The nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with l-lactic acid oligomer for bone repair

Nanohydroxyapatite (op-HA) surface-modified with l-lactic acid oligomer (LAc oligomer) was prepared by LAc oligomer grafted onto the hydroxyapatite (HA) surface. The nanocomposite of op-HA/PLGA with different op-HA contents of 5, 10, 20 and 40 wt.% in the composite was fabricated into three-dimensional scaffolds by the melt-molding and particulate leaching methods. PLGA and the nanocomposite of HA/PLGA with 10 wt.% of ungrafted hydroxyapatite were used as the controls. The scaffolds were highly porous with evenly distributed and interconnected pore structures, and the porosity was around 90%. Besides the macropores of 100–300 μm created by the leaching of NaCl particles, the micropores (1–50 μm) in the pore walls increased with increasing content of op-HA in the composites of op-HA/PLGA. The op-HA particles could disperse more uniformly than those of pure HA in PLGA matrix. The 20 wt.% op-HA/PLGA sample exhibited the maximum mechanical strength, including bending strength (4.14 MPa) and compressive strength (2.31 MPa). The cell viability and the areas of the attached osteoblasts on the films of 10 wt.% op-HA/PLGA and 20 wt.% op-HA/PLGA were evidently higher than those on the other composites. For the animal test, there was rapid healing in the defects treated with 10 and 20 wt.% op-HA/PLGA, where bridging by a large bony callus was observed at 24 weeks post-surgery. There was non-union of radius defects implanted with PLGA and in the untreated group. This was verified by the Masson’s trichrome staining photomicrographs of histological analysis. All the data extrapolated that the composite with 10 and 20 wt.% op-HA exhibited better comprehensive properties and were the optimal composites for bone repairing.     

A poly(lactide-co-glycolide)/hydroxyapatite composite scaffold with enhanced osteoconductivity

Biodegradable polymer/ceramic scaffolds can overcome the limitations of conventional ceramic bone substitutes. However, the conventional methods of polymer/ceramic scaffold fabrication often use organic solvents, which might be harmful to cells or tissues. Moreover, scaffolds fabricated with the conventional methods have limited ceramic exposure on the scaffold surface since the polymer solution envelopes the ceramic particles during the fabrication process. In this study, we developed a novel fabrication method for the efficient exposure of ceramic onto the scaffold surface, which would enhance the osteoconductivity and wettability of the scaffold. Poly(D,L-lactide-co-glycolide)/nanohydroxyapatite (PLGA/HA) scaffolds were fabricated by the gas foaming and particulate leaching (GF/PL) method without the use of organic solvents. Selective staining of ceramic particles indicated that HA nanoparticles exposed to the scaffold surface were observed more abundantly in the GF/PL scaffold than in the conventional solvent casting and particulate leaching (SC/PL) scaffold. Both types of scaffolds were implanted to critical size defects in rat skulls for 8 weeks. The GF/PL scaffolds exhibited significantly enhanced bone regeneration when compared with the SC/PL scaffolds. Histological analyses and microcomputed tomography of the regenerated tissues showed that bone formation was more extensive on the GF/PL scaffolds than on the SC/PL scaffolds. Compared with the SC/PL scaffolds, the enhanced bone formation on the GF/PL scaffolds may result from the higher exposure of HA nanoparticles to the scaffold surface. These results show that the biodegradable polymer/ceramic composite scaffolds fabricated with the novel GF/PL method can enhance bone regeneration compared with those fabricated with the conventional SC/PL method.     

Enhancement of osteogenesis by poly(lactide-co-glycolide) sponges loaded with surface-embedded hydroxyapatite particles and rhBMP-2

The bone mesenchymal stem cells (BMSCs) were seeded on [poly(lactide-co-glycolide) scaffolds with hydroxyapatite (HA) coating, and "s" stands for surface] (PLGA/HA-S), PLGA/HA-M (containing the same HA amount in the matrix as that of the PLGA/HA-S and "m" stands for matrix), and PLGA scaffolds, which were then cultured in a medium-containing Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2). In vitro culture of rat BMSCs found no different cell morphology in all the scaffolds, but the alkaline phosphatase activity and osteogenic gene expression of type I collagen (COL I) and osteocalcin (OCN) in the PLGA/HA-S scaffolds were always highest and were significantly improved in comparison with those in the PLGA scaffolds. In a rat calvarial defect model, new bone formation was enhanced in the PLGA/HA-S/ErhBMP-2 implants at 4 and 8 weeks after implantation too. Therefore, the PLGA/HA-S scaffold can better enhance the ErhBMP-2-induced osteogenic differentiation of BMSCs in vitro and osteogenesis in vivo.     

An injectable scaffold: rhBMP-2-loaded poly(lactide-co-glycolide)/hydroxyapatite composite microspheres

Poly(lactide-co-glycolide)/hydroxyapatite(50/50) (PLGA/HA(50/50)) composite microspheres were fabricated and treated with a mixture of 0.25 M NaOH aqueous solution and ethanol (v/v = 1/1) at 37 °C. The properties of untreated and treated PLGA/HA(50/50) composite microspheres were determined and compared. The results showed that the surface roughness, HA content and hydrophilicity of the treated PLGA/HA(50/50) composite microspheres increased with treatment time. However, the treatment time should be kept within 2 h in order to maintain the shape of the PLGA/HA(50/50) microspheres. At the same time, a degradation study showed that both the untreated and treated microspheres degraded gradually with time, with the treated microspheres degrading faster in the first 4 weeks. The rhBMP-2-loaded PLGA/HA(50/50) composite microspheres were prepared by solution dipping treated PLGA/HA(50/50) composite microspheres. Mouse OCT-1 osteoblast-like cells were cultured on the untreated, treated and rhBMP-2-loaded PLGA/HA(50/50) composite microspheres and the cell affinity of the various microspheres was assessed and compared. It was found that the surface-treated PLGA/HA(50/50) composite microspheres clearly promoted osteoblast attachment, proliferation and alkaline phosphatase activity. It was considered that the hydrophilicity, osteoconductivity and surface roughness were increased by the increase in the HA component, which facilitated cell growth. Moreover, the rhBMP-2 loaded on the treated PLGA/HA(50/50) composite microspheres could be slowly released and further enhanced osteoblast differentiation. The good cell affinity and enhanced osteogenic potential of the rhBMP-2-loaded PLGA/HA composite microspheres indicate that they could be used as an injectable scaffold.     

In vitro and in vivo degradation of mineralized collagen-based composite scaffold: nanohydroxyapatite/collagen/poly(L-lactide)

The objective of this article was to investigate the in vitro and in vivo biodegradation of a novel biomimetic bone scaffold composite, nanohydroxyapatite/collagen/poly(L-lactide), that could be used for bone tissue engineering. For evaluation of in vitro degradation specimens were immersed into 1% trypsin/phosphate-buffered saline solution at 37 degrees C. In vivo evaluation involved the implantation of samples into the posterolateral lumbar spine of rabbits, and the retrieved specimens were analyzed by Fourier transform-infrared spectroscopy. The results demonstrated that weight loss increased continuously in vitro with a reduction in mass of 19.6% after 4 weeks. During the experimental period in vitro, the relative rate of reduction of the three components in this material was shown to differ greatly: collagen decreased the fastest, from 40% by weight to 20% in the composite; hydroxyapatite content increased from 45 to 60%; and PLA changed little. The pore structure was maintained throughout the whole experimental period in vitro; however, the thickness of the walls of the pores decreased and the surface of the walls increased in roughness. In vivo, the ratio of collagen to hydroxyapatite appeared to be slightly higher near the transverse process than in the central part of the intertransverse process. This finding may have been due to new bone matrix formation extending from the transverse to the intertransverse process.     

In vitro evaluation of a poly(lactide-co-glycolide)-collagen composite scaffold for bone regeneration

Numerous materials have been proposed for bone tissue regeneration. However, none has been shown to be entirely satisfactory. In this study we fabricated a hybrid composite scaffold composed of poly(D,L-lactide-co-glycolide) (PLGA) and a naturally derived collagen matrix derived from porcine bladder submucosa matrix (BSM), and evaluated the biological activities and physical properties of the scaffold for use in bone tissue regeneration. The BSM-PLGA composite scaffolds are able to promote cellular interactions and possess uniformly interconnected pores with adequate structural integrity. The composite scaffolds were tested with both human embryonic stem (hES) cells and bovine osteoblasts (bOB). Cells seeded on the composite scaffolds readily attached, infiltrated and proliferated, as confirmed by cell viability and mitochondrial metabolic activity. Use of the composite scaffolding system with cells may enhance the formation of bone tissue for therapeutic regeneration.     

Degradation of poly(lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by electron beam radiation

This paper seeks to examine the effects of electron beam (e-beam) radiation on biodegradable polymers (PLGA and PLLA), and to understand their radiation-induced degradation mechanisms. PLGA (80:20) and PLLA polymer films were e-beam irradiated at doses from 2.5 to 50 Mrad and the degradation of these films were studied by measuring the changes in their molecular weights, FTIR spectra, thermal and morphological properties. The dominant effect of e-beam irradiation on both PLGA and PLLA is chain scission. Chain scission occurs first through scission of the polymer main chain, followed by hydrogen abstraction. Chain scission, though responsible for the reduction in the average molecular weight, Tc, Tg and Tm of both polymers, encourages crystallization in PLGA. PLLA also undergoes chain scission upon irradiation but to a lesser degree compared to PLGA. The higher crystallinity of PLLA is the key factor in its greater stability to e-beam radiation compared to PLGA. A linear relationship is also established between the decrease in molecular weight with respect to radiation dose.     

In vivo biocompatibility studies of poly(D,L-lactide)/poly(ethylene glycol)-poly(L-lactide) microspheres containing all-trans-retinoic acid

Biocompatibility studies of all-trans-retinoic acid (RA)-loaded microspheres were carried out after they were subcutaneously injected into rats. To characterize the inflammatory response to these microspheres, tissue reactions at the implantation site and cell types in the interstices of the microspheres were evaluated for 180 days. On the 15th day, the cross-sectional area of the fibrous capsules surrounding the implantation site of the RA-loaded microspheres was four times larger than that of the control microspheres. The size of the fibrous capsules surrounding the implantation site of the RA-loaded microspheres decreased significantly over a period of 75 days, while the size of the fibrous capsules surrounding the implantation site of the control microspheres remained almost constant throughout the entire course of 180 days. The tissue response to the RA-loaded microspheres was more intensified by the increased extensive cellular infiltration of macrophages, granulation tissue, and fibrosis than that to the control microspheres. The difference in the inflammatory response between the RA-loaded microspheres and the control microspheres was significant for 75 days after implantation. It was suggested that the released RA from the microspheres stimulated inflammatory responses. However, no further enhanced inflammation reactions were detected after RA had been completely released from the microspheres.     

Composites of poly(lactide-co-glycolide) and the surface modified carbonated hydroxyapatite nanoparticles

To improve the mechanical properties of the composites of poly(lactide-co-glycolide) (PLGA, LA/GA = 80/20) and the carbonate hydroxyapatite (CHAP) particles, the rice-form or claviform CHAP particles with 30-40 nm in diameter and 100-200 nm in length were prepared by precipitation method. The uncalcined CHAP particles have a coarse surface with a lot of global protuberances, which could be in favor of the interaction of the matrix polymer to the CHAP particles. The nanocomposites of PLGA and surface grafted CHAP particles (g-CHAP) were prepared by solution mixing method. The structure and properties of the composites were subsequently investigated by the emission scanning electron microscopy, the tensile strength testing, and the cell culture. When the contents of g-CHAP were in the range of 2-15 wt %, the PLGA/g-CHAP nanocomposites exhibited an improved elongation at break and tensile strength. At the 2 wt % content of g-CHAP, the fracture strain was increased to 20% from 4-5% for neat PLGA samples. Especially at g-CHAP content of 15 wt %, the tensile strength of PLGA/g-CHAP composite was about 20% higher than that of neat PLGA materials. The tensile moduli of composites were increased with the increasing of filler contents, so that the g-CHAP particles had both reinforcing and toughening effects on the PLGA composites. The results of biocompatibility test showed that the higher g-CHAP contents in PLGA composite facilitated the adhesion and proliferation properties of osteoblasts on the PLGA/g-CHAP composite film.     

Preparation and properties of poly(L-lactide)/hydroxyapatite composites

In this study, two different viscosity-average molecular weight (η = 4.0 and 7.8) poly(L-lactide) (PLLA) were synthesized by ring-opening polymerization and the poly(L-lactide)/hydroxyapatite composites (PLLA/HA) were prepared by blending HA particles (size range: 25-45 μm and Ca/P = 1.69) with a content of 10, 30, and 50 wt% in PLLA solution with further evaporation of the solvent. The plain PLLA polymers and PLLA/HA composites were compressionmolded and machined to yield 25×3×2 mm3 specimens. The molar mass of resulting specimens was decreased drastically due to the hydrolytic and thermal degradation of ester bonds. Scanning electron microscopy and thermal gravimetric results indicated that the compositions of HA in PLLA were well dispersed. With increasing HA content, the crystallinity of PLLA/HA composites are slightly increased due to the effect of HA as a nucleating agent. The dynamic mechanical analysis is useful in studying the viscoelastic behaviour of the PLLA/HA composites and no secondary relaxation was observed below the glass-to-rubber transition (60°C). The mechanical properties of the PLLA/HA composites were found to vary with HA content. Increased levels of HA resulted in increased bending modulus and strength.     

