pinecone/core-2020-05-10-deduplication huggingface dataset:
Delivery of BMP-2 by two clinically available apatite materials: In vitro and in vivo comparison

Bone morphogenetic proteins (BMPs) are deposited in bone and responsible for osteoinduction. The interplay between delivery system and BMP, resulting in a characteristic release profile, is crucial for clinical success. We here report on two apatite based commercially available granules which could potentially be used in a combination product with recombinant human BMP-2 (rhBMP-2). Regardless of their similar chemistry, their interaction with rhBMP-2 differs. Deproteinized bovine bone matrix (DBBM), a clinically well-established bone substitute, has a high affinity to rhBMP-2 and releases only 50% of the growth factor during the first 2 weeks in vitro. Activity of the physio-adsorbed rhBMP-2 is indicated by an enhanced bone augmentation in vivo. In contrast, all rhBMP-2 delivered in combination with synthetic hydroxyapatite/β-tricalcium phosphate (HA/TCP) granules is released during the first 24 h. For both HA/TCP and DBBM, the released rhBMP-2 is active in vitro. Our results suggest that the different release behavior from these two apatite granules is due to the 1000-fold higher specific surface area of DBBM compared to HA/TCP
Enhancement of adhesion and promotion of osteogenic differentiation of human adipose stem cells by poled electroactive poly(vinylidene fluoride)

Poly(vinylidene fluoride)  (PVDF) is a biocompatible material  with  excellent electroactive properties.  Non-electroactive  α-PVDF and electroactive β-PVDF were used to investigate the substrate polarization and polarity  influence on the focal adhesion size and number as well as on human adipose stem cells  (hASCs)  differentiation.  hASCs  were cultured on different PVDF surfaces adsorbed with fibronectin and  focal adhesion size and number, total adhesion area, cell size, cell aspect ratio and focal adhesion density were estimated using cells expressing EGFP-vinculin.  Osteogenic differentiation was  also  determined using a quantitative alkaline phosphatase assay. The surface charge of the poled PVDF films (positive or negative)  influenced the hydrophobicity  of the samples, leading to variations in the  conformation of adsorbed extracellular matrix (ECM) proteins, which ultimately modulated the stem cell adhesion on  the films and induced their osteogenic differentiation.The study was supported financially by the Academy of Finland (136288, 
140978 and 256931), the Sigrid Jusélius Foundation, the Pirkanmaa Hospital District and the 
Finnish Funding Agency for Technology and Innovation (TEKES). This study was also 
supported by FEDER through the COMPETE Program, by the Portuguese Foundation for 
Science and Technology (FCT) in the framework of the Strategic Project PEST- C/FIS/UI607/2011 and by projects NANO/NMed-SD/0156/2007 and PTDC/CTM
NAN/112574/2009.  The autors also thank the project Matepro – Optimizing Materials and 
Processes”, ref. NORTE-07-0124-FEDER-000037”, co-funded by the “Programa Operacional 
Regional do Norte” (ON.2 – O Novo Norte), under the “Quadro de Referência Estratégico 
Nacional” (QREN), through the “Fundo Europeu de Desenvolvimento Regional” (FEDER). V.S. 
and C.R. thank the FCT for the SFRH/BPD/63148/2009 and SFRH/BPD/90870/2012 grants, 
respectively
Extracellular matrix elasticity and topography: Material‐based cues that affect cell function via conserved mechanisms

Chemical, mechanical, and topographic extracellular matrix (ECM) cues have been extensively studied for their influence on cell behavior. These ECM cues alter cell adhesion, cell shape, and cell migration and activate signal transduction pathways to influence gene expression, proliferation, and differentiation. ECM elasticity and topography, in particular, have emerged as material properties of intense focus based on strong evidence these physical cues can partially dictate stem cell differentiation. Cells generate forces to pull on their adhesive contacts, and these tractional forces appear to be a common element of cells' responses to both elasticity and topography. This review focuses on recently published work that links ECM topography and mechanics and their influence on differentiation and other cell behaviors. We also highlight signaling pathways typically implicated in mechanotransduction that are (or may be) shared by cells subjected to topographic cues. Finally, we conclude with a brief discussion of the potential implications of these commonalities for cell based therapies and biomaterial design. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1246–1258, 2015
VA-086 methacrylate gelatine photopolymerizable hydrogels: A parametric study for highly biocompatible 3D cell embedding

