Immobilization Of RGD Peptide Research Articles

The promoting effect of the TiO2 nano-porous arrays after polydopamine-based modification and Arg-Gly-Asp peptide immobilization on biomineralization and osteogenesis

TiO2 nano-porous arrays with appropriate structural parameters, roughness and wettability have application potential in implantable titanium-based (Ti-based) alloys. In this research, the polydopamine (PDA) and Arg-Gly-Asp (RGD) peptide are adopted to construct a favorable osteogenic microenvironment on the anodized TiO2 nano-porous arrays before and after heat treatment. The characterization of surface morphologies and chemical compositions has been conducted to confirm the feasibility of the PDA-based modification and RGD peptide immobilization. Via immersion in the modified-simulated body fluid (m-SBF) for 7 days, the PDA-based modified samples have represented enhanced biomineralization performance. Moreover, the cell adhesion and proliferation assay, alkaline phosphatase (ALP) activity assay and quantitative real-time polymerase chain reaction (qRT-PCR) assay in vitro have indicated that the heat-treated TiO2 nano-porous arrays modified with PDA and RGD peptide have endowed the seeded MC3T3-E1 mouse pre-osteoblasts with excellent osteogenic performance. Such modified TiO2 nano-porous arrays have great latent capacity in implantable materials for biomineralization and osteogenesis.

A low-fouling, self-assembled, graft co-polymer and covalent surface coating for controlled immobilization of biologically active moieties

Current biointerfaces aiming to steer specific biological responses frequently lack either stability due to purely electrostatic interactions, bioactivity due to unspecific conjugation chemistries, specificity due to uncontrolled biological interactions such as fouling, or cytocompatibility due to harsh and toxic coating procedures. Here, we report a versatile surface modification platform for covalent tethering of selected biomolecules. New in this approach is the particular combination of modular binding blocks as graft co-polymer. Grafted to the backbone of PAcrAmTM multiple functionalities are strategically combined: covalent (silane) and non-covalent (lysine) surface binding groups for stability and self-assembly in mild buffered solution, PEG-azide chains for low fouling properties, and specific, controlled, covalent, linking of biologically active molecules. This modular strategy overcomes the previously mentioned limitations, for instance regarding bioactivity of the biological moiety due to highly specific strain-promoted azide-alkyne cycloaddition. The successful grafting of the copolymer was confirmed by 1H NMR. The immobilization of RGD peptides was characterized by combining surface analytical techniques, such as ToF-SIMS and ellipsometry, allowing quantification of immobilized molecules over an extensive range of concentrations (0.008–1.95 pmol·cm−2). The bioactivity over this range of concentrations was confirmed by in vitro cell studies, presenting a differential endothelial cell attachment and spreading. The modified substrates enabled the formation of an interconnected monolayer of endothelial cells. Furthermore, the modular platform allowed the co-immobilization of two bioactive functional groups, RGD and biotin, on the same surface, which could be exploited for the further development of controlled multi-functional biointerfaces for diverse biological applications in the future.

RGD-functionalization of anodized zirconium as a potential strategy for biomedical application: An in vitro study

The effect of functionalization of anodized zirconium (Zr) with RGD peptides on cell behavior as a feasible approach to stimulate early bone integration is presented. The surface modifications were evaluated by Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). Electrochemical tests were performed to determine the effect of functionalization on the stability of the anodized zirconium oxide film. Finally, the biocompatibility of the material was evaluated in an in vitro cell model. Surface analysis showed the presence of peptides on the surface after functionalization, and that the crystal structure of the oxide formed by anodization is predominantly monoclinic. The immobilization of RGD peptides on anodized Zr does not alter the corrosion protection provided by the anodic oxide and significantly promote cell adhesion and spreading in vitro. Thus, the combination of RGD peptides with anodic oxide on Zr surface would represent a useful strategy to increases the biocompatibility of the material.

Synergistic regulation of osteoimmune microenvironment by IL-4 and RGD to accelerate osteogenesis.

