Injectable, compression-resistant polymer/ceramic composite bone grafts promote lateral ridge augmentation without protective mesh in a canine model.

OBJECTIVE: The objective of this study was to test the hypothesis that a compression-resistant bone graft augmented with recombinant human morphogenetic protein-2 (rhBMP-2) will promote lateral ridge augmentation without the use of protective mesh in a canine model. MATERIALS & METHODS: Compression-resistant (CR) bone grafts were evaluated in a canine model of lateral ridge augmentation. Bilateral, right trapezoidal prism-shaped defects (13-14 mm long × 8-9 mm wide × 3-4 mm deep at the base) in 13 hounds (two defects per hound) were treated with one of four groups: (i) absorbable collagen sponge + 400 µg rhBMP-2/ml (ACS, clinical control) protected by titanium mesh, (ii) CR without rhBMP-2 (CR, negative control), (iii) CR + 200 µg rhBMP-2 (CR-L), or (iv) CR + 400 µg rhBMP-2 (CR-H). All animals were euthanized after 16 weeks. Ridge height and width and new bone formation were assessed by µCT, histology, and histomorphometry. The release kinetics of rhBMP-2 from CR bone grafts in vitro and in vivo in a femoral condyle defect model in rabbits was also evaluated. RESULTS: All four bone grafts promoted new bone formation (11-31.6 volume%) in the lateral ridge defects. For CR grafts, ridge height and width increased in a dose-responsive manner with increasing rhBMP-2 concentration. Ridge height and width measured for CR-H without the use of protective mesh was comparable to that measured for ACS with a protective mesh. CONCLUSIONS: At the same dose of rhBMP-2, an injectable, compression-resistant bone graft resulted in a comparable volume of new bone formation with the clinical control (ACS). These findings highlight the potential of compression-resistant bone grafts without the use of protective mesh for lateral ridge augmentation.

Remodeling of injectable, low-viscosity polymer/ceramic bone grafts in a sheep femoral defect model.

Ceramic/polymer composite bone grafts offer the potential advantage of combining the osteoconductivity of ceramic component with the ductility of polymeric component, resulting in a graft that meets many of the desired properties for bone void fillers (BVF). However, the relative contributions of the polymer and ceramic components to bone healing are not well understood. In this study, we compared remodeling of low-viscosity (LV) ceramic/poly(ester urethane) composites to a ceramic BVF control in a sheep femoral condyle plug defect model. LV composites incorporating either ceramic (LV/CM) or allograft bone (LV/A) particles were evaluated. We hypothesized that LV/CM composites which have the advantageous handling properties of injectability, flowability, and settability would heal comparably to the CM control, which was evaluated for up to 2 years to study its long-term degradation properties. Remodeling of LV/CM was comparable to that observed for the CM control, as evidenced by new bone formation on the surface of the ceramic particles. At early time points (4 months), LV/CM composites healed similar to the ceramic clinical control, while LV/A components showed more variable healing due to osteoclast-mediated resorption of the allograft particles. At longer time points (12-15 months), healing of LV/CM composites was more variable due to the nonhomogeneous distribution and lower concentration of the ceramic particles compared to the ceramic clinical control. Resorption of the ceramic particles was almost complete at 2 years. This study highlights the importance of optimizing the loading and distribution of ceramic particles in polymer/ceramic composites to maximize bone healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2333-2343, 2017.

Effects of Recombinant Human Bone Morphogenetic Protein-2 Dose and Ceramic Composition on New Bone Formation and Space Maintenance in a Canine Mandibular Ridge Saddle Defect Model.

Treatment of mandibular osseous defects is a significant clinical challenge. Maintenance of the height and width of the mandibular ridge is essential for placement of dental implants and restoration of normal dentition. While guided bone regeneration using protective membranes is an effective strategy for maintaining the anatomic contour of the ridge and promoting new bone formation, complications have been reported, including wound failure, seroma, and graft exposure leading to infection. In this study, we investigated injectable low-viscosity (LV) polyurethane/ceramic composites augmented with 100 µg/mL (low) or 400 µg/mL (high) recombinant human bone morphogenetic protein-2 (rhBMP-2) as space-maintaining bone grafts in a canine mandibular ridge saddle defect model. LV grafts were injected as a reactive paste that set in 5-10 min to form a solid porous composite with bulk modulus exceeding 1 MPa. We hypothesized that compression-resistant LV grafts would enhance new bone formation and maintain the anatomic contour of the mandibular ridge without the use of protective membranes. At the rhBMP-2 dose recommended for the absorbable collagen sponge carrier in dogs (400 µg/mL), LV grafts maintained the width and height of the host mandibular ridge and supported new bone formation, while at suboptimal (100 µg/mL) doses, the anatomic contour of the ridge was not maintained. These findings indicate that compression-resistant bone grafts with bulk moduli exceeding 1 MPa and rhBMP-2 doses comparable to that recommended for the collagen sponge carrier support new bone formation and maintain ridge height and width in mandibular ridge defects without protective membranes.

Development and characterization of a porous poly(methyl methacrylate) scaffold with controllable modulus and permeability.

