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Table 1 Summary of descriptive characteristics of the included studies

From: Effects of intra-articular injection of platelet-rich plasma on the inflammatory process and histopathological characteristics of cartilage and synovium in animals with osteoarthritis: a systematic review with meta-analysis

Study

Population

Comparison groups

Intervention

Outcomes

Authors

(year)

Animal model

strain, sex, weight, age

OA induction

(number)

Dose of PRP

Treatment protocol

Variable

Tool

Statistical results

p-value

Effect size

(95% confidence interval)

Ahmad et al. (2020)

Rat

Sprague Dawley

N/A

400–550 g

4–5 mo.

Anterior cruciate ligament transection and Medial Meniscectomy

CG (10)

PRP Group (10)

1 mL of PRP

Single injection

Inflammatory markers (TNF-α levels)

Inflammatory markers (IL-6 levels)

Molecular markers (COL2 levels)

Molecular markers (proteoglycans)

Cartilage histology, Mankin Score

ELISA

ELISA

N/A

Semi-quantitative analysis

N/A

+

+

+

+

=

p = 0.039

p = 0.003

p = 0.12

p = 0.035

p > 0.05

2.45 (4.87 to 10.93)

5.09 (26.42 to 38.38)

N/A

2.55 (−9.17 to −4.23)

0.95 (0.01 to 2.19)

Almasry et al. (2014)

Albino rat

Wistar

25 ♂

250–350 g

Adult

Medial Meniscectomy

CG (12)

PRP Group (13)

0.085 mL of PRP

3x/wk. for 2 wk.

Molecular markers (PDGF-A levels)

Molecular markers (VEGF-A levels)

Molecular markers (PDGF-A localization)

Molecular markers (VEGF-A localization)

Cartilage histology (Matrix loss)

Cartilage histology (Degeneration)

Cartilage histology (Zonal depth ratio of lesions)

Cartilage histology (Total degeneration width)

Cartilage histology (Significant degeneration width)

Cartilage histology (Osteophyte)

Cartilage histology (Medial capsule width)

Cartilage histology (Subchondral bone damage)

Synovium histology (Synovial reaction)

ELISA

ELISA

Quantitative analysis

Quantitative analysis

Modified OARSI Score

Modified OARSI Score

Modified OARSI Score

Modified OARSI Score

Modified OARSI Score

Modified OARSI Score

Modified OARSI Score

Modified OARSI Score

Modified OARSI Score

+

+

+

+

+

+

+

+

+

+

+

+

+

p < 0.001

p < 0.001

p = 0. 007

p = 0. 002

p = 0.001

p < 0.001

p < 0.001

p < 0.001

p = 0.001

p = 0.041

p < 0.001

p < 0.001

p < 0.003

6.43 (22.04 to 28.56)

14.97 (43.64 to 48.76)

4.89 (7.92 to 11.16)

5.67 (6.46 to 8.72)

−7.44 (−618.41 to −464.54)

N/A

−9.00 (−0.98 to −0.82)

−8.75 (−673.87 to −555.13)

−7.23 (−460.29 to −375.71)

N/A

−7.51 (−105.47 to −84.53)

N/A

N/A

Arican et al. (2018)

Dog

Mixed breed

N/A

25–50 kg

8–10 yr.

Naturally occurring

CG (6)

PRP Group (14)

4–5 mL of PRP

Single injection

Molecular markers (MMP-2)

Molecular markers (MMP-9)

ELISA

ELISA

=

+

p > 0.05

p < 0.05

N/A

N/A

Asjid et al. (2018)

Rat

Sprague Dawley

N/A

200–300 g

3–4 mo.

MIA injection

CG (8)

PRP Group (8)

0.5 mL of PRP

Single injection

Cartilage histology

Mankin Score

+

p = 0.003

−1.78 (−3.20 to −0.80)

Chouhan et al. (2019)

Guinea pig

Dunkin-Hartley

N/A

600–800 g

5 mo.