The control of early inflammatory reactions and recruitment of progenitor cells are critical for subsequent tissue repair and regeneration after biomaterial implantation. The aim of this study was to design a multi-functional biomaterial with a controlled drug delivery system to create an optimal local environment for early osteogenesis. Here, the anti-inflammatory cytokine IL-4 and pro-osteogenic RGD peptide were assembled layer-by-layer on TiO2 nanotubes. A poly(dopamine) (DOP) coating was employed onto TiO2 nanotubes (T/DOP) to functionalized with IL-4 (T/DOP-IL4). Then, a carboxymethyl chitosan hydrogel layer (CG) was generated on T/DOP-IL4 to control IL-4 release and RGD peptide immobilization. Cell co-culture models were applied to study macrophage polarization on various material surfaces and the regulation of mesenchymal stromal cell (MSC) osteogenic differentiation. Our data suggest that T/DOP-IL4/CG-RGD surfaces developed in this study are multi-functional, and can not only drive phenotypic changes in macrophages (switching to anti-inflammatory M2 phenotype), resulting in the production of reparative cytokines such as IL-10, but also enhance MSC differentiation related to the activation of BMP/SMAD/RUNX2 signaling. This study further confirmed that the introduction of anti-inflammatory cytokine (IL-4) and cell adhesive motif (RGD) onto Ti substrate can work synergistically to generate a more favorable early-stage osteo-immune environment with superior osteogenic properties, thus representing a potential ideal surface for the generation of bone biomaterials.

Impact of Bioactive Peptide Motifs on Molecular Structure, Charging, and Nonfouling Properties of Poly(ethylene oxide) Brushes

Polymer layers capable of suppressing protein adsorption from biological media while presenting extracellular matrix-derived peptide motifs offer valuable new options for biomimetic surface engineering. Herein, we provide detailed insights into physicochemical changes induced in a nonfouling poly(ethylene oxide) (PEO) brush/polydopamine (PDA) system by incorporation of adhesion ligand (RGD) peptides. Brushes with high surface chain densities (σ ≥ 0.5 chains·nm-2) and pronounced hydrophilicity (water contact angles ≤ 10°) were prepared by end-tethering of heterobifunctional PEOs ( Mn ≈ 20 000 g·mol-1) to PDA-modified surfaces from a reactive melt. Using alkyne distal end group on the PEO chains, azidopentanoic-bearing peptides were coupled through a copper-catalyzed Huisgen azide-alkyne "click" cycloaddition reaction. The surface concentration of RGD was tuned from complete saturation of the PEO surface with peptides (1.7 × 105 fmol·cm-2) to values which may induce distinct differences in cell adhesion (<6.0 × 102 fmol·cm-2). Infrared reflection-absorption and X-ray photoelectron spectroscopies proved the PDA-PEO layers covalent structure and the immobilization of RGD peptides. The complete reconstruction of experimental electrohydrodynamics data utilizing mean-field theory predictions further verified the attained brush structure of the end-tethered PEO chains which provided hydrodynamic screening of the PDA anchor. Increasing the surface concentration of immobilized RGD peptides led to increased interfacial charging. Supported by simulations, this observation was attributed to the ionization of functional groups in the amino acid sequence and to the pH-dependent adsorption of water ions (OH- > H3O+) from the electrolyte. Despite the distinct differences observed in the electrokinetic analysis of the surfaces bearing different amounts of RGD, it was found that the peptide presence on PEO(20 000)-PDA layers does not have a significant effect on the nonfouling properties of the system. Notably, the presented PEO(20 000)-PDA layers bearing RGD peptides in the surface concentration range 5.9 to 1.7 × 105 fmol·cm-2 reduced the protein adsorption from fetal bovine serum to less than 30 ng·cm-2, that is, values comparable to the ones obtained for pristine PEO(20 000)-PDA layers.

Influence of mixed organosilane coatings with variable RGD surface densities on the adhesion and proliferation of human osteosarcoma Saos-2 cells to magnesium alloy AZ31

In the last decade, the use of magnesium and its alloys as biodegradable implant materials has become increasingly accepted. However, surface modification of these materials to control the degradation rate in the early stages of healing and improve their biocompatibility is crucial to the successful implementation of magnesium alloy implants in medicine. Cell adhesion and proliferation at the implant surface is a vital factor for successful integration of a biomaterial within the body. Cells accomplish this task by binding to ligands such as the arginine-glycine-aspartic acid peptide sequence (RGD) commonly found on adhesive proteins present in the extracellular matrix. In this paper, we report a biomimetic surface modification strategy involving deposition of a mixed organosilane layer on Mg AZ31 followed by covalent immobilization of RGD peptides through a heterobifunctional cross-linker molecule. Our results indicate that with optimized deposition conditions uniform organosilane coatings were successfully deposited on the Mg AZ31 substrate. Furthermore, we have demonstrated that the surface density of immobilized RGD can be varied by depositing organosilane layers from solutions containing two different organosilanes in specified ratios. Increases in cell adhesion and cell proliferation were observed on the surface modified substrates.

