PDLLA Films Research Articles

Porous Polymeric Nanofilms for Recreating the Basement Membrane in an Endothelial Barrier-on-Chip.

Organs-on-chips (OoCs) support an organotypic human cell culture in vitro. Precise representation of basement membranes (BMs) is critical for mimicking physiological functions of tissue interfaces. Artificial membranes in polyester (PES) and polycarbonate (PC) commonly used in in vitro models and OoCs do not replicate the characteristics of the natural BMs, such as submicrometric thickness, selective permeability, and elasticity. This study introduces porous poly(d,l-lactic acid) (PDLLA) nanofilms for replicating BMs in in vitro models and demonstrates their integration into microfluidic chips. Using roll-to-roll gravure coating and polymer phase separation, we fabricated transparent ∼200 nm thick PDLLA films. These nanofilms are 60 times thinner and 27 times more elastic than PES membranes and show uniformly distributed pores of controlled diameter (0.4 to 1.6 μm), which favor cell compartmentalization and exchange of large water-soluble molecules. Human umbilical vein endothelial cells (HUVECs) on PDLLA nanofilms stretched across microchannels exhibited 97% viability, enhanced adhesion, and a higher proliferation rate compared to their performance on PES membranes and glass substrates. After 5 days of culture, HUVECs formed a functional barrier on suspended PDLLA nanofilms, confirmed by a more than 10-fold increase in transendothelial electrical resistance and blocked 150 kDa dextran diffusion. When integrated between two microfluidic channels and exposed to physiological shear stress, despite their ultrathin thickness, PDLLA nanofilms upheld their integrity and efficiently maintained separation of the channels. The successful formation of an adherent endothelium and the coculture of HUVECs and human astrocytes on either side of the suspended nanofilm validate it as an artificial BM for OoCs. Its submicrometric thickness guarantees intimate contact, a key feature to mimic the blood-brain barrier and to study paracrine signaling between the two cell types. In summary, porous PDLLA nanofilms hold the potential for improving the accuracy and physiological relevance of the OoC as in vitro models and drug discovery tools.

Gelatinized PLCL Electrospun Membrane for the Prevention of Postoperative Abdominal Adhesion Through Fibrinolysis Activation

AbstractAbdominal adhesion is a common complication after surgery, which causes pain to patient and increases the risks of reoperation. Electrospinning polyester membrane serving as a physical barrier is used for preventing abdominal adhesion; however, the efficacy is limited due to the lacking of bioactivity necessary for antiadhesion. Here, hydrophobic poly(l‐lactide‐co‐caprolactone) (PLCL) electrospinning membranes are hydrophilized with photo‐crosslinked methacrylic anhydride gelatin (GelMA) hydrogel for postoperative abdominal adhesion prevention. The composite membranes show fibrous network architecture, good cytocompatibility, and hydrophilicity than commercial poly(d,l‐lactide acid) (PDLLA) film. Importantly, the composite membrane provides superior antiadhesion effect over PLCL membrane alone or commercial PDLLA film, against abdominal wall–cecum adhesion models in Sprague Dawley (SD) rats. The underlying mechanism is that PLCL/GelMA membrane successfully promotes the secretion of matrix metalloproteinases 9 (MMP‐9) that can reduce the collagen deposition in extracellular matrix (ECM). Furthermore, the composite membrane significantly upregulates the expression of tissue‐type plasminogen activator (t‐PA) and downregulates the production of plasminogen activator inhibitor‐1 (PAI‐1), leading to the activation of fibrinolytic system, which inhibits the formation of adhesive tissues. Collectively, gelatinized PLCL electrospun membrane is a promising bioactive barrier for preventing postsurgery abdominal adhesions.

Ultra-Thin Porous PDLLA Films Promote Generation, Maintenance, and Viability of Stem Cell Spheroids.

Three-dimensional (3D) culture bridges and minimizes the gap between in vitro and in vivo states of cells and various 3D culture systems have been developed according to different approaches. However, most of these approaches are either complicated to operate, or costive to scale up. Therefore, a simple method for stem cell spheroid formation and preservation was proposed using poly(D,L-lactic acid) porous thin film (porous nanosheet), which were fabricated by a roll-to-roll gravure coating method combining a solvent etching process. The obtained porous nanosheet was less than 200 nm in thickness and had an average pore area of 6.6 μm2 with a porosity of 0.887. It offered a semi-adhesive surface for stem cells to form spheroids and maintained the average spheroid diameter below 100 μm for 5 days. In comparison to the spheroids formed in suspension culture, the porous nanosheets improved cell viability and cell division rate, suggesting the better feasibility to be applied as 3D culture scaffolds.