The ability to replicate in vitro the native extracellular matrix (ECM) features and to control the three-dimensional (3D) cell organization plays a fundamental role in obtaining functional engineered bioconstructs. In tissue engineering (TE) applications, hydrogels have been successfully implied as biomatrices for 3D cell embedding, exhibiting high similarities to the natural ECM and holding easily tunable mechanical properties. In the present study, we characterized a promising photocrosslinking process to generate cell-laden methacrylate gelatin (GelMA) hydrogels in the presence of VA-086 photoinitiator using a ultraviolet LED source. We investigated the influence of prepolymer concentration and light irradiance on mechanical and biomimetic properties of resulting hydrogels. In details, the increasing of gelatin concentration resulted in enhanced rheological properties and shorter polymerization time. We then defined and validated a reliable photopolymerization protocol for cell embedding (1.5% VA-086, LED 2 mW/cm2) within GelMA hydrogels, which demonstrated to support bone marrow stromal cells viability when cultured up to 7 days. Moreover, we showed how different mechanical properties, derived from different crosslinking parameters, strongly influence cell behavior. In conclusion, this protocol can be considered a versatile tool to obtain biocompatible cell-laden hydrogels with properties easily adaptable for different TE applications
A mechanistic model for drug release in PLGA biodegradable stent coatings coupled with polymer degradation and erosion

Biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) coating for applications in drug-eluting stents has been receiving increasing interest as a result of its unique properties compared with biodurable polymers in delivering drug for reducing stents-related side effects. In this work, a mathematical model for describing the PLGA degradation and erosion and coupled drug release from PLGA stent coating is developed and validated. An analytical expression is derived for PLGA mass loss that predicts multiple experimental studies in the literature. An analytical model for the change of the number-average degree of polymerization [or molecular weight (MW)] is also derived. The drug transport model incorporates simultaneous drug diffusion through both the polymer solid and the liquid-filled pores in the coating, where an effective drug diffusivity model is derived taking into account factors including polymer MW change, stent coating porosity change, and drug partitioning between solid and aqueous phases. The model is used to describe in vitro sirolimus release from PLGA stent coating, and demonstrates the significance of simultaneous sirolimus release via diffusion through both polymer solid and pore space. The proposed model is compared to existing drug transport models, and the impact of model parameters, limitations and possible extensions of the model are also discussed.National Institute for Biomedical Imaging and Bioengineering (U.S.) (NIBIB, contract grant number: 5RO1EB005181
Surface roughness dependent osteoblast and fibroblast response on poly(l-lactide) films and electrospun membranes

Poly(l-lactide) electrospun mats with random and aligned fiber orientation and films have been produced with degrees of crystallinity ranging from 0 up to nearly 50%. The overall surface roughness is practically constant irrespective of the sampling areas (1 × 1 µm to 20 × 20 µm) for degrees of crystallinity below 30%, increasing for higher degrees of crystallinity for the larger sampling areas. Further, due to fiber confinement, surface roughness variations are smaller in electrospun mats. Samples with 50% of crystallinity show the lowest osteoblast and the highest fibroblast proliferation. Therefore, it is verified that higher roughness promotes lower osteoblast but higher fibroblast proliferation. The overall results indicate the relevant role of the sub-microenvironment variations associated to the microscale roughness in determining the different cell responses.Portuguese Foundation for Science and Technology (FCT); contract grant numbers: C/FIS/UI607/2011, PTDC/CTM-NAN/112574/2009, contract grant numbers: SFRH/BPD/63148/2009, SFRH/BPD/90870/2012, Matepro—Optimizing Materials and Processes, Programa Operacional Regional do Norte, Quadro de Referência
Estratégico Nacional” (QREN), “Fundo Europeu de Desenvolvimento Regional” (FEDER); contract grant number: NORTE-07–0124-FEDER-000037
Dynamic piezoelectric stimulation enhances osteogenic differentiation of human adipose stem cells

