rhPDGF-BB Promotes Early Healing in a Rat Rotator Cuff Repair Model (original) (raw)
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Journal of Orthopaedic Research, 2012
The purpose of this study was to assess whether intra-tendon delivery of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) would improve Achilles tendon repair in a rat collagenase-induced tendinopathy model. Seven days following collagenase induction of tendinopathy, one of four intra-tendinous treatments was administered: (i) Vehicle control (sodium acetate buffer), (ii) 1.02 mg rhPDGF-BB, (iii) 10.2 mg rhPDGF-BB, or (iv) 102 mg rhPDGF-BB. Treated tendons were assessed for histopathological (e.g., proliferation, tendon thickness, collagen fiber density/orientation) and biomechanical (e.g., maximum load-to-failure and stiffness) outcomes. By 7 days post-treatment, there was a significant increase in cell proliferation with the 10.2 and 102 mg rhPDGF-BBtreated groups (p ¼ 0.049 and 0.015, respectively) and in thickness at the tendon midsubstance in the 10.2 mg of rhPDGF-BB group (p ¼ 0.005), compared to controls. All groups had equivalent outcomes by Day 21. There was a dose-dependent effect on the maximum load-to-failure, with no significant difference in the 1.02 and 102 mg rhPDGF-BB doses but the 10.2 mg rhPDGF-BB group had a significant increase in load-to-failure at 7 (p ¼ 0.003) and 21 days (p ¼ 0.019) compared to controls. The rhPDGF-BB treatment resulted in a dose-dependent, transient increase in cell proliferation and sustained improvement in biomechanical properties in a rat Achilles tendinopathy model, demonstrating the potential of rhPDGF-BB treatment in a tendinopathy application. Consequently, in this model, data suggest that rhPDGF-BB treatment is an effective therapy and thus, may be an option for clinical applications to treat tendinopathy.
The Journal of hand …, 2008
Purpose Surgically repaired intrasynovial tendons are at greatest risk of failure in the first 3 weeks after surgery. Attempts to improve the strength of repair by modifying rehabilitation parameters have not always been successful. Manipulation of the biological environment of the sutured tendon holds great promise for accelerating the repair process. The goals of this study were to examine (1) the range of conditions (eg, dosage, delivery system formulation, presence of cells) over which delivery of platelet-derived growth factor-BB (PDGF-BB) can be sustained from fibrin matrices using a heparin-binding delivery system (HBDS) and (2) the biological activity of the PDGF-BB released from this system on canine tendon fibroblasts in vitro.
Annals of biomedical …, 2010
Flexor tendon injuries are often encountered clinically and typically require surgical repair. Return of function after repair is limited due to adhesion formation, which leads to reduced tendon gliding, and due to a lack of repair site strength, which leads to repair site gap formation or rupture. The application of the growth factors basic fibroblastic growth factor (bFGF) and platelet derived growth factor BB (PDGF-BB) has been shown to have the potential to enhance tendon healing. The objectives of this study were to examine: (1) the conditions over which delivery of bFGF can be controlled from a heparin-binding delivery system (HBDS) and (2) the effect of bFGF and PDGF-BB released from this system on tendon fibroblast proliferation and matrix gene expression in vitro over a 10-day interval. Delivery of bFGF was controlled using a HBDS. Fibrin matrices containing the HBDS retained bFGF better than did matrices lacking the delivery system over the 10-day period studied. Delivery of bFGF and PDGF-BB using the HBDS stimulated tendon fibroblast proliferation and promoted changes in the expression of matrix genes related to tendon gliding, strength, and remodeling. Both growth factors may be effective in enhancing tendon healing in vivo.
Improved tendon healing using bFGF, BMP-12 and TGFβ1 in a rat model
Several growth factors (GFs) are expressed as tendons heal, but it remains unknown whether their combined application enhances the healing process. This matter was addressed by applying a combination of basic fibroblast growth factor (bFGF), bone morphogenetic protein 12 (BMP-12) and transforming growth factor beta 1 (TGFβ 1 ) in a rat Achilles tendon transection model. GFs were applied in one of the three following ways: i) direct application of all three factors at the time of surgery; ii) sequential, tiered percutaneous injection of individual factors immediately after surgery, 48 h and 96 h later; iii) load of all three factors onto a collagen sponge implanted at the time of surgery. After 1, 2, 4 and 8 weeks, healing was assessed based on tendon length and thickness, mechanical strength, stiffness and histology. Best results were achieved when GFs were loaded onto a collagen sponge -with a rapid increase in mechanical strength (load to failure, 71.2 N vs. 7.7 N in controls), consistent tendon length over time (9.9 mm vs. 16.2 mm in controls) and faster tendon remodelling, as measured by histology -followed by tiered injection therapy over 96 h.
