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Comparison of the biomechanics and histology of two soft-tissue fixators composed of bioabsorbable copolymers.

The purpose of this study was to assess the dynamic in vitro and in vivo characteristics of two different bioabsorbable copolymer soft-tissue fixation devices and to determine their efficacy in reattaching soft tissue to bone. Suretac fixators (Smith & Nephew/Acufex MicroSurgical Inc., Northwood, MA), made of polyglyconate (2:1 glycolic acid:trimethylene carbonate), and Pop Rivets (Arthrotek, Warsaw, IN), made of LactoSorb (82% poly L-lactic acid, 18% polyglycolic acid), were anchored into synthetic bone, and their pull-out strengths were evaluated. The devices were also evaluated with the use of an in vivo goat model in which the medial collateral ligament (MCL) was elevated from the tibia and directly reattached. In the in vitro biomechanical study, the Suretac fixators had negligible strength remaining by four weeks, whereas the Pop Rivets retained 50% of their strength at 4 weeks, 20% at 8 weeks, and negligible strength at 12 weeks. The in vivo strength of MCL repairs affected by each implant was not statistically different at any of the time points. Histologically, both implants were absorbed by 52 weeks, and there was no appreciable adverse tissue response. In conclusion, both copolymer fixators were found to be biocompatible. The Pop Rivet fixators demonstrated in vivo performance comparable to the Suretac fixators, although the Pop Rivets retained strength longer in vitro. Our results suggest that both devices provide adequate strength of fixation before degrading to allow the healing soft tissues to reach or surpass their native strength.

Absorption↗

A composite polymer/tricalcium phosphate membrane for guided bone regeneration in maxillofacial surgery.

The aim of the study was the development of a resorbable membrane for guided bone regeneration (GBR) with improved biocompatibility, which should be stiff enough to avoid membrane collapse during bone healing. Combining a bioactive ceramic with a resorbable polymer may improve the biocompatibility and osteoconductivity of resorbable devices. The present article describes the preparation, the mechanical properties, and the in vitro degradation characteristic of a composite membrane made of poly(L, DL-lactide) and alpha-tricalcium phosphate in comparison to a membrane made of pure poly(L, DL-lactide). The tensile strength and the elastic modulus as well as the molecular weight of the membranes were measured after in vitro degradation in buffer at 37 degrees C up to 28 weeks. The initial tensile strength of the composite and the polymer membrane was 37.3 +/- 2.4 MPa and 27.7 +/- 2.3 MPa and the elastic modulus 3106 +/- 108 MPa and 3101 +/- 104 MPa, respectively. The mechanical properties remained constant up to 8 weeks and then decreased slowly until week 28. The molecular weight of both membranes decreased steadily from 170,000 D to 30,000 D. It was concluded that the mechanical requirements for a membrane for GBR were fulfilled by the composite membrane.

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Resorbable polymer fibers for ligament augmentation.

Resorbable augmentation devices for cruciate ligament surgery have been developed to temporarily protect healing tendon grafts or sutured ligaments against high tensile loads during the postoperative healing period. Materials available at present [e.g., polydioxanone (PDS)] show a half-life tensile strength of only 4-6 weeks, whereas the process of revitalization and recovering of the transplanted tendon graft can take up to 12 months. Therefore, a device that provides gradually decreasing mechanical properties with a half-time strength of at least 6 months would be desirable. In order to obtain a suitable material, we investigated the degradation kinetics of a variety of different resorbable fibers made of poly(L-lactide) and poly(L-lactide-co-glycolide). The fiber materials differed in processing and treatment parameters like thermal posttreatment, irradiation, and fiber diameter. The fibers were degraded in vitro and were tested for mechanical properties and molecular weight at various time points up to 72 weeks. The half-time strength of the materials ranged between 5 and 64 weeks, depending on their treatment parameters. In contrast, the stiffness did not decrease adequately. However, an augmentation stiffness that does not change much versus time could not provide a gradual increase in graft load, which is important to stimulate the orientation of the collagenous tissue. Therefore, design of an augmentation construct braided out of more than one quickly degrading fiber materials is suggested. After the breakdown of the faster-degrading fiber components the stiffness would automatically decrease by the diminution of the load-carrying fiber volume.

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Fabrication of poly(alpha-hydroxy acid) foam scaffolds using multiple solvent systems.

