Endothelial progenitor/stem cells in engineered vessels for vascular transplantation.

BACKGROUND: Dysfunction of blood vessel leads to aneurysms, myocardial infarction and other thrombosis conditions. Current treatment strategies are transplantation of blood vessels from one part of the body to other dysfunction area, or allogenic, synthetic. Due to shortage of the donor, painful dissection, and lack of efficacy in synthetic, there is a need for alternative to native blood vessels for transplantation. METHODS: Human umbilical-cord tissue obtained from the hospital with the informed consent. Umbilical-cord blood vessels were isolated for decellularization and to establish endothelial cell culture. Cultured cells were characterized by immunophenotype, gene expression and in vitro angiogenesis assay. Decellularized blood vessels were recellularized with the endothelial progenitors and Wharton jelly, CL MSCs (1:1), which was characterized by MTT, biomechanical testing, DNA content, SEM and histologically. Bioengineered vessels were transplanted into the animal models to evaluate their effect. RESULTS: Cultured cells express CD31 and CD14 determining endothelial progenitor cells (EPCs). EPCs expresses various factors such as angiopoitin1, VWF, RANTES, VEGF, BDNF, FGF1, FGF2, HGF, IGF, GDNF, NGF, PLGF, NT3, but fail to express NT4, EGF, and CNTF. Pro and anti-inflammatory cytokine expressions were noticed. Functionally, these EPCs elicit in vitro tube formation. Negligible DNA content and intact ECM confirms the efficient decellularization of tissue. The increased MTT activity in recellularized tissue determines proliferating cells and biocompatibility of the scaffolds. Moreover, significant (P < 0.05) increase in maximum force and tensile of recellularized biomaterial as compared to the decellularized scaffolds. Integration of graft with host tissue, suggesting biocompatible therapeutic biomaterial with cells. CONCLUSION: EPCs with stem cells in engineered blood vessels could be therapeutically applicable in vascular surgery.

Spinal cord injury: pathophysiology, treatment strategies, associated challenges, and future implications.

Axonal regeneration and formation of tripartite (axo-glial) junctions at damaged sites is a prerequisite for early repair of injured spinal cord. Transplantation of stem cells at such sites of damage which can generate both neuronal and glial population has gained impact in terms of recuperation upon infliction with spinal cord injury. In spite of the fact that a copious number of pre-clinical studies using different stem/progenitor cells have shown promising results at acute and subacute stages, at the chronic stages of injury their recovery rates have shown a drastic decline. Therefore, developing novel therapeutic strategies are the need of the hour in order to assuage secondary morbidity and effectuate improvement of the spinal cord injury (SCI)-afflicted patients' quality of life. The present review aims at providing an overview of the current treatment strategies and also gives an insight into the potential cell-based therapies for the treatment of SCI.

Surface engineering of LENS-Ti-6Al-4V to obtain nano- and micro-surface topography for orthopedic application.

Two distinct surface topographies consisting of micro- and nano-surface were developed using laser texturing (LT) and anodization process respectively and their effect on the surface-related properties of Ti-6Al-4V fabricated using Laser Engineered Net Shaping (LENS) were determined. The topographies developed using laser texturing (25, 50 and 75% overlap) were examined using 3D profilometer, whereas, Field Emission Scanning Electron Microscopy (FE-SEM) was used to analyze Titania NanoTubes (TNT) formed using anodization. Though all the surface modified specimens exhibited hydrophilic behavior, least contact angle values were observed for the specimen surface modified with TNT. 25LT and 50LT specimens offered about 8 fold higher corrosion resistance than TNT specimens. All the surface modified samples exhibited non-toxicity to blood cells as well as to the mesenchymal stem cells (hMSCs) with a higher rate of proliferation and differentiation hMSCs observed on 75LT specimens and TNT specimen.

Hydrothermal treatment of etched titanium: A potential surface nano-modification technique for enhanced biocompatibility.

Nanoengineering the topology of titanium (Ti) implants has the potential to enhance cytocompability and biocompatibility properties as implant surfaces play a decisive role in determining clinical success. Despite developments in various surface engineering strategies, antibacterial properties of Ti still need to be enhanced. Here a facile, cost-effective hydrothermal route was used to develop nano-patterned structures on a Ti surface. Changing hydrothermal treatment parameters such as temperature, pressure, and time, resulted in various topographies, crystal phases, and hydrophobicity. Specifically, hydrothermal treatment performed at 225 °C for 5 h, presented a novel topography with nanoflower features, exhibited no mammalian cell cytotoxicity for a time period of 14 days, and increased calcium deposition from osteoblasts. Treated samples also demonstrated antibacterial properties (without resorting to the use of antibiotics) against Staphylococcus aureus and methicillin resistant Staphylococcus aureus. In conclusion, hydrothermal oxidation on an etched Ti surface can generate surface properties that have excellent prospects for the biomedical field.

Progress of Regenerative Therapy in Orthopedics.

PURPOSE OF REVIEW: To conduct a thorough appraisal of recent and inventive advances in the field of bone tissue engineering using biomaterials, cell-based research, along with the incorporation of biomimetic properties using surface modification of scaffolds. RECENT FINDINGS: This paper will provide an overview on different biomaterials and emerging techniques involved in the fabrication of scaffolds, brief description of signaling pathways involved in osteogenesis, and the effect of surface modification on the fate of progenitor cells. The current strategies used for regenerative medicine like cell therapy, gene transfer, and tissue engineering have opened numerous therapeutic avenues for the treatment of various disabling orthopedic disorders. Precise strategy utilized for the reconstruction, restoration, or repair of the bone-related tissues exploits cells, biomaterials, morphogenetic signals, and appropriate mechanical environment to provide the basic constituents required for creating new tissue. Combining all the above strategies in clinical trials would pave the way for successful "bench to bedside" transformation in bone healing.

Studies on Mechanical, Biocompatibility and Antibacterial Activity of Plasma Sprayed Nano/Micron Ceramic Bilayered Coatings on Ti-6Al-4V Alloy for Biomedical Application.

Ceramic oxides such as alumina and zirconia are used to fