可注射聚富马酸丙二醇酯/β-磷酸三钙骨水泥的体外生物活性及其降解性

BACKGROUND: Poly(propylene fumarate) (PPF) can crosslink at room temperature, and β-tricalcium phosphate (β-TCP) has good biocompatibility, but PPF/β-TCP composite bone cement has not yet been systematically studied. OBJECTIVE: To prepare PPF/β-TCP composite bone cement and to explore its in vitro bioactivity and degradability. METHODS: β-TCP and PPF were respectively synthesized by liquid-phase precipitation and a two-step method, and PPF/β-TCP composite bone cement was prepared through mixing PPF with β-TCP. The    in vitro bioactivity of PPF/β-TCP was compared with the commercial poly(methyl methacrylate) (PMMA) through the ability of forming hydroxyapatite after immersed in simulated body fluid for 7 days. The in vitro degradability of PPF/β-TCP was studied via investigating the transformation of pH values, water uptake and mass loss, compressive strength and morphology at each time point. RESULTS AND CONCLUSION: There were hydroxyapatites formed on the PPF/β-TCP material, but none on the commercial PMMA material. The pH values of the PPF/β-TCP were stable in PBS for 63 days, indicating its degradation is moderate; the mass loss was up to 13.5% after 84 days. Scanning electron microscope displayed the degraded PPF/β-TCP surface, and its compressive strength was decreased gradually, which good for the integrity and sustainability of mechanical properties during degradation. These results suggest that PPF/β-TCP bone cement holds mineralization and degradability in vitro.     

Marrow stromal osteoblast function on a poly(propylene fumarate)/beta-tricalcium phosphate biodegradable orthopaedic composite

The objective of this study was to assess the osteoconductivity of a poly(propylene fumarate)/beta-tricalcium phosphate (PPF/beta-TCP) composite in vitro. We examined whether primary rat marrow stromal cells would attach, proliferate, and express differentiated osteoblastic function when seeded on PPF/beta-TCP substrates. Attachment studies showed that a confluent monolayer of cells had adhered to the substrates within an 8 h time frame for marrow stromal cells seeded at confluent numbers. Proliferation and differentiated function of the cells were then investigated for a period of 4 weeks for an initial seeding density of 42,000 cells/cm2. Rapid proliferation during the first 24 h as determined by 3H-thymidine incorporation was mirrored by an initial rapid increase in total cell number by DNA assay. A lower proliferation rate and a gradual increase in cell number persisted for the remainder of the study, resulting in a final cell number of 128,000 cells/cm2. Differentiated cell function was assessed by measuring alkaline phosphatase (ALP) activity and osteocalcin (OC) production throughout the time course. Both markers of osteoblastic differentiation increased significantly over a 4-week period. By day 28, cells grown on PPF/beta-TCP reached a maximal ALP activity of 11 (+/- 1) x 10(-7) micromol/min/cell, while the OC production reached 40 (+/- 1) x 10(-6) ng/cell. These data show that a PPF/beta-TCP composite exhibits in vitro osteoconductivity similar to or better than that of control tissue culture polystyrene.     

In vitro degradation and fracture toughness of multilayered porous poly(propylene fumarate)/beta-tricalcium phosphate scaffolds

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.     

Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate)