Naturally occurring

CG A (5)

CG B (5)

S. PRP Group A (5)

M. PRP Group A (6)

S. PRP Group B (5)

M. PRP Group B (6)

Unclear

Single injection (S)

1x/wk. for 3 wk. (M)

CG A Vs. S. PRP Group A

Synovium histology

Cartilage histology

CG A Vs. M. PRP Group A

Synovium histology

Cartilage histology

CG B Vs. S. PRP Group B

Synovium histology

Cartilage histology

CG B Vs. M. PRP Group B

Synovium histology

Cartilage histology

Pelletier Score

Mankin Score

Pelletier Score

Mankin Score

Pelletier Score

Mankin Score

Pelletier Score

Mankin Score

+

=

+

=

+

=

+

=

p = 0.011

p = 0.442

p = 0.002

p = 0.005

p = 0.562

p ≥ 0.999

p = 0.000

p = 0.146

−0.19 (−3.46 to 2.66)

0.08 (−3.66 to 4.06)

-0.46 (−4.8 to 2.40)

-0.90 (−6.14 to 1.28)

1.54 (0.11 to 4.29)

1.42 (−0.13 to 8.93)

-0.01 (−3.15 to 3.09)

0.43 (−1.26 to 2.40)

Coskun et al. (2018)

Rabbit

New Zealand

32 ♂

3–3,5 kg

Adult

MIA injection

S. CG (8)

M. CG (8)

S. PRP Group (8)

M. PRP Group (8)

0.8–1 mL of PRP

Single injection (S)

1x/wk. for 3 wk. (M)

S. CG Vs. S. PRP Group

Cartilage histology (Cartilage structure)

Cartilage histology (Osteochondral junction)

Cartilage histology (Chondrocyte appearance)

Cartilage histology (Subchondral bone structure)

M. CG Vs. M. PRP Group

Cartilage histology (Cartilage structure)

Cartilage histology (Osteochondral junction)

Cartilage histology (Chondrocyte appearance)

Cartilage histology (Subchondral bone structure)

Qualitative Score

Qualitative Score

Qualitative Score

Qualitative Score

Qualitative Score

Qualitative Score

Qualitative Score

Qualitative Score

=

=

=

=

=

=

=

=

p > 0.05

p > 0.05

p > 0.05

p > 0.05

p > 0.05

p > 0.05

p > 0.05

p > 0.05

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

Gamal et al. (2019)

Albino rat

Wistar

15 ♂

200–250 g

4–5 mo.

Cartilage defect surgical procedure

CG A* (5)

CG B* (5)

PRP Group (5)

0.2 mL of PRP

3x/wk. for 2 wk.

Molecular markers (PDGF-A levels)

Cartilage histology (thickness)

Immunohistochemical analysis

Qualitative analysis

+

+

p < 0.05

p < 0.05

9.02 (−12.88 to −3.39)

33.81 (333.57 to 363.63)

Guner & Buyukbebeci (2013)

Albino rat

Wistar

20 ♂

250–300 g

Adult

Formalin injection

CG (10)

PRP Group (10)

0.05 mL of PRP

1x/wk. for 3 wk.

Cartilage histology

Degeneration Score

=

p > 0.05

N/A

Hermeto et al. (2016)

Rabbit

New Zealand

12 ♂

3.5–4,5 kg

Adult

Collagenase injection

CG (6)

PRP Group (6)

Unclear

Unclear

Cartilage histology

Modified Mankin Score

=

p > 0.05

−3.00 (−6.67 to −2.67)

Jayaram et al. (2020)

Mice

FVB/N

33 ♂

N/A

3 mo.

Destabilization of the Medial Meniscus

CG (10)

LP-PRP Group (11)

LR-PRP Group (12)

0.005 mL of PRP

3 injections

CG Vs. LP-PRP Group

Cartilage histology

Synovium histology

CG Vs. LR-PRP Group

Cartilage histology

Synovium histology

OARSI Score

Synovitis Score

OARSI Score

Synovitis Score

=

=

=

=

p = 0.3157

p = 0.9999

p = 0.9999

p = 0.9999

N/A (−23.96 to 3.66)

N/A

N/A (18.50 to 9.120)

N/A

Ji et al. (2015)

Rabbit

New Zealand

N/A ♀ N/A ♂

1.75–2.75 kg

58 mo.

Modified Hulth Protocol

CG (10)

PRP Group (11)

0.5 mL of PRP

1x/wk. for 5 wk.

Inflammatory markers (IL-1 levels)

Inflammatory markers (IL-6 levels)

Inflammatory markers (TNF-α levels)

ELISA

ELISA

ELISA

+

+

+

p < 0.05

p < 0.05

p < 0.05

0.64 (−1.50 to 0.26)

2.43 (−3.50 to −1.17)

3.24 (−4.47 to −1.76)

Kanwat et al. (2017)

Guinea pig

Dunkin-Hartley

24 ♂

600–700 g

N/A

Naturally occurring

CG A (6)

CG B (6)

PRP Group A (6)

PRP Group B (6)

Unclear

1x/wk. for 3 wk.