Well-ordered chitin whiskers layer with high stability on the surface of poly(d,l-lactide) film for enhancing mechanical and osteogenic properties

In order to better utilize and combine the advantages of poly(d,l-lactide) (PDLLA) matrix and natural polysaccharide chitin whiskers (CHWs), needle-like CHWs with chiral nematic liquid crystal characteristics and remarkable moduli were chosen to surface modify PDLLA film. By a vertical coating method, a stable and well-ordered CHWs coating was formed on the surface of the PDLLA film through a polydopamine (PDA) interlayer. The high stability of the well-ordered CHWs coating on the surface of the PDLLA film was confirmed by PBS soaking experiment in terms of the changes of weight and surface morphology of the film. The surface microstructure and composition of the resulting PDLLA-PDA-CHWs film were characterized by field emission scanning electron microscopy (FESEM), atomic force microscope (AFM) and X-ray photoelectron spectroscopy (XPS), and the thickness of the PDLLA, PDA and CHWs layers was determined using FESEM, too. Comparing with traditional PDLLA/CHWs film, prepared by solution blending with optimal content of 5 wt% CHWs, the hydrophilicity and mechanical properties of the PDLLA-PDA-CHWs film were significantly improved owing to the immobilization of a highly ordered CHWs coating. Furthermore, in vitro cell culture showed that the well-ordered CHWs coating had a more significant effect on promoting the adhesion, spreading, proliferation and osteogenic differentiation of MC3T3-E1 cells. All these results showed that the resulting PDLLA-PDA-CHWs film with well-ordered CHWs coating designed through simple and effective approach has promising application in bone repair material field.

In vitro release study of sirolimus from a PDLLA matrix on a bioresorbable drug-eluting stent

Releasing the correct therapeutic drug dose from a bioresorbable drug-eluting stent (DES) is important for inhibiting smooth muscle cell growth, neointimal hyperplasia and in-stent restenosis (ISR). In this study, the in vitro release profiles of sirolimus-in-poly (D, l-lactide) (PDLLA) coatings were investigated under various conditions. First, single-layer, bilayer and various ratios of sirolimus/PDLLA coatings on biodegradable poly (l-lactide) (PLLA) stents and tubes were prepared. There was no apparent delamination or cracking on the stent coating surfaces that had undergone crimping and expansion. Second, the degradation performance of drug-free PDLLA films was investigated to analyse the effects of changes in molecular weight and mass loss. Finally, the in vitro sirolimus release profiles of various coating formulas in phosphate-buffered saline (PBS) were studied by high-performance liquid chromatography (HPLC). The results indicated that the profiles exhibited similar two-phase release kinetics, but the initial release rates were quite different. Moreover, coatings with polyethylene glycol (PEG) additives were prepared to assess their controlled release behaviours. The work reported herein represents a step towards establishing an in vitro release model, which will be verified in future works after comparison with in vivo release profiles.

Poly(trimethylene carbonate) as an elastic biodegradable film for human embryonic stem cell-derived retinal pigment epithelial cells.

Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cell therapies show tremendous potential for the treatment of retinal degenerative diseases. A tissue engineering approach, where cells are delivered to the subretinal space on a biodegradable carrier as a sheet, shows great promise for these RPE cell therapies. The aim of the present study was to assess whether a flexible, elastic and biodegradable poly(trimethylene carbonate) (PTMC) film promotes the formation of functional hESC-RPE and performs better than often used biodegradable poly(d,l-lactide) (PDLLA) film. Human ESC-RPE maturation and functionality on PTMC films was assessed by cell proliferation assays, RPE-specific gene and protein expression, phagocytic activity and growth factor secretion. It is demonstrated that the mechanical properties of PTMC films have close resemblance to those of the native Bruch's membrane and support the formation hESC-RPE monolayer in serum-free culture conditions with high degree of functionality. In contrast, use of PDLLA films did not lead to the formation of confluent monolayers of hESC-RPE cells and had unsuitable mechanical properties for retinal application. In conclusion, the present study indicates that flexible and elastic biodegradable PTMC films show potential for retinal tissue engineering applications. Copyright © 2017 John Wiley & Sons, Ltd.

