Temporal growth factor release from platelet‐rich plasma, trehalose lyophilized platelets, and bone marrow aspirate and their effect on tendon and ligament gene expression

Abstract

Platelet-rich plasma (PRP) has generated substantial interest for tendon and ligament regeneration because of the high concentrations of growth factors in platelet a-granules. This study compared the temporal release of growth factors from bone marrow aspirate (BMA), PRP, and lyophilized platelet product (PP), and measured their effects on tendon and ligament gene expression. Blood and BMA were collected and processed to yield PRP and plasma. Flexor digitorum superficialis tendon (FDS) and suspensory ligament (SL) explants were cultured in 10% plasma in DMEM (control), BMA, PRP, or PP. TGF-b1 and PDGF-BB concentrations were determined at 0, 24, and 96 h of culture using ELISA. Quantitative RT-PCR for collagen types I and III (COL1A1, COL3A1), cartilage oligomeric matrix protein (COMP), decorin, and matrix metalloproteinases-3 and 13 (MMP-3, MMP-13) was performed. TGF-b1 and PDGF-BB concentrations were highest in PRP and PP. Growth factor quantity was unchanged in BMA, increased in PRP, and decreased in PP over 4 days. TGF-b1 and platelet concentrations were positively correlated. Lyophilized PP and PRP resulted in increased COL1A1:COL3A1 ratio, increased COMP, and decreased MMP-13 expression. BMA resulted in decreased COMP and increased MMP-3 and MMP-13 gene expression. Platelet concentration was positively correlated with COL1A1, ratio of COL1A1:COL3A1, and COMP, and negatively correlated with COL3A1, MMP-13, and MMP-3. White blood cell concentration was positively correlated with COL3A1, MMP3, and MMP13, and negatively correlated with a ratio of COL1A1:COL3A1, COMP, and decorin. These findings support further in vivo investigation of PRP and PP for treatment of tendonitis and desmitis. ß

Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds

“…While some of the collagen measured is likely degraded from the original scaffold, all scaffolds were identical with slow degradation kinetics based on the crosslinking density used. 59 Additionally, since soluble factor treatment can affect matrix metalloproteinase activity, 60 it is possible that this also contributed to the soluble collagen readout, although this needs to be investigated further. Again, the PDGF-BB and IGF-1 groups supported a significantly increased collagen synthesis compared to the negative control, while the other three groups promoted minimal changes from the baseline.…”

Human articular chondrocytes on macroporous gelatin microcarriers form structurally stable constructs with blood-derived biological gluesin vitro

“…This beneficial effect may be contributed to the release of growth factors from platelet alpha granules upon activation, as a number of these growth factors are known chondrogenic stimulants, such as for example TGF-ß and IGF and [Yoo et al, 1998, Landesberg et al, 2000, Jakob et al, 2001, Blunk et al, 2002, Weibrich et al, 2002, Gaissmaier et al, 2005, Akeda et al, 2006. This instant burst of growth factors may however have been too short-lived to have an effect on the end result following the long-term three-dimensional in vitro culture investigated here [McCarrel and Fortier, 2009], where the citrated plasma was evaluated in a glue capacity. The use of platelet rich plasma supernatant as additive in the cell culture medium presents an alternative to ensure a continuous supply of these signals in vitro [Gaissmaier et al, 2005, Akeda et al, 2006.…”

The state of cartilage regeneration: current and future technologies

“…As the cellular component includes platelets and MSCs, growth factors secreted include PDGF, TGF-B, and VEGF [34,35]. Using the Harvest system (Harvest Technologies, Plymouth, Massachusetts), significant increases in platelet, leukocytes, and red Using this system in an equine model, treatment of an osteochondral defect with microfracture and BM-MSCs demonstrated increased defect fill and type II collagen compared to microfracture alone [36••].…”