MODIFICATION BY RGD-PEPTIDES OF VASCULAR GRAFTS OF SMALL DIAMETER FROM POLYPAROLACTONE: EXPERIMENTAL STUDY RESULTS

. To endow the luminal surface of the vascular grafts of functional, we applied arginine-glycineaspartic acid (RGD)-containing peptides, which are the ligands for integrins. The aim to study the effect of modification of small-diameter vascular grafts from polycaprolactone on the patency, speed and quality of endothelization of the internal surface after implantation of grafts into the abdominal part of the aorta of small laboratory animals by the RGD peptides. Materials and methods .Vascular grafts diameter 2 mm were fabricated of poly(ε-caprolactone) (PCL) using electrospinning following optional conjugation with RGD peptides by the method of carbodiimide binding. The surface morphology, physical-mechanical properties of PCL and PCL-RGD grafts was studied before implantation. Either PCL and PCL-RGD grafts were implanted into abdominal aorta of rats for 1, 3, 6, or 9 months following explantation along with the adjacent aortic regions and further histological and immunofluorescence examination. Results . We found that immobilization of RGD peptides at the luminal surface did not alter structure and mechanical properties of PCL grafts. Primary patency of the RGD-treated grafts was 50% higher while the prevalence of inflammation was 2-fold lower compared to PCL grafts at all the time points. Moreover, we identified CD31+vWF+ cells at the luminal surface of RGD-PCL grafts as early as 1 month postimplantation in comparison with 3 months postimplantation in PCL grafts. Conclusion . Immobilization of RGD peptides at the PCL grafts increases the primary grafts patency, induces rapid endothelialization and decreases granulomatous inflammation.

타이타늄 표면에 대한 생리활성물질 고정화에 관한 연구

The ultimate purpose of the various surface treatment of titanium is improvement of osseointegration of titanium. Recently, the surface treatment of titanium has focused on bioactive molecules deposition, such as RGD, BMP, and growth factor related on osteoblast proliferation and adhesion to enhance the osseointegration when titanium implant was applied in clinically. The RGD motif plays an important role in cell-matrix adhesion and activation of cell proliferation, apoptosis, and differentiation. In this study, after RGD peptide immobilization, the effect of RGD-immobilized titanium surface to osteoblast adhesion and proliferation were evaluated. RGD immobilized titanium by covalent bond promoted the MG63 osteoblast adhesion and spreading. The proliferation of MG 63 cells grown on RGD immobilized titanium was enhanced.

RGD functionalized poly(ε-caprolactone)/poly(m-anthranilic acid) electrospun nanofibers as high-performing scaffolds for bone tissue engineering RGD functionalized PCL/P3ANA nanofibers

ABSTRACTRGD functionalized nanofibers of poly(ε-caprolactone)/poly(m-anthranilic acid) (PCL/P3ANA) were fabricated to address the mechanical, structural and functional requirements of bone tissue engineering. Nanofibers containing the highest amount of P3ANA with more carboxyl groups for functionalization have exhibited higher surface area and better mechanical properties. FTIR-ATR and UV-visible measurements evidenced the covalent RGD immobilization. After RGD peptide immobilization, the surface properties of nanofibers changed as evidenced by contact angle and electrochemical impedance spectroscopy (EIS). The effects of RGD functionalized nanofibers (PCL/P3ANA-RGD) on Saos-2 cell attachment, proliferation, and osteogenic activity were investigated. PCL/P3ANA-RGD nanofibers favored cell attachment, proliferation, and osteogenic activity.

Immobilization of RGD peptide onto the surface of apatite-wollastonite ceramic for enhanced osteoblast adhesion and bone regeneration

The arginine-glycine-aspartic (RGD) acid peptide was grafted to the surface of apatite-wollastonite (AW) ceramic in an effort to improve its cell adhesion, proliferation and osteoinduction. RGD peptide was covalently immobilized onto the surface of AW ceramic via the synthetic cross linker AAPTS-E and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The modified surfaces were characterized by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The chemical analysis indicated that RGD peptide had been immobilized onto the AW surface successfully. The growth of osteoblast-like cells (MG63) showed that modifying the AW surface with RGD peptide enhanced the cell adhesion and proliferation. And the histological evaluation of RGD-AW showed that the bone regeneration and remodeling process were significantly enhanced compared to the original AW ceramics after 2, 4 and 8 weeks implantation in rabbit’s femoral condyles.