This work reports on the influence of the substrate polarization of electroactive β-PVDF on human adipose stem cells (hASCs) differentiation under static and dynamic conditions. hASCs were cultured on different β-PVDF surfaces (non-poled and “poled -”) adsorbed with fibronectin and osteogenic differentiation was determined using a quantitative alkaline phosphatase assay. “Poled -” β-PVDF samples promote higher osteogenic differentiation, which is even higher under dynamic conditions. It is thus demonstrated that electroactive membranes can provide the necessary electromechanical stimuli for the differentiation of specific cells and therefore will support the design of suitable tissue engineering strategies, such as bone tissue engineering.This work is funded by FEDER funds through the "Programa Operacional Fatores de Competitividade – COMPETE" and by national funds arranged by FCT- Fundação para a Ciência e a Tecnologia, project references PTDC/CTM-NAN/112574/2009 and PEST-C/FIS/UI607/2014. The authors also thank funding from Matepro –Optimizing Materials and Processes”, ref. NORTE-07-0124-FEDER-000037”, co-funded by the “Programa Operacional Regional do Norte” (ON.2 – O Novo Norte), under the “Quadro de Referência Estratégico Nacional” (QREN), through the “Fundo Europeu de Desenvolvimento Regional” (FEDER). CR, VS and VC thank the FCT for the SFRH/BPD/90870/2012, SFRH/BPD/64958/2009 and SFRH/BPD/97739/2013 grants, respectively. Academy of Finland is acknowledged for research funding (projects 136288 (VH) and 256931 (JP))
Biocompatibility and biodegradation of protein microparticle and film scaffolds made from kafirin (sorghum prolamin protein) subcutaneously implanted in rodent models

Kafirin, the sorghum prolamin protein, like its maize homologue zein, can be made into
micropatticles and films and potentially used as a biomaterial. Zein has good bio- and cytocompatibility.
Kafirin could be advantageous as it is more hydrophobic, more cross-linked, more
slowly digested by mammalian proteases than zein and is non-allergenic. The safety and
biocompatibility of kafirin implants in two forms was determined in rodent models. One week
post subcutaneous injection of kafirin micropatticles (size S[!m diameter) in mice, chronic
inflammation, abnormal red blood cells and gross fibrin formation were observed. This chronic
inflammatory response was possibly caused by the release of hydrolysis products such as
glutamate during the degradation of the kafirin microparticles. In contrast, films made from
kaftrin microparticles (50 [!ill thickness, folded into I cm3
) implanted in rats showed no
abnormal inflammatory reactions and were only partially degraded by day 28. The slower
degradation of the kafirin films was probably due to their far smaller surface area when
compared to kafirin micropatticles. Thus, kafirin films appear to have potential as a biomaterial.
This study also raises awareness that the form of prolamin based biomaterials, (kafirin and zein)
should be considered when assessing the safety of such materials.http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1552-49652016-08-31hb201
Effect of microgrooved surface topography on osteoblast maturation and protein adsorption

Microgrooved surfaces have been used extensively to influence cell contact guidance. Guiding cell growth, extracellular matrix deposition, and mineralization is important for bone implant longevity. In this study, we investigated the osteoblast response to microgrooved metallic surfaces in serum-supplemented medium. Groove spacing was comparable with the spread osteoblast size. Focal adhesions were observed to confine to the intervening ridge/groove boundaries. Osteoblasts bridged over the grooves and were unable to conform to the concave shape of the underlying grooves. Microgrooved surfaces induced higher osteoblast proliferation and metabolic activity after 14 days in osteogenic medium compared with as-received surfaces, resulting in higher mineralization and alignment of cell-secreted collagen after 28 days. To establish whether preferential cell attachment at the ridge/groove boundaries was influenced by the adhesion proteins contained in the serum-supplemented media, fluorescently labeled fibronectin was adsorbed onto the microgrooved substrates at low concentrations, mimicking the concentrations found in blood serum. Fibronectin was found to selectively adsorb onto the ridge/groove boundaries, the osteoblast focal adhesion sites, suggesting that protein adsorption may have influenced the cell attachment pattern.This research was supported by the European Research Council (Grant No. 240446). XPS, AFM and fibronectin experiments were carried out at the IOM Leipzig and the University of Leipzig, and were funded in parts by the German Federal Ministry of Education and Research (BMBF 1315883), the European Union and the Free State of Saxony (SAB 100121467).This is the accepted manuscript. The final version is available at http://dx.doi.org/10.1002/jbm.a.3540
In vitro osteoclast formation and resorption of silicon-substituted hydroxyapatite ceramics

