Next-generation resorbable polymer scaffolds with surface-precipitated calcium phosphate coatings

Kim, Jinku; Magno, Maria Hanshella R.; Ortiz, Ophir; McBride, Sean; Darr, Adnan; Kohn, Joachim; Hollinger, Jeffrey O.

doi:10.1093/rb/rbu019

Cited by 14 publications

(12 citation statements)

References 29 publications

(35 reference statements)

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“…Other contributing factors may be the polymer chemistry and pore structure. A series of studies in vitro and in the rabbit calvarial CSD model demonstrated that E1001(1k) has a high degree of bone biocompatibility and osteoconductivity [9,23,26]. These studies also described the bimodal pore structure of E1001(1k) scaffolds.…”

Section: Discussionmentioning

confidence: 96%

“…After conducting a series of bone regeneration studies in the rabbit calvarial CSD model [9,24,26], we selected the goat calvarial model as a clinically relevant large animal model. Goats have metabolic and bone remodeling rates similar to those of humans [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

“…A recently published paper, using the goat calvarial CSD model for the evaluation of a bone regeneration scaffold [30], showed that poly(lactideco-glycolide) (PLGA)/tricalcium phosphate (TCP) scaffolds prepared by low-temperature rapid prototyping failed to regenerate bone at 12 and 24 weeks without the addition of rhBMP-2. In addition, reviewing the existing bone regeneration studies using rats [31], rabbits [9,26], goats [30,32], sheep [33], and dogs [34,35], no bone scaffold has demonstrated the ability to completely bridge a critical size defect without the addition of osteogenic growth factors. Most of these studies showed minimal bone formation limited to the margin of the defect, similar to the results we observed for defects treated with E1001(1k)/β-TCP and chronOS.…”

Section: Discussionmentioning

confidence: 99%

“…E1001(1k) is a member of a large combinatorial library of tyrosine-derived polycarbonates (TyrPC) whose properties can be tailored for different tissue engineering applications by small variations in the polymer composition [24,25]. E1001(1k) scaffolds have demonstrated favorable pore size, porosity, and interconnectivity for permitting in vivo bone and vascular ingrowth in rabbit calvarial defect models [9,24,26].…”

Section: Introductionmentioning

confidence: 99%

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Hybrid Bone Scaffold Induces Bone Bridging in Goat Calvarial Critical Size Defects Without Growth Factor Augmentation

Chen

Ortiz

Pastino

et al. 2020

Regen. Eng. Transl. Med.

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In the present study, a series of four different scaffolds were comparatively evaluated in a goat calvarial critical size defect model. Such studies are only rarely reported in the literature. In our work, E1001(1k), a member of a large combinational library of tyrosine-derived polycarbonates (TyrPC), was used to prepare two calcium phosphate hybrid, biodegradable bone scaffolds. In one formulation, the widely used β-tricalcium phosphate (β-TCP) was incorporated into the polymer scaffold. In the second formulation, a coating of dicalcium phosphate dihydrate (DCPD, also known as brushite) was used as the mineral phase. These scaffolds were evaluated for bone regeneration in goat calvarial 20-mm critical size defects (CSD) after 16 weeks. Results were compared with chronOS (a clinically used product) and E1001(1k)/β-TCP scaffolds, augmented with 400 μg of recombinant human bone morphogenetic protein-2 (rhBMP-2). Microcomputed tomography (micro-CT) and histomorphometry were used to assess bone regeneration within the defects. Histomorphometry showed that rhBMP-2-augmented E1001(1k)/β-TCP scaffolds completely healed the defect in all animals within 16 weeks. Among the hybrid scaffolds that were not augmented with rhBMP-2, the degree of bone regeneration within the defect area was low for the clinically used chronOS, which is a poly(lactide co-εcaprolactone)/β-TCP hybrid scaffold. Similar results were obtained for E1001(1k)/β-TCP scaffolds, indicating that replacing poly(lactide co-ε-caprolactone) with E1001(1k) does not improve bone regeneration is this model. However, a statistically significant improvement of bone regeneration was observed for E1001(1k)/DCPD scaffolds. These scaffolds resulted in significant levels of bone regeneration in all animals and in complete bridging of the defect in three of six tests. This is the first report of a synthetic bone scaffold being able to heal a critical size calvarial defect in a large animal model without the addition of exogenous growth factors. Lay SummaryReconstruction of large bone defects is a significant clinical problem. The overwhelming majority of all research results are obtained in vitro or in small animal models (mouse, rat, rabbit) that cannot predict the clinical outcomes in humans. We address this problem by conducting our studies in a goat calvarial critical size defect model, which is widely regarded as predictive of human outcomes. Among the three rhBMP-2-free scaffolds tested, only one specific formulation, E1001(1k)/DCPD, resulted in massive bone ingrowth into the center of the defect in all animals and in complete bridging of the defect 50% of the animals. This is the first time, a synthetic bone scaffold was able to heal a critical size calvarial defect in a large animal model without the addition of biological growth factors. Given the high cost of biologically enhanced bone grafts and the regulatory complexities of their FDA market clearance, the development of E1001(1k)/DCPD hybrid scaffolds addresses a significant clinical need.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hybrid Bone Scaffold Induces Bone Bridging in Goat Calvarial Critical Size Defects Without Growth Factor Augmentation

Chen

Ortiz

Pastino

et al. 2020

Regen. Eng. Transl. Med.