In vitro and in vivo studies on bioabsorbable ultra-high-strength poly(L-lactide) rods.

Ultra-high-strength poly(L-lactide) (PLLA) rods were fabricated using a drawing technique. Rods with a diameter of 3.2 mm and a draw ratio of 2.5:1 showed initial bending strength and modulus values of 240 MPa and 13 GPa, respectively. The purpose of this study was to investigate the in vitro and in vivo degradation of PLLA rods with a draw ratio of 2.5:1. The greater the rod diameter, the longer the bending strength was maintained in phosphate buffered saline at 37 degrees C. The bending strength retention of rods (diam. 3.2 mm) implanted in the subcutis of rabbits was almost equal to that of rods in the in vitro study, while those rods implanted in the medullary cavity of rabbit femora showed a slightly lower bending strength retention. Molecular weight was reduced to the greatest extent in the medullary cavity, followed by in the subcutis and in vitro. The weight of PLLA rods in the medullary cavity was reduced by 22% at 52 weeks and by 70% at 78 weeks after implantation. Histologically, no inflammatory or foreign body reaction was observed in the medullary cavity for 52 weeks. The drawn PLLA rods maintained a bending strength exceeding that of human cortical bone in the medullary canal for a period of 8 weeks, suggesting that the drawn PLLA rods may be useful in the repair of fractured human bones.     

Preparation and properties of poly(L-lactide)/hydroxyapatite composites

In this study, two different viscosity-average molecular weight (eta = 4.0 and 7.8) poly(L-lactide) (PLLA) were synthesized by ring-opening polymerization and the poly(L-lactide)/hydroxyapatite composites (PLLA/HA) were prepared by blending HA particles (size range: 25-45 microm and Ca/P = 1.69) with a content of 10, 30, and 50 wt% in PLLA solution with further evaporation of the solvent. The plain PLLA polymers and PLLA/HA composites were compression-molded and machined to yield 25 x 3 x 2 mm3 specimens. The molar mass of resulting specimens was decreased drastically due to the hydrolytic and thermal degradation of ester bonds. Scanning electron microscopy and thermal gravimetric results indicated that the compositions of HA in PLLA were well dispersed. With increasing HA content, the crystallinity of PLLA/HA composites are slightly increased due to the effect of HA as a nucleating agent. The dynamic mechanical analysis is useful in studying the viscoelastic behaviour of the PLLA/HA composites and no secondary relaxation was observed below the glass-to-rubber transition (60 degrees C). The mechanical properties of the PLLA/HA composites were found to vary with HA content. Increased levels of HA resulted in increased bending modulus and strength.     

Thermal and mechanical characteristics of poly(L-lactic acid) nanocomposite scaffold

Inorganic nanosized silicate nanoplatelets were incorporated into biodegradable poly(L-lactic acid) (PLLA) for the purpose of tailoring mechanical stiffness of PLLA porous scaffold systems. Increasing the nucleation density around the foreign body surfaces, the montmorillonite (MMT) nanoplatelets modified with dimethyl dihydrogenated tallow ammonium cations decreased the glass transition temperature and the degree of PLLA crystallinity, which seemingly caused the accelerated biodegradation rate of PLLA nanocomposites due to the enhanced segmental mobility of backbone chains and the expanded amorphous region of PLLA matrix. The tensile modulus was increased from 121.2MPa of pristine polymer scaffold to 170.1MPa of MMT/PLLA nanocomposite scaffold (ca. 40% increment) by the addition of small amount of MMT platelets (5.79 vol%) acting as a mechanical reinforcement of polymer chains in the nanoscale molecular level. Overall, the nanotechnology used in this study may be applied to various scaffold systems of biodegradable polymers and hard/soft scaffold structures requiring critical control and design characteristics of mechanical stiffness and biodegradation rate.     

