Previous studies support resorbable biocomposites made of poly(l-lactic acid) (PLA) and β-tricalcium phosphate (TCP) produced by supercritical gas foaming as a suitable scaffold for tissue engineering. The present study was undertaken to demonstrate the biocompatibility and osteoconductive properties of such a scaffold in a large animal cancellous bone model. The biocomposite (PLA/TCP) was compared with a currently used β-TCP bone substitute (ChronOS™, Dr. Robert Mathys Foundation), representing a positive control, and empty defects, representing a negative control. Ten defects were created in sheep cancellous bone, three in the distal femur and two in the proximal tibia of each hind limb, with diameters of 5mm and depths of 15mm. New bone in-growth (osteoconductivity) and biocompatibility were evaluated using microcomputed tomography and histology at 2, 4 and 12months after surgery. The in vivo study was validated by the positive control (good bone formation with ChronOS™) and the negative control (no healing with the empty defect). A major finding of this study was incorporation of the biocomposite in bone after 12months. Bone in-growth was observed in the biocomposite scaffold, including its central part. Despite initial fibrous tissue formation observed at 2 and 4months, but not at 12months, this initial fibrous tissue does not preclude long-term application of the biocomposite, as demonstrated by its osteointegration after 12months, as well as the absence of chronic or long-term inflammation at this time point.

Bone tissue engineering aims at developing scaffolds, or porous structures, as supports for cell migration, proliferation and differentiation, in order to favor bone healing. L-poly lactic acid (PLA) foams, which were reinforced or not with β-tricalcium phosphate (β-TCP) particles, were obtained by melt-extrusion followed by supercritical gas foaming. After tailoring their morphology and mechanical properties to those of natural cancellous bone, their in vitro biocompatibility was tested. Promising results led to in vivo studies, using calvarial critical size defect in rats and bone filling of tibial and femoral defects in sheep

Reference EPFL-CONF-179731View record in Web of Science Record created on 2012-07-04, modified on 2017-05-10

Phosphate glass (PG) of the composition 0.46(CaO)-0.04(Na(2)O)-0.5(P(2)O(5)) was used as filler in poly-L-lactic acid (PLA) foams developed as degradable scaffolds for bone tissue engineering. The effect of PG on PLA was assessed both in bulk and porous composite foams. Composites with various PG content (0, 5, 10, and 20 wt %) were melt-extruded, and either compression-molded or foamed through supercritical CO(2). Dynamic mechanical analysis on the bulk composites showed that incorporating 20 wt % PG resulted in a significant increase in storage modulus. Aging studies in deionized water in terms of weight loss, pH change, and ion release inferred that the degradation was due to PG dissolution, and dependent on the amount of glass in the composites. Foaming was only possible for composites containing 5 and 10 wt % PG, as an increase in PG increased the foam densities; however, the level of porosity was maintained above 75%. PLA-T(g) in the foams was higher than those obtained for the bulk. Compressive moduli showed no significant reinforcement with glass incorporation in either expansion direction, indicating no anisotropy. Biocompatibility showed that proliferation of human fetal bone cells was more rapid for PLA compared to PLA-PG foams. However, the proliferation rate of PLA-PG foams were similar to those obtained for foams of PLA with either hydroxyapatite or beta-tricalcium phosphate.

Fetal bone cells were shown to have an interesting potential for therapeutic use in bone tissue engineering due to their rapid growth rate and their ability to differentiate into mature ostcoblasts in vitro. We describe hereafter their capability to promote bone repair in vivo when combined with porous scaffolds based on poly(L-lactic acid) (PLA) obtained by supercritical gas foaming and reinforced with 5 wt.% beta-tricalcium phosphate (TCP).Bone regeneration was assessed by radiography and histology after implantation of PLA/TCP scaffolds alone, seeded with primary fetal bone cells, or coated with demineralized bone matrix. Craniotomy critical size defects and drill defects in the femoral condyle in rats were employed. In the cranial defects, polymer degradation and cortical bone regeneration were studied up to 12 months postoperatively. Complete bone ingrowth was observed after implantation of PLA/TCP constructs seeded with human fetal bone cells. Further tests were conducted in the trabecular neighborhood of femoral condyles, where scaffolds seeded with fetal bone cells also promoted bone repair.We present here a promising approach for bone tissue engineering using human primary fetal bone cells in combination with porous PLA/TCP structures. Fetal bone cells could be selected regarding osteogenic and immune-related properties, along with their rapid growth, ease of cell banking and associated safety. (c) 2007 Elsevier Inc. All rights reserved.

The aim of this investigation was to test the biocompatibility of three-dimensional bioresorbable foams made of poly(L-lactic acid) (PLA), alone or filled with hydroxyapatite (HA) or beta-tricalcium phosphate (beta-TCP), with human primary osteoblasts, using a direct contact method. Porous constructs were processed by supercritical gas foaming, after a melt-extrusion of ceramic/polymer mixture. Three neat polymer foams, with pore sizes of 170, 310, and 600 microm, and two composite foams, PLA/5 wt% HA and PLA/5 wt% beta-TCP, were examined over a 4-week culture period. The targeted application is the bone tissue-engineering field. For this purpose, human fetal and adult bone cells were chosen because of their highly osteogenic potential. The association of fetal bone cells and composite scaffold should lead to in vitro bone formation. The polymer and composite foams supported adhesion and intense proliferation of seeded cells, as revealed by scanning electron microscopy. Cell differentiation toward osteoblasts was demonstrated by alkaline phosphatase (ALP) enzymatic activity, gamma-carboxylated Gla-osteocalcin production, and the onset of mineralization. The addition of HA or beta-TCP resulted in higher ALP enzymatic activity for fetal bone cells and a stronger production of Gla-osteocalcin for adult bone cells.

tissue engineering techniques based on the delivery of cells to the defect through the use of 3-D scaffold materials, are currently investigated. As part of the bone tissue engineering project developed in Lausanne, two bioresorbable polymers (PLA, Boerhinger Ingelheim and PLGA 85/15, Pürac Biochem) were used to create a structure that could guide bone formation by facilitating cell migration, proliferation and differentiation. The 3-D foam morphology could be modified varying the processing conditions. In addition, the possibility of integrating ceramic materials into the polymer matrix might improve its mechanical properties. Hydroxyapatite (HA) and β-tricalciumphosphate (β-TCP) were chosen for this purpose due to their capacity to stimulate natural bone repair and for their stability2. For this project, we choose to use fetal bone cells that, in comparison to adult cells, show a higher proliferation capacity, are less differentiated into mature osteoblasts and present less immunological compatibility issues if used as tissue gafts3. The