The ideal biomaterial for the repair of bone defects is expected to have good mechanical properties, be fabricated easily into a desired shape, support cell attachment, allow controlled release of bioactive factors to induce bone formation, and biodegrade into nontoxic products to permit natural bone formation and remodeling. The synthetic polymer poly(propylene fumarate) (PPF) holds great promise as such a biomaterial. In previous work we developed poly(DL-lactic-co-glycolic acid) (PLGA) and PPF microspheres for the controlled delivery of bioactive molecules. This study presents an approach to incorporate these microspheres into an injectable, porous PPF scaffold. Model drug Texas red dextran (TRD) was encapsulated into biodegradable PLGA and PPF microspheres at 2 microg/mg microsphere. Five porous composite formulations were fabricated via a gas foaming technique by combining the injectable PPF paste with the PLGA or PPF microspheres at 100 or 250 mg microsphere per composite formulation, or a control aqueous TRD solution (200 microg per composite). All scaffolds had an interconnected pore network with an average porosity of 64.8 +/- 3.6%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy and confocal microscopy. The composite scaffolds exhibited a sustained release of the model drug for at least 28 days and had minimal burst release during the initial phase of release, as compared to drug release from microspheres alone. The compressive moduli of the scaffolds were between 2.4 and 26.2 MPa after fabrication, and between 14.9 and 62.8 MPa after 28 days in PBS. The scaffolds containing PPF microspheres exhibited a significantly higher initial compressive modulus than those containing PLGA microspheres. Increasing the amount of microspheres in the composites was found to significantly decrease the initial compressive modulus. The novel injectable PPF-based microsphere/scaffold composites developed in this study are promising to serve as vehicles for controlled drug delivery for bone tissue engineering.     

Photocrosslinking characteristics and mechanical properties of diethyl fumarate/poly(propylene fumarate) biomaterials

The development of tissue engineered materials for the treatment of large bone defects would provide attractive alternatives to the autografts, allografts, non-degradable polymers, ceramics, and metals that are currently used in clinical settings. To this end, poly(propylene fumarate) (PPF), a viscous polyester synthesized from diethyl fumarate (DEF), has been studied for use as an engineered bone graft. We have investigated the photocrosslinking of PPF dissolved in its precursor, DEF, using the photoinitiator bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide (BAPO) and low levels of ultraviolet light exposure. A three factor, 2 x 2 x 4 factorial design was developed, studying the effects of PPF number average molecular weight, BAPO initiator content, and DEF content upon photocrosslinking characteristics and mechanical properties. Uncured DEF/PPF solution viscosity fell over three orders of magnitude as DEF content was increased from 0% to 75%. The exothermic photocrosslinking reaction released low levels of heat, with no more than 160J/g released from any formulation tested. As a result, the maximum photocrosslinking temperature remained below 47 degrees C for all samples. Both sol fraction and swelling degree generally increased with increasing DEF content. Compressive mechanical properties were within the range of trabecular bone, with the strongest samples possessing an elastic modulus of 195.3 +/- 17.5 MPa and a fracture strength of 68.8 +/- 9.4MPa. Finally, the results indicate that PPF crosslinking was facilitated at low DEF precursor concentrations, but hindered at higher precursor concentrations. These novel DEF/PPF solutions may be preferred over pure PPF as the basis for an engineered bone graft because they (1) exhibit reduced viscosity and thus are easily handled, (2) form polymer networks with compressive strength at fracture suitable for consideration for trabecular bone replacement, and (3) may be readily fabricated into solids with a wide range of structures.     

Osteoconductivity of an injectable and bioresorbable poly(propylene glycol-co-fumaric acid) bone cement

We have investigated an injectable form of a resorbable bone cement based on in situ crosslinking of the unsaturated polyester, poly(propylene glycol-co-fumaric acid) (PPF). This material, filled with calcium gluconate/hydroxyapatite (CG/HA), cures to a hard cement degradable by hydrolysis. The purpose of this study was to evaluate the osteoconductive properties of this injectable cement. The cement was used as an adjunct to fixation with an intramedullary rod in the rat femoral osteotomy model. Ingrowth of new bone into the cement was examined in vivo. Negative and positive controls with rigid and loose internal fixation were included for comparison. Animals were evaluated histologically and histomorphometrically at 4 weeks postoperatively. Results of this study showed osteoblastic activity and new bone formation at the interface between the femoral bone and the cement in the experimental group. However, there was little bone remodeling at the endosteal surface in positive and negative controls. Histologic evaluation of the cement revealed the formation of cavitations, which likely resulted from leaching of the highly soluble calcium gluconate portion of the filler from the cement. These cavitations were sites of ingrowth of vascular and bony tissues. Intimate contact between the bone cement and the endosteal surface of the cortex was found. Quantitative histomorphometric analysis corroborated these observations. Findings of this study demonstrated the osteoconductivity of this type of injectable PPF-based bone cement.     

