Recent Approaches to the Manufacturing of Biomimetic Multi-Phasic Scaffolds for Osteochondral Regeneration
Abstract
:1. Introduction
2. Osteochondral Tissue Anatomy
3. Biomimetic Multi-Phasic Structure for Osteochondral Regeneration
3.1. Bi-Phasic Scaffolds
3.2. Tri-Phasic/Multi-Phasic Scaffolds
4. Clinical Progress and Insight into the Still Open Challenges
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ALP | Alkaline phosphate activity |
BMSCs | Bone marrow mesenchymal stem |
β-TCP | Beta-tricalcium phosphate |
CCZ | Calcified cartilage zone |
ECM | Extracellular matrix |
Gel | Gelatin |
HA | Hydroxyapatite |
hMSCs | Human mesenchymal stromal/stem cells |
IKDC | International Knee Documentation Committee |
Mg-HA | Magnesium-doped hydroxyapatite |
MRI | Magnetic Resonance Imaging |
n-HA | Nano-Hydroxyapatite |
OC | Osteochondral |
PA6 | Polyamide-6 |
PEG | Polyethylene glycol |
PEG-Da | Polyethylene glycol diacrylate |
PGA | Poly-glycolic acid |
PLGA | Poly(lactide-co-glycolide) |
PLCL | Poly-lactide-co-caprolactone |
PVA | Poly-vinyl alcohol |
STZ | Superficial tangential zone |
V | Vanillin |
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Type of scaffold | Properties | ||
---|---|---|---|
Monophasic Scaffold | Acellular |
| |
Biological |
| ||
Bi-phasic Scaffold | Acellular |
| |
Biological |
| ||
Tri-phasic or Multi-phasic Scaffolds | Acellular |
| |
Biological |
|
Scaffold Type and Composition | Manufacturing Process | In Vitro and/or In Vivo Analysis | Reference | |
---|---|---|---|---|
Bi-phasic | Acellular scaffold Top: Alginate + TGF-β1-loaded microspheres Bottom: PLGA + BMP2-loaded microspheres | Top: Freeze-drying Bottom: Gas foaming | In vivo implant in cylindrical osteochondral defects (diameter 4.5 mm, deep 4 mm) in adult male New Zealand rabbits for 24 weeks:
| Reyes et al. 2014 [46] |
Acellular scaffold Top: silk fibroin Bottom: silk fibroin + nano calcium phosphate powder | Salt leaching + freeze-drying | In vivo implant in cylindrical osteochondral defects (diameter 4.5 mm, deep 5 mm) in New Zealand White rabbits (9–11 weeks old) for 4 weeks:
| Yan et al. 2015 [47] | |
Cellular scaffold (BMSCs seeded on the construct for 3 days before implant) Top: PLCL Bottom: PLGA/ β-TCP | Top: sintering Bottom: gel pressing | In vivo implant in subcutaneous implantation in nude mice (7 week old) for 6 weeks:
| Kim et al. 2015 [21] | |
Cellular scaffold (MSCs seeded on the construct before implant) Top: PVA/Gel/V Bottom: n-HA/PA6 | Freezing-thawing | In vivo implant osteochondral defects (diameter 4 mm, deep 6 mm) in New Zealand rabbits for 12 weeks:
| Li et al. 2015 [32] | |
Cellular scaffold (hMSCs seeded on the construct before implant) Top: Type I atelocollagen Bottom: Mg-doped HA | Freeze-drying | In vivo subcutaneous implant in mice for 8 weeks:
| Sartori et al. 2017 [20] | |
Acellular scaffold Top: type I and II collagen and hyaluronic acid Middle: type I and II collagen and HA Bottom: HydroxyCollTM, composed of type I collagen and HA, commercialised by SurgaColl Technologies | Freeze-drying | In vivo implant in cylindrical osteochondral defects (diameter 3 mm, deep 5 mm) in New Zealand White rabbits (9 months old) for 12 weeks:
| Levingstone et al. 2016 [48] | |
Multi-phasic | Cellular scaffold (MSCs seeded on the construct before implant) Cartilage layer: different layers of CS- glycidyl methacrylate( GMA) and Gel-GMA loaded with TGF-β1 Bone layer: PLGA loaded with BMP-2 | Cartilage layer: hydrogels via UV polymerisation Bone layer: separation/particle leaching method | In vivo implant in cylindrical osteochondral defects (diameter 5 mm, deep 6 mm) in New Zealand White rabbits for 8 weeks:
| Han et al. 2014 [38] |
Cellular scaffold Cartilage layer: Top: alginate with superficial chondrocytes Bottom: alginate with middle-deep chondrocytes Bone layer: PCL with osteoblasts | Cartilage layer: ionic crosslinked alginate with CaCl2Bone layer: FDM | Ectopic osteochondral model. Bovine osteochondral cores prepared from bovine knees were filled with the construct prior to subcutaneous implantation in nude mice (8 week old) for 12 weeks:
| Jeon et al. 2018 [37] |
Scaffold | Name and Sponsor | Materials | Plug Size and Depth | References |
---|---|---|---|---|
TruFit CB™, Smith & Nephew | Bi-phasic implant consisting of semi-porous PLGA-PGA (75:25) and Calcium-phosphate | Diam 5–11 mm, 18 mm | [50,51,52,53,54] | |
Agili-C™, CartiHeal Ltd. | Crystalline aragonite (calcium carbonate based) and hyaluronic acid | Diam 6–18 mm,15 or 20 mm | [4,55]. | |
Maioregen™, Finceramica | Cartilage layer: equine type I collagenTidemark like layer: type I collagen (60%), Mg-HA (40%) Lower layer: mineralised blend of type I collagen (30%), Mg-HA (70%) | 35 × 35 mm, 6 mm (±2 mm due to the swelling) | [56,57,58] |
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Longley, R.; Ferreira, A.M.; Gentile, P. Recent Approaches to the Manufacturing of Biomimetic Multi-Phasic Scaffolds for Osteochondral Regeneration. Int. J. Mol. Sci. 2018, 19, 1755. https://doi.org/10.3390/ijms19061755
Longley R, Ferreira AM, Gentile P. Recent Approaches to the Manufacturing of Biomimetic Multi-Phasic Scaffolds for Osteochondral Regeneration. International Journal of Molecular Sciences. 2018; 19(6):1755. https://doi.org/10.3390/ijms19061755
Chicago/Turabian StyleLongley, Ryan, Ana Marina Ferreira, and Piergiorgio Gentile. 2018. "Recent Approaches to the Manufacturing of Biomimetic Multi-Phasic Scaffolds for Osteochondral Regeneration" International Journal of Molecular Sciences 19, no. 6: 1755. https://doi.org/10.3390/ijms19061755