Table 3.
Effects of PRP on Bone Healing in Pre-Clinical in vivo Animal Models
| Author (Year) | Animal Model (Bone) | Scaffold Used | PRP Group(s) | Control Group(s) | Endpoint | Blinded Evaluation? | Radiographic Outcome | Histopathologic Outcome | Biomechanical Outcome |
|---|---|---|---|---|---|---|---|---|---|
| Rai et al (2007)164 | Rat (femur) | Polycaprolactone tricalcium phosphate (PCL-TCP) | PCL-TCP + PRP | PCL-TCP | 12 weeks | X-rays | Increased bone formation in PRP group by x-ray and micro-CT | Similar qualitative outcomes between PRP group and control group | PRP group stiffer but no difference in yield and maximum torque |
| Cho et al (2013)177 | Dog (tibia) | None | PRP | Untreated | 16 weeks | None | Bone activity index on nuclear scan greater at 4 weeks in PRP group, but less in PRP group at weeks 8, 12, and 16 | Bone-to-implant contact (BIC) was higher for the PRP group | None |
| Dallari et al (2006)178 | Rabbit (femur) | Freeze-dried bone allograft (FDBA) | PRP Bone marrow stromal cells (BMSCs)+PRP FDBA+PRP BMSCs+FDBA+PRP |
Untreated | 12 weeks | Histology | None | Increased bone healing in all experimental groups compared to control. Increased bone healing in FDBA+PRP, and BMSCs+FDBA+PRP compared to PRP alone |
None |
| Guzel et al (2015)196 | Rat (femur) | None | PRP | Untreated | 9 weeks | Histology and biomechanics | None | Increased bone healing in the PRP group | Higher ultimate failure load in PRP group |
| Hakimi et al (2010)197 | Mini pig (tibia) | Autologous bone graft | Autologous bone graft+PRP | Autologous bone graft | 6 weeks | None | Similar rates of osseous bridging on x-rays | Superior bone formation in central and cortical defect zone in PRP group | None |
| Hokugo et al (2005)123 | Rabbit (ulnar) | Gelatin hydrogel | Gelatin Hydrogel+PRP Fibrin+PRP PRP |
Gelatin hydrogel Untreated |
4 weeks | None | Greatest rate of bone healing in Gelatin hydrogel+PRP group followed by the Fibrin+PRP group | Greatest rate of bone healing in Gelatin hydrogel+PRP group followed by the Fibrin+PRP group | None |
| Jungbluth et al (2010)198 | Mini pig (tibia) | Calcium phosphate granules (CPG) | CPG+PRP | CPG | 6 weeks | X-rays | Semi-quantitative analysis showed slightly more osseous bridging in PRP group | Greater new bone formation in PRP group in central and cortical defect zones | None |
| Kanthan et al (2011)150 | Rabbit (tibia) | Artificial bone graft (ABG) | ABG+PRP PRP |
ABG Untreated |
11 weeks | X-rays | Greatest healing in ABG+PRP group compared to all other groups. PRP alone better than untreated control but no different to ABG alone | Greatest healing in ABG+PRP group. ABG better healing than control. PRP did NOT have better histologic healing than untreated control. | None |
| Kasten et al (2008)151 | Rabbit (radius) | Calcium-deficient hydroxyapatite ceramic scaffold (CDHA) | CDHA+PRP CDHA+PRP+mesenchymal stem cells (MSCs) |
CDHA Untreated |
16 weeks | None | Bone formation greater in CDHA+PRP and CDHA+PRP+MSC groups compared to CDHA alone, as measured by micro-CT | Bone formation greater in CDHA+PRP and CDHA+PRP+MSC groups compared to CDHA alone | All test groups were stiffer than untreated control. No difference in stiffness between test groups |
| Kroese-Deutamn et al (2008)152 | Rabbit (radius) | Titanium fiber mesh (TFM) | TFM+autologous bone+PRP TFM autologous bone |
TFM | 12 weeks | None | Bone healing seen in all test groups but not in all control groups | Greater bone formation in TFM+autologous bone+PRP than all other groups | None |
| Kurikchy et al (2013)153 | Rabbit (femur) | Xenogeneic bone graft (XBG) | XBG+PRP | XFG Untreated |
4 weeks | None | None | Increased number of osteocytes, osteon diameter, and lamellar thickness in XBG+PRP groups compared to all other groups | None |
| Lin et al (2013)154 | Rabbit (femur) | Nanohydroxyapatite-type I collagen beads (CIB) | CIB+BMSCs+PRP CIB+PRP PRP+BMSCs PRP |
Untreated | 8 weeks | Histology | Greater bone healing in all experimental groups compared to untreated control as assessed on micro-CT | Increased bone formation in CIB+BMSCs+PRP and PRP+BMSCs groups | None |