Porous poly(DL-lactic-co-glycolic acid)/calcium phosphate cement composite for reconstruction of bone defects

Calcium phosphate (Ca-P) cements are injectable, self-setting ceramic pastes generally known for their favorable bone response. Ingrowth of bone and subsequent degradation rates can be enhanced by the inclusion of macropores. Initial porosity can be induced by CO(2) foaming during setting of the cement, whereas secondary porosity can develop after hydrolysis of incorporated poly(DL-lactic- co-glycolic acid) (PLGA) microparticles. In this study, we focused on the biological response to porous PLGA/Ca-P cement composites. Pre-set composite discs of four formulations (4 wt% or 15 wt% PLGA microparticles and low or high CO(2) induced porosity) were implanted subcutaneously and in cranial defects in rats for 12 weeks. Histological analysis of the explanted composites revealed that bone and fibrous tissue ingrowth was facilitated by addition of PLGA microparticles (number average diameter of 66 +/- 25 microm). No adverse tissue reaction was observed in any of the composites. Significant increases in composite density due to bone ingrowth in cranial implants were found in all formulations. The results suggest that the PLGA pores are suitable for bone ingrowth and may be sufficient to enable complete tissue ingrowth without initial CO(2) induced porosity. Finally, bone-like mineralization in subcutaneous implants suggests that, under appropriate conditions and architecture, porous PLGA/Ca-P cement composites can exhibit osteoinductive properties. These PLGA/Ca-P composites are a promising scaffolding material for bone regeneration and bone tissue engineering.     

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. I. Preparation and characterization

We developed poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres and investigated the effects of various processing parameters on the characteristics of these microspheres. The advantage of these blend microspheres is that the carbon-carbon double bonds along the PPF backbone could be used for their immobilization in a PPF scaffold. Microspheres containing the model drug Texas red dextran were fabricated using a double emulsion-solvent extraction technique. The effects of the following six processing parameters on the microsphere characteristics were investigated: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) (PVA) in the internal aqueous phase, and PVA concentration in the external aqueous phase. Our results showed that the microsphere surface morphology was affected most by the viscosity of the polymer solution. Microspheres fabricated with a kinematic viscosity of 39 centistokes had a smooth, nonporous surface. In most microsphere formulations, the model drug was dispersed uniformly in the polymer matrix. For all fabricated formulations, the average microsphere diameter ranged between 19.0 and 76.9 microm. The external PVA concentration and vortex speed had most effect on the size distribution. Entrapment efficiencies varied from 60 to 98% and were most affected by the amount of internal aqueous phase, vortex speed, and polymer viscosity. Overall, we demonstrated the ability to fabricate PPF/PLGA blend microspheres with similar surface morphology, entrapment efficiency, and size distribution as conventional PLGA microspheres.     

In vivo degradation of porous poly(propylene fumarate)/poly(DL-lactic-co-glycolic acid) composite scaffolds

This study investigated the in vivo degradation of poly(propylene fumarate) (PPF)/poly(DL-lactic-co-glycolic acid) (PLGA) composite scaffolds designed for controlled release of osteogenic factors. PPF/PLGA composites were implanted into 15.0mm segmental defects in the rabbit radius, harvested after 12 and 18 weeks, and analyzed using histological techniques to assess the extent of polymer degradation as well as the tissue response within the pores of the scaffolds. Polymer degradation was limited to micro-fragmentation of the scaffold at the ends and edges of the implant at both 12 and 18 weeks. The tissue within the pores of the scaffold consisted of fibrous tissue, blood vessels and some inflammatory cells. In areas where polymer breakdown was evident, an increased inflammatory response was observed. In contrast, areas of bone ingrowth into the polymer scaffold were characterized by minimal inflammatory response and polymer degradation. Our results show that minimal degradation of porous PPF occurs within 18 weeks of implantation in a rabbit model. Further, the in vivo degradation data of porous PPF/PLGA scaffolds are comparable with earlier obtained in vitro data.     

