Journal of Biomedical Materials Research - Part A

Bệnh van tim là một vấn đề sức khỏe cộng đồng nghiêm trọng và ngày càng gia tăng, trong đó việc thay thế bằng bộ phận giả là điều thường thấy. Các thiết bị giả hiện tại không đủ tốt cho người lớn trẻ tuổi và trẻ em đang phát triển. Các kênh van động mạch chủ sống được thiết kế mô có tiềm năng để tái cấu trúc, tái tạo, và phát triển, nhưng việc chế tạo độ phức tạp giải phẫu tự nhiên với tính không đồng nhất của tế bào vẫn còn là thách thức. Trong nghiên cứu hiện tại, chúng tôi áp dụng công nghệ sinh học in 3D để chế tạo các kênh van bằng chất dẻo alginate/gelatin sống với cấu trúc giải phẫu và việc kết hợp trực tiếp các loại tế bào kép theo cách bị hạn chế vùng. Các tế bào cơ trơn xoang gốc động mạch (SMC) và tế bào mô liên kết của nắp van động mạch (VIC) được bao bọc trong các đĩa hydrogels alginate/gelatin có khả năng sống qua 7 ngày trong môi trường nuôi cấy. Các hydrogels không có tế bào in 3D thể hiện sự giảm xu hướng, sức mạnh tối đa, và ứng suất tối đa giảm nhẹ trong suốt thời gian nuôi cấy 7 ngày, trong khi sinh học cơ học kéo của hydrogel chứa tế bào vẫn được duy trì. Các kênh van động mạch được in sinh học thành công với sự bao bọc trực tiếp SMC ở gốc van và VIC ở các nắp. Cả hai loại tế bào đều có khả năng sống (81,4 ± 3,4% đối với SMC và 83,2 ± 4,0% đối với VIC) trong các mô được in 3D. Tế bào SMC bao bọc biểu hiện mức alpha‐sợi cơ trơn cao, trong khi VIC biểu hiện mức vimentin cao. Những kết quả này chứng minh rằng các kênh van động mạch sống có độ phức tạp giải phẫu và bao bọc không đồng nhất có thể được chế tạo bằng công nghệ sinh học in 3D. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Phần A, 2013.

Integrin‐mediated cell adhesion to proteins adsorbed onto synthetic surfaces anchors cells and triggers signals that direct cell function. In the case of fibronectin (Fn), adsorption onto substrates of varying properties alters its conformation/structure and its ability to support cell adhesion. In the present study, self‐assembled monolayers (SAMs) of alkanethiols on gold were used as model surfaces to investigate the effects of surface chemistry on Fn adsorption, integrin binding, and cell adhesion. SAMs presenting terminal CH₃, OH, COOH, and NH₂ functionalities modulated adsorbed Fn conformation as determined through differences in the binding affinities of monoclonal antibodies raised against the central cell‐binding domain (OH > COOH = NH₂ > CH₃). Binding of α₅β₁ integrin to adsorbed Fn was controlled by SAM surface chemistry in a manner consistent with antibody binding (OH > COOH = NH₂ > CH₃), whereas α_V integrin binding followed the trend: COOH >> OH = NH₂ = CH₃, demonstrating α₅β₁ integrin specificity for Fn adsorbed onto the NH₂ and OH SAMs. Cell adhesion strength to Fn‐coated SAMs correlated with α₅β₁ integrin binding (OH > COOH = NH₂ > CH₃), and experiments with function‐perturbing antibodies demonstrated that this receptor provides the dominant adhesion mechanism in this cell model. This work establishes an experimental framework to analyze adhesive mechanisms controlling cell‐surface interactions and provides a general strategy of surface‐directed control of adsorbed protein activity to manipulate cell function in biomaterial and biotechnological applications. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 247–259, 2003