Journal of Orthopaedic …
Despite advances in surgical technique, rotator cuff repairs are plagued by a high rate of failure. This failure rate is in part due to poor tendon-to-bone healing; rather than regeneration of a fibrocartilaginous attachment, the repair is filled with disorganized fibrovascular (scar) tissue. Transforming growth factor beta 3 (TGF-b3) has been implicated in fetal development and scarless fetal healing and, thus, exogenous addition of TGF-b3 may enhance tendon-to-bone healing. We hypothesized that: TGF-b3 could be released in a controlled manner using a heparin/fibrin-based delivery system (HBDS); and delivery of TGF-b3 at the healing tendon-to-bone insertion would lead to improvements in biomechanical properties compared to untreated controls. After demonstrating that the release kinetics of TGF-b3 could be controlled using a HBDS in vitro, matrices were incorporated at the repaired supraspinatus tendon-to-bone insertions of rats. Animals were sacrificed at 14-56 days. Repaired insertions were assessed using histology (for inflammation, vascularity, and cell proliferation) and biomechanics (for structural and mechanical properties). TGF-b3 treatment in vivo accelerated the healing process, with increases in inflammation, cellularity, vascularity, and cell proliferation at the early timepoints. Moreover, sustained delivery of TGF-b3 to the healing tendon-to-bone insertion led to significant improvements in structural properties at 28 days and in material properties at 56 days compared to controls. We concluded that TGF-b3 delivered at a sustained rate using a HBDS enhanced tendon-to-bone healing in a rat model. ß
Arthroscopy: The Journal of Arthroscopic & Related Surgery, 2010
Purpose: The purpose of this study was to determine whether suture could be coated with recombinant human platelet-derived growth factor BB (rhPDGF-BB) and whether the coated suture would improve histologic scores and biomechanical strength of sheep rotator cuff repairs. Methods: FiberWire sutures (Arthrex, Naples, FL) were dip coated in a collagen-rhPDGF-BB solution. Coating was confirmed by use of enzyme-linked immunosorbent assay. Rotator cuff tears were created in 18 sheep. The tendons were wrapped in Gortex (Gore Medical, Flagstaff, AZ) and allowed to scar for 2 weeks. Tendons were then repaired to bone by use of standard anchors loaded with either rhPDGF-BB-coated sutures or uncoated sutures. Gross examination, histologic analysis, and biomechanical testing were performed 6 weeks after repair. Results: Enzyme-linked immunosorbent assay confirmed successful loading of the growth factor onto the sutures. Gross examination showed well-healed tendon-to-bone interfaces in both rhPDGF-BB-augmented repairs and controls. Histologic analysis using a semiquantitative rating scale showed improved tendon-to-bone healing in the rhPDGF-BB-augmented repairs. There was no significant difference in the ultimate load to failure of rhPDGF-BB-augmented rotator cuff repairs compared with standard suture repairs at 6 weeks after repair. Conclusions: We were able to coat No. 2 FiberWire with rhPDGF-BB. At short-term follow-up, rhPDGF-BB-coated sutures enhanced histologic scores of sheep rotator cuff repairs; however, ultimate load to failure was equivalent to standard suture repairs. Clinical Relevance: rhPDGF-BB-coated sutures seem to produce a more histologically normal tendon insertion.
Enhanced flexor tendon healing through controlled delivery of PDGF‐BB
Journal of …, 2009
A fibrin/heparin-based delivery system was used to provide controlled delivery of PDGF-BB in an animal model of intrasynovial flexor tendon repair. We hypothesized that PDGF-BB, administered in this manner, would stimulate cell proliferation and matrix remodeling, leading to improvements in the sutured tendon's functional and structural properties. Fifty-six flexor digitorum profundus tendons were injured and repaired in 28 dogs. Three groups were compared: 1) controlled delivery of PDGF-BB using a fibrin/heparin-based delivery system, 2) delivery system carrier control, and 3) repair only control. The operated forelimbs were treated with controlled passive motion rehabilitation. The animals were euthanized at 7, 14, and 42 days, at which time the tendons were assessed using histologic (hyaluronic acid content, cellularity, and inflammation), biochemical (total DNA and reducible collagen crosslink levels), and biomechanical (gliding and tensile properties) assays. We found that cell activity (as determined by total DNA, collagen crosslink analyses, and hyaluronic acid content) was accelerated due to PDGF-BB at 14 days. Proximal interphalangeal joint rotation and tendon excursion (i.e., tendon gliding properties) were significantly higher for the PDGF-BB treated tendons compared to the repair alone tendons at 42 days. Improvements in tensile properties were not achieved, possibly due to sub-optimal release kinetics or other factors. In conclusion, PDGF-BB treatment consistently improved the functional but not the structural properties of sutured intrasynovial tendons through 42 days following repair.
Journal of Orthopaedic Research, 2005
Blood platelets become activated and aggregate at the site of vessel injury. Upon activation by thrombin, platelets release storage pools of proteins and growth factors (GFs), including those involved in tissue repair. Our goal was to evaluate the potential beneficial effect of proteins released from platelet-rich clots on tendon healing. PDGF, TGF-P-I, IGF-I, HGF, VEGF and EGF were measured in human platelet-poor plasma (PPP) and in the releasates collected from either platelet-poor or platelet-rich clots prepared in vitro. We then studied the effects of the releasates on human tendon cells in culture. Releasates from both platelet-rich and platelet-poor clots stimulated tendon cell proliferation, in contrast to un-clotted PPP. The mitogenic activity of the supernatants was not decreased by the thrombin inhibitor, hirudin. Cultured tendon cells synthesise VEGF and HGF in the presence of PPP-clots and PRP-clot releasates, thus the synthesised amount was significantly higher with supernatants from platelet-rich clots than supernatants from a platelet-poor clot zyxwvutsr @ < 0.05). These results suggest that administering autologous platelet-rich clots may be beneficial to the treatment of tendon injuries by inducing cell proliferation and promoting the synthesis of angiogenic factors during the healing process. zyxwvutsr