francine goulet, ph.d., pht nanomedical biological device in development for torn acl replacement
TRANSCRIPT
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Francine Goulet, Ph.D., phtFrancine Goulet, Ph.D., pht
Nanomedical Biological Device in Development for Torn ACL Replacement.
Nanomedical Biological Device in Development for Torn ACL Replacement.
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INTRODUCTIONINTRODUCTION
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Ligaments, including ACL, extend between adjacent bone structures and serve a primary function of providing appropriate stability to the joints, especially when subjected to loads in tension or upon torsional movement.
Type I collagen can be regenerated after tissue injury.
However, the anterior cruciate ligament (ACL) has little ability to heal itself.
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ACL REPLACEMENTACL REPLACEMENT
100, 000 total ruptures / yr (USA)
50,000 reconstructive surgeries / yr (USA)
100, 000 total ruptures / yr (USA)
50,000 reconstructive surgeries / yr (USA)
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Repeated shocksRepeated shocks
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Langer R, et al. 1993
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Therapeutic optionsTherapeutic options
• Synthetic prosthesesCarbonedacronLAD
• Allograft
• Autograft
• Synthetic prosthesesCarbonedacronLAD
• Allograft
• Autograft
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Option used oftenOption used often
1/3 patellar tendon + patella and tibia fragments1/3 patellar tendon + patella and tibia fragments
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Clinical drawbacksClinical drawbacks
•Knee joint fibrosis•Patellar impegement•Anterior knee pain•Patellar fracture•Patellar tendon’s rupture•Quads weaknesses
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ACL : complex features ACL : complex features
Histological content:•Fibroblasts•Collagen fibers•Proteoglycans•Elastin…..
Ultrastructure:•Fibrocartilage•Sharpey’s fibers•Vascular network•Nervous receptors
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ACL: Knee stabilizerACL: Knee stabilizer
•Average length: 32 mm•Average diameter: 11 mm•Diam. at its insertions: 23 mm (femoral) and 30 mm (tibial)
•Functional limits: -Max. elongation: 6% (about 2 mm)-Max. load: 1730 N (390 pds)
-Walking: 169 N-Intensive sport: 400-500N
•Average length: 32 mm•Average diameter: 11 mm•Diam. at its insertions: 23 mm (femoral) and 30 mm (tibial)
•Functional limits: -Max. elongation: 6% (about 2 mm)-Max. load: 1730 N (390 pds)
-Walking: 169 N-Intensive sport: 400-500N
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« LIGAMENTISATION » POST-IMPLANTATION« LIGAMENTISATION » POST-IMPLANTATION
6 weeks; Vascularisation of the implant
30 weeks: histological and functional recoveries
6 weeks; Vascularisation of the implant
30 weeks: histological and functional recoveries
Questions:Innervation: ?Mechanisms?
Questions:Innervation: ?Mechanisms?
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ACL tissue engineeringACL tissue engineering
Tissue engineering seems to be a promising alternative to produce ACL/ligament models:
- for fundamental studies in vitro;
- to develop tissue-emgineered human ACL substitutes
Tissue engineering seems to be a promising alternative to produce ACL/ligament models:
- for fundamental studies in vitro;
- to develop tissue-emgineered human ACL substitutes
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ACL tissue engineeringACL tissue engineering
To understand ACL healing and to establish new options for torn ACL replacement, the potential of tissue-engineered collagen scaffolds has to be assessed in vitro and in vivo.
To understand ACL healing and to establish new options for torn ACL replacement, the potential of tissue-engineered collagen scaffolds has to be assessed in vitro and in vivo.
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Tissue-engineered ACLTissue-engineered ACL
Appropriate scaffold is needed to provide support and promote cell adhesion, migration and growth, leading to tissue regeneration.
The scaffold must be biocompatible, biodegradable, suitable for cell attachment, and have a three-dimensional, porous structure.
Since collagen is a major structural element in so many tissues and organs, collagen fibers are a logical choice for scaffolds.
Appropriate scaffold is needed to provide support and promote cell adhesion, migration and growth, leading to tissue regeneration.
The scaffold must be biocompatible, biodegradable, suitable for cell attachment, and have a three-dimensional, porous structure.
Since collagen is a major structural element in so many tissues and organs, collagen fibers are a logical choice for scaffolds.
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Objective:Objective:Develop a new alternative for torn ACL replacement through the tissue-engineering approach.Develop a new alternative for torn ACL replacement through the tissue-engineering approach.
Hypothesis:Hypothesis:
Based on our expertise with tissue-engineered human epidermal substitutes, we postulated that ACL regeneration can be achieved by providing a biocompatible scaffold that can be colonized, remodeled and renewed by living cells in situ post-grafting.
Based on our expertise with tissue-engineered human epidermal substitutes, we postulated that ACL regeneration can be achieved by providing a biocompatible scaffold that can be colonized, remodeled and renewed by living cells in situ post-grafting.
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We tested our collagen-based ACL scaffolds in the goat model…We tested our collagen-based ACL scaffolds in the goat model…We tested our collagen-based ACL scaffolds in the goat model…We tested our collagen-based ACL scaffolds in the goat model…
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MATERIAL AND METHODSMATERIAL AND METHODS
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Characterization of the collagen scaffolds Characterization of the collagen scaffolds
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ACL collagen scaffold cultured without tensionACL collagen scaffold cultured without tension
© F.G./LOEX
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ACL collagen scaffold subjected to tensionACL collagen scaffold subjected to tension
© F.G./LOEX
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Before graftingBefore grafting Native ACLNative ACLPeriodicity: 67 nmPeriodicity: 67 nm
Collagen fibers alignmentCollagen fibers alignment
© F.G./LOEX
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© F.G./LOEX
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6.0 9.03.0
Elongation (mm)
Force (N)
1,0
2,0
3,0
0
0.0
bACL rupture assay before graftingbACL rupture assay before grafting
RuptureRupture
6.0 9.03.0
Elongation (mm)
Force (N)
1,0
2,0
3,0
0
0.0
bACL rupture assay before graftingbACL rupture assay before grafting
RuptureRupture
© F.G./LOEX
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Average cross section of 100 mm2Average cross section of 100 mm2
Scaffold structure Force /resistance to rupture (N)
Site of rupture
1 layer of hydrated collagen (gel) 0.2-0.5 (+ 5%) Interface bone-collagen
+ 1 layer of lyophilized collagen (rehydrated) 2 (+ 5%) Mid-portion of the scaffold
+ 1 layer of lyophilized collagen (rehydrated)Dipped in 10% glycerol
20 (+ 10%) Mid-portion of the scaffold
+ 2 layers of lyophilized collagen (rehydrated)Dipped in 10% glycerol
40- 50N (+ 10%) Mid-portion of the scaffold
+ 1 layer of lyophilized collagen (rehydrated)around a surgical thread (Maxon 3.0)
> 60N (grafted) Not determined
© F.G./LOEX