The present studies describe the fabrication and characterization of highly porous and interconnected poly(alpha-hydroxy acid) foam scaffolds produced using a phase separation multisolvent system, followed by a sublimation process. Fabrication parameters, including solvent composition, polymer concentration, freezing temperature, polymer type, and polymer molecular weight, were optimized to produce the desired foam microstructure. Analyses of selected samples with scanning electron microscopic images and mercury intrusion porosimetry indicated polymer foams with pore size ranges of 100-350 microm, a porosity >90%, and an interconnecting open-pore foam structure. Scaffold degradation profiles varied according to the type and molecular weight of the polymers. Cytocompatibility assays demonstrated that the preferred foam structures were nontoxic and osteoprecursor cells seeded into the scaffolds exhibited the ability to attach, propagate, and differentiate into a calcified structure.

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Preparation, degradation, and calcification of biodegradable polyurethane foams for bone graft substitutes.

Autogenous cancellous bone graft is used to heal critical-size segmental long bone defects and defects in the maxillofacial skeleton. Harvesting of bone graft is traumatic, causes morbidity of the donor site, and often results in complications. Thus, there is a need for new biologically functional bone graft substitutes that, instead of autogenous bone graft, could be used to facilitate bone regeneration in critical-size defects. Porous biodegradable elastomeric polyurethane scaffolds combined with the patient's own bone marrow could potentially be such bone substitutes. The elastomeric bone substitute prevents shear forces at the interface between bone and rigid, e.g., ceramic bone substitutes and establishes an intimate contact with the native bone ends, thus facilitating the proliferation of osteogenic cells and bone regeneration. Crosslinked 3D biodegradable polyurethane scaffolds (foams) with controlled hydrophilicity for bone graft substitutes were synthesized from biocompatible reactants. The scaffolds had hydrophilic-to-hydrophobic content ratios of 70:30, 50:50, and 30:70. The reactants used were hexamethylene diisocyanate, poly(ethylene oxide) diol (MW = 600) (hydrophilic component), and poly(epsilon-caprolactone) diol (M(w) = 2000), amine-based polyol (M(w) = 515) or sucrose-based polyol (M(w) = 445) (hydrophobic component), water as the chain extender and foaming agent, and stannous octoate, dibutyltin dilaurate, ferric acetylacetonate, and zinc octoate as catalysts. Citric acid was used as a calcium complexing agent, calcium carbonate, glycerol phosphate calcium salt, and hydroxyapatite were used as inorganic fillers, and lecithin or solutions of vitamin D(3) were used as surfactants. The scaffolds had an open-pore structure with pores whose size and geometry depended on the material's chemical composition. The compressive strengths of the scaffolds were in the range of 4-340 kPa and the compressive moduli in the range of 9-1960 kPa, the values of which increased with increasing content of polycaprolactone. Of the two materials with the same amount of polycaprolactone the compressive strengths and moduli were higher for the one containing inorganic fillers. The scaffolds absorbed water and underwent controlled degradation in vitro. The amount of absorbed water and susceptibility to degradation increased with the increasing content of the polyethylene oxide segment in the polymer chain and the presence in the material of calcium complexing moiety. All polyurethane scaffolds induced the deposition of calcium phosphate crystals, the structure and calcium:phosphorus atomic ratio of which depended on the chemical composition of the polyurethane and varied from 1.52-2.0.

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Preparation and characterization of macroporous chitosan-gelatin/beta-tricalcium phosphate composite scaffolds for bone tissue engineering.

A biodegradable composite scaffold was developed using beta-tricalcium phosphate (beta-TCP) with chitosan (CS) and gelatin (Gel) in the form of a hybrid polymer network (HPN) via co-crosslinking with glutaraldehyde. Various types of scaffolds were prepared by freezing and lyophilizing. These scaffolds were characterized by Fourier transform infrared, X-ray diffractometer, and scanning electron microscopy. The macroporous composite scaffolds exhibited different pore structures. Compressive properties were improved, especially compressive modulus from 3.9-10.9 MPa. Biocompatibility was evaluated subcutaneously on rabbits. A mild inflammatory response was observed over 12 weeks. The results suggest that the scaffolds can be utilized in nonloading bone regeneration.

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Platelet responses and coagulation activation on polylactide and heparin-polycaprolactone-L-lactide-coated polylactide stent struts.

Despite modern stent technology and effective antiplatelet therapy, metallic stents carry the risk of (sub)acute thrombosis. Our aim was to examine short-term differences in platelet deposition and coagulation activation between biodegradable polylactide (PLA), heparin-polycaprolactone-L-lactide-coated polylactide (hepa-P(CL95/L-LA5)-PLA), and stainless steel (SS) stent struts. Gel-filtered platelets (GFP) and platelet-rich plasma (PRP) were labeled with 10 nM (3)H-serotonin. Platelet deposition was measured after incubation of the stent struts in human serum albumin-coated wells at 37 degrees C in either GFP or PRP. Platelet morphology was studied by scanning electron microscopy (SEM). For coagulation activation, the stent struts were incubated in either PRP or platelet-poor plasma (PPP), anticoagulated with D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK), followed by measurement of fibrinogen, thrombin time (TT), prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complex (TAT). SS showed adherence of larger amounts of GFPs than did PLA at a platelet density of 300 x 10(6)/mL (p < 0.05). Furthermore, representative SEM studies showed more platelet spreading on SS than on PLA stent struts. Between PLA and SS, coagulation activity did not differ at any assessment. Based on prolonged TT values in plasma, the heparin coating strongly inhibited coagulation (p < 0.05). The values of soluble TAT and F1+2 for PLA were similar to those of controls, i.e., to incubated suspensions without a stent strut. In conclusion, when compared with stainless steel, both PLA and hepa-P(CL95/L-LA5)-PLA appear hemocompatible as intravascular stent materials.

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Porous polymer scaffolds surface-modified with arginine-glycine-aspartic acid enhance bone cell attachment and differentiation in vitro.

This study was designed to determine if the surface modification of porous poly(lactic acid) (PLA) scaffolds would enhance osteogenic precursor cell (OPC) attachment, growth, and differentiation. A covalently grafted amino group (-NH(2)), poly(L-lysine) (PLL), and the peptide arginine-glycine-aspartic acid (RGD) were selected for the evaluation. The hypothesis was that surface modification would have a positive impact on cell-substratum interactions. The experiment was performed by OPC cells being placed on PLA films and scaffolds modified with NH(2), PLL, or RGD in tissue culture media. OPC attachment to PLA films was assessed after 24 h of incubation. The growth and differentiation of the adherent OPCs on porous PLA scaffolds were assessed after 14 and 28 days for alkaline phosphatase (APase) activity and calcium levels, both of which increase as OPCs differentiate into mature bone cells. All assays were accomplished in triplicate, and data were tested with post hoc orthogonal contrasts (i.e., Fisher's least significant difference) at p < or = 0.05. The PLA film surface-modified with RGD showed better OPC cell attachment than the other films. The cells on the PLA scaffolds surface-modified with RGD also exhibited an increase in APase activity and calcium levels in comparison with those on other scaffolds. This difference was apparent at both time intervals and was especially evident in the tissue culture media containing an osteogenic supplement. The results of this study indicate that modifying the surface of PLA polymer scaffolds with RGD enhances bone cell attachment and differentiation and may improve their ability to regenerate bone tissue more efficiently in wound models.

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Efficacy of glow discharge gas plasma treatment as a surface modification process for three-dimensional poly (D,L-lactide) scaffolds.

Gas plasma surface modification of three-dimensional poly (D,L-lactide) scaffolds fabricated by a novel vibrating particle fabrication technique was demonstrated to enhance cell adhesion, proliferation, and differentiation over 10 days in culture using human embryonic palatal mesenchyme cells. Characterization of corresponding two-dimensional treated surfaces revealed decreased contact angle measurements of 54.2 +/- 0.6 degrees for treated surfaces compared to 72.3 +/- 0.7 degrees for control surfaces (p < 0.05). SEM of treated surfaces revealed increased surface roughness combined with marked pitting and erosion. This may contribute to increased cell adhesion. WST-1 cell proliferation assay measurements as an index of cell numbers revealed a statistically significant increase in proliferation activity on treated surfaces on days 1 and 4 compared with controls. There was a fivefold increase in WST-1 activity for both control and treated groups over 10 days. Confocal laser micrographs revealed increased cell numbers on treated specimens throughout all layers of the scaffold, indicating that the glow discharge process enhanced cell proliferation throughout the entire scaffold architecture. Scanning electron micrographs demonstrated increased cell adhesion for treated specimens at the polymer surface most evident after days 1 and 4 of culture. Alkaline phosphatase (ALP)-specific activity peaked by day 7 for control and treated surfaces, indicating cellular differentiation. There was a trend for increased protein production on the treated specimens compared with controls at the initial time points although the differences were not statistically significant. These results demonstrated that gas plasma surface modification enhances osteoblast-like cell function in a three-dimensional scaffold model.