Bio‐inspired Immobilization of Cell‐Adhesive Ligands on Electrospun Nanofibrous Patches for Cell Delivery

AbstractAn electrospun fibrous mesh functionalized with a cell‐adhesive peptide inspired by polydopamine coating is developed as a novel cardiac patch. The amount of polydopamine on the PLCL meshes is affected by several parameters such as pH, concentration, reaction time, and temperature. Immobilization of RGD peptide is then easily achieved on the polydopamine‐coated meshes. The RGD‐peptide‐immobilized meshes increase adhesion of the myoblasts under serum‐free conditions, and also significantly up‐regulate their proliferation and the formation of multi‐nucleated myotubes. Therefore, RGD‐peptide‐functionalized, electrospun cardiac patches prepared by polydopamine coating method can be a useful tool to replace damaged myocardium. magnified image

Bone healing of commercial oral implants with RGD immobilization through electrodeposited poly(ethylene glycol) in rabbit cancellous bone

Immobilization of RGD peptides on titanium (Ti) surfaces enhances implant bone healing by promoting early osteoblastic cell attachment and subsequent differentiation by facilitating integrin binding. Our previous studies have demonstrated the efficacy of RGD peptide immobilization on Ti surfaces through the electrodeposition of poly(ethylene glycol) (PEG) (RGD/PEG/Ti), which exhibited good chemical stability and bonding. The RGD/PEG/Ti surface promoted differentiation and mineralization of pre-osteoblasts. This study investigated the in vivo bone healing capacity of the RGD/PEG/Ti surface for biomedical application as a more osteoconductive implant surface in dentistry. The RGD/PEG/Ti surface was produced on an osteoconductive implant surface, i.e. the grit blasted micro-rough surface of a commercial oral implant. The osteoconductivity of the RGD/PEG/Ti surface was compared by histomorphometric evaluation with an RGD peptide-coated surface obtained by simple adsorption in rabbit cancellous bone after 2 and 4weeks healing. The RGD/PEG/Ti implants displayed a high degree of direct bone apposition in cancellous bone and achieved greater active bone apposition, even in areas of poor surrounding bone. Significant increases in the bone to implant contact percentage were observed for RGD/PEG/Ti implants compared with RGD-coated Ti implants obtained by simple adsorption both after 2 and 4weeks healing (P<0.05). These results demonstrate that RGD peptide immobilization on a Ti surface through electrodeposited PEG may be an effective method for enhancing bone healing with commercial micro-rough surface oral implants in cancellous bone by achieving rapid bone apposition on the implant surface.

Gradient immobilization of a cell adhesion RGD peptide on thermal responsive surface for regulating cell adhesion and detachment

Using surface initiated atomic transfer radical polymerization (ATRP) and an injection method, a poly(N-isopropylacrylamide)-b-poly(acrylic acid)-g-RGD (PNIPAAm-b-PAA-g-RGD) gradient surface was prepared. First, a thermoresponsive surface with a constant thickness of PNIPAAm was fabricated, onto which the AA monomers were block copolymerized using the PNIPAAm macromolecules as initiators. During this process, a continuous injection method was employed to yield a molecular weight gradient of PAA on the underlying uniform PNIPAAm layer. RGD peptide was finally covalently immobilized onto the PAA gradient by carbodiimide chemistry. In vitro culture of HepG2 cells showed that immobilization of the RGD peptide could accelerate cell attachment, while the thermoresponsive layer beneath could effectively release the cells by simply lowering temperature. Thus, the PNIPAAm-b-PAA-g-RGD gradient surface, combining the thermal response with cell affinity properties, can well regulate the cell adhesion and detachment, which may thus be useful for investigation of cell-substrate interactions with a smaller number of samples.

