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Table 1 Summary of scaffold-free cell-based therapies for cartilage repair

From: Scaffold-free tissue engineering for injured joint surface restoration

Authors

Journal

Year

Experimental Model

Scaffold-free Technique

Shape

Cell Source

Matrix

Amount of Cells

Defect Size (in vivo)

Graft fixation (in vivo)

Adkisson HD

Clin Orthop Relat Res

2001

in vitro

High-density in Monolayer

Disc

Chondrocyte

Catilage-like

2 × 105/cm2 per plate

N/A

N/A

Mainil-Varlet P, et al.

Osteoarthritis Cartilage

2001

Minipig

Bioreactor

Spheroid

Chondrocyte

Catilage-like

2 × 107

4 mm diameter(Full-thickness cartilage defect)

Press-fit

Anderer U, et al.

J Bone Miner Res

2002

in vitro

Self Aggregating

Spheroid

Chondrocyte

Catilage-like

2 × 105

N/A

N/A

Masuda K, et al.

J Orthop Res

2003

in vitro

Alginate Recovered Chondrocyte Method

Sheet

Chondrocyte

Catilage-like

4 × 106per mL

N/A

N/A

Lu Y, et al.

J Knee Surg

2005

Sheep

High-density in Monolayer

Disc

Chondrocyte

Catilage-like

2 × 105/cm2 per plate

5.5 mm diameter 400–500 μm depth

Suture

Stoddart MJ, et al.

J Cell Mol Med

2006

in vitro

Cell Pellet After Culture in Alginate

Disc

Chondrocyte

Catilage-like

4 × 106per mL

N/A

N/A

Stoddart MJ, et al.

Biotechnol Bioeng

2006

in vitro

Cell Pellet After Culture in Alginate

Spheroid

Chondrocyte

Catilage-like

4 × 106per mL

N/A

N/A

Kaneshiro N, et al.

Biochem Biophys Res Commun

2006

in vitro

Layered Chondrocyte Sheet

Sheet

Chondrocyte

Catilage-like

1 × 104per cm2

N/A

N/A

Hu JC, et al.

Tissue Eng

2006

in vitro

High-density in Monolayer

Disc

Chondrocyte

Catilage-like

5.5 × 106

N/A

N/A

Park K, et al.

Artificial Organs

2006

Pig

High-density in Monolayer

Disc

Chondrocyte

Catilage-like

1.9 × 105/cm2per plate

6 mm diameter 3–4 mm depth

Bovine collagen gel

Brehm W, et al.

Osteoarthritis Cartilage

2006

Goat

Bioreactor

Disc

Chondrocyte

Catilage-like

2 × 107

6 mm diameter 0.8 mm depth

Periosteal falp, PRP, Fibrin

Hayes AJ, et al.

J Histochem Cytochem

2007

in vitro

High-density in Monolayer

Sheet

Chondrocyte

Catilage-like

6 × 106

N/A

N/A

aAndo W, et al.

Biomaterials

2007

Pig

High-density in Monolayer

Sheet

Synovial MSC

Collagen I, III-rich

4 × 105/cm2per plate

8.5 mm diameter2 mm depth

Nether glue nor suture

Murdoch AD, et al.

Stem Cells

2007

in vitro

Transwell Culture

Disc

Bone Marrow MSC

Catilage-like

5 × 105

N/A

N/A

aAndo W, et al.

Tissue Eng Part A

2008

in vitro

High-density in Monolayer

Sheet

Synovial MSC

Catilage-like

4 × 105/cm2per plate

N/A

N/A

Ofek G, et al.

ProS One

2008

in vitro

High-density in Monolayer

Spheroid

Chondrocyte

Catilage-like

5.5 × 106

N/A

N/A

Nagai T, et al.

Tissue Eng Part A

2008

Rabbit

High-density in Monolayer

Disc

Chondrocyte

Catilage-like

6 × 106

5 mm diameter3 mm depth

Nether glue nor suture

Jubel A, et al.

Am J Sports Med

2008

Sheep

Cell Pellet After Culture in Alginate

Disc

Chondrocyte

Catilage-like

4 × 106 per mL

4 mm diameter(Full-thickness cartilage defect)

Periosteal flap

Schubert T, et al.

Int J Mol Med

2009

Mouse

Self Aggregating

Spheroid

Chondrocyte

Catilage-like

2 × 105

5 mm diameter3-4 mm depth(Human cartilageco-implant model)

Nether glue nor suture

Lewis PB, et al.

J Knee Surg

2009

Goat

High-density in Monolayer

Disc

Chondrocyte

Catilage-like

2 × 105/cm2per plate

4 or 6 mm diameter

Fibrin glue

aShimomura K, et al.

Biomaterials

2010

Pig

High-density in Monolayer

Sheet

Synovial MSC

Collagen I, III-rich

4 × 105/cm2per plate

8.5 mm diameter2 mm depth

Nether glue nor suture

Kraft JJ, et al.

Cartilage

2011

in vitro

Self Aggregating

Disc

Chondrocyte

Catilage-like

2 × 107per mL

N/A

N/A

Zhang B, et al.

Tissue Eng Part C

2011

in vitro

Self Aggregating

Round or Oval

Bone MarrowMSC

Catilage-like

2.5 × 107per mL

N/A

N/A

Maeda S, et al.