Titanium (Ti) is used for implantable devices because of its biocompatible oxide surface layer. TiO₂ surfaces that have a complex microtopography increase bone‐to‐implant contact and removal torque forces in vivo and induce osteoblast differentiation in vitro. Studies examining osteoblast response to controlled surface chemistries indicate that hydrophilic surfaces are osteogenic, but TiO₂ surfaces produced until now exhibit low surface energy because of adsorbed hydrocarbons and carbonates from the ambient atmosphere or roughness induced hydrophobicity. Novel hydroxylated/hydrated Ti surfaces were used to retain high surface energy of TiO₂. Osteoblasts grown on this modified surface exhibited a more differentiated phenotype characterized by increased alkaline phosphatase activity and osteocalcin and generated an osteogenic microenvironment through higher production of PGE₂ and TGF‐β1. Moreover, 1α,25(OH)₂D₃ increased these effects in a manner that was synergistic with high surface energy. This suggests that increased bone formation observed on modified Ti surfaces in vivo is due in part to stimulatory effects of high surface energy on osteoblasts. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005

Tissue engineering aims at resolving problems such as donor shortage and immune rejection faced by transplantation. Scaffolds (artificial extracellular matrices) have critical roles in tissue engineering. Recently, we developed nano‐fibrous poly(L‐lactic acid) scaffolds under the hypothesis that synthetic nano‐fibrous scaffolding, mimicking the structure of natural collagen fibers, could create a more favorable microenvironment for cells. This is the first report that the nano‐fibrous architecture built in three‐dimensional scaffolds improved the features of protein adsorption, which mediates cell interactions with scaffolds. Scaffolds with nano‐fibrous pore walls adsorbed four times more serum proteins than scaffolds with solid pore walls. More interestingly, the nano‐fibrous architecture selectively enhanced protein adsorption including fibronectin and vitronectin, even though both scaffolds were made from the same poly(L‐lactic acid) material. Furthermore, nano‐fibrous scaffolds also allowed >1.7 times of osteoblastic cell attachment than scaffolds with solid pore walls. These results demonstrate that the biomimetic nano‐fibrous architecture serves as superior scaffolding for tissue engineering. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 531–537, 2003

In the United States alone, there are approximately 500,000 burn injuries that require medical treatment every year. Limitations of current treatments necessitate the development of new methods that can be applied quicker, result in faster wound regeneration, and yield skin that is cosmetically similar to undamaged skin. The development of new hydrogel biomaterials and bioprinting deposition technologies has provided a platform to address this need. Herein we evaluated characteristics of twelve hydrogels to determine their suitability for bioprinting applications. We chose hydrogels that are either commercially available, or are commonly used for research purposes. We evaluated specific hydrogel properties relevant to bioprinting applications, specifically; gelation time, swelling or contraction, stability, biocompatibility and printability. Further, we described regulatory, commercial and financial aspects of each of the hydrogels. While many of the hydrogels screened may exhibit characteristics suitable for other applications, UV‐crosslinked Extracel, a hyaluronic acid‐based hydrogel, had many of the desired properties for our bioprinting application. Taken together with commercial availability, shelf life, potential for regulatory approval and ease of use, these materials hold the potential to be further developed into fast and effective wound healing treatments. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:272–284, 2013.

In this study, magnetite (Fe₃O₄) nanoparticles with a size range of 8–20 nm were prepared by the modified controlled chemical coprecipitation method from the solution of ferrous/ferric mixed salt‐solution in alkaline medium. In the process, two kinds of surfactant (sodium oleate and polyethylene glycol) were studied; then, sodium oleate was chosen as the apt surfactant to attain ultrafine, nearly spherical and well‐dispersed (water‐base) Fe₃O₄ nanoparticles, which had well magnetic properties. The size and size distribution of nanoparticles were determined by particle size analyzer. And the magnetite nanoparticles was characterized by X‐ray powder diffraction (XRD) analysis, transmission electron microscopy (TEM), electron diffraction (ED) photography, Fourier transform infrared spectrometer (FT‐IR), and vibrating‐sample magnetometer (VSM). Also the effect of many parameters on the Fe₃O₄ nanoparticles was studied, such as reaction temperature, pH of the solution, stirring rate and concentration of sodium oleate. And the 5‐dimethylthiazol‐2‐yl‐2,5‐ diphenyltetrazolium bromide (MTT) assay was performed to evaluate the biocompatibility of magnetite nanoparticles. The results showed that the Fe₃O₄ nanoparticles coated by sodium oleate had a better biocompatibility, better magnetic properties, easier washing, lower cost, and better dispersion than the magnetite nanoparticles coated by PEG. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007