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show abstract

“…In this first study, we have been able to demonstrate how the early two steps in osteoclast activity, namely the formation of the “actin ring” and the formation of the “ruffled border”, can occur by using the CaP-free tyrosine-derived polycarbonate (E1001(1k)). E1001(1k) has shown promise in vivo where the polymer-bone interface exhibited morphological signs of integration and remodeling [ 15 , 16 ]. We investigated the ability of E1001(1k) to support osteoclast recruitment and activation in vitro , alone or in blends with RGD polypeptide, collagen type I and β-TCP (beta-tricalcium phosphate), factors involved in steps 1, 2 and 3 respectively.…”

Section: Introductionmentioning

confidence: 99%

“Ruffled border” formation on a CaP-free substrate: A first step towards osteoclast-recruiting bone-grafts materials able to re-establish bone turn-over

Merolli

Fung

Murthy

et al. 2018

J Mater Sci: Mater Med

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Osteoclasts are large multinucleated giant cells that actively resorb bone during the physiological bone turnover (BTO), which is the continuous cycle of bone resorption (by osteoclasts) followed by new bone formation (by osteoblasts). Osteoclasts secrete chemotactic signals to recruit cells for regeneration of vasculature and bone. We hypothesize that a biomaterial that attracts osteoclasts and re-establishes BTO will induce a better healing response than currently used bone graft materials. While the majority of bone regeneration efforts have focused on maximizing bone deposition, the novelty in this approach is the focus on stimulating osteoclastic resorption as the starter for BTO and its concurrent new vascularized bone formation. A biodegradable tyrosine-derived polycarbonate, E1001(1k), was chosen as the polymer base due to its ability to support bone regeneration in vivo. The polymer was functionalized with a RGD peptide or collagen I, or blended with β-tricalcium phosphate. Osteoclast attachment and early stages of active resorption were observed on all substrates. The transparency of E1001(1k) in combination with high resolution confocal imaging enabled visualization of morphological features of osteoclast activation such as the formation of the “actin ring” and the “ruffled border”, which previously required destructive forms of imaging such as transmission electron microscopy. The significance of these results is twofold: (1) E1001(1k) is suitable for osteoclast attachment and supports osteoclast maturation, making it a base polymer that can be further modified to optimize stimulation of BTO and (2) the transparency of this polymer makes it a suitable analytical tool for studying osteoclast behavior.

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Bone morphogenetic protein‐2 immobilization on porous PCL‐BCP‐Col composite scaffolds for bone tissue engineering

Song

Amirian

Linh

et al. 2017

J of Applied Polymer Sci

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The objective of this study was to develop novel porous composite scaffolds for bone tissue engineering through surface modification of polycaprolactone-biphasic calcium phosphate-based composites (PCL-BCP). PCL-BCP composites were first fabricated with salt-leaching method followed by aminolysis. Layer by layer (LBL) technique was then used to immobilize collagen (Col) and bone morphogenetic protein (BMP-2) on PCL-BCP scaffolds to develop PCL-BCP-Col-BMP-2 composite scaffold. The morphology of the composite was examined by scanning electron microscopy (SEM). The efficiency of grafting of Col and BMP-2 on composite scaffold was measured by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Both XPS and FTIR confirmed that Col and BMP-2 were successfully immobilized into PCL-BCP composites. MC3TC3-E1 preosteoblasts cells were cultivated on composites to determine the effect of Col and BMP-2 immobilization on cell viability and proliferation. PCL-BCP-Col-BMP-2 showed more cell attachment, cell viability, and proliferation bone factors compared to PCL-BCP-Col composites. In addition, in vivo bone formation study using rat models showed that PCL-BCP-Col-BMP-2 composites had better bone formation than PCL-BCP-Col scaffold in critical size defect with 4 weeks of duration. These results suggest that PCL-BCP-Col-BMP-2 composites can enhance bone regeneration in critical size defect in a rat model with 4 weeks of duration.

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Next-generation resorbable polymer scaffolds with surface-precipitated calcium phosphate coatings

Cited by 14 publications

References 29 publications

Hybrid Bone Scaffold Induces Bone Bridging in Goat Calvarial Critical Size Defects Without Growth Factor Augmentation

Hybrid Bone Scaffold Induces Bone Bridging in Goat Calvarial Critical Size Defects Without Growth Factor Augmentation

“Ruffled border” formation on a CaP-free substrate: A first step towards osteoclast-recruiting bone-grafts materials able to re-establish bone turn-over

Bone morphogenetic protein‐2 immobilization on porous PCL‐BCP‐Col composite scaffolds for bone tissue engineering

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