Effect of a poly(propylene fumarate) foaming cement on the healing of bone defects.

Regeneration of skeletal tissues has been recognized as a new means for reconstruction of skeletal defects. We investigated the feasibility of an injectable and expandable porous implant system for in situ regeneration of bone. Therefore, a composite biodegradable foaming cement based on poly(propylene fumarate) was injected into a critical size defect made in the rat tibia. Animals were divided into two groups comparing the foam in the experimental group against sham-operated animals having a drill hole but no implant in the control group. Eight animals were included in each group. Animals were sacrificed at 1, 3, and 7 weeks postoperatively. Implantation sites were then evaluated with histologic and histomorphometric methods. Results of this study showed that defects did not heal in sham-operated animals. In the experimental group, metaphyseal and cortical defects healed within the first postoperative week by formation of immature woven bone. At the site of the cortical drill hole defect, healing was noted to progress to complete closure by formation of mature bone. Histomorphometry corroborated these findings and showed that metaphyseal bone remodeling peaked at 1 week postoperatively and then decreased as healing of the cortical defect progressed. This suggests that near-complete restoration of the original state of the tibial bone occurred in this animal model supporting the concept of in situ bone regeneration by application of engineered biodegradable porous scaffolds. () ()     

In vitro degradation of porous poly(propylene fumarate)/poly(DL-lactic-co-glycolic acid) composite scaffolds

This study investigated the in vitro degradation of porous poly(propylene fumarate) (PPF-based) composites incorporating microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) during a 26-week period in pH 7.4 phosphate-buffered saline at 37 degrees C. Using a fractional factorial design, four formulations of composite scaffolds were fabricated with varying PEG content of the microparticles, microparticle mass fraction of the composite material, and initial leachable porogen content of the scaffold formulations. PPF scaffolds without microparticles were fabricated with varying leachable porogen content for use as controls. The effects of including PLGA/PEG microparticles in PPF scaffolds and the influence of alterations in the composite formulation on scaffold mass, geometry, water absorption, mechanical properties and porosity were examined for cylindrical specimens with lengths of 13 mm and diameters of 6.5 mm. The composite scaffold composition affected the extent of loss of polymer mass, scaffold length, and diameter, with the greatest loss of polymer mass equal to 15+/-5% over 26 weeks. No formulation, however, exhibited any variation in compressive modulus or peak compressive strength over time. Additionally, sample porosity, as determined by both mercury porosimetry and micro-computed tomography did not change during the period of this study. These results demonstrate that microparticle carriers can be incorporated into PPF scaffolds for localized delivery of bioactive molecules without altering scaffold mechanical or structural properties up to 26 weeks in vitro.     

Poly(propylene fumarate) reinforced dicalcium phosphate dihydrate cement composites for bone tissue engineering