Vertically aligned yet laterally spaced nanoscale TiO₂ nanotubes have been grown on Ti by anodization, and the growth of MC3T3‐E1 osteoblast cells on such nanotubes has been investigated. The adhesion/propagation of the osteoblast is substantially improved by the topography of the TiO₂ nanotubes with the filopodia of growing cells actually going into the nanotube pores, producing an interlocked cell structure. The presence of the nanotube structure induced a significant acceleration in the growth rate of osteoblast cells by as much as ∼300–400%. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

Poly(ethylene glycol) (PEG) hydrogels, modified with RGD, are promising platforms for cell encapsulation and tissue engineering. While these hydrogels offer tunable mechanical properties, the extent of the host response may limit their in vivo applicability. The overall objective was to characterize the effects of hydrogel stiffness on the in vitro macrophage response and in vivo host response. We hypothesized that stiffer substrates induce better attachment, adhesion, and increased cell spreading, which elevates the macrophage classically activated phenotype and leads to a more severe foreign body reaction (FBR). PEG‐RGD hydrogels were fabricated with compressive moduli of 130, 240, and 840 kPa, and the same RGD concentration. Hydrogel stiffness did not impact macrophage attachment, but elicited differences in cell morphology. Cells retained a round morphology on 130 kPa substrates, with localized and dense F‐actin and localized α_V integrin stainings. Contrarily, cells on stiffer substrates were more spread, with filopodia protruding from the cell, a more defined F‐actin, and greater α_V integrin staining. When stimulated with lipopolysaccharide, macrophages had a classical activation phenotype, with increased expression of TNF‐α, IL‐1β, and IL‐6, however the degree of activation was significantly reduced with the softest hydrogels. A FBR ensued in response to all hydrogels when implanted subcutaneously in mice, but 28 days postimplantation the layer of macrophages at the implant surface was significantly lower in the softest hydrogels. In conclusion, hydrogels with lower stiffness led to reduced macrophage activation and a less severe and more typical FBR, and therefore are more suited for in vivo tissue engineering applications. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.

Tissue engineering scaffolds should ideally mimic the natural ECM in structure and function. Electrospun nanofibrous scaffolds are easily fabricated and possess a biomimetic nanostructure. Scaffolds can mimic ECM function by acting as a depot for sustained release of growth factors. bFGF, an important growth factor involved in tissue repair and mesenchymal stem cell proliferation and differentiation, is a suitable candidate for sustained delivery from scaffolds. In this study, we present two types of PLGA nanofibers incorporated with bFGF, fabricated using the facile technique of blending and electrospinning (Group I) and by the more complex technique of coaxial electrospinning (Group II). bFGF was randomly dispersed in Group I and distributed as a central core within Group II nanofibers; both scaffolds showed similar protein encapsulation efficiency and release over 1–2 weeks. Although both scaffold groups favored bone marrow stem cell attachment and subsequent proliferation, cells cultured on Group I scaffolds demonstrated increased collagen production and upregulated gene expression of specific ECM proteins, indicating fibroblastic differentiation. The study shows that the electrospinning technique could be used to prolong growth factor release from scaffolds and an appropriately sustained growth factor release profile in combination with a nanofibrous substrate could positively influence stem cell behavior and fate. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010

Adherent cells are strongly influenced by the mechanical aspects of biomaterials, but little is known about the cellular effects of spatial variations in these properties. This work describes a novel method to produce polymeric cell culture surfaces containing micrometer‐scale regions of variable stiffness. Substrates made of acrylamide or poly(dimethylsiloxane) were patterned with 100‐ or 10‐μm resolution, respectively. Cells were cultured on fibronectin‐coated acrylamide having Young's moduli of 34 kPa and 1.8 kPa, or fibronectin‐coated PDMS having moduli of 2.5 MPa and 12 kPa. Over several days, NIH/3T3 cells and bovine pulmonary arterial endothelial cells accumulated preferentially on stiffer regions of substrates. The migration, not proliferation, of cells in response to mechanical patterning (mechanotaxis) was responsible for the accumulation of cells on stiffer regions. Differential remodeling of extracellular matrix protein on stiff versus compliant regions was observed by immunofluorescence staining, and may have been responsible for the observed mechanotaxis. These results suggest that mechanically patterned substrates might provide a general means to study mechanotaxis, and a new approach to patterning cells. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 605–614, 2003