Preparation and characterization of uniaxial poly(lactic acid)-based self-reinforced composites

Abstract Uniaxial poly(lactic acid)-based self-reinforced composites have been developed by bonding poly ( l -lactic acid) (PLLA) fibers by depositing poly(D, l -lactic acid) (PDLLA) which was dissolved in ethyl acetate. The microstructure and the thermal and mechanical properties of this self-reinforced composite have been characterized using scanning electron microscopy, dynamic mechanical analysis, and tensile testing. The results revealed that after ethyl acetate treatment, the PLLA fibers maintained their geometry and orientation well, had an increased crystallinity, and showed a slightly damaged surface. Electron microscopy and thermal analysis showed that the interface between the PLA fiber and the PLA matrix had good compatibility, which was expected since they possess the same chemical structure. The modulus, tensile strength, and elongation, as well as the thermal stability of uniaxial poly(lactic acid) self-reinforced composites, were all significantly greater than those of the PDLLA film. The results showed that we have developed a method to prepare PLA composites with enhanced mechanical properties, without the problem of narrow processing temperature window normally required when using traditional thermal processing techniques.

Microcantilever sensors for fast analysis of enzymatic degradation of poly (d, l-lactide)

In this work we have performed a detailed analysis of enzymatic degradation of amorphous poly (d, l-lactide) (PDLLA) by measuring the resonance frequencies of polymer coated microcantilevers before and after degradation. The miniaturized cantilever system provides a fast analysis of the biodegradation rate of PDLLA with a minute amount of sample and without the need of thermal and chemical acceleration. The degradation rate of the polymer has been estimated by multilayer cantilever theory and model simulation. A bulk degradation rate of 0.24 μg mm−2 hour−1 is estimated which agrees well with values reported in literature. The role of enzyme concentrations, pre-hydration in buffer, surface morphologies of PDLLA films and adsorption time of enzymes on the rate of degradation has been investigated. An increase in degradation rate is observed with an increase in enzyme concentration and after pre-hydration in buffer. A polymer film with a non-uniform surface degrades faster than the uniform one due to the preference of enzyme attack at film defects. A threshold time of around 3 h is estimated for irreversible enzyme adsorption on the polymer surface after which degradation can proceed even in buffer solution in the absence of enzyme.

An application of field-effect sensors for in-situ monitoring of degradation of biopolymers

The characterization of the degradation kinetics of biodegradable polymers is mandatory with regard to their proper application. In the present work, polymer-modified electrolyte–insulator–semiconductor (PMEIS) field-effect sensors have been applied for in-situ monitoring of the pH-dependent degradation kinetics of the commercially available biopolymer poly(d,l-lactic acid) (PDLLA) in buffer solutions from pH 3 to pH 13. PDLLA films of 500nm thickness were deposited on the surface of an Al–p-Si–SiO2–Ta2O5 structure from a polymer solution by means of spin-coating method. The PMEIS sensor is, in principle, capable to detect any changes in bulk, surface and interface properties of the polymer induced by degradation processes. A faster degradation has been observed for PDLLA films exposed to alkaline solutions (pH 9, pH 11 and pH 13).

RGD gifted PDLLA-PRGD conduits promotes the sciatic nerve regeneration

Schwann cells play a key role in peripheral nerve growth and regeneration. The aim of this study was to evaluate the effects of RGD peptides on Schwann cell behavior, and to identify the effects of the modified PDLLA films with RGD in vivo. The results revealed that RGD coating with the concentration of 100–500 ug/mL promoted the cell proliferation and boosted the cell migration. Molecularly, RGD coating also enhanced the expression of the proliferation related genes (c-fos and c-jun) and the cell behavior related genes (actin, tublin, tau and MAP1) at first stages of the seeding, which is similar to the effects from laminin coating. In vivo, RGD addition improved the recovery efficiency of the transected nerve in regard of the more survived Schwann cells in vivo and the formation of more mature myelin sheath. Taken together, RGD peptides are good candidates to enhance the biocompatibility of the biomaterials and facilitate the peripheral nerve regeneration by prompting responses in Schwann cells.

