Design of Biodegradable Hydrogel for the Local and Sustained Delivery of Angiogenic Plasmid DNA

Kong, Hyun Joon; Kim, Eun Seok; Huang, Yann-Chang; Mooney, David J.

doi:10.1007/s11095-007-9526-7

Cited by 92 publications

(81 citation statements)

References 35 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The highest dose in our study was three times less than the dose previously reported in studies investigating the effects of PDGF-BB on soft tissue healing [16,20]. A recent study investigating growth factor expression profile after rotator cuff surgery in a rabbit model noted that PDGF-BB expression was most prominent during Days 7 through 14 postsurgery [18].…”

Section: Discussioncontrasting

confidence: 52%

“…In a rat patellar tendon-defect model, a single bolus injection of 1 lg PDGF into the wound site led to greater cellular proliferation at 2 weeks for early supplementation and increased peak load, cross-sectional area, and pyridinoline content for later supplementation [5]. In contrast, in a rabbit model of partial anterior cruciate ligament (ACL) laceration treated with 20 lg of PDGF in fibrin sealant applied to the injured ligament at the time of surgery, there was significantly decreased maximum load and stiffness of the femur-ACL-tibia complex, by 56% and 41%, respectively, compared with no treatment to the injured ACL [20]. After ACL reconstruction with flexor tendon autograft in sheep, 60 lg of PDGF mixed with poly(D, L-lactide), coated on sutures at the time of surgery, increased failure load at early time points compared with the control group [31].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Kovacevic

Gulotta

Liang

et al. 2015

Clinical Orthopaedics &Amp; Related Research

View full text Add to dashboard Cite

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

show abstract

Section: Discussioncontrasting

confidence: 52%

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

View full text Add to dashboard Cite

show abstract

“…Other authors report higher optimal doses of pDNA at 40μg/10 6 cells 236 or pDNA polymer complex of 50 μg/10 6 cells 93 or inject 25 μg in the hind limb of mice 85 .…”

Section: Results and Discussion Dna Dose Determinationmentioning

confidence: 98%

“…The weight of the porous constructs measured 60% +/-7% (n =6) of the solid grafts, resulting in average porosity of 40%. Cell viability of the printed constructs assessed by live/dead assay after 7 and 14 day of culture showed respectively for day 7 and 14: 90% (CI [85][86][87][88][89][90][91][92][93][94][95][96] and 79% (CI [73][74][75][76][77][78][79][80][81][82][83][84][85][86] for the porous control, 91% (CI 87-96) and 80% (CI for the porous with pBMP-2, and 85% (CI 81-89) and 69% (CI 59-78) for the solid constructs (Fig. 4).…”

Section: D Printingmentioning

confidence: 99%

Non-viral gene therapy for bone tissue engineering

Wegman

2013

Biotechnology and Genetic Engineering Reviews

View full text Add to dashboard Cite

“…Naked DNA has been successfully incorporated inside hydrogels composed of collagen (18), pluronic-hyaluronic acid (19), dimethacrylated poly(lactic acid)-bpoly(ethylene glycol)-b-poly(lactic acid) triblock copolymers (20), alginate (21), oligo(polyethylene glycol) fumarate (22), and engineered silk elastin (23). Although naked DNA has shown gene expression and ability to guide regeneration in vivo (18,24), limitations with low gene transfer efficiency and rapid diffusion of the DNA from the hydrogel scaffold motivated the use of DNA nanoparticles instead of naked DNA.…”

Section: Introductionmentioning

confidence: 99%

Surface- and Hydrogel-Mediated Delivery of Nucleic Acid Nanoparticles

Pannier

Segura

2012

Nanotechnology for Nucleic Acid Delivery

View full text Add to dashboard Cite

Gene expression within a cell population can be directly altered through gene delivery approaches. Traditionally for nonviral delivery, plasmids or siRNA molecules, encoding or targeting the gene of interest, are packaged within nanoparticles. These nanoparticles are then delivered to the media surrounding cells seeded onto tissue culture plastic; this technique is termed bolus delivery. Although bolus delivery is widely utilized to screen for efficient delivery vehicles and to study gene function in vitro, this delivery strategy may not result in efficient gene transfer for all cell types or may not identify those delivery vehicles that will be efficient in vivo. Furthermore, bolus delivery cannot be used in applications where patterning of gene expression is needed. In this chapter, we describe methods that incorporate material surfaces (i.e., surface-mediated delivery) or hydrogel scaffolds (i.e., hydrogel-mediated delivery) to efficiently deliver genes. This chapter includes protocols for surface-mediated DNA delivery focusing on the simplest and most effective methods, which include nonspecific immobilization of DNA complexes (both polymer and lipid vectors) onto serum-coated cell culture polystyrene and self-assembled monolayers of alkanethiols on gold. Also, protocols for the encapsulation of DNA/cationic polymer nanoparticles into hydrogel scaffolds are described, including methods for the encapsulation of low amounts of DNA (<0.2 μg/μL) and high amounts of DNA (>0.2 μg/μL) since incorporation of high amounts of DNA poses significant challenges due to aggregation.

show abstract

Design of Biodegradable Hydrogel for the Local and Sustained Delivery of Angiogenic Plasmid DNA

Abstract: This strategy to control the hydrogel degradation rate may be useful in regulating the delivery of a broad array of macromolecular drugs, and subsequently improve their therapeutic efficacy.

Cited by 92 publications

References 35 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

Non-viral gene therapy for bone tissue engineering

Surface- and Hydrogel-Mediated Delivery of Nucleic Acid Nanoparticles

Contact Info

Product

Resources

About