CG A Vs. PRP Group A

Synovium histology

Cartilage histology

CG B Vs. PRP Group B

Synovium histology

Cartilage histology

Pelletier Score

Modified Mankin Score

Pelletier Score

Modified Mankin Score

=

+

+

+

p = 0.147

p = 0.002

p = 0.001

p = 0.0001

−1.33 (−6.23 to −0.11)

−2.45 (−1.76 to 1.08)

−2.50 (−7.57 to −2.43)

−3.00 (−9.91 to −3.09)

Kutuk et al. (2014)

Rabbit

New Zealand

N/A

2.64–3 kg

12 mo.

Bilateral TMJ surgical procedure

CG (10)

PRP Group (10)

1 mL of PRP

Unclear

Cartilage histology (Fibrocartilage regeneration)

Cartilage histology (Regeneration hyaline cartilage)

Quantitative analysis

Quantitative analysis

=

=

p = 0.143

p = 0.579

N/A

N/A

Lu et al. (2020)

Rabbit

New Zealand

17 ♀ 13 ♂

3.0–4.5 kg

± 11 wk.

Modified Hulth Protocol

CG (15)

PRP Group (15)

0.5 mL of PRP

1x/wk. for 10 wk.

Inflammatory markers (IL-1 levels)

Inflammatory markers (IL-6 levels)

Inflammatory markers (TNF-α levels)

Cartilage histology

ELISA

ELISA

ELISA

Mankin Score

+

+

+

+

p < 0.01

p < 0.01

p < 0.01

p < 0.05

−2.60 (−23.75 to −13.13)

−4.50 (−54.56 to −39.00)

−5.93 (−74.08 to −57.48)

N/A

Parlak & Arican (2020)

Dog

Mixed breed

6 ♀ 30 ♂

29–31 kg

4–6 yr.

Naturally occurring

CG (16)

S. PRP Group (8)

M. PRP Group (8)

Unclear

Single injection (S)

1x/wk. for 2 wk. (M)

Inflammatory markers (TNF-α levels)

Inflammatory markers (IL-10 levels)

Inflammatory markers (IL-6 levels)

Inflammatory markers (IL-1β levels)

ELISA

ELISA

ELISA

ELISA

=

+

+

+

p > 0.05

p < 0.05

p < 0.05

p < 0.05

N/A

N/A

N/A

N/A

Ragab et al. (2021)

Albino rat

Wistar

20 ♂

100–120 g

7–9 wk.

MIA injection

CG (10)

PRP Group (10)

0.05 mL of PRP

1x/wk. for 3 wk.

Anti-inflammatory markers (IL-4 levels)

Inflammatory markers (IL-17 levels)

Inflammatory markers (TNF-α levels)

ELISA

ELISA

ELISA

+

+

+

p < 0.05

p < 0.05

p < 0.05

N/A

N/A

N/A

Wang et al. (2018)

Goat

Boer

12 ♂

40–50 kg

12–18 mo.

Anterior cruciate ligament transection and Medial Meniscectomy

CG (6)

PRP Group (6)

2 mL of PRP

3x every 4 wk.

Inflammatory markers (IL-1β levels)

Inflammatory markers (IL-6 levels)

Inflammatory markers (TNF-α levels)

Molecular markers (PGE2 levels)

Cartilage histology

ELISA

ELISA

ELISA

ELISA

Pelletier Score

+

=

=

+

+

p < 0.05

p > 0.05

p > 0.05

p < 0.05

p < 0.05

N/A

N/A

N/A

N/A

N/A

Wu et al. (2016)

Rabbit

New Zealand

32 ♀ 28 ♂

2.5–3.0 kg

4–5 mo.

Modified Hulth Protocol

CG (15)

PRP Group (15)

0.5 mL of PRP

1x/wk. for 6 wk.

Inflammatory markers (IL-1β levels in the joint fluid)

Inflammatory markers (IL-1β levels in the serum)

Inflammatory markers (IL-1β positive chondrocytes

Inflammatory markers (Density of IL-1β staining)

Cartilage histology

Cartilage histology

ELISA

ELISA

Immunohistochemical analysis

Immunohistochemical analysis

Mankin Score

Pelletier Score

+

+

+

+

+

+

p = 0.0079

p = 0.0086

p = 0.0068

p = 0.0073

p = 0.0081

p < 0.05

N/A

N/A

N/A

N/A

N/A

N/A

Xin et al. (2020)

Rat

Sprague Dawley

N/A

200–300 g

3–4 mo.