Materials that participate in bone remodeling at the implant/tissue interface represent a modern tissue engineering approach with the aim of balancing implant resorption and nascent tissue formation. Silicon-substituted hydroxyapatite (SiHA) ceramics are capable of stimulating new bone formation, but little is known about their interaction with osteoclasts (OC). The effects of soluble silicate and SiHA on OCs were investigated in this study. Soluble silicate below 500 μM did not stimulate cell metabolism at 4 days or alter resorption area at 7 days on calcium phosphate discs. On sintered ceramics, OC numbers were similar on HA, (Si_0.3)HA (0.5 wt % Si) and (Si_0.5)HA (1.2 wt % Si) after 21 days in vitro, but actin ring sealing zone morphology on SiHA resembled that commonly found on bone or on carbonate-substituted hydroxyapatite (CHA). Smaller and thicker actin rings on SiHA as compared to HA were probably the result of altered surface chemistry and solubility differences. The more stable sealing zones and increased lattice solubility likely contributed to increased individual pit volumes observed on (Si_0.5)HA. The delayed formation of OCs on (Si_0.5)HA (lower numbers at day 14) excludes earlier differentiation as a possible mechanism of increased individual OC pit volumes at later times (day 21). Materials characterization of Si containing biomaterials remains paramount as the Si type and amounts can subsequently impact downstream OC behaviour in a complex manner.Funded by
-  National Science Foundation Graduate Research Fellowship (RJF). Grant Number:       DGE-1042796
-  Cambridge International Scholarship from the Cambridge Overseas Trusts (RJF)
-  National Institute for Health Research (RAB)This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/jbm.a.3547
Cell seeding density is a critical determinant for copolymer scaffolds-induced bone regeneration

Constructs intended for bone tissue engineering (TE) are influenced by the initial cell seeding density. Therefore, the objective of this study was to determine the effect of bone marrow stromal stem cells (BMSCs) density loaded onto copolymer scaffolds on bone regeneration. BMSCs were harvested from rat's bone marrow and cultured in media with or without osteogenic supplements. Cells were seeded onto poly(l-lactide-co-ε-caprolactone) [poly(LLA-co-CL)] scaffolds at two different densities: low density (1 × 106 cells/scaffold) or high density (2 × 106 cells/scaffold) using spinner modified flasks and examined after 1 and 3 weeks. Initial attachment and spread of BMSC onto the scaffolds was recorded by scanning electron microscopy. Cell proliferation was assessed by DNA quantification and cell differentiation by quantitative real-time reverse transcriptase-polymerized chain reaction analysis (qRT-PCR). Five-millimeter rat calvarial defects (24 defects in 12 rats) were implanted with scaffolds seeded with either low or high density expanded with or without osteogenic supplements. Osteogenic supplements significantly increased cell proliferation (p < 0.001). Scaffolds seeded at high cell density exhibited higher mRNA expressions of Runx2 p = 0.001, Col1 p = 0.001, BMP2 p < 0.001, BSP p < 0.001, and OC p = 0.013. More bone was formed in response to high cell seeding density (p = 0.023) and high seeding density with osteogenic medium (p = 0.038). Poly (LLA-co-CL) scaffolds could be appropriate candidates for bone TE. The optimal number of cells to be loaded onto scaffolds is critical for promoting Extracellular matrix synthesis and bone formation. Cell seeding density and osteogenic supplements may have a synergistic effect on the induction of new bone
Drug Diffusion, Integration, and Stability of Nanoengineered Drug-Releasing Implants in Bone Ex-Vivo

