fumarates and tricalcium-phosphate

Reconstruction of critical size defects in the load-bearing area has long been a challenge in orthopaedics. In the past, we have demonstrated the feasibility of using a biodegradable load-sharing scaffold fabricated from poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) loaded with bone morphogenetic protein-2 (BMP-2) to successfully induce healing in those defects. However, there is limited osteoconduction observed with the PPF/TCP scaffold itself. For this reason, 13-93 bioactive glass scaffolds with local BMP-2 delivery were investigated in this study for inducing segmental defect repairs in a load-bearing region. Furthermore, a recent review on BMP-2 revealed greater risks in radiculitis, ectopic bone formation, osteolysis and poor global outcome in association with the use of BMP-2 for spinal fusion. We also evaluated the potential side effects of locally delivered BMP-2 on the structures of adjacent bones. Therefore, cylindrical 13-93 glass scaffolds were fabricated by indirect selective laser sintering with side holes on the cylinder filled with dicalcium phosphate dehydrate as a BMP-2 carrier. The scaffolds were implanted into critical size defects created in rat femurs with and without 10 μg of BMP-2. The x-ray and micro-CT results showed that a bridging callus was found as soon as three weeks and progressed gradually in the BMP group while minimal bone formation was observed in the control group. Degradation of the scaffolds was noted in both groups. Stiffness, peak load and energy to break of the BMP group were all higher than the control group. There was no statistical difference in bone mineral density, bone area and bone mineral content in the tibiae and contralateral femurs of the control and BMP groups. In conclusion, a 13-93 bioactive glass scaffold with local BMP-2 delivery has been demonstrated for its potential application in treating large bone defects.

Topics: Animals; Biomechanical Phenomena; Bone Cements; Bone Development; Bone Morphogenetic Protein 2; Calcium Phosphates; Femur; Fracture Fixation; Fumarates; Glass; Male; Microscopy, Electron, Scanning; Polypropylenes; Rats; Rats, Long-Evans; Spectroscopy, Fourier Transform Infrared; Surface Properties; Tissue Scaffolds; X-Ray Diffraction; X-Ray Microtomography

This study investigated the in vitro degradation of poly(propylene fumarate)/beta-tricalcium phosphate (PPF/beta-TCP) scaffolds in pH 7.4 phosphate-buffered saline at 37 degrees C. Scaffold design consisted of three layers: two solid layers about a central layer of porous PPF foam. Solid PPF with molecular weights of 810 and 1450 Da was crosslinked under UV light. PPF foam was prepared by a photocrosslinking, porogen-leaching method with an initial porogen content of 80 wt % and two sizes, 150-300 and 300-500 microm. Comparison of initial and residual weights demonstrated a 14.3 +/- 2.0% loss of mass at 3 weeks and a 16.6 +/- 1.8% loss of mass at 6 weeks. Observed pH values for all constructs remained stable (7.15-7.40) throughout the 3 to 6 weeks. Scanning electron micrographs of these scaffolds revealed some loss of foam material between 3 and 6 weeks; however, foam microarchitecture was intact. Solid PPF fracture toughness was tested for high and low molecular weight PPF, 0.376 +/- 0.004 and 0.134 +/- 0.015 MPa(m)1/2, respectively. These values are roughly one magnitude less than human cortical bone.

Topics: Biomechanical Phenomena; Bone Cements; Calcium Phosphates; Fumarates; Hydrogen-Ion Concentration; Microscopy, Electron, Scanning; Polypropylenes; Porosity; Tissue Engineering

Poly (Propylene Fumarate) (PPF), a novel, bulk erosion, biodegradable polymer, has been shown to have osteoconductive effects in vivo when used as a bone regeneration scaffold (Peter, S. J., Suggs, L. J., Yaszemski, M. J., Engel, P. S., and Mikos, A. J., 1999, J. Biomater. Sci. Polym. Ed., 10, pp. 363-373). The material properties of the polymer allow it to be injected into irregularly shaped voids in vivo and provide mechanical stability as well as function as a bone regeneration scaffold. We fabricated a series of biomaterial composites, comprised of varying quantities of PPF, NaCl and beta-tricalcium phosphate (beta-TCP), into the shape of right circular cylinders and tested the mechanical properties in four-point bending and compression. The mean modulus of elasticity in compression (Ec) was 1204.2 MPa (SD 32.2) and the mean modulus of elasticity in bending (Eb) was 1274.7 MPa (SD 125.7). All of the moduli were on the order of magnitude of trabecular bone. Changing the level of NaCl from 20 to 40 percent, by mass, did not decrease Ec and Eb significantly, but did decrease bending and compressive strength significantly. Increasing the beta-TCP from 0.25 g/g PPF to 0.5 g/g PPF increased all of the measured mechanical properties of PPF/NVP composites. These results indicate that this biodegradable polymer composite is an attractive candidate for use as a replacement scaffold for trabecular bone.

Topics: Absorbable Implants; Biomechanical Phenomena; Bone Regeneration; Calcium Phosphates; Compressive Strength; Culture Techniques; Elasticity; Fumarates; Humans; Materials Testing; Polypropylenes; Porosity; Regression Analysis

This study was designed to investigate the in vivo biodegration and biocompatibility of a poly(propylene fumarate) (PPF)-based orthopedic biomaterial. The effects of varying the PPF to N-vinyl pyrrolidinone ratio and PPF to beta-tricalcium phosphate content were studied. The composite mechanical properties and local tissue interactions were analyzed over 12 weeks. An initial increase in both compressive modulus and strength was seen for composite formulations that incorporated beta-tricalcium phosphate. The samples incorporating a higher PPF to N-vinyl pyrrolidinone ratio reached a maximal compressive strength of 7.7 MPa and a maximal compressive modulus of 191.4 MPa at 3 weeks. The lower PPF to N-vinyl pyrrolidinone ratio samples gained a maximum compressive strength of 7.5 MPa initially and a compressive modulus of 134.0 MPa at 1 week. At 6 weeks, all samples for formulations incorporating beta-tricalcium phosphate crumbled upon removal and were not mechanically tested. Samples that did not incorporate beta-tricalcium phosphate were very weak and insufficient for bone replacement at the 4-day time point and beyond. Tissue interactions resulted in a mild inflammatory response at the initial time points and mature fibrous encapsulation by 12 weeks.

Topics: Animals; Biocompatible Materials; Biodegradation, Environmental; Bone Regeneration; Calcium Phosphates; Composite Resins; Fumarates; Guided Tissue Regeneration; Inflammation; Male; Materials Testing; Polypropylenes; Rats; Rats, Inbred Lew