Anterior cruciate ligament transection

CG (5)

PRP Group (5)

0.05 mL of PRP

1x/wk. for 4 wk.

Inflammatory markers (IL-1β levels)

Inflammatory markers (IL-18 levels)

Inflammatory markers (TNF-α levels)

Molecular markers (Col2 levels)

Cartilage histology

Cartilage histology

ELISA

ELISA

ELISA

ELISA

Mankin Score

OARSI Score

+

+

+

+

+

+

p < 0.05

p < 0.05

p < 0.05

p < 0.05

p < 0.01

p < 0.01

N/A

N/A

N/A

N/A

N/A

N/A

Yin et al. (2016)

Rabbit

New Zealand

25 ♀ 25 ♂

2.5–3.0 kg

Adult

Anterior cruciate ligament transection

CG (10)

PRP Group (10)

3 mL of PRP

1x/wk. for 3 wk.

Inflammatory markers (IL-1β levels)

Molecular markers (PGE2 levels)

ELISA

ELISA

+

+

p < 0.05

p < 0.05

N/A

N/A

Yun et al. (2016)

Dog

Beagle

6 ♀ 30 ♂

29–31 kg

4–6 yr.

Cranial cruciate ligament transection

CG (6)

PRP Group (6)

1 mL of PRP

1x/wk. for 4 wk.

Femoral cartilage (TNF-α levels)

Femoral cartilage (IL-1β + levels)

Tibial cartilage (TNF-α levels)

Tibial cartilage (IL-1β + levels)

Femoral cartilage (Surface damage)

Femoral cartilage (Hypocellularity)

Femoral cartilage (Clone)

Femoral cartilage (Stain intensity)

Tibial cartilage (Surface damage)

Tibial cartilage (Hypocellularity)

Tibial cartilage (Clone)

Tibial cartilage (Stain intensity)

Immunohistochemical analysis

Immunohistochemical analysis

Immunohistochemical analysis

Immunohistochemical analysis

Mankin Score

Mankin Score

Mankin Score

Mankin Score

Mankin Score

Mankin Score

Mankin Score

Mankin Score

+

+

+

+

+

+

+

+

+

+

+

+

p < 0.01

p < 0.01

p < 0.01

p < 0.01

p < 0.01

p < 0.01

p > 0.05

p > 0.05

p < 0.01

p > 0.05

p > 0.05

p > 0.05

−6.29 (−115.62 to 76.38)

−7.14 (−152.65 to 106.03)

−2.83 (−134.09 to −50.25)

−4.21 (−170.39 to −90.61)

−3.44 (−2.29 to −1.05)

−1.79 (−1.44 to −0.24)

−0.77 (−1.33 to −0.33)

−1.82 (−1.14 to −0.20)

−3.44 (−2.29 to −1.05)

−2.22 (−2.12 to −0.56)

−0.57 (−1.07 to −0.41)

−0.68 (−0.95 to −0.29)

  1. Note The effect size and confidence interval were calculated for each outcome considering the sample as well as the mean and standard deviation values of the PRP-treated and comparison groups
  2. Abbreviations: ♀ female; ♂ male; CG control group; CG A control group analyzed at three months; CG A* control group analyzed at four weeks; CG B control group analyzed at six months; CG B* control group analyzed at six weeks; COL2 collagen 2; ELISA enzyme-Linked immunosorbent assay; IL-1 interleukin 1; L-1β interleukin 1β; IL-6 interleukin 6; IL-10 interleukin 10; M. CG multiple injections control group; M.PRP Group A multiple injections intervention group analyzed at three months; M.PRP Group B multiple injection intervention group analyzed at six months; MMP-2 matrix metalloproteinase-2; MMP-9 matrix metallopeptidase-9; MMP-13 matrix metallopeptidase-13; MIA monosodium iodoacetate; Mo. months; N/A not available; OA osteoarthritis; OARSI osteoarthritis research society international; PBS phosphate buffered saline; PDGF platelet-derived growth factor; PGE2 prostaglandin E2; PRP platelet-rich plasma; PRP Group A intervention group analyzed at three months; PRP Group B intervention group analyzed at six months; S. CG single injection control group; S.PRP Group A single injection intervention group analyzed at three months; S.PRP Group B single injection intervention group analyzed at six months; TMJ temporomandibular joint; TNF-α tumor necrosis factor alpha; VEGF vascular endothelial growth factor; Wk. week; Yr. years