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Elastic biodegradable poly(glycolide-co-caprolactone) scaffold for tissue engineering.

Cyclic mechanical strain has been demonstrated to enhance the development and function of engineered smooth muscle (SM) tissues, and it would be necessary for the development of the elastic scaffolds if one wishes to engineer SM tissues under cyclic mechanical loading. This study reports on the development of an elastic scaffold fabricated from a biodegradable polymer. Biodegradable poly(glycolide-co-caprolactone) (PGCL) copolymer was synthesized from glycolide and epsilon-caprolactone in the presence of stannous octoate as catalyst. The copolymer was characterized by (1)H-NMR, gel permeation chromatography and differential scanning calorimetry. Scaffolds for tissue engineering applications were fabricated from PGCL copolymer using the solvent-casting and particle-leaching technique. The PGCL scaffolds produced in this fashion had open pore structures (average pore size = 250 microm) without the usual nonporous skin layer on external surfaces. Mechanical testing revealed that PGCL scaffolds were far more elastic than poly(lactic-co-glycolic acid) (PLGA) scaffolds fabricated using the same method. Tensile mechanical tests indicated that PGCL scaffolds could withstand an extension of 250% without cracking, which was much higher than withstood by PLGA scaffolds (10-15%). In addition, PGCL scaffolds achieved recoveries exceeding 96% at applied extensions of up to 230%, whereas PLGA scaffolds failed (cracked) at an applied strain of 20%. Dynamic mechanical tests showed that the permanent deformation of the PGCL scaffolds in a dry condition produced was less than 4% of the applied strain, when an elongation of 20% at a frequency of 1 Hz (1 cycle per second) was applied for 6 days. Moreover, PGCL scaffolds in a buffer solution also had permanent deformations less than 5% of the applied strain when an elongation of 10% at a frequency of 1 Hz was applied for 2 days. The usefulness of the PGCL scaffolds was demonstrated by engineering SM tissues in vivo. This study shows that the elastic PGCL scaffolds produced in this study could be used to engineer SM-containing tissues (e.g. blood vessels and bladders) in mechanically dynamic environments.

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Novel poly(ethylene glycol) scaffolds crosslinked by hydrolyzable polyrotaxane for cartilage tissue engineering.

Highly porous poly(ethylene glycol) (PEG) hydrogel scaffolds crosslinked with hydrolyzable polyrotaxane for cartilage tissue engineering were prepared by a solvent casting/salt leaching technique. The resultant scaffolds have well interconnected microporous structures ranging from 87 to 90%. Pore sizes ranging from 115.5-220.9 microm appeared to be dependent on the size of the sieved sodium chloride particulates. Moreover, a dense surface skin layer was not found on either side of the scaffold surfaces. Using microscopic Alcian blue staining of the chondrocyte-seeded scaffolds, well adhered cells and newly produced glycosaminoglycans (GAG) were confirmed. Following the initial chondrocyte seeding onto the hydrogel scaffolds, the cell number was significantly increased, reaching 149, 877, and 1228 cells/mg of tissue at 8, 15, and 21 days in culture, respectively. The micrograph shows well adhered and spread chondrocytes in the interior pores and a cartilaginous extracellular matrix with a GAG fraction produced from the chondrocytes. Results suggest that the PEG hydrogel scaffolds crosslinked with the hydrolyzable polyrotaxane are a promising candidate for chondrocyte culture.

Absorbable Implants↗

Molecular responses of vascular smooth muscle cells to paclitaxel-eluting bioresorbable stent materials.

