Ch 4 PRP Flashcards
What is regenerative medicine?
RRR, goals (3)
interdisciplinary field of research and clinical therapy
focused on repair, replacement, or regeneration of cells, tissues, and organs
goals
restoring structure and function to the affected tissue or organ
reduction of inflammation and pain
improved healing of injured tissues
inc stem cell, Gene therapy, PRP
when analysed in the context of RCT, a clear positive effect for platelet-rich plasma becomes less apparent
case series without control groups, involve relatively low sample sizes, are underpowered, and exhibit enrollment bias
what is PRP
how much higher?
plasma fraction of
autologous blood with a concentration of platelets and growth factors/cytokines that is higher than baseline
At least 3-5 times higher
How does PRP act?
proliferation of MSC and fibroblasts
TGF-B > collagen type 1 production in tendons
Platelet role
promote (6)
hemostasis and wound healing
alpha granules > growth factors and cytokines
promote:
1.cell recruitment
2. cell migration,
3. cell proliferation,
4. angiogenesis
5. osteogenesis
6. recruit, stimulate, and provide a scaffold for stem cells
what cytokines and GF platelets have? (9)
platelet-derived growth factor (PDGF)
transforming growth factor (TGF-a), (TGF-b)
vascular endothelial growth factor (VEGF),
fibroblastic growth factor (bFGF),
epidermal growth factor (EGF)
connective tissue growth factor (CTGF),
insulin-like growth factor (IGF),
hepatocyte growth factor (HGF),
keratinocyte growth factor
(KGF)
what does PDGF do?
Mitogenic for mesenchymal cells and osteoblasts.
Stimulates chemotaxis pf WBC and fibroblasts
TGF-a, TGF-b
Stimulates undifferentiated mesenchymal cell proliferation.
Regulates endothelial, fibroblastic, and osteoblastic mitogenesis
Regulates collagen synthesis and collagenase secretion
TNF
Regulates monocyte migration, fibroblast proliferation,
macrophage activation
angiogenesis.
VEGF
Stimulates angiogenesis and mitogenesis for endothelial cells
FGF
Promotes growth and differentiation of chondrocytes and osteoblasts.
Mitogenic for mesenchymal cells,
IGF - 1
Chemotactic for fibroblasts and promotes protein synthesis
What else does PRP contain?PRP for wound healing
Clotting factors
Plasma proteins
antibacterial and fungicidal effects
membrane glycoproteins (influence inflammation)
800 unique proteins
Depending on prep > leukocyte- and platelet-rich plasma (L-PRP)
reasons fo variability in product? (6)
Individual donor variability
concurrent drug therapy
coagulation state
venipuncture technique
processing and isolation method
degree of platelet activation
studies have demonstrated marked variability
major challenge for PRP therapy
Carr 2016
Canine platelet-rich plasma systems: a prospective analysis.
Front Vet Sci.
Franklin 2015
Characteristics of canine platelet-rich plasma prepared with five commercially available systems.
Am J Vet Res.
OA
recent studies > PRP seems to be beneficial in dogs with OA
alpha granules > modulate inflammation and promote tissue healing
treated with a single injection of
PRP may have improvement in validated client survey results and subjective pain
and gait scores as well as objective kinetic gait
ihibit nuclear factor κB and decrease expression of cyclooxygenase-2, which are both important mediators of the inflammatory component of osteoarthritis.
wound healing
4 functions
people and dogs
promotes wound epithelialization,
reduces scar formation,
exhibits antimicrobial activity,
stimulates angiogenesis
moderate (2–3x) and high (4–6x) platelet concentrations are
beneficial for soft tissue and bone healing
still no consensus on the ideal platelet concentration for specific applications.