Calcium phosphate cements have many desirable properties for bone tissue engineering, including osteoconductivity, resorbability, and amenability to rapid prototyping-based methods for scaffold fabrication. In this study, we show that dicalcium phosphate dihydrate (DCPD) cements, which are highly resorbable but also inherently weak and brittle, can be reinforced with poly(propylene fumarate) (PPF) to produce strong composites with mechanical properties suitable for bone tissue engineering. Characterization of DCPD-PPF composites revealed significant improvements in mechanical properties for cements with a 1.0 powder to liquid ratio. Compared with nonreinforced controls, flexural strength improved from 1.80 ± 0.19 MPa to 16.14 ± 1.70 MPa, flexural modulus increased from 1073.01 ± 158.40 MPa to 1303.91 ± 110.41 MPa, maximum displacement during testing increased from 0.11 ± 0.04 mm to 0.51 ± 0.09 mm, and work of fracture improved from 2.74 ± 0.78 J/m(2) to 249.21 ± 81.64 J/m(2) . To demonstrate the utility of our approach for scaffold fabrication, 3D macroporous scaffolds were prepared with rapid prototyping technology. Compressive testing revealed that PPF reinforcement increased scaffold strength from 0.31 ± 0.06 MPa to 7.48 ± 0.77 MPa. Finally, 3D PPF-DCPD scaffolds were implanted into calvarial defects in rabbits for 6 weeks. Although the addition of mesenchymal stem cells to the scaffolds did not significantly improve the extent of regeneration, numerous bone nodules with active osteoblasts were observed within the scaffold pores, especially in the peripheral regions. Overall, the results of this study suggest that PPF-DCPD composites may be promising scaffold materials for bone tissue engineering.     

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. II. Controlled drug release and microsphere degradation

This article describes the effects of six processing parameters on the release kinetics of a model drug Texas red dextran (TRD) from poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres as well as the degradation of these microspheres. The microspheres were fabricated using a double emulsion-solvent extraction technique in which the following six parameters were varied: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) in the internal aqueous phase, and poly(vinyl alcohol) concentration in the external aqueous phase. We have previously characterized these microspheres in terms of microsphere morphology, size distribution, and TRD entrapment efficiency. In this work, the TRD release profiles in phosphate-buffered saline were determined and all formulations showed an initial burst release in the first 2 days followed by a decreased sustained release over a 38-day period. The initial burst release varied from 5.1 (+/-1.1) to 67.7 (+/-3.4)% of the entrapped TRD, and was affected most by the viscosity of the polymer solution used for microsphere fabrication. The sustained release between day 2 and day 38 ranged from 7.9 (+/-0.8) to 27.2 (+/-3.1)% of the entrapped TRD. During 11 weeks of in vitro degradation, the mass of the microspheres remained relatively constant for the first 3 weeks after which it decreased dramatically, whereas the molecular weight of the polymers decreased immediately upon placement in phosphate-buffered saline. Increasing the PPF content in the PPF/PLGA blend resulted in slower microsphere degradation. Overall, this study provides further understanding of the effects of various processing parameters on the release kinetics from PPF/PLGA blend microspheres thus allowing modulation of drug release to achieve a wide spectrum of release profiles.     

Effect of physiological temperature on the mechanical properties and network structure of biodegradable poly(propylene fumarate)-based networks

Poly(propylene fumarate) (PPF)-based networks have exhibited increases in mechanical properties during their initial stages of degradation. This study was designed to investigate whether physiological temperatures are the source of this reinforcing behavior by influencing the formation of additional crosslinks within the network. Utilizing a model PPF network formed with the crosslinking agent poly(propylene fumarate)-diacrylate (PPF-DA), cylindrical specimens were stored in an inert environment and conditioned at -20 and 37 degrees C while their mechanical properties and network structure were monitored over a six week period. The PPF/PPF-DA specimens exposed to physiological temperatures showed an increase in compressive modulus from 1674 +/- 88 to 2059 +/- 75 MPa. The double bond conversion improved as well, from 64 +/- 1 to 70 +/- 1%, indicating that crosslinks were being formed in the network. The additional reactivity occurred exclusively with unreacted fumarate bonds. PPF/PPF-DA networks stored at -20 degrees C showed no changes in mechanical properties; however, they increased when subsequently conditioned at 37 degrees C. The results were used to explain that PPF-based networks undergo a biphasic degradation behavior due to the competing hydrolytic degradation and thermal induced crosslinking. In addition, heat treating the networks at higher temperatures can be utilized as a means to further reinforce PPF-based materials.     