Poly(trimethylene carbonate) and biphasic calcium phosphate composites for orbital floor reconstruction: a feasibility study in sheep

In the treatment of orbital floor fractures, bone is ideally regenerated. The materials currently used for orbital floor reconstruction do not lead to the regeneration of bone. Our objective was to render polymeric materials based on poly(trimethylene carbonate) (PTMC) osteoinductive, and to evaluate their suitability for use in orbital floor reconstruction. For this purpose, osteoinductive biphasic calcium phosphate (BCP) particles were introduced into a polymeric PTMC matrix. Composite sheets containing 50 wt% BCP particles were prepared. Also laminates with poly(D,L-lactide) (PDLLA) were prepared by compression moulding PDLLA films onto the composite sheets. After sterilisation by gamma irradiation, the sheets were used to reconstruct surgically-created orbital floor defects in sheep. The bone inducing potential of the different implants was assessed upon intramuscular implantation. The performance of the implants in orbital floor reconstruction was assessed by cone beam computed tomography (CBCT). Histological evaluation revealed that in the orbital and intramuscular implantations of BCP containing specimens, bone formation could be seen after 3 and 9 months. Analysis of the CBCT scans showed that the composite PTMC sheets and the laminated composite sheets performed well in orbital floor reconstruction. It is concluded that PTMC/BCP composites and PTMC/BCP composites laminated with PDLLA have osteoinductive properties and seem suitable for use in orbital floor reconstruction.

Impedance spectroscopy: A tool for real‐time in situ monitoring of the degradation of biopolymers

AbstractInvestigation of the degradation kinetics of biodegradable polymers is essential for the development of implantable biomedical devices with predicted biodegradability. In this work, an impedimetric sensor has been applied for real‐time and in situ monitoring of degradation processes of biopolymers. The sensor consists of two platinum thin‐film electrodes covered by a polymer film to be studied. The benchmark biomedical polymer poly(D,L‐lactic acid) (PDLLA) was used as a model system. PDLLA films were deposited on the sensor structure from a polymer solution by using the spin‐coating method. The degradation kinetics of PDLLA films have been studied in alkaline solutions of pH 9 and 12 by means of an impedance spectroscopy (IS) method. Any changes in a polymer capacitance/resistance induced by water uptake and/or polymer degradation will modulate the global impedance of the polymer‐covered sensor that can be used as an indicator of the polymer degradation. The degradation rate can be evaluated from the time‐dependent impedance spectra. As expected, a faster degradation has been observed for PDLLA films exposed to pH 12 solution.

Characterization of biodegradable polymers with capacitive field-effect sensors

In vitro studies of the degradation kinetic of biopolymers are essential for the design and optimization of implantable biomedical devices. In the presented work, a field-effect capacitive sensor has been applied for the real-time and in situ monitoring of degradation processes of biopolymers for the first time. The polymer-covered field-effect sensor is, in principle, capable to detect any changes in bulk, surface and interface properties of the polymer induced by degradation processes. The feasibility of this approach has been experimentally proven by using the commercially available biomedical polymer poly(d,l-lactic acid) (PDLLA) as a model system. PDLLA films of different thicknesses were deposited on the Ta2O5-gate surface of the field-effect structure from a polymer solution by means of spin-coating method. The polymer-modified field-effect sensors have been characterized by means of capacitance–voltage and impedance-spectroscopy method. The degradation of the PDLLA was accelerated by changing the degradation medium from neutral (pH 7.2) to alkaline (pH 9) condition, resulting in drastic changes in the capacitance and impedance spectra of the polymer-modified field-effect sensor.

Plasticization of poly(lactide) by sorption of volatile organic compounds at low concentration

Polylactide (PLA) is one of the most promising bio-based polyester for wide applications and in particular for food packaging. However aroma compounds can interact with packaging in contact leading to modification of its thermal properties during storage. Up to date, no study has focused on aroma sorption in PLA at realistic food packaging conditions implying low vapor activities, and thus using dedicated methodology ranging over concentrations below 200 μg of aroma compound per gram of polymer. In the present study the sorption of four ethyl esters (C4, C6, C7 and C8), benzaldehyde and 2-nonanone in three different types of poly(d,l-lactide) (PDLLA) at 25 °C was investigated in order to determine their solubility coefficients and their impacts on the thermal properties of the tested PDLLA. The sorption of aroma compounds at low vapor activities was studied using two methods of headspace extraction (MHE and MHS-SPME) after 20 days of conditioning in a hermetic flask. The results showed that PLA films studied have a very high affinity for benzaldehyde. Ethyl acetate solubility coefficient in PLA was comparatively similar to poly(ethylene terephthalate), polypropylene (PP) and low-density polyethylene (LDPE). Differential Scanning Calorimetry results showed a decrease in glass transition temperature (Tg) of PDLLA films and an increase in the crystallinity degree that depend on the concentration of the sorbed aroma compounds. It could be clearly demonstrated that plasticization of PDLLA by aroma compounds occurred at very low vapor activities (0.01) and that the importance of the effect depended on the chemical nature of the molecule.