To treat skeletal conditions such as bone infections, osteoporotic fractures, and osteosarcoma, it would be ideal to introduce drugs directly to the affected site. Localized drug delivery from the bone implants is a promising alternative to systemic drug administration. In this study we investigated electrochemically nanoengineered Ti wire implants with titania nanotubes (TNTs), as minimally invasive drug‐releasing implants for the delivery of drugs directly into the bone tissue. Since trabecular bone in vivo contains a highly interconnected bone marrow, we sought to determine the influence of marrow on drug release and diffusion. Electrochemical anodization of Ti wires (length 10 mm) was performed to create an oxide layer with TNTs on the surface, followed by loading with a fluorescent model drug, Rhodamine B (RhB). Cores of bovine trabecular bone were generated from the sternum of a young steer, and were processed to have an intact bone marrow, or the marrow was removed. RhB‐loaded TNTs/Ti wires were inserted into the bone cores, which were then cultured ex vivo using the ZetOS™ bioreactor system to maintain bone viability. Release and diffusion of RhB inside the bone was monitored using fluorescence imaging and different patterns of drug transport in the presence or absence of marrow were observed. Scanning electron microscopy of the implants after retrieval from bone cores confirmed survival of the TNTs structures. Histological investigation showed the presence of bone cells adherent on the implants. This study shows a potential of Ti drug‐releasing implants based on TNTs technology towards localized bone therapy.Full Tex
High orientation of long chain branched poly (lactic acid) with enhanced blood compatibility and bionic structure

YesHighly-oriented poly (lactic acid) (PLA) with bionic micro-grooves was
fabricated through solid hot drawing technology for further improving the mechanical
properties and blood biocompatibility of PLA. In order to enhance the melt strength
and thus obtain high orientation degree, long chain branched PLA (LCB-PLA) was
prepared at first through a two-step ring-opening reaction during processing. Linear
viscoelasticity combined with branch-on-branch (BOB) model was used to predict
probable compositions and chain topologies of the products, and it was found that the
molecular weight of PLA increased and topological structures with star like chain
with three arms and tree-like chain with two generations formed during reactive
processing, and consequently draw ratio as high as1200% can be achieved during the
subsequent hot stretching. With the increase of draw ratio, the tensile strength and
orientation degree of PLA increased dramatically. Long chain branching and
orientation could significantly enhance the blood compatibility of PLA by prolonging
clotting time and decreasing platelet activation. Micro-grooves can be observed on the
surface of the oriented PLA which were similar to the intimal layer of blood vessel,
and such bionic structure resulted from the formation of the oriented shish kebab-like
crystals along the draw direction
Local delivery of parathyroid hormone-related protein-derived peptides coated onto a hydroxyapatite-based implant enhances bone regeneration in old and diabetic rats

Diabetes mellitus (DM) and aging are associated with bone fragility and increased fracture risk. Both (1-37) N- and (107-111) C-terminal parathyroid hormone-related protein (PTHrP) exhibit osteogenic properties. We here aimed to evaluate and compare the efficacy of either PTHrP (1-37) or PTHrP (107-111) loaded into gelatin-glutaraldehyde-coated hydroxyapatite (HA-Gel) foams to improve bone repair of a transcortical tibial defect in aging rats with or without DM, induced by streptozotocin injection at birth. Diabetic old rats showed bone structural deterioration compared to their age-matched controls. Histological and -computerized tomography studies showed incomplete bone repair at 4 weeks after implantation of unloaded Ha-Gel foams in the transcortical tibial defects, mainly in old rats with DM. However, enhanced defect healing, as shown by an increase of bone volume/tissue volume and trabecular and cortical thickness and decreased trabecular separation, occurred in the presence of either PTHrP peptide in the implants in old rats with or without DM. This was accompanied by newly formed bone tissue around the osteointegrated HA-Gel implant and increased gene expression of osteocalcin and vascular endothelial growth factor (bone formation and angiogenic markers, respectively), and decreased expression of Sost gene, a negative regulator of bone formation, in the healing bone area. Our findings suggest that local delivery of PTHrP (1-37) or PTHrP (107-111) from a degradable implant is an attractive strategy to improve bone regeneration in aged and diabetic subjects. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2060-2070, 2016