Effect of physiological temperature on the mechanical properties and network structure of biodegradable poly(propylene fumarate)-based networks

Poly(propylene fumarate) (PPF)-based networks have exhibited increases in mechanical properties during their initial stages of degradation. This study was designed to investigate whether physiological temperatures are the source of this reinforcing behavior by influencing the formation of additional crosslinks within the network. Utilizing a model PPF network formed with the crosslinking agent poly(propylene fumarate)-diacrylate (PPF-DA), cylindrical specimens were stored in an inert environment and conditioned at -20 and 37°C while their mechanical properties and network structure were monitored over a six week period. The PPF/PPF-DA specimens exposed to physiological temperatures showed an increase in compressive modulus from 1674 ± 88 to 2059 ± 75 MPa. The double bond conversion improved as well, from 64 ± 1 to 70 ± 1%, indicating that crosslinks were being formed in the network. The additional reactivity occurred exclusively with unreacted fumarate bonds. PPF/PPF-DA networks stored at -20°C showed no changes in mechanical properties; however, they increased when subsequently conditioned at 37°C. The results were used to explain that PPF-based networks undergo a biphasic degradation behavior due to the competing hydrolytic degradation and thermal induced crosslinking. In addition, heat treating the networks at higher temperatures can be utilized as a means to further reinforce PPF-based materials.     

Crosslinking characteristics of and cell adhesion to an injectable poly(propylene fumarate-co-ethylene glycol) hydrogel using a water-soluble crosslinking system

The crosslinking characteristics of an injectable poly(propylene fumarate-co-ethylene glycol) [P(PF-co-EG)]-based hydrogel were investigated. A water-soluble crosslinking system was used, consisting of poly(ethylene glycol) diacrylate (PEG-DA), ammonium persulfate (APS), and ascorbic acid (AA). The effects of PEG block length of the P(PF-co-EG), APS concentration, AA concentration, and PEG-DA concentration on equilibrium water content, sol fraction, onset of gelation, mechanical properties, and endothelial cell adhesion were studied. The equilibrium water content of the hydrogels ranged from 57.1 +/- 0.3 to 79.7 +/- 0.2% whereas the sol fraction ranged from 2.5 +/- 0.0 to 3.33 +/- 5.4%. The onset of gelation times varied from 1.1 +/- 0.1 to 4.3 +/- 0.2 min. For all hydrogel formulations, the tensile strength fell between 61.7 +/- 18.2 and 401.3 +/- 67.5 kPa and tensile moduli ranged from 0.4 +/- 0.0 to 3.3 +/- 0.3 MPa. Endothelial cells attached to the hydrogels in a range of 3.9 +/- 1.4 to 31.1 +/- 14.1% of cells seeded. These findings suggest that injectable poly(propylene fumarate-co-ethylene glycol) hydrogel formulations in conjunction with a novel water-soluble crosslinking system may be useful for in situ crosslinkable tissue-engineering applications.     

Polypropylene fumarate/phloroglucinol triglycidyl methacrylate blend for use as partially biodegradable orthopaedic cement.

Polypropylene fumarate/phloroglucinol triglycidyl methacrylate oligomeric blend-based bone cement was studied. Higher the percentage of phloroglucinol triglycidyl methacrylate, lesser the setting time. An optimum setting time could be arrived with 50:50 blend composition of the two oligomers. Composite cement of 50:50 blend prepared with hydroxyapatite granules of particle size 125 microm binds bovine rib bones. The tensile strength of this adhesive bond was found to be 1.11 kPa. The thermal studies suggest the onset of cross-linking reaction in the cured blend if the blend is heated. The absence of softening endotherm in the cured blend shows the thermosetting-like amorphous nature of blend system, which may restrict the changes in creep properties. The in vitro biodegradation studies reveal possible association of calcium ions with negatively charged units of degrading polymer chain resulting in slow down of degradation. Relatively slow degradation was observed in Ringer's solution. The study reveals the potential use of polypropylene fumarate/phloroglucinol triglycidyl methacrylate as partially degradable polymeric cement for orthopaedic applications.     