A strategy to establish a gene-activated matrix on titanium using gene vectors protected in a polylactide coating

Bioactive implants are promising tools in regenerative medicine. Here we describe a versatile procedure for preparing a gene-activated matrix on titanium. Lyophilized copolymer-protected gene vectors ( COPROGs) suspended in poly( d, l-lactide) (PDLLA) solutions in ethyl acetate were used to varnish solid surfaces. The gene-activated PDLLA surfaces were first established on polypropylene 96-well plates. Vector release from these surfaces in aqueous buffer, cell viability and gene transfer efficiency to NIH 3T3 fibroblasts was strongly dependent on the vector dose and its ratio to PDLLA film thickness. A detailed analysis of these relationships allowed establishing correlations which can be used to calculate suitable combinations of COPROGs and PDLLA yielding optimal gene transfer efficiency. This was verified with COPROG-activated PDLLA coatings on titanium foils. HEK 293 and mesenchymal stem cells expressed the BMP-2 gene comprised in the gene-activated surface in a manner that was consistent with the predicted dose–response and toxicity profiles found in NIH 3T3 cells. The systematic procedure presented here for identifying optimal coating compositions can be applied to any combination of vector type and coating material.

The pro-angiogenic properties of multi-functional bioactive glass composite scaffolds

The angiogenic properties of micron-sized (m-BG) and nano-sized (n-BG) bioactive glass (BG) filled poly(D,L lactide) (PDLLA) composites were investigated. On the basis of cell culture work investigating the secretion of vascular endothelial growth factor (VEGF) by human fibroblasts in contact with composite films (0, 5, 10, 20 wt %), porous 3D composite scaffolds, optimised with respect to the BG filler content capable of inducing angiogenic response, were produced. The in vivo vascularisation of the scaffolds was studied in a rat animal model and quantified using stereological analyses. The prepared scaffolds had high porosities (81–93%), permeability ( k = 5.4–8.6 × 10 −9 m 2) and compressive strength values (0.4–1.6 MPa) all in the range of trabecular bone. On composite films containing 20 wt % m-BG or n-BG, human fibroblasts produced 5 times higher VEGF than on pure PDLLA films. After 8 weeks of implantation, m-BG and n-BG containing scaffolds were well-infiltrated with newly formed tissue and demonstrated higher vascularisation and percentage blood vessel to tissue (11.6–15.1%) than PDLLA scaffolds (8.5%). This work thus shows potential for the regeneration of hard-soft tissue defects and increased bone formation arising from enhanced vascularisation of the construct.

Effects of hydrolysis on dodecyl alcohol-modified bioactive glasses and PDLLA/modified bioactive glass composite films

In this article, mesoporous 58S and 58S bioactive glasses (BGs) were surface modified by dodecyl alcohol through esterification reaction and PDLLA/modified BGs composite films were prepared. The purpose of this study was to investigate the properties of the modified BGs particles and the PDLLA/modified BGs composite films before and after hydrolytic treatment. The modified BGs powders and composite films were treated in boiling water for 20 min to remove the dodecyl chains. After hydrolytic treatment, the modified BGs powders showed increased hydrophilicity and the FTIR analysis revealed that most dodecyl chains were removed. Furthermore, the hydrophilicity of the PDLLA/modified BGs composite films was also greatly improved. The tensile strength of the composite films after hydrolysis decreased slightly, but was still much higher than that of pure PDLLA film. In addition, bone marrow mesenchymal stem cells from dogs on the composite films after hydrolytic treatment showed the highest proliferation rate. The results suggest that hydrolytic treatment is an effective and practicable method to remove alcohol chains from surface-modified BGs and polymers/modified BG composites, which may be used for preparation of bioactive scaffolds for tissue engineering applications.