J Biosci Bioeng

2011

in vitro

Culture on Membrane (polyethylene terephthalate)

Disc

Bone MarrowMSC

Catilage-like

3.1 × 106

N/A

N/A

Cheuk YC, et al.

J Orthop Res

2011

Rabbit

Pellet Culture

Spheroid

AllogenicChondrocyte

Not assessed

5 × 105

3 mm diameter3 mm depth

Press-fit

Yoshioka T, et al.

J Tissue Eng Regen Med

2011

Rabbit

Rotatory Culture(Bioreactor)

Spheroid

Bone MarrowMSC

Mainly hyaline-like appearance

1.5 - 3.0 × 107

5 mm diameter4 mm depth

Nether glue nor suture

Qu C, et al.

Cell Tissue Res

2012

in vitro

Transwell Culture

Disc

Chondrocyte

Catilage-like

6 × 106

N/A

N/A

aAndo W, et al.

Eur Cell Mater

2012

Pig

High-density in Monolayer

Sheet

Synovial MSC

Collagen I, III-rich

4 × 105/cm2per plate

8.5 mm diameter2 mm depth

Nether glue nor suture

Ebihara G, et al.

Biomaterials

2012

Minipig

Layered Chondrocyte Sheet

Sheet

Chondrocyte

Catilage-like

5 × 104per cm2

6 mm diameter5 mm depth

Suture

Sato Y, et al.

J Biosci Bioeng

2013

in vitro

Culture on Membrane (polyethylene terephthalate)

Disc

Bone MarrowMSC

Catilage-like

1.86 × 106

N/A

N/A

Brenner JM, et al.

Biotechnol Prog

2013

in vitro

Bioreactor

Sheet

Chondrocyte

Catilage-like

2 × 104

N/A

N/A

Giardini-Rosa R, et al.

Tissue Eng Part A

2014

in vitro

Bioreactor

Sheet

Chondrocyte

Catilage-like

6.5 or 13 × 103per cm2

N/A

N/A

Mohanraj B, et al.

J Biomech

2014

in vitro

High-density in Monolayer

Disc

Chondrocyte

Catilage-like

1 × 106

N/A

N/A

Liu T, et al.

Tissue Eng Part A

2014

in vitro

Self Assembling

Disc

Fat Pad-derivedStem Cell

Catilage-like

3.8 × 106

N/A

N/A

Ylärinne JH, et al.

Cell Tissue Res

2014

in vitro

Transwell Culture

Disc

Chondrocyte

Catilage-like

6 × 106

N/A

N/A

Oda K, et al.

J Orthop Sci

2014

Rabbit

High-density in Monolayer

Disc

Chondrocyte

Catilage-like

6 × 106per cm2

4 mm diameter(Osteochondral defect)

Not addressed

Ishihara K, et al.

J Orthop Surg Res

2014

Rabbit

Spheroid Formation

Cylinder

Bone MarrowMSC

Not stained with Safranion O

4 × 104per well

4.8 mm diameter4-5 mm depth

Nether glue nor suture

Brenner JM, et al.

Artificial Organs

2014

Rabbit

Bioreactor

Sheet

Chondrocyte

Catilage-like

2 × 104

4 mm diameter(Chondral only defect)

Fibrin glueand Suture

aFujie H, et al.

J Biomech

2015

Pig

High-density in Monolayer

Sheet

Synovial MSC

Collagen I, III-rich

4 × 105/cm2per plate

8.5 mm diameter2 mm depth

Nether glue nor suture

Yamashita A, et al.

Stem Cell Reports

2015

Minipig

Staged Differentiation Media

Spheroid

iPSC

Catilage-like

1-2 × 105

Not addressed

Fibrin glue

He P, et al.

Acta Biomater

2016

in vitro

Culture on Alginate-based Micro-cavity Hydrogel

Disc

iPSC

Catilage-like

1 × 107per mL

N/A

N/A

Islam A, et al.

Eur Cell Mater

2016

in vitro

Pellet Culture

Spheroid

Umbilical Cord MSC

Catilage-like

5 × 104

N/A

N/A

aYasui Y, et al.

Tissue Eng Part A

2016

in vitro

High-density in Monolayer

Sheet

Synovial MSC

Catilage-like

4 × 105/cm2per plate

N/A

N/A

Kimura T, et al.

Tissue Eng Part A

2016

in vitro

Staged Differentiation Media

Spheroid

iPSC

Catilage-like

1-2 × 105

N/A

N/A

Bartz C, et all.

J Transl Med

2016

ex vivo

Self Aggregating

Spheroid

Chondrocyte

Catilage-like

2 × 105

4 mm diameter

Nether glue nor suture

aKoizumi K, et al.

OsteoarthritisCartilage

2016

Rat

High-density in Monolayer

Sheet

Synovial MSC

Collagen I, III-rich

4 × 105/cm2per plate

1.5 mm diameter1 mm depth

Nether glue nor suture

Itokazu M, et al.

Cartilage

2016

Rat

Culture on Membrane (polyethylene terephthalate)

Disc

Bone MarrowMSC

Catilage-like

1.86 × 106

2 mm diameter1 mm depth

Fibrin glue

Becher C, et al.

J Orthop Surg Res

2017

Clinical

Self Aggregating

Spheroid

Chondrocyte

Catilage-like

2 × 105

4 - 10 cm2ICRS grade III or IV

Not addressed

  1. MSC mesencymal stem cell, PRP platelet rich plasma, iPSC induced pluripotent stem cell
  2. a:Our study