Functional restoration following extensive bone injury often requires bone grafting. The primary source of graft material is either autograft or allograft. The use of both material sources is well established, however both suffer limitations. In response, grafting alternatives are being investigated. This manuscript presents the development of a highly porous scaffold with controllable elastic modulus and permeability for use in tissue grafting and tissue engineering applications that is manufactured from FDA approved poly(methyl methacrylate) (PMMA). Fifteen protocol variations based on the commonly used porogen leaching technique for porous scaffold fabrication were employed to control scaffold pore size, pore interconnectivity, and structural strength. Scaffolds were tested for porosity, permeability, elastic modulus, cell culture compatibility, and fatigue tested in compression. Scaffold permeability ranged from 6.6 x 10(-16) m(2) to 1.4 x 10(-10) m(2), and elastic modulus was adjustable between 14 and 322 MPa; data similar to cancellous bone specimens from a variety of species and anatomic locations. Fatigue evaluations revealed 65% strength maintenance after 80,000 loading cycles, and in vitro culture with marrow-derived stromal cells show no cytotoxic effects based on Live/Dead assay. The scaffolds detailed herein will help broaden the spectrum of available orthopaedic tissue scaffolds for research in this evolving field. , 2007.

Effect of porosity on the fluid flow characteristics and mechanical properties of tantalum scaffolds.

In many cases of traumatic bone injury, bone grafting is required. The primary source of graft material is either autograft or allograft. The use of both material sources are well established, however, both suffer limitations. In response, many grafting alternatives are being explored. This article specifically focuses on a porous tantalum metal grafting material (Trabecular Metaltrade mark) marketed by Zimmer. Twenty-one cylindrical scaffolds were manufactured (66% to 88% porous) and tested for porosity, intrinsic permeability, tangent elastic modulus, and for yield stress and strain behavior. Scaffold microstructural geometries were also measured. Tantalum scaffold intrinsic permeability ranged from 2.1 x 10(-10) to 4.8 x 10(-10) m(2) and tangent elastic modulus ranged from 373 MPa to 2.2 GPa. Both intrinsic permeability and tangent elastic modulus closely matched porosity-matched cancellous bone specimens from a variety of species and anatomic locations. Scaffold yield stress ranged from 4 to 12.7 MPa and was comparable to bovine and human cancellous bone. Yield strain was unaffected by scaffold porosity (average = 0.010 mm/mm). Understanding these structure-function relationships will help complete the basic physical characterization of this new material and will aid in the development of realistic mathematical models, ultimately enhancing future implant designs utilizing this material.

Comparison of in vitro mineralization by murine embryonic and adult stem cells cultured in an osteogenic medium.

Nearly half a million bone-grafting procedures occurred in the United States in the year 2000. Tissue-engineered bone substitutes may mitigate difficulties associated with current grafting options. Embryonic stem cells (ESCs) could be a potential cell source for bone substitutes; however, direct comparisons between ESCs and other cell sources are lacking. Here we provide a direct, long-term, in vitro comparison of mineralization processes in adult, marrow-derived, mesenchymal stem cells (MSCs) and ESCs from the 129/Sv+c/+p mouse strain. MSCs were observed to grow at a slower rate than ESCs. MSCs expressed seven times more alkaline phosphatase (AP) per cell than did ESCs and immediately showed type I collagen and osteocalcin production. ESCs also produced type I collagen and osteocalcin, but production was delayed. Mineral deposition by ESCs was nearly 50 times higher than by MSCs. Spectroscopic analysis showed the calcium-to-phosphorus ratio (Ca:P) of the ESC mineral (1.26:1) to be significantly higher than that of the MSCs (0.29:1), but still 25% lower than hydroxyapatite (1.67:1). Addition of basic fibroblast growth factor significantly inhibited AP expression, mineral deposition, and Ca:P ratios in MSCs and had little effect on ESCs. These functional characteristics may assist with cell selection for purposes of bone tissue engineering.

A device for long term, in vitro loading of three-dimensional natural and engineered tissues.

In vitro studies of mechanical loads applied to three-dimensional tissue constructs are important to the design and production of functional, engineered bone tissue. This study reports the development and characterization of a mechanical device capable of subjecting a three-dimensional section of natural or engineered tissue to precise, reproducible four-point bending deformations over a range of programmable magnitudes and frequencies. To test the biological and mechanical capabilities of the system, a low-cycle (360 cycles/day), medium-range strain (2500 microstrain), long-term (16 day) loading regime was applied to rat bone marrow stromal cells cultured in porous DL-polylactic acid scaffolds. Cells proliferated in culture throughout the experiment, and with time showed an increase in alkaline phosphatase expression per cell. Calcium and phosphorus mineral deposition by the unloaded group was significantly greater (p<0.05) than that deposited by the loaded group. The molar ratio of calcium to phosphorus in the unloaded group (0.94:1) was significantly greater (p<0.05) than that of the loaded group (0.41:1). The loading device presented here is a tool which can be used to help elucidate contributions of mechanical loading/fatigue on biodegradable materials, as well as study the effects of mechanical loading on natural or engineered tissues in vitro.