In vitro and in vivo evaluation of a novel nanosize hydroxyapatite particles/poly(ester-urethane) composite scaffold for bone tissue engineering

Scaffolds for bone tissue engineering should provide an osteoconductive surface to promote the ingrowth of new bone after implantation into bone defects. This may be achieved by hydroxyapatite loading of distinct scaffold biomaterials. Herein, we analyzed the in vitro and in vivo properties of a novel nanosize hydroxyapatite particles/poly(ester-urethane) (nHA/PU) composite scaffold which was prepared by a salt leaching–phase inverse process. Microtomography, scanning electron microscopy and X-ray spectroscopy analyses demonstrated the capability of the material processing to create a three-dimensional porous PU scaffold with nHA on the surface. Compared to nHA-free PU scaffolds (control), this modified scaffold type induced a significant increase in in vitro adsorption of model proteins. In vivo analysis of the inflammatory and angiogenic host tissue response to implanted nHA/PU scaffolds in the dorsal skinfold chamber model indicated that the incorporation of nHA particles into the scaffold material did not affect biocompatibility and vascularization when compared to control scaffolds. Thus, nHA/PU composite scaffolds represent a promising new type of scaffold for bone tissue engineering, combining the flexible material properties of PU with the advantage of an osteoconductive surface.     

Preparation and mechanical properties of nanocomposites of poly(D,L-lactide) with Ca-deficient hydroxyapatite nanocrystals

Nanocomposites of high molecular poly(D,L-lactide) (PLA) with Ca-deficient hydroxyapatite nanocrystals (d-HAP) were successfully prepared through solvent-cast technique. Such composites are of great importance to make bone-like substitutes as d-HAP nanocrystals have similar composition, morphology and crystal structure as natural apatite crystals. Of all the PLA solvents studied, N,N-dimethylformamide is the best one to disperse d-HAP nanocrystals. The resultant sol is a blue, stable dispersion that could preserve several days with only slight precipitation. The bright-field TEM micrograph shows that d-HAP nanocrystals form homogeneous dispersion in the PLA matrix at a microscopic level. The tensile modulus for PLA/d-HAP nanocomposites increases with d-HAP loading. Theoretical prediction of the modulus has been made by assuming the nanocomposites as short fiber filled systems. The calculated values based on Halpin-Tsai equations show excellent agreement with the experimental results. The yield stress for the nanocomposites has not been undermined by the presence of the nanocrystals. This preservation of strength for PLA/d-HAP nanocomposites may be due to the homogeneous dispersion of d-HAP nanocrystals in the PLA matrix as well as the good interfacial adhesion.     

Nano-composite of poly(L-lactide) and surface grafted hydroxyapatite: mechanical properties and biocompatibility

In order to improve the bonding between hydroxyapatite (HAP) particles and poly(L-lactide) (PLLA), and hence to increase mechanical properties of the PLLA/HAP composite as potential bone substitute material, the HAP nano-particles were surface-grafted with PLLA and further blended with PLLA. The structure and properties of the composites were subsequently investigated by the mechanical property testing, the differential scanning calorimeter measurements (DSC), the scanning electron microscopy (SEM), the polarized optical microscopy (POM), and the cell culture. The PLLA molecules grafted on the HAP surfaces, as inter-tying molecules, played an important role in improving the adhesive strength between the particles and the polymer matrix. At a low content (approximately 4 wt%) of surface grafted-HAP (g-HAP), the PLLA/g-HAP nano-composites exhibited higher bending strength and impact energy than the pristine PLLA, and at a higher g-HAP content (e.g., 20 wt%), the modulus was remarkably increased. It implied that PLLA could be strengthened as well as toughened by g-HAP nano-particles. The results of biocompatibility test showed that the g-HAP existing in the PLLA composite facilitated both adhesion and proliferation of chondrocytes on the PLLA/g-HAP composite film.     

Resorbable materials of poly(L-lactide). VII. In vivo and in vitro degradation

In vivo and in vitro degradation of high molecular weight poly(L-lactide) used for internal bone fixation has been investigated. Within 3 months as-polymerized, microporous PLLA (Mv = 6.8-9.5 X 10(5] exhibited a massive strength-loss (sigma b = 68-75 MPa to sigma b = 4 MPa) and decrease of Mv (90-95%). At week 39, the first signs of resorption were evident (mass-loss 5 wt%). Except for dynamically loaded bone plates no differences between in vivo and in vitro degradation of PLLA were observed. The increase of crystallinity of PLLA upon degradation (up to 83%) is likely to be attributed to recrystallization of tie-chain segments. A more ductile PLLA exhibiting a lower rate of degradation was prepared by extraction of low molecular weight compounds with ethyl acetate.     