The effect of immobilized RGD peptide in alginate scaffolds on cardiac tissue engineering

Cardiac tissue engineering aims to regenerate damaged myocardial tissues by applying heart patches created in vitro. The present study was undertaken to explore the possible role of matrix-attached RGD peptide in the engineering of cardiac tissue within macroporous scaffolds . Neonatal rat cardiac cells were seeded into RGD-immobilized or unmodified alginate scaffolds. The immobilized RGD peptide promoted cell adherence to the matrix, prevented cell apoptosis and accelerated cardiac tissue regeneration. Within 6 days, the cardiomyocytes reorganized their myofibrils and reconstructed myofibers composed of multiple cardiomyocytes in a typical myofiber bundle. The nonmyocyte cell population, mainly cardiofibroblasts, benefited greatly from adhering to the RGD–alginate matrix and consequently supported the cardiomyocytes. They often surrounded bundles of cardiac myofibers in a manner similar to that of native cardiac tissue. The benefits of culturing the cardiac cells in RGD-immobilized alginate scaffolds were further substantiated by Western blotting, revealing that the relative expression levels of α-actinin, N-cadherin and connexin-43 were better maintained in cells cultured within these scaffolds. Collectively, the immobilization of RGD peptide into macroporous alginate scaffolds proved to be a key parameter in cardiac tissue engineering, contributing to the formation of functional cardiac muscle tissue and to a better preservation of the regenerated tissue in culture.

Characterization of bioactive RGD peptide immobilized onto poly(acrylic acid) thin films by plasma polymerization

Plasma surface modification can be used to improve the surface properties of commercial pure Ti by creating functional groups to produce bioactive materials with different surface topography. In this study, a titanium surface was modified with acrylic acid (AA) using a plasma treatment and immobilized with bioactive arginine-glycine-aspartic acid (RGD) peptide, which may accelerate the tissue integration of bone implants. Both terminals containing the –NH2 of RGD peptide sequence and –COOH of poly(acrylic acid) (PAA) thin film were combined with a covalent bond in the presence of 1-ethyl-3-3-dimethylaminopropyl carbodiimide (EDC). The chemical structure and morphology of AA film and RGD immobilized surface were investigated by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR), atomic force microscopy (AFM), and scanning electron microscopy (SEM). All chemical analysis showed full coverage of the Ti substrate with the PAA thin film containing COOH groups and the RGD peptide. The MC3T3-E1 cells were cultured on each specimen, and the cell alkaline phosphatase (ALP) activity were examined. The surface-immobilized RGD peptide has a significantly increased the ALP activity of MC3T3-E1 cells. These results suggest that the RGD peptide immobilization on the titanium surface has an effect on osteoblastic differentiation of MC3T3-E1 cells and potential use in osteo-conductive bone implants.

The effect of immobilized RGD peptide in macroporous alginate scaffolds on TGFβ1-induced chondrogenesis of human mesenchymal stem cells

Human bone marrow-derived mesenchymal stem cells (hMSCs) are promising cell candidates for cartilage regeneration. Building the appropriate microenvironment for cell differentiation in response to exogenous stimuli is a critical step towards the clinical utilization of hMSCs. In this study, the effects of RGD peptide immobilization onto macro-porous alginate scaffolds on TGF-β1-induced hMSC chondrogenesis were evaluated. The results revealed different cell morphology, viability and proliferation extent in the RGD-immobilized vs. un-modified scaffolds. The TGF-β1-induced activation of both Smad-dependent (SMAD2) and Smad-independent (ERK1/2) signaling pathways was stronger and persisted for over 3 weeks in the RGD-immobilized scaffolds, indicating greater accessibility of the cells to the inducer. By contrast, in the un-modified alginate scaffolds, the cells aggregated into compacted clusters resulting in lesser effects of TGF-β1. The efficient and prolonged exposure to the chondrogenic inducer in the RGD-modified scaffolds ensured the appropriate progression of MSC differentiation from the initial phase of cell condensation until the appearance of committed chondrocytes, at 3 weeks of cultivation. Taken together, our results highlight the fundamental importance of the microenvironment design of the scaffold as well as the presentation of the inductive cue for inducing efficient stem-cell controlled differentiation.

Immobilization of RGD peptide on HA coating through a chemical bonding approach

In this work, Arg-Gly-Asp (RGD) sequence containing peptide was immobilized on hydroxyapatite (HA) coatings through a chemical bonding approach in two steps, surface modification with 3-aminopropyltriethoxysilane (APTES) and RGD immobilization. The results indicate that RGD has been successfully immobilized on HA coatings. Comparing with physical adsorption coatings, the chemically bonded RGD on the coatings shows much better anti-wash-out ability. Since RGD is able to recognize cell-membrane integrins on biointerfaces, the present method will be an effective way to favor interaction of cells with HA coatings.

