M. Rikkers (Utrecht, NL)

UMC Utrecht Orthopaedics

Presenter Of 2 Presentations

Poster Biomaterials and Scaffolds

P044 - A Personalized, Regenerative Implant for Open-Wedge Osteotomy - From Scan to Surgery

Presentation Topic
Biomaterials and Scaffolds
Date
13.04.2022
Lecture Time
09:30 - 09:30
Room
Exhibition Foyer
Session Name
7.3 - Poster Viewing / Coffee Break / Exhibition
Session Type
Poster Session
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Unicompartmental osteoarthritis of the knee joint can be treated with open-wedge osteotomy. However, the procedure faces several challenges as postoperative pain and non-union. Here, we aimed to design personalized implants using an osteopromotive and degradable biomaterial, that closes the gap left after an open-wedge osteotomy.

Methods and Materials

An open-wedge osteotomy procedure was preplanned using computed tomography (CT) scans. Based on this, a porous wedge scaffold was designed and printed using a magnesium strontium phosphate-polycaprolactone (MgPSr-PCL) biomaterial ink. The wedges were mechanically characterized and in vitro osteopromotive properties of the material were assessed using expanded human bone marrow-derived mesenchymal stromal cells (MSCs) and bone marrow concentrate (BMC). Next, personalized implants were fabricated for ex vivo implantation in three osteotomies with different heights (5 mm, 10 mm, 15 mm), and the wedges were implemented into the standard osteotomy surgical procedure in human cadaveric legs.

Results

Personalized wedge implants with inter-fibre spacing (IFS) of 0.7 mm, 1.0 mm, and 1.3 mm with closed outer edges were fabricated (Figure 1). Implants with IFS-1.0 resulted in scaffolds that maintained top and bottom porosity, while exhibiting significant mechanical stability. MSCs and BMC cells attached to the MgPSr-PCL material and proliferated over 21 days in culture. Alkaline phosphatase activity, calcium, and osteocalcin production were promoted in all culture conditions, independent of osteogenic induction medium. Finally, three “personalized” wedges were implanted ex vivo during a high tibial open-wedge osteotomy procedure. A small fraction of one side of the wedges were trimmed off to assure fit into the biplanar osteotomy gap. Pre-planned wedge heights were maintained after implantation as measured by micro-CT.

figure 1.png

Conclusion

To conclude, we have designed and manufactured personalized implants to fill the gap in open-wedge osteotomies. The implants supported osteogenesis of MSCs and BMC in vitro and were successfully implemented into the surgical procedure, without compromising pre-planned wedge height.

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Poster Stem Cells

P231 - Progenitor Cells Derived from Healthy and Osteoarthritic Human Cartilage show Potential for Cartilage Repair Therapies

Presentation Topic
Stem Cells
Date
13.04.2022
Lecture Time
09:30 - 09:30
Room
Exhibition Foyer
Session Name
7.3 - Poster Viewing / Coffee Break / Exhibition
Session Type
Poster Session
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Articular cartilage-derived progenitor cells (ACPCs) are a potential new cell source for cartilage tissue engineering. Unlike mesenchymal stromal cells (MSCs), ACPCs do not have the tendency to undergo terminal hypertrophic differentiation. This study aims to isolate and characterize ACPCs from human hyaline cartilage. ACPCs derived from healthy and osteoarthritic cartilage are compared and their potential for cartilage tissue engineering and clinical application is assessed.

Methods and Materials

Cells were isolated from macroscopically healthy-scored (n=6, age 46-49, mean age 48) and osteoarthritic (n=6, age 41-82, mean age 62) human knee cartilage. Subsequently, ACPCs were isolated from the total cell population by clonal growth after differential adhesion on fibronectin. MSCs were isolated from human bone marrow by plastic adherence after separating the mononuclear fraction using a Ficoll-paque density gradient. Healthy and osteoarthritic ACPCs were characterized by surface marker expression, growth kinetics, colony-forming efficiency, and multilineage differentiation. The populations were compared to full-depth chondrocytes derived from the same donors. Next, ACPCs were cultured in 3D pellets to investigate neo-cartilage formation.

Results

Healthy and osteoarthritic ACPCs were successfully isolated and differentiated into the adipogenic and chondrogenic lineage, but failed to produce calcified matrix when exposed to osteogenic induction media. Full-depth chondrocytes derived from the same donors were able to produce calcified matrix upon induction of osteogenic differentiation. Both ACPC populations, as well as full-depth chondrocytes met the criteria for surface marker expression to define MSCs as determined by flow cytometry. Cartilage-like matrix production was successful in ACPC pellet cultures.

