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      Achieving Interconnected Pore Architecture in Injectable PolyHIPEs for Bone Tissue Engineering

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          Abstract

          Template polymerization of a high internal phase emulsion (polyHIPE) is a relatively new method to produce tunable high-porosity scaffolds for tissue regeneration. This study focuses on the development of biodegradable injectable polyHIPEs with interconnected porosity that have the potential to fill bone defects and enhance healing. Our laboratory previously fabricated biodegradable polyHIPEs that cure in situ upon injection; however, these scaffolds possessed a closed-pore morphology, which could limit bone ingrowth. To address this issue, HIPEs were fabricated with a radical initiator dissolved in the organic phase rather than the aqueous phase of the emulsion. Organic-phase initiation resulted in macromer densification forces that facilitated pore opening during cure. Compressive modulus and strength of the polyHIPEs were found to increase over 2 weeks to 43±12 MPa and 3±0.2 MPa, respectively, properties comparable to cancellous bone. The viscosity of the HIPE before cure (11.0±2.3 Pa·s) allowed for injection and filling of the bone defect, retention at the defect site during cure under water, and microscale integration of the graft with the bone. Precuring the materials before injection allowed for tuning of the work and set times. Furthermore, storage of the HIPEs before cure for 1 week at 4°C had a negligible effect on pore architecture after injection and cure. These findings indicate the potential of these emulsions to be stored at reduced temperatures and thawed in the surgical suite before injection. Overall, this work highlights the potential of interconnected propylene fumarate dimethacrylate polyHIPEs as injectable scaffolds for bone tissue engineering.

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          Most cited references42

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          Potential of ceramic materials as permanently implantable skeletal prostheses.

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            Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study.

            Extensive bone loss is still a major problem in orthopedics. A number of different therapeutic approaches have been developed and proposed, but so far none have proven to be fully satisfactory. We used a new tissue engineering approach to treat four patients with large bone diaphysis defects and poor therapeutic alternatives. To obtain implantable three-dimensional (3D) living constructs, cells isolated from the patients' bone marrow stroma were expanded in culture and seeded onto porous hydroxyapatite (HA) ceramic scaffolds designed to match the bone deficit in terms of size and shape. During the surgical session, an Ilizarov apparatus or a monoaxial external fixator was positioned on the patient's affected limb and the ceramic cylinder seeded with cells was placed in the bone defect. Patients were evaluated at different postsurgery time intervals by conventional radiographs and computed tomography (CT) scans. In one patient, an angiographic evaluation was performed at 6.5 years follow-up. In this study we analyze the long-term outcome of these patients following therapy. No major complications occurred in the early or late postoperative periods, nor were major complaints reported by the patients. No signs of pain, swelling, or infection were observed at the implantation site. Complete fusion between the implant and the host bone occurred 5 to 7 months after surgery. In all patients at the last follow-up (6 to 7 years postsurgery in patients 1 to 3), a good integration of the implants was maintained. No late fractures in the implant zone were observed. The present study shows the long-term durability of bone regeneration achieved by a bone engineering approach. We consider the obtained results very promising and propose the use of culture-expanded osteoprogenitor cells in conjunction with porous bioceramics as a real and significant improvement in the repair of critical-sized long bone defects.
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              Pore size of porous hydroxyapatite as the cell-substratum controls BMP-induced osteogenesis.

              To elucidate the biochemical mechanism of osteogenesis, the effect of matrix geometry upon the osteogenesis induced by bone morphogenetic protein (BMP) was studied. A series of five porous hydroxyapatites with different pore sizes, 106-212, 212-300, 300-400, 400-500, and 500-600 microns, was prepared. A block (approximately 5 x 5 x 1 mm, 40.0 mg) of each hydroxyapatite ceramics was combined with 4 micrograms of recombinant human BMP-2 and implanted subcutaneously into the back skin of rat. Osteoinductive ability of each implant was estimated by quantifying osteocalcin content and alkaline phosphatase activity in the implant up to 4 wk after implantation. In the ceramics of 106-212 microns, the highest alkaline phosphatase activity was found 2 wk after implantation, and the highest osteocalcin content 4 wk after implantation, consistent with the results observed with particulate porous hydroxyapatite [Kuboki, Y. et al. (1995) Connect. Tissue Res. 32: 219-226]. Comparison of the alkaline phosphatase activities at 2 wk and the osteocalcin contents at 4 wk after implantation revealed that the highest amount of bone was produced in the ceramics implants with pore size of 300-400 microns. In the ceramics with smaller or larger pore sizes, the amount of bone formation decreased as the pore size deviated from 300-400 microns. The results indicated that the optimal pore size for attachment, differentiation and growth of osteoblasts and vascularization is approximately 300-400 microns. This study using chemically identical but geometrically different cell substrata is the first demonstration that a matrix with a certain geometrical size is most favorable for cell differentiation.
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                Author and article information

                Journal
                Tissue Engineering Part A
                Tissue Engineering Part A
                Mary Ann Liebert Inc
                1937-3341
                1937-335X
                March 2014
                March 2014
                : 20
                : 5-6
                : 1103-1112
                Article
                10.1089/ten.tea.2013.0319
                3938937
                24124758
                b537e1cb-6290-4fa1-aa6e-404e9f253aa6
                © 2014
                History

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