Spatio–temporal VEGF and PDGF Delivery Patterns Blood Vessel Formation and Maturation

Chen, Ruth R.; Silva, Eduardo A.; Yuen, William W.; Mooney, David J.

doi:10.1007/s11095-006-9173-4

Cited by 359 publications

(273 citation statements)

References 24 publications

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“…Two strategies that hold promise for improving tendonbone healing include gene transfer of PDGF-BB into tenocytes that can then be delivered to the repair site [23,30] and the design of new biodegradable material carriers for local and sustained delivery of cytokines at the healing enthesis [6,7,21]. Further studies, in larger animal models, where the healing environment is slower, are needed to optimize the delivery of this potentially useful growth factor to possibly augment structural healing and reduce the retear rate after rotator cuff repair.…”

Section: Discussionmentioning

confidence: 99%

rhPDGF-BB Promotes Early Healing in a Rat Rotator Cuff Repair Model

Kovacevic

Gulotta

Liang

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Tendon-bone healing after rotator cuff repair occurs by fibrovascular scar tissue formation, which is weaker than a normal tendon-bone insertion site. Growth factors play a role in tissue formation and have the potential to augment soft tissue healing in the perioperative period. Questions/purposes Our study aim was to determine if rhPDGF-BB delivery on a collagen scaffold can improve tendon-to-bone healing after supraspinatus tendon repair compared with no growth factor in rats as measured by (1) gross observations; (2) histologic analysis; and (3) biomechanical testing. Methods Ninety-five male Sprague-Dawley rats underwent acute repair of the supraspinatus tendon. Rats were randomized into one of five groups: control (ie, repair only), scaffold only, and three different platelet-derived growth factor (PDGF) doses on the collagen scaffold. Animals were euthanized 5 days after surgery to assess cellular proliferation and angiogenesis. The remaining animals were analyzed at 4 weeks to assess repair site integrity by gross visualization, fibrocartilage formation with safranin-O staining, and collagen fiber organization with picrosirius red staining, and to determine the biomechanical properties (ie, load-to-failure testing) of the supraspinatus tendon-bone construct. Results The repaired supraspinatus tendon was in continuity with the bone in all animals. At 5 days, rhPDGF-BB delivery on a scaffold demonstrated a dose-dependent response in cellular proliferation and angiogenesis compared with the control and scaffold groups. At 28 days, with the numbers available, rhPDGF-BB had no effect on increasing fibrocartilage formation or improving collagen fiber maturity at the tendon-bone insertion site compared with controls. The control group had higher tensile loads to failure and stiffness (35.5 ± 8.8 N and 20.3 ± 4.5 N/mm) than all the groups receiving the scaffold, including the PDGF groups (scaffold: 27 ± 6.4 N, p = 0.021 and 13 ± 5.7 N/mm, p = 0.01; 30 lg/mL PDGF: 26.5 ± 7.5 N, p = 0.014 and 13.3 ± 3.2 N/mm, p = 0.01; 100 lg/mL PDGF: 25.7 ± 6

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Section: Discussionmentioning

confidence: 99%

rhPDGF-BB Promotes Early Healing in a Rat Rotator Cuff Repair Model

Kovacevic

Gulotta

Liang

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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“…Research has shown that this method significantly enhances tissue regeneration compared with the controlled release of single biological cues. [293][294][295] For example, one group recently reported enhanced pluripotent cellular differentiation, ALP activity, and matrix mineralization through sequential delivering BMP-2 and IGF-I through a novel layered biodegradable polymer scaffold. 222 Another group demonstrated enhanced osteogenic differentiation in vitro through sequential administration of BMP-2 and -7 via polymer degradation.…”

Section: Delivery Of Multiple Bioactive Moleculesmentioning

confidence: 99%

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Porter

Ruckh

Popat

2009

Biotechnology Progress

685

499

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Critical‐sized defects in bone, whether induced by primary tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold standard treatment for bone repair. The primary purpose of a tissue‐engineered scaffold is to use engineering principles to incite and promote the natural healing process of bone which does not occur in critical‐sized defects. A synthetic bone scaffold must be biocompatible, biodegradable to allow native tissue integration, and mimic the multidimensional hierarchical structure of native bone. In addition to being physically and chemically biomimetic, an ideal scaffold is capable of eluting bioactive molecules (e.g., BMPs, TGF‐βs, etc., to accelerate extracellular matrix production and tissue integration) or drugs (e.g., antibiotics, cisplatin, etc., to prevent undesired biological response such as sepsis or cancer recurrence) in a temporally and spatially controlled manner. Various biomaterials including ceramics, metals, polymers, and composites have been investigated for their potential as bone scaffold materials. However, due to their tunable physiochemical properties, biocompatibility, and controllable biodegradability, polymers have emerged as the principal material in bone tissue engineering. This article briefly reviews the physiological and anatomical characteristics of native bone, describes key technologies in mimicking the physical and chemical environment of bone using synthetic materials, and provides an overview of local drug delivery as it pertains to bone tissue engineering is included. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009

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“…Many recent strategies have concentrated on enhancing vessel stabilization in vitro, such as encapsulating different growth factors within the scaffold, or use of different mural cell types 22, 23, 24. In this study, we present application of oscillatory strain as a simple means of enhancing vessel stabilization and morphogenesis within engineered tissues.…”

Section: Discussionmentioning

confidence: 99%

Oscillatory Strain Promotes Vessel Stabilization and Alignment through Fibroblast YAP‐Mediated Mechanosensitivity

2018

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Endothelial cells form the interior layer of blood vessels and, as such, are constantly exposed to shear stress and mechanical strain. While the impact of shear stress on angiogenesis is widely studied, the role of mechanical strain is less understood. To this end, endothelial cells and fibroblasts are cocultured under oscillatory strain to create a vessel network. The two cell types show distinctly different sensitivities to the mechanical stimulation. The fibroblasts, sense the stress directly, and respond by increased alignment, proliferation, differentiation, and migration, facilitated by YAP translocation into the nucleus. In contrast, the endothelial cells form aligned vessels by tracking fibroblast alignment. YAP inhibition in constructs under mechanical strain results in vessel destruction whereas less damage is observed in the YAP‐inhibited static control. Moreover, the mechanical stimulation enhances vessel development and stabilization. Additionally, vessel orientation is preserved upon implantation into a mouse dorsal window chamber and promotes the invading host vessels to orient in the same manner. This study sheds light on the mechanisms by which mechanical strain affects the development of blood vessels within engineered tissues. This can be further utilized to engineer a more organized and stable vasculature suitable for transplantation of engineered grafts.

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Spatio–temporal VEGF and PDGF Delivery Patterns Blood Vessel Formation and Maturation

Abstract: Spatially localizing and temporally controlling growth factor presentation for angiogenesis can create spatially organized tissues.

Cited by 359 publications

References 24 publications

rhPDGF-BB Promotes Early Healing in a Rat Rotator Cuff Repair Model

rhPDGF-BB Promotes Early Healing in a Rat Rotator Cuff Repair Model

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Oscillatory Strain Promotes Vessel Stabilization and Alignment through Fibroblast YAP‐Mediated Mechanosensitivity

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