE THAN 1 TYPE OF TISSUE NEEDS TO BE ABLE TO REGENERATE- "Thus interface scaffold design
must consider the need to regenerate more than one type of
tissue" - STRUCTURE-FUNCTION PERSPECTIVE
- REGIONAL TENSION- "when the joint is loaded in tension, the deformation
across the insertion site is region-dependent, with the
highest displacement found at the ACL, then decreasing in
magnitude from the fibrocartilage interface to bone" - COW STATS ACL REGION- "bovine ACL-bone interface,
the compressive modulus of the non-mineralized fibrocartilage
region was 0.32 ± 0.14 MPa [71], which is more
than 50% lower than that of the mineralized fibrocartilage
region which averaged 0.68 ± 0.39 MPa [71]. Both of these
values are lower than that of trabecular bone which is reported to be 173 ± 97 MPa in the neonatal bovine model" - FIGURE 1 Biomimetic Stratified Scaffold Design for Ligament-to-Bone Interface Tissue Engineering
- STRATEGY TO ENGINEER MECH. INHOMOGENITY IN SCAFFOLD- "one strategy to engineer controlled mechanical
inhomogeneity on the interface scaffold is by regulating the
distribution and concentration of calcium phosphate on the
scaffold phases." - LAYERED SCAFFOLD- "a stratified scaffold is required
to recapitulate the multi-tissue organization observed at the
native ligament-to-bone interface" - CHALLENGE B/C DIFFERENT TISSUE TYPES IN ACL- "The multi-tissue transition from ligament to fibrocartilage
and to bone at the ACL-bone interface represents a significant
challenge for functional interface tissue engineering
as several distinct types of tissue are observed at this insertion
site." - DIFF. TISSUE TYPES-"supporting the
growth and differentiation of relevant cell populations, must
direct heterotypic and homotypic cellular interactions while
promoting the formation and maintenance of controlled matrix
heterogeneity" - DIFF. TISSUE TYPES- "The interface scaffold must also exhibit mechanical properties
comparable to those of the ligament-to-bone interface. In
addition, the scaffold phases should be biodegradable so that
it can be gradually replaced by living tissue, and the degradation
process must be balanced with respect to the scaffold
mechanical properties in order to permit physiological loading
and neo-interface function." - STRENGTH- "strength of the ligamentous
tissue is crucial to the success of the ACL graft" - FROM OTHER ARTICLE COOPER ET. AL.- "Recently, Cooper et
al. [6] reported on a multi-phased design of a synthetic ACL
graft with a ligament proper as well as two bony regions.
This novel ACL scaffold was fabricated from 3-D braiding
of polylactide-co-glycolide fibers, and scaffold porosity differed
between the bone and ligament regions, with the extended
goal of promoting ACL graft integration within the
bone tunnels. In vitro [7] and in vivo [91] evaluation of this
ACL fibroblast seeded scaffold demonstrated biocompatibility,
healing and mechanical strength in a rabbit model. This
new design represents a significant improvement over single-
phased ACL grafts, and the next step is to address the
challenge of graft integration with bone, by including the
fibrocartilage interface in the ligament scaffold design." - 3 PHASE SCAFFOLD
- tri-phasic scaffold
- "With this scaffold design, a biomimetic
phase-specific cell distribution was established, with osteoblasts
and fibroblasts localized in their respective regions,
while their interaction was restricted to Phase B, the interface
region." - 3 PHASE- "While both anatomic ligament- and bone-like matrices
were formed on the tri-phasic scaffold in vitro and in vivo,
no fibrocartilage-like tissue was observed in the interface
phase through osteoblast-fibroblast co-culture." - OPTIMAL CLINICAL OUTCOME- "The optimal clinical outcome is to have a completely mineralized tissue within the bone tunnel, accompanied by the formation
of an anatomic fibrocartilage insertion on the soft tissue
graft."
Tuesday, October 20, 2009
Biomimetic Stratified Scaffold Design for Ligament-to-Bone Interface Tissue Engineering
http://www.ncbi.nlm.nih.gov/sites/entrez
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