Osteoarthritis
Alves 2021
bilateral hip OA vs placebo
dogs with moderate and severe osteoarthritis
that were treated with 2 intra-articular injections of PRP 14 days apart found that
the PRP group had significantly better clinical metrology instruments than saline control group at multiple time points, some up to 180 days
wound healing
Angelou 2022 – topical PRP in experimentally created wounds in cats
- PRP → improved wound perfusion, quicker wound granulation, contraction and healing
vs control
CCL
Venator 2020
– PRP with uni- or bilateral stifle OA (non-stabilized CrCL stifle)
- increased symmetry indices from w4-12
- PVF and VI increased in treated limb but not statistically significnat
Literature review details and supports the application
of platelet-rich plasma products in canine medicine,
particularly as an orthobiologic agent for osteoarthritis
Brittany J. Carr 2024
OA
- shown to reduce pain and lameness associated with naturally occurring OA of various joints with intraarticular injections in prospective controlled clinical trials
- CCL dz > PRP alone or in combination with mesenchymal stem cells showeshowed a positive effect on
lameness and preservation of tissue mechanics and histology compared to controls.
- product compositions differed, the total study populations were small, experinmental vs clincal
Soft tissue injury
- Intratendinous PRP application,
particularly when leukocyte rich, can induce transient inflammation that may subsequently stimulate cell recruitment and proliferation to promote tissue
regeneration
- dependent on the site of injury, product used, and stage of disease, adding to the complexity and uncertainty of optimal patient selection
- canine surgical tendon repair has been shown to increase neovascularization and fibrocyte proliferation, supporting its use in tendon healing
- weak support for PRP-based product use in supraspinatus tendinopathy
in dogs.
- only a paucity of research directly assesses PRP’s effects on healing the CCL
- no evidence that PRP can effectively repair a degenerative canine CCL or prevent progression toward rupture of the affected ligament
soft tissue injury
still limited evidence available
Tendons and ligaments > poor self-repair capability.
Histologic > tendinosis is not an acute inflammatory condition, failure of normal tendon repair mechanism
shown to have a beneficial immunomodulatory effect on tenocytes to stimulate the secretion of angiogenic proteins in injured tenocytes
How is PRP osteopromotive?
Chondropromotive?
augment bone grafts
Stimulates the production of osteoclast-like cells
Platelets contain a number of grwoth factors to initiate bone healing - PDGF, TGF-B, VEGF, BMP
Chondro:
- Significant increased in chondrocyte proliferation and celular accumulation of GAGs and collagen tpe 2 in porcine chondrocytes with platelet lysate
List 2 contraindications of PRP treatment
Thrombocytopaenia
Coagulation defects
in the human
literature it has been proposed that platelet concentration greater than 6x baseline (or >1800 x 103 platelets/m) may be detrimental and lead to cellular apoptosis
Most recent studies agree that it is best to reduce RBC in PRP as they have been
shown to have a deleterious inflammatory effect.
limitations (3)
Deficits in basic science research,
inherent variability in “product” due to discrepancies between donors and preparation systems
inability to completely assess individual platelet-rich plasma samples prior to clinical application
Effect of intra-articular platelet-rich plasma or hyaluronic acid on limb function recovery in dogs with TPLO for cranial cruciate ligament rupture:
a randomised controlled trial
F. Volz 2024
62 dogs
prospective, randomised, double-blind, controlled study
they received either a single intra-articular injection of platelet-rich plasma, hyaluronic acid or no injection intraoperatively.
Limb function was primarily assessed by measuring the ground reaction forces.
No additive effect on faster recovery was demonstrated with the additional intra-articular injection of platelet-rich plasma or hyaluronic acid
(lack of benefit observed up to 6 months postoperatively)
soft tissue and bone repair is a temporally complex process
> ideal platelet number, growth factor concentration, and delivery timeline necessary to successfully treat specific diseases remain unknown
efficacy
- some studies report single injections whereas others have utilized a series of injections.
- Due to differences in preparation systems and dosing regimens, difficult to make comparisons and draw conclusions regarding the ideal dosing schedule