An injectable,biodegradable calcium phosphate cement containing poly lactic-co-glycolic acid as a bone substitute in ex vivo human vertebral compression fracture and rabbit bone defect models

Purpose/Aim of the study: To evaluate the biomechanical characteristics and biocompatibility of an injectable, biodegradable calcium phosphate cement (CPC) containing poly lactic-co-glycolic acid (PLGA). Materials and methods: A vertebral compression fracture model was established using 20 human cadaveric vertebrae (T11-L3) divided into CPC/PLGA composite versus PMMA groups for biomechanical testing. In addition, 35 New Zealand rabbits were used to evaluate biodegradability and osteoconductive properties of CPC/PLGA using a bone defect model. In vitro cytotoxicity was evaluated by culturing with L929 cells. Results: The CPC/PLGA composite effectively restored vertebral biomechanical properties. Compared with controls, the maximum load and compression strength of the CPC/PLGA group were lower, and stiffness was lower after kyphoplasty (all p <.05). Degradation was much slower in the control CPC compared with CPC/PLGA group. The bone tissue percentage in the CPC/PLGA group (44.9 ± 23.7%) was significantly higher compared with control CPC group (25.7 ± 10.9%) (p <.05). The viability of cells cultured on CPC/PLGA was greater than 70% compared with the blanks. Conclusions: Our biodegradable CPC/PLGA composite showed good biomechanical properties, cytocompatibility, and osteoconductivity and may represent an ideal bone substitute for future applications.     

An injectable porous poly(propylene glycol-co-fumaric acid) bone repair material as an adjunct for intramedullary fixation

A bioresorbable bone repair material made from the unsaturated polyester poly(propylene glycol-co-fumaric acid), PPF, was investigated for its potential to act as an adjunct to alleviate the disadvantages associated with wire fixation. The PPF bone repair material is an injectable system that can be delivered to the intramedullary site and crosslinked in the presence of a hydroxylapatite filler and effervescent agents. To test the feasibility of using a bioabsorbable material as an adjunct in fracture fixation, femoral osteotomies were created in two groups of 10 Sprague-Dawley rats. Osteotomies were fixed with a threaded Kirschner wire or stabilized with a Kirshner wire augmented with the PPF bone repair material. The quantity of new bone across the osteotomy site was assessed at 4 weeks postoperatively. Histologic analysis of the healing process revealed enhanced osteoconduction across the osteotomy with the PPF bone repair material. These findings were corroborated by histomorphometric analysis of new bone formation. These findings imply suitability of the PPF bone repair material to act as an adjunct to wire fixation, such as techniques used in hand surgery.     

Copolymerization of photocrosslinkable anhydride monomers for use as a biodegradable bone cement

A multifunctional anhydride monomer, methacrylated sebacic anhydride (MSA), was synthesized and copolymerized with methacrylic anhydride via photoinitiated polymerization to form highly crosslinked, degradable networks. This material system was investigated as a potential degradable bone cement. Several aspects were examined, including curing characteristics, degradation rates and mechanical properties. These copolymer networks reached high double-bond conversions on clinically acceptable time scales (<5 min). Furthermore, these divinyl monomer copolymerizations exhibit features of classical crosslinking polymerizations, including autoacceleration, autodeceleration and limited double-bond conversion. Additionally, the networks degrade via a surface erosion mechanism by which the degradation rate can be controlled through varying the degree of oligomerization of the multifunctional monomer backbone, varying the copolymer precursor composition and changing the monomer backbone chemistry. Finally, the copolymer was found to have improved mechanical properties over homopolymerized MSA. Compressive strengths as high as 78 +/- 5 MPa were attained with a 70/30 wt% MSA/methacrylic anhydride copolymer, which are comparable to measured (91 +/- 7 MPa) and literature (approx. 100 MPa) values for conventional poly(methyl methacrylate) bone cement.