| Lysiak et al (2008)155 | Rabbit (femur) | Collagen | Collagen+PRP | Untreated | 12 weeks | None | None | Greater bone formation in experimental groups compared to control group | None |
| Malhotra et al (2014)156 | Sheep (tibia) | Biphasic calcium phosphate (BCP) | BCP+PRP | BCP Untreated |
4 weeks | X-ray and histology | Greater bone healing in BCP+PRP compared to all other groups via micro-CT Greater bone healing in BCP+PRP group compared to untreated but no different to BCP alone on x-ray. |
Greater bone formation in BCP+PRP compared to BCP alone and untreated control. | None |
| Manitha et al (2009)158 | Goat (femur) | Tri-phasic ceramic-coated hydroxyapatite (HASi) | HASi+BMSCs+PRP | HASi | 8 weeks | None | Greater bone formation in the experimental group compared to HASi alone | No significant difference in bone formation between all groups | None |
| Niemeyer et al (2010)160 | Sheep (tibia) | Collagen sponges (CS) | CS+Adipose-tissue derived stems cells (ASCs)+PRP | CS | 26 weeks | None | No significant difference in bone formation between test group and control assessed on x-ray | No significant difference in bone formation between test group and control assessed on histology | None |
| Parizi et al (2012)162 | Rabbit (radius) | Coral | Coral+PRP | Coral Untreated |
8 weeks | Gross evaluation | Improved bone healing in the coral and coral+PRP groups compared to untreated control | Improved bone healing in the coral and coral+PRP groups compared to untreated control | PRP with coral group had higher ultimate load than the negative control group, whereas coral group alone did not |
| Simman et al (2008)166 | Rat (femur) | None | PRP | Untreated | 4 weeks | Fully blinded analysis | Higher callus to cortex width ratio in PRP group | No difference in BMP2 or total TGF-B expression between the groups | Increased strength in PRP group |
| Souza et al (2012)167 | Dog (radius) | None | PRP | Untreated | 8 weeks | Fully blinded analysis | Greater healing in the PRP group | PRP group showed new bone formation superior to control group | None |
| Sugimori et al (2006)168 | Rat (tibia) | Apatite foam (AF) | AF+PRP PRP |
AF Untreated |
12 weeks | None | None | AF+PRP has more bone formation than all other groups | None |
| Zhang et al (2013)169 | Rabbit (radius) | Deproteinized bone matrix (DBM) | DBM+PR DBM+PRP+MSCs |
DBM | 12 weeks | None | Greater bone formation in all experimental groups compared to control, and greater bone formation in DBM+PRP+MSC compared to DBM+PRP | Greater bone formation in all experimental groups compared to control, and greater bone formation in DBM+PRP+MSC compared to DBM+PRP | None |
| Chaput et al (2007)148 | Rabbit (femur) | Beaded metal implant (BMI) | BMI+PRP | BMI | 5 weeks | None | None | No difference in bone growth between groups | None |
| Hernandez-Fernandez et al (2013)149 | Sheep (femur) | None | PRP | Untreated | 6 weeks | Fully blinded analysis | No difference in bone growth between groups | No difference in bone growth between groups | None |
| Molina-Minano et al (2009)157 | Rabbit (tibia) | Autologous bone graft (ABG) | ABG+PRP PRP |
ABG Untreated |
8 weeks | Fully blinded analysis | No difference in bone growth between groups | No difference in bone growth between groups | None |
| Nather et al (2012)159 | Rabbit (tibia) | Autologous bone graft Allograft |
Allograft+PRP | Allograft | 24 weeks | None | None | Allograft+PRP had more osteocytes than allograft alone. The greatest new bone formation, callus encasement index, and osteocyte count was seen in autograft compared to all other groups |
None |
| Rabillard et al (2009)163 | Dog (ulnar) | Calcium phosphate ceramic granules (CaP) | CaP+PRP | CaP | 16 weeks | None | None | No difference in bone growth between groups | None |
| Sarkar et al (2006)165 | Sheep (tibia) | Collagen matrix (CM) | CM+PRP | CM | 12 weeks | None | No difference between groups on x-ray or CT | No difference between groups | No difference between groups |