We studied the influence of paclitaxel, eluted from poly(L-lactic acid) (PLLA), on cultured vascular smooth muscle cell (VSMC) proliferation as a model of bioresorbable stent-induced restenosis. We blended paclitaxel in cast PLLA films (P-PLLA), demonstrating controlled release of the drug, then studied VSMC adhesion, proliferation, and gene expression profiles. No difference in cell adhesion was found between P-PLLA and PLLA controls (105 +/- 12% of PLLA controls). However, P-PLLA significantly reduced VSMC proliferation (40 +/- 15% of PLLA controls, p < 0.05). Using cDNA microarray technology, we identified major effects of P-PLLA, including: upregulation of genes related to apoptosis, anti-proliferation and antioxidation; and suppression of cell cycle regulators and cell survival markers. The expression patterns indicate that P-PLLA regulates gene expression and cell functions via new pathways, including receptor tyrosine kinase (RTKs), mitogen-activated protein kinase (MAPKs), and protein kinase (PKs, e.g., PKA) pathways, in addition to the stabilization of polymerized-microtubules.

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Engineering bone-like tissue in vitro using human bone marrow stem cells and silk scaffolds.

Porous biodegradable silk scaffolds and human bone marrow derived mesenchymal stem cells (hMSCs) were used to engineer bone-like tissue in vitro. Two different scaffolds with the same microstructure were studied: collagen (to assess the effects of fast degradation) and silk with covalently bound RGD sequences (to assess the effects of enhanced cell attachment and slow degradation). The hMSCs were isolated, expanded in culture, characterized with respect to the expression of surface markers and ability for chondrogenic and osteogenic differentiation, seeded on scaffolds, and cultured for up to 4 weeks. Histological analysis and microcomputer tomography showed the development of up to 1.2-mm-long interconnected and organized bonelike trabeculae with cuboid cells on the silk-RGD scaffolds, features still present but to a lesser extent on silk scaffolds and absent on the collagen scaffolds. The X-ray diffraction pattern of the deposited bone corresponded to hydroxyapatite present in the native bone. Biochemical analysis showed increased mineralization on silk-RGD scaffolds compared with either silk or collagen scaffolds after 4 weeks. Expression of bone sialoprotein, osteopontin, and bone morphogenetic protein 2 was significantly higher for hMSCs cultured in osteogenic than control medium both after 2 and 4 weeks in culture. The results suggest that RGD-silk scaffolds are particularly suitable for autologous bone tissue engineering, presumably because of their stable macroporous structure, tailorable mechanical properties matching those of native bone, and slow degradation.

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Fabrication of biodegradable elastomeric scaffolds with sub-micron morphologies.

The native extracellular matrix (ECM) of elastic tissues is strong and flexible and supports cell adhesion and enzymatic matrix remodeling. In an attempt to convey these ECM properties to a synthetic scaffold appropriate for soft tissue engineering applications, a biodegradable, elastomeric poly(ester urethane)urea (PEUU) was combined with type I collagen at various ratios (2.5, 5, 10, 20, 50, 60, 70, 80, and 90 wt% collagen) and electrospun to construct elastic matrices. Randomly orientated fibers in the electrospun matrices ranged in diameter from 100-900 nm, dependent on initial polymer concentration. Picrosirius red staining of matrices and CD spectroscopy of released collagen confirmed collagen incorporation and preservation of collagen structure at the higher collagen mass fractions. Matrices were strong and distensible possessing strengths of 2-13 MPa with breaking strains of 160-280% even with low PEUU content. Collagen incorporation significantly enhanced smooth muscle cell adhesion onto electrospun scaffolds. An approach has been demonstrated that mimics elastic extracellular matrices by using a synthetic component to provide mechanical function together with a biomacromolecule, collagen. Such matrices may find application in engineering soft tissue.

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Preparation and characterization of a highly macroporous biodegradable composite tissue engineering scaffold.

A unique composite scaffold for bone-tissue engineering applications has been prepared by combining biodegradable poly(lactide-co-glycolide) (PLGA) with bioresorbable calcium phosphate (CaP) cement particles through the process of particle fusion and phase separation/particle leaching. The scaffold is characterized by a highly interconnected macroporosity, with macropores of 0.8-1.8 mm and porosities ranging from 81% to 91%, and improved mechanical properties with respect to the polymer alone, producing excellent dimensional stability. The scaffold properties were controlled by adjusting the processing parameters, including PLGA molar mass and concentration, CaP/PLGA ratio, and porogen size. The differences in mechanical properties between dry, wet/room temperature, and wet/37 degrees C testing conditions, of which the latter are more relevant for materials to be employed in a biological milieu, were investigated. Thus, a scaffold made from PLGA IV 1.13, PLGA concentration 12.5%, and CaP/PLGA ratio 2:1 exhibited significantly different compressive strengths of 0.16 MPa and 0.04 MPa when tested under dry and wet/37 degrees C conditions, respectively. .