Conclusion

In conclusion, this study provides further insight into a progenitor cell population in both healthy and osteoarthritic human articular cartilage. The populations show similarities to MSCs, yet ACPCs did not produce calcified matrix under well-established osteogenic and mineralization culture conditions. Furthermore, ACPCs show potential for cartilage tissue engineering and possibly for clinical application, as promising alternatives to MSCs.

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Presenter Of 2 Presentations

Biomaterials and Scaffolds

P044 - A Personalized, Regenerative Implant for Open-Wedge Osteotomy - From Scan to Surgery

Abstract

Purpose

Unicompartmental osteoarthritis of the knee joint can be treated with open-wedge osteotomy. However, the procedure faces several challenges as postoperative pain and non-union. Here, we aimed to design personalized implants using an osteopromotive and degradable biomaterial, that closes the gap left after an open-wedge osteotomy.

Methods and Materials

An open-wedge osteotomy procedure was preplanned using computed tomography (CT) scans. Based on this, a porous wedge scaffold was designed and printed using a magnesium strontium phosphate-polycaprolactone (MgPSr-PCL) biomaterial ink. The wedges were mechanically characterized and in vitro osteopromotive properties of the material were assessed using expanded human bone marrow-derived mesenchymal stromal cells (MSCs) and bone marrow concentrate (BMC). Next, personalized implants were fabricated for ex vivo implantation in three osteotomies with different heights (5 mm, 10 mm, 15 mm), and the wedges were implemented into the standard osteotomy surgical procedure in human cadaveric legs.

Results

Personalized wedge implants with inter-fibre spacing (IFS) of 0.7 mm, 1.0 mm, and 1.3 mm with closed outer edges were fabricated (Figure 1). Implants with IFS-1.0 resulted in scaffolds that maintained top and bottom porosity, while exhibiting significant mechanical stability. MSCs and BMC cells attached to the MgPSr-PCL material and proliferated over 21 days in culture. Alkaline phosphatase activity, calcium, and osteocalcin production were promoted in all culture conditions, independent of osteogenic induction medium. Finally, three “personalized” wedges were implanted ex vivo during a high tibial open-wedge osteotomy procedure. A small fraction of one side of the wedges were trimmed off to assure fit into the biplanar osteotomy gap. Pre-planned wedge heights were maintained after implantation as measured by micro-CT.

figure 1.png

Conclusion

To conclude, we have designed and manufactured personalized implants to fill the gap in open-wedge osteotomies. The implants supported osteogenesis of MSCs and BMC in vitro and were successfully implemented into the surgical procedure, without compromising pre-planned wedge height.

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Stem Cells

P231 - Progenitor Cells Derived from Healthy and Osteoarthritic Human Cartilage show Potential for Cartilage Repair Therapies

Abstract

Purpose

Articular cartilage-derived progenitor cells (ACPCs) are a potential new cell source for cartilage tissue engineering. Unlike mesenchymal stromal cells (MSCs), ACPCs do not have the tendency to undergo terminal hypertrophic differentiation. This study aims to isolate and characterize ACPCs from human hyaline cartilage. ACPCs derived from healthy and osteoarthritic cartilage are compared and their potential for cartilage tissue engineering and clinical application is assessed.

Methods and Materials

Cells were isolated from macroscopically healthy-scored (n=6, age 46-49, mean age 48) and osteoarthritic (n=6, age 41-82, mean age 62) human knee cartilage. Subsequently, ACPCs were isolated from the total cell population by clonal growth after differential adhesion on fibronectin. MSCs were isolated from human bone marrow by plastic adherence after separating the mononuclear fraction using a Ficoll-paque density gradient. Healthy and osteoarthritic ACPCs were characterized by surface marker expression, growth kinetics, colony-forming efficiency, and multilineage differentiation. The populations were compared to full-depth chondrocytes derived from the same donors. Next, ACPCs were cultured in 3D pellets to investigate neo-cartilage formation.

Results

Healthy and osteoarthritic ACPCs were successfully isolated and differentiated into the adipogenic and chondrogenic lineage, but failed to produce calcified matrix when exposed to osteogenic induction media. Full-depth chondrocytes derived from the same donors were able to produce calcified matrix upon induction of osteogenic differentiation. Both ACPC populations, as well as full-depth chondrocytes met the criteria for surface marker expression to define MSCs as determined by flow cytometry. Cartilage-like matrix production was successful in ACPC pellet cultures.

Conclusion

In conclusion, this study provides further insight into a progenitor cell population in both healthy and osteoarthritic human articular cartilage. The populations show similarities to MSCs, yet ACPCs did not produce calcified matrix under well-established osteogenic and mineralization culture conditions. Furthermore, ACPCs show potential for cartilage tissue engineering and possibly for clinical application, as promising alternatives to MSCs.

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