| Lopez et al (2019)63 | Dog (radius/ulnar and tibia/fibula) | None | PRP | Untreated | 24 weeks | Fully blinded analysis | Faster rate of bone healing in the PRP group | None | None |
| Orth et al (2018)161 | Mouse (femur) | Microcalcite (MCA) | MCP+PRP PRP |
Untreated | 5 weeks | None | Bone volume higher in MCRP+PRP group compared to controls | Smaller callus formation in MCP+PRP group compared to control | Polar moment of inertia (PMOI—used as surrogate for mechanical stability) higher in MCRP+PRP group compared to controls |
| Szponder et al (2018)173 | Rabbit (tibia) | Tri-calcium phosphate (TCP) | External fixator or intramedullary nail with TCP+PRP | None | 12 weeks | None | Bone formation observed in both ex-fix and IMN group | Bone formation observed in both ex-fix and IMN group | None |
| Canbeyli et al (2018)170 | Rabbit (femur) | None | PRP | Untreated | 12 weeks | X-rays | Increased union rate in PRP group | Greater cortical callus formation, woven bone percentage area, fibroblast proliferation, and mature bone formation in PRP group | None |
| Kim et al (2014)172 | Rat (ulna) | Gelatin hydrogel | PRP+SEW2871 (macrophage recruiter) PRP |
Untreated | 6 weeks | None | Greater bony healing and bone density observed in the PRP+SEW and PRP groups compared to controls as assessed by micro-CT | Greater bony healing observed in the PRP+SEW and PRP groups compared to controls | None |
| He et al (2015)171 | Rabbit (radius) | Poly (lactic-co-glycolic acid) with calcium phosphate cement (PLGA-CPC) | PLGA-CPC+PRP | PLGA-CPC | 12 weeks | None | No difference in healing at 12 weeks between groups. However, micro-CT showed more bone healing in PRP group compared to control | More bone formation in PRP group compared to control | None |
| Shafiei-Sarvestani et al (2015)174 | Rabbit (radius) | None | PRP | Untreated | 8 weeks | Histology | More bone growth and union in PRP group | Greater bony healing in PRP group | Greater ultimate strength in PRP group |
| Weibrich et al (2004)189 | Rabbit (femur) | None | PRP | Untreated | 4 weeks | None | None | Higher platelet concentration in PRP group but no difference in bone healing | None |
| Wiltfang et al (2004)190 | Mini pig (forehead) | Autologous bone graft Tricalcium-phosphate granules (Cerasorb) Bovine spongious blocks (BioOss) Bovine bone-inducing collagenous sponge (Colloss) |
4 different scaffolds (listed left) with PRP (2 different concentrations) | 4 scaffolds without PRP | 12 weeks | None | PRP increased bone healing in the autologous bone group but not the other bone scaffold groups | PRP did not change bone healing | None |
| Thorwarth et al (2006)188 | Pig (skull) | Autologous bone graft Deproteinized bovine bone matrix (DBBM) |
2 scaffolds with PRP (2 different concentrations) | Autologous bone alone DBBM alone |
26 weeks | None | No significant difference in bone mineralization | No difference in expression of bone-related gene expression | None |
| Bi et al (2010)139 | Goat (tibia) | Tricalcium phosphate/chitosan composite (TCP) | TCP+PRP | Untreated | 16 weeks | None | Improved bone healing in the TCP+PRP group | Higher rate of newly formed bone in the TCP+PRP group | TCP+PRP biomechanically equivalent to TCP alone |
| Kon et al (2010)184 | Sheep (femur) | Hydroxyapatite-collagen nanocomposite scaffold | Hydroxyapatite-collagen nanocomposite scaffold+PRP | Untreated | 24 weeks | Histology | Scaffold+PRP had worse bone regeneration than scaffold alone | Scaffold+PRP had worse bone regeneration than scaffold alone | None |
| Oryan et al (2012)186 | Rabbit (radius) | Hydroxyapatite scaffold | Hydroxyapatite+PRP | Untreated | 8 weeks | N/A | Scaffold+PRP and scaffold without PRP had equal bone formation but better than negative control | Scaffold+PRP and scaffold without PRP had equal bone formation but better than negative control | Ultimate strength greater in scaffold+PRP group compared to untreated defect control |
| Neves et al (2013)185 | Rabbit (fibula) | None | PRP Hyperbaric oxygen + PRP |
Untreated | 8 weeks | None | None | Hyperbaric oxygen and PRP together or alone showed increased bone formation | None |
