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Orthopedic implant failure has been attributed mainly to loosening of the implant from host bone, which may be due to poor bonding of the implant material to bone tissue, as well as to bacterial infection. One promising strategy to enhance tissue integration is to develop a selective biointeractive surface that simultaneously enhances bone cell function while decreasing bacterial adhesion. In this in vitro study, the surfaces of titanium alloy substrates were functionalized by first covalently grafting carboxymethyl chitosan (CMCS), followed by the conjugation of bone morphogenetic protein-2 (BMP-2) to the CMCS-grafted surface. Bacterial adhesion on the substrates was assayed with Staphylococcus aureus and Staphylococcus epidermidis . Cell functions were investigated using osteoblasts and human bone marrow-derived mesenchymal stem cells. The results showed that bacterial adhesion on both the CMCS and CMCS-BMP-2 functionalized surfaces was significantly reduced compared to that on the pristine substrates. In addition, the CMCS-BMP-2 modified substrates significantly promoted attachment, alkaline phosphatase activity, and calcium mineral deposition of both osteoblast and human bone marrow-derived mesenchymal stem cells. The achievement of the dual functions of bacterial adhesion reduction and cell function promotion by the CMCS-BMP-2 modified titanium substrates illustrates the good potential of such surfaces for enhancement of tissue integration and implant longevity.

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Adipose-derived stem cells (ADSCs) have great potential as a cell source for tissue engineering and regenerative medicine because they are easier to obtain, have lower donor-site morbidity and are available in larger numbers than stem cells harvested using bone marrow aspiration. Until now, little has been known about how nanotopography affects the proliferation and endothelial differentiation of ADSCs. In the present study, two nanograting substrates with a period (ridge and groove) of about 250 and 500 nm, respectively, were fabricated on quartz and their effect on ADSC fate was investigated. The results showed that proliferation of ADSCs on nanograting substrates decreased while cell attachment was not significantly affected compared to a flat substrate. Endothelial differentiation of ADSCs on both flat and nanograting substrates can be induced with vascular endothelial growth factor, as shown by immunofluorescent staining. Quantitative real-time PCR analysis showed significantly enhanced upregulation of vWF, PECAM-1 and VE-cadherin at the gene level by ADSCs on the nanograting substrates. In vitro angiogenesis assay on Matrigel showed that nanograting substrates enhanced capillary tube formation. This study highlights the beneficial influence of nanotopography on the differentiation of ADSC into endothelial cells which play an important role in vascularization.

Poly (lactic-co-glycolic acid) (PLGA) is a biodegradable polymer used to make resorbable sutures, and is also used in other applications in tissue engineering. Being an artificial polymer, its degradation rate can be tailored to suit its application. It can be easily moulded into structures with suitable mechanical strength and degrades into relatively harmless products in the body. Its adjustable degradation rate also makes it a potentially excellent controlled release delivery device. However, the functionalization of PLGA with bioactive molecules usually requires extensive chemical modification. Chemical modification may compromise the mechanical strength of PLGA and inactivate the bioactive molecules. In this paper, a study is done to investigate the coating of an angiogenic factor on unmodified PLGA suture substrates for the differentiation of human mesenchymal stem cells (hMSC) into endothelial cells (EC). The results show that the method used to anchor vascular endothelial growth factor (VEGF) onto the PLGA surface can enable the gradual release of VEGF from the substrate into solution to induce the differentiation of hMSCs into ECs. Thus, this method can potentially be used to coat PLGA materials like sutures, meshes and scaffolds, rendering them functional as effective controlled release delivery devices for a wide range of bioactive molecules.