Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

Hafeman, Andrea E.; Li, Bing; Yoshii, Toshitaka; Zienkiewicz, Katarzyna J.; Davidson, Jeffrey M.; Guelcher, Scott A.

doi:10.1007/s11095-008-9618-z

Cited by 114 publications

(133 citation statements)

References 45 publications

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“…The half-life of the polymer ranged from 10.5 to 11.5 weeks, which is substantially longer compared with the allograft but slightly shorter than t 1/2 = 14 weeks reported in vitro. 37 Similar to observations from in vitro studies, the degradation profile of the poly(ester urethane) is consistent with an autocatalytic mechanism 37 and does not follow the first-order kinetics associated with ester hydrolysis. 38 Local delivery of rhBMP-2 (Fig.…”

Section: Histology and Histomorphometrysupporting

confidence: 68%

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

Dumas

Prieto

Zienkiewicz

et al. 2014

Tissue Engineering Part A

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There is a compelling clinical need for bone grafts with initial bone-like mechanical properties that actively remodel for repair of weight-bearing bone defects, such as fractures of the tibial plateau and vertebrae. However, there is a paucity of studies investigating remodeling of weight-bearing bone grafts in preclinical models, and consequently there is limited understanding of the mechanisms by which these grafts remodel in vivo. In this study, we investigated the effects of the rates of new bone formation, matrix resorption, and polymer degradation on healing of settable weight-bearing polyurethane/allograft composites in a rabbit femoral condyle defect model. The grafts induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6 to 12 weeks. However, the mismatch between the rates of autocatalytic polymer degradation and zero-order (independent of time) new bone formation resulted in incomplete healing in the interior of the composite. Augmentation of the grafts with recombinant human bone morphogenetic protein-2 not only increased the rate of new bone formation, but also altered the degradation mechanism of the polymer to approximate a zero-order process. The consequent matching of the rates of new bone formation and polymer degradation resulted in more extensive healing at later time points in all regions of the graft. These observations underscore the importance of balancing the rates of new bone formation and degradation to promote healing of settable weight-bearing bone grafts that maintain bone-like strength, while actively remodeling.

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Section: Histology and Histomorphometrysupporting

confidence: 68%

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

Dumas

Prieto

Zienkiewicz

et al. 2014

Tissue Engineering Part A

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“…To test the effects of D-AAs in vivo, a 1:1:1 mixture (by weight) of D-Met:D-Phe:D-Pro was mixed by hand with the reactive polymer before injection. Lowviscosity grafts were prepared by mixing lysine triisocyanate-poly(ethylene glycol) prepolymer (index 115 [21]), polyester triol, the mixture of powdered D-AAs (0 or 200 mmol/L based on the volume of the defect), triethylenediamine, and ceramic particles (45 weight % for low viscosity and 40 weight % for low viscosity + D-AAs).…”

Section: Biofilm Inhibition and Dispersal Assaysmentioning

confidence: 99%

d-amino Acid Inhibits Biofilm but not New Bone Formation in an Ovine Model

Harmata

Sánchez

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Infectious complications of musculoskeletal trauma are an important factor contributing to patient morbidity. Biofilm-dispersive bone grafts augmented with D-amino acids (D-AAs) prevent biofilm formation in vitro and in vivo, but the effects of D-AAs on osteocompatibility and new bone formation have not been investigated.Questions/purposes We asked: (1) Do D-AAs hinder osteoblast and osteoclast differentiation in vitro? (2) Does local delivery of D-AAs from low-viscosity bone grafts inhibit new bone formation in a large-animal model? Methods Methicillin-sensitive Staphylococcus aureus and methicillin-resistant S aureus clinical isolates, mouse bone marrow stromal cells, and osteoclast precursor cells were treated with an equal mass (1:1:1) mixture of D-Pro:DMet:D-Phe. The effects of the D-AA dose on biofilm inhibition (n = 4), biofilm dispersion (n = 4), and bone marrow stromal cell proliferation (n = 3) were quantitatively measured by crystal violet staining. Osteoblast differentiation was quantitatively assessed by alkaline phosphatase staining, von Kossa staining, and quantitative reverse transcription for the osteogenic factors a1Col1 and Ocn (n = 3). Osteoclast differentiation was quantitatively measured by tartrate-resistant acid phosphatase staining (n = 3). Bone grafts augmented with 0 or 200 mmol/L D-AAs were injected in ovine femoral condyle defects in four sheep. New bone formation was evaluated by lCT and histology 4 months later. An a priori power analysis indicated that a sample size of four would detect a 7.5% difference of bone volume/total volume between groups assuming a mean and SD of 30% and 5%, respectively, with a power of 80% and an alpha level of 0.05 using a two-tailed t-test between the means of two independent samples. Results Bone marrow stromal cell proliferation, osteoblast differentiation, and osteoclast differentiation were inhibited at D-AAs concentrations of 27 mmol/L or greater in a dose-responsive manner in vitro (p \ 0.05). InThe institution of one or more of the authors (SAG, FE, JCW) has received, during the study period, funding from the Orthopaedic Extremity Trauma Research Program (SAG and JCW), the National Institute of Arthritis and Musculoskeletal Diseases (SAG, JCW, and FE), Medtronic, Inc (SAG); Oak Ridge Institute (AJH); and the National Institutes of Health (SAG). One of the authors certifies that he (SAG), or a member of his or her immediate family, has or may receive payments or benefits, during the study period, an amount less than USD 10,000, from Medtronic Spine and Biologics (Memphis, TN, USA).

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“…The tests were carried out on a Thermal Instruments dynamic mechanical analyser (Q800 TA). The frequency dependent storage modulus was also evaluated with a 5-10 Hz frequency sweep at a constant temperature 37°C with 1.5% strain and 0.01 N static force (similar parameters were used by [32]. The storage modulus (E`) value was recorded as a function of frequency.…”

Section: Dynamic Mechanical Analysismentioning

confidence: 99%

Architecture and Properties of PUR/Calcite Composite Scaffolds for Bone Tissue Engineering

Dulińska-Molak¹,

Jaroszewicz²,

Kurzydłowski³

2014

J Bioprocess Biotech

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Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

Cited by 114 publications

References 45 publications

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

d-amino Acid Inhibits Biofilm but not New Bone Formation in an Ovine Model

Architecture and Properties of PUR/Calcite Composite Scaffolds for Bone Tissue Engineering

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