| Kasten et al (2012)183 | Rabbit (radius) | Calcium-deficient hydroxyapatite (CDHA) | CDHA+PRP | CDHA alone | 16 weeks | None | CDHA+PRP had greater bone formation | CDHA+PRP had greater bone formation | None |
| Chen et al (2013)67 | Rat (femur) | None | PRP clot with low, medium, and high PRP concentrations | Untreated | 8 weeks | Histology and radiology | Medium concentration PRP has increased bone healing | Medium concentration PRP has increased bone healing | Ultimate strength higher in medium concentration PRP |
| Gumieiro et al (2010)181 | Rat (tibia) | None | PRP | Untreated | 12 weeks | None | None | Increased bone formation in the PRP group | None |
| Filardo et al (2014)180 | Sheep (metatarsal) | Biomorphic silicon carbide (BioSiC) scaffold | BioSiC+PRP | BioSiC alone | 16 weeks | None | No radiographic difference in the PRP group | Increased bone formation in the PRP group | None |
| Velev et al (2015)179 | Rabbit (tibia) | Calcium phosphate cement (CPC) | CPC+PRP | CPC alone | 4 weeks | None | None | Increased bone formation in the PRP group | None |
| Zhong et al (2014)192 | Dog (tibia) | Tricalcium phosphate (TCP) | TCP+PRP | TCP alone | 12 weeks | None | Increased bone formation in the PRP group | Increased bone formation in the PRP group | Ultimate strength higher in TCP+PRP group |
| Qi et al (2015)141 | Rat (femur) | Calcium phosphate particles (CPP) | CPP+PRP | CPP alone | 4 weeks | None | Increased bone formation in the PRP group | Increased bone formation in the PRP group | None |
| Yilmaz et al (2014)191 | Pig (tibia) | Tricalcium phosphate (TCP) | TCP+PRP | TCP alone | 12 weeks | None | None | Increased bone formation in the PRP group | None |
| Hakimi et al (2014)182 | Mini pig (tibia) | Calcium phosphate granules (CPG) | CPG+PRP+bone marrow concentrate (BMC) | CPG alone | 6 weeks | None | Increased bone formation in the CPG+PRP+BMC group | Increased bone formation in the CPG+PRP+BMC group | None |
| Chen et al (2016)176 | Rabbit (radius) | Calcium sulfate (CS) | CS+PRP PRP alone |
CS alone | 10 weeks | None | Increased bone formation in the CP+PRP group | Increased bone formation in the CP+PRP group | None |
| Bölükbaşı et al (2013)175 | Sheep (tibia) | Biphasic calcium phosphate (BCP) | BCP+PRF PRF alone |
Untreated | 6 weeks | None | Increased bone formation in the BCP+PRF group | None | None |
| Schneppendahl et al (2015)187 | Rabbit (tibia) | Autologous bone graft | Autograft+PRP | Autograft | 6 weeks | N/A | Increased bone formation in the Autograft+PRP group | Increased bone formation in the Autograft+PRP group | None |
| Batista et al (2011)194 | Rabbit (tibia) | Tricalcium phosphate (TCP) | TCP+PRP | TCP+bone marrow concentrate | 4 weeks | None | Similar bone formation in the TCP+PRP group on x-ray but increased bone formation in the TCP+PRP group on micro-CT | Increased bone formation in the TCP+PRP group | |
| Park et al (2016)200 | Dog (femur) | None | PRF | Untreated | 4 weeks | None | None | Increased bone formation in PRF group | None |
| Sindel et al (2017)202 | Rat (skull) | None | PRF | Untreated | 3 weeks | None | None | Increased bone formation in PRF group | None |
| Dulgeroglu et al73 (2017)195 | Rat (femur) | None | PRF | Untreated | 4 weeks | Histology | Increased bone formation in PRF group | Increased bone formation in PRF group | None |
| Akyildiz et al (2018)193 | Rat (tibia) | None | PRF | Untreated | 6 weeks | Radiology and histology | Reduced bone formation in PRF group | Reduced bone formation in PRF group | None |
| Raafat et al (2018)201 | Rat (tibia) | None | PRF Simvastatin+PRF |
Untreated | 8 weeks | None | Increased bone formation in simvastatin+PRF group | Increased bone formation in simvastatin+PRF group | None |
| Lucarelli et al (2005)199 | Sheep (metatarsal) | Allograft | Allograft+bone-marrow-derived stromal stem cells (BmMSCs)+PRP+collagen | Allograft alone | 16 weeks | Histology | Increased bone formation in PRP group | Increased bone formation in PRP group | Higher extraction torque values in the PRP group |