Preparation,in vitro degradability,cytotoxicity, and in vivo biocompatibility of porous hydroxyapatite whisker-reinforced poly(L-lactide) biocomposite scaffolds

Biodegradable and bioactive scaffolds with interconnected macroporous structures, suitable biodegradability, adequate mechanical property, and excellent biocompatibility have drawn increasing attention in bone tissue engineering. Hence, in this work, porous hydroxyapatite whisker-reinforced poly(L-lactide) (HA-w/PLLA) composite scaffolds with different ratios of HA and PLLA were successfully developed through compression molding and particle leaching. The microstructure, in vitro mineralization, cytocompatibility, hemocompatibility, and in vivo biocompatibility of the porous HA-w/PLLA were investigated for the first time. The SEM results revealed that these HA-w/PLLA scaffolds possessed interconnected pore structures. Compared with porous HA powder-reinforced PLLA (HA-p/PLLA) scaffolds, HA-w/PLLA scaffolds exhibited better mechanical property and in vitro bioactivity, as more formation of bone-like apatite layers were induced on these scaffolds after mineralization in SBF. Importantly, in vitro cytotoxicity displayed that porous HA-w/PLLA scaffold with HA/PLLA ratio of 1:1 (HA-w₁/PLLA₁) produced no deleterious effect on human mesenchymal stem cells (hMSCs), and cells performed elevated cell proliferation, indicating a good cytocompatibility. Simultaneously, well-behaved hemocompatibility and favorable in vivo biocompatibility determined from acute toxicity test and histological evaluation were also found in the porous HA-w₁/PLLA₁ scaffold. These findings may provide new prospects for utilizing the porous HA whisker-based biodegradable scaffolds in bone repair, replacement, and augmentation applications.     

Shape memory properties of poly(D,L-lactide)/hydroxyapatite composites

Poly(D,L-lactide) (PDLLA) and Hydroxyapatite (HA) are compounded, which possess biodegradation, biocompatibility and shape memory properties. In the paper, we prepared serial imposing shape memory composites with different shapes, composite ratios and sample thicknesses. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) were carried out to examine surface morphology, glass transition temperature (Tg), dynamic mechanical properties, and shape memory effect of PDLLA/HA composites, respectively. Moreover, some interesting shape memory behaviors were investigated. The results show that the better disperse morphology of HA grains using the experiment methods, and PDLLA/HA composites at a definite range of compound ratio have much better shape memory effect than pure PDLLA polymer. It indicates that HA particles can improve shape memory effect and PDLLA/HA composites are potential for biomedical applications.     

In vivo evaluation of a novel electrically conductive polypyrrole/poly(D,L-lactide) composite and polypyrrole-coated poly(D,L-lactide-co-glycolide) membranes

This study evaluated the in vivo biocompatibility and biodegradation behavior of a novel polypyrrole (PPy)/poly(D,L-lactide) (PDLLA) composite and PPy-coated poly(D,L-lactide-co-glycolide) membranes. Test membranes were implanted subcutaneously in rats for 3-120 days. The biocompatibility was assessed by quantifying the alkaline and acid phosphatase secretion, the immunohistochemical staining of the ED-2-positive macrophages, and the histology at the tissue/material interface. The degradation was investigated using scanning electron microscopy. Pure PDLLA and poly(D,L-lactide-co-glycolide) membranes were used as references, whereas expanded polytetrafluoroethylene and a commercial styrene-butadiene rubber were used as controls. The enzyme activity of the PPy-containing specimens was shown to be similar to that of the references. The histological findings were consistent with the enzymatic results, showing a mild-to-moderate acute inflammation followed by a resolution of the inflammatory response with a decrease in inflammatory cells for each biodegradable membrane. The tissue reactions to the PPy, which was either in the form of nanoparticles or surface coating, were comparable to the response to the neighboring biodegradable materials. Elevated ED-2-positive macrophage populations appeared as early as day 3 in the loose connective tissue surrounding the implants. The density of these populations was related to the degree of inflammation. Scanning electron microscopy showed that the degradation of the PPy/PDLLA composite was not affected by the presence of PPy.