Effect of RGD‐Immobilized Dual‐Pore Poly(l‐Lactic Acid) Scaffolds on Chondrocyte Proliferation and Extracellular Matrix Production

Interactions between cell and polymer surface have great implications in tissue engineering. In this study, chondrocyte proliferation and matrix production were examined using porous poly(L-lactide) (PLLA) scaffolds that have different surface characteristics. PLLA scaffolds were prepared using a gas-foaming method, and subjected to surface modifications through plasma treatment and subsequent in situ grafting of hydrophilic acrylic acid (AA). To immobilize peptide ligands, the AA-grafted PLLA scaffolds (PLLA-PAA) were further reacted with either Gly-Arg-Asp-Gly (GRDG) or Gly-Arg-Gly-Asp (GRGD) to produce PLLA-PAA-GRDG or PLLA-PAA-GRGD scaffold, respectively. The average porosities of the scaffolds were more than 90%, and their pore sizes ranged from 200 approximately 300 to 10 approximately 50 microm for large and small pores, respectively. The concentrations of each bound component were 2.14 x 10(-4) mmol/cm(2) for AA, 1.87 nmol/g for GRDG, and 1.68 nmol/g for GRGD. When chondrocytes were seeded onto the different PLLA scaffolds, cell adhesion and proliferation were highly affected as the substrate types vary. The RGD-immobilized scaffolds resulted in higher cellularity and better accumulation of total glycosaminoglycan than the others. Histological staining of Safranin O showed that the deposited extracellular matrix was more intense and widely distributed in the PLLA-PAA-GRGD scaffold. The present data suggest that immobilization of RGD peptide on the AA-grafted PLLA scaffold can be an effective tool for chondrocyte attachment and proliferation, and that it may also be helpful to facilitate cartilaginous tissue formation.

Immobilization of RGD peptides onto decellularized valve scaffolds to promote cell adhesion

Porcine aortic valves were decellularized with trypsinase/EDTA and Triton-100. With the help of a coupling reagent Sulfo-LC-SPDP, the biological valve scaffolds were immobilized with one of RGD (arginine-glycine-aspartic acid) containing peptides, called GRGDSPC peptide. Myofibroblasts harvested from rats were seeded onto them. Based on the spectra of X-ray photoelectron spectroscopy, we could find conjugation of GRGDSPC peptide and the scaffolds. Cell count by both microscopy and MTT assay showed that myofibroblasts were easier to adhere to the modified scaffolds. It is proved that it is feasible to immobilize RGD peptides onto decellularized valve scaffolds, and effective to promote cell adhesion, which is beneficial for constructing tissue engineering heart valves in vitro.

Surface modification and fibrovascular ingrowth of porous polyethylene anophthalmic implants

The purpose of this study was to determine the effect of surface modification on the fibrovascular ingrowth into porous polyethylene (PE) spheres (Medpor®), which are used as an anophthalmic socket implant material. To make the inert, hydrophobic PE surface hydrophilic, nonporous PE film and porous PE spheres were subjected to plasma treatment andin situ acrylic acid (AA) grafting followed by the immobilization of arginine-glycineaspartic acid (RGD) peptide. The surface-modified PE was evaluated by performing surface analyses and tested for fibroblast adhesion and proliferationin vitro. In addition, the porous PE implants were inserted for up to 3 weeks in the abdominal area of rabbits and, after their retrieval, the level of fibrovascular ingrowth within the implants was assessedin vivo. As compared to the unmodified PE control, a significant increase in the hydrophilicity of both the AA-grafted (PE-g-PAA) and RGD-immobilized PE (PE-g-RGD) was observed by the measurement of the water contact angle. The cell adhesion at 72 h was most notable in the PE-g-RGD, followed by the PE-g-PAA and PE control. There was no significant difference between the two modified surfaces. When the cross-sectional area of tissue ingrowthin vivo was evaluated, the area of fibrovascularization was the largest with PE-g-RGD. The results of immunostaining of CD31, which is indicative of the degree of vascularization, showed that the RGD-immobilized surface could elicit more widespread fibrovascularization within the porous PE implants. This work demonstrates that the present surface modifications, viz. hydrophilic AA grafting and RGD peptide immobilization, can be very effective in inducing fibrovascular ingrowth into porous PE implants.