Regulation of endothelial cells migration on poly( d, l-lactic acid) films immobilized with collagen gradients

To investigate the effect of protein surface-density gradient on the motility of endothelial cells, we developed a novel approach for the fabrication of a collagen density gradient onto poly( d, l-lactic acid) (PDLLA) films in this study. The approach involves a sequential alkali hydrolysis of PDLLA films to produce a density gradient of –COOH moieties onto the films, which were activated and then covalently linked with collagen. A collagen surface-density gradient onto PDLLA films was thus generated by this approach. Contact angle measurement and confocal laser scanning microscopy (CLSM) were employed to confirm the formation of –COOH gradient and collagen gradient, respectively. All results proved the feasibility of the fabrication of a collagen density gradient onto PDLLA films via the approach. Endothelial cells cultured on the gradient areas with low and moderate collagen surface-densities displayed a strong motility tendency, with the values such as net displacement, total distance, chemotactic index, migration rate and cell trajectories in parallel to the gradient. However, endothelial cells grew on the gradient area with high collagen density demonstrated a reverse response to the collagen gradient clue. These results suggest that cell motility is regulated by the collagen gradient with a surface-density dependent manner. This study provides an alternative for the fabrication of protein surface-density gradient onto biodegradable substrates to investigate chemical stimuli induced cell directional motility. It is potentially important for understanding the controlled angiogenesis for implantation of tissue-engineered constructs.

Functionalized Poly(D,L‐lactide) for Pulmonary Epithelial Cell Culture

AbstractFunctional groups on a material surface affect the response of many cell types. As part of our strategy aimed at engineering lung tissue, we introduced functional groups into the surface of Poly(D,L‐lactide) (PDLLA) films to improve its suitability for the culture of mature pulmonary epithelial cells (A549 line) using two different methods. The first method, aminolysis, can introduce primary amines into PDLLA films by transesterification using 1–15% of ethylenediamine in isopropanol. The second method, a branching modification, can generate amine‐terminated or carboxylic acid‐terminated tree‐like branched architectures. All modified PDLLA surfaces exhibited lower water contact angles, i.e. are more hydrophilic than unmodified PDLLA. PDLLA treated with 15% ethylenediamine exhibited a rougher surface than the control, and PDLLA with branching modification had a droplet‐like surface topography as visualized by atomic force microscopy (AFM). PDLLA treated with 15% ethylenediamine and branching modification with two and three generations enhanced the attachment of pulmonary epithelial cells measured using Hoechst dye. Immunostaining demonsatrated that amine‐terminated branched architectures allowed for better focal adhesion point formation than the control 24 h after cell seeding. Furthermore, they also induced higher A549 cell populations and levels of activity after 4 days in culture measured using Hoechst dye and WST1 cell proliferation reagents, respectively. In contrast, carboxylic acid‐terminated branching architectures were found to reduce the cell population size after 4 days. It was concluded that the concentration, type and distribution of surface functional groups can affect significantly the behavior of pulmonary epithelial cells growing on a PDLLA surface, and PDLLA film modified with two or three generations of amine‐terminated branched architectures is a suitable 2D scaffold for the culture of of pulmonary epithelial cells.

Construction of Polyethyleneimine‐β‐cyclodextrin/pDNA Multilayer Structure for Improved In Situ Gene Transfection

AbstractThis study reports in situ gene delivery from gene‐functionalized poly(D,L‐lactic acid) (PDLLA, Mw of around 2.0 × 105 g mol−1) films, which were constructed via layer‐by‐layer (LbL) assembly technique with low molecular weight polyethylenimine‐β‐cyclodextrin (PEI‐CD) conjugate and plasmid DNA (pDNA). PEI‐CD was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR), respectively. The buildup of multilayered PEI‐CD/pDNA pairs onto PDLLA films was monitored with contact angle measurements and UV–Vis spectrometer, respectively. A sustained release of pDNA from multilayered films was observed for 28 h. The mechanism of in situ gene delivery on PDLLA film was investigated in this study as well. Spherical PEI‐CD/pDNA complexes were formed and released following the deconstruction of multilayered films, which was confirmed by transmission electron microscopy (TEM) and gel electrophoresis, respectively. Surface mediated in situ gene transfection was achieved when culturing hepatoma G2 (HepG2) and human embryonic kidney 293 (HEK293) onto PEI‐CD/pDNA multilayered films. Furthermore, PEI‐CD improved the gene transfection efficiency when compared with that of PEI. Such gene‐functionalized biomaterial reported here has potential application in tissue engineering and implant technology.