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Changes in mechanical properties and cellularity during long-term culture of collagen fiber ACL reconstruction scaffolds.

Resorbable scaffolds for anterior cruciate ligament (ACL) reconstruction should provide temporary mechanical function then gradually breakdown while promoting matrix synthesis by local cells. Crosslinking influences collagen's mechanical properties, degradation rate, and interactions with cells. Our objective was to compare the effects of different crosslinkers on cellularity and mechanical properties during long-term (8 week) culture of collagen fiber scaffolds. Fibers were fabricated from an acid-insoluble dispersion of bovine dermal collagen and crosslinked with either ultraviolet irradiation (UV; a physical crosslinker) or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC; a chemical crosslinker). Scaffolds consisted of 50 fibers bundled in parallel. Initial attachment of fibroblasts was similar on both scaffolds; however, from 1 to 8 weeks in culture, UV-crosslinked scaffolds had significantly more cells attached than EDC-crosslinked scaffolds. The initial breaking load (3.50 N) and stiffness (2.23 N/mm) of EDC-crosslinked scaffolds were significantly greater than those of UV-crosslinked scaffolds (2.32 N; 1.21 N/mm) and were unaffected by long-term fibroblast culture. In contrast, the load-bearing capacity of fibroblast-seeded UV-crosslinked scaffolds decreased 60% to 0.91 N after 8 weeks in culture. EDC-crosslinked scaffolds maintained strength and moderate cellularity; UV-crosslinked scaffolds, in contrast, were highly cellular, but had poor mechanical properties that decreased during culture. These in vitro results suggest that collagen fiber scaffolds crosslinked with EDC may be more suitable for ACL reconstruction than those crosslinked with UV.

Absorbable Implants↗

Physical characteristics of small intestinal submucosa scaffolds are location-dependent.

Using biodegradable scaffolds as an alternative to engineer new tissues has become an attractive candidate in various transplantation protocols. In particular, small intestinal submucosa (SIS), a dense connective matrix harvested from the small intestine, has gained attention due to a number of favorable properties. However, use of SIS is constrained by obtaining reliable, reproducible products in large-scale preparations that affect the regenerative process. To better understand the heterogeneous nature of SIS, this study focused on evaluating the location-dependent alterations in the physical characteristics of the matrices harvested from distal and proximal ends and processed in-house (referred as hand-made). Additionally, results were compared with a commercially available machine-made Cook SIS. Tensile properties during monotonic loading and cyclical loading were compared in wet conditions. Furthermore, permeability of these membranes to urea was analyzed using a custom-built chamber, and the microarchitecture was analyzed via scanning electron microscopy. These results showed that distal samples were more elastic and less permeable to urea relative to other samples. However, permeability in each sample was direction-dependent, that is, mucosal to serosal direction was less permeable compared to sorasal to mucosal direction in all the samples. Cook SIS was more susceptible to cyclical loading and had a shorter range of load carrying capacity. In summary, results show that physical characteristics of SIS are location-dependent.

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Mechanism(s) of increased vascular cell adhesion on nanostructured poly(lactic-co-glycolic acid) films.

Studies have shown that poly(lactic-co-glycolic acid) (PLGA) films with nanometer surface features promote vascular endothelial and smooth muscle cell adhesion. The objective of this in vitro research was to begin to understand the mechanisms behind this observed increase in vascular cell adhesion. Results provided evidence that nanostructured PLGA adsorbed significantly more vitronectin and fibronectin from serum compared to conventional (or those not possessing nanometer surface features) PLGA. When separately preadsorbing both vitronectin and fibronectin, increased vascular smooth muscle and endothelial cell density was observed on nanostructured (compared to conventional) PLGA. Additionally, blocking of cell-binding epitopes of fibronectin and vitronectin significantly decreased vascular cell adhesion on nanostructured (compared to conventional) PLGA. For this reason, results of the present in vitro study demonstrated that cell adhesive proteins adsorbed in different quantities and altered bioactivity on nanostructured compared to conventional PLGA topographies, which (at least in part) may account for the documented increased vascular cell adhesion on nanostructured PLGA. In this manner, this study continues to provide evidence for the promise of nanostructured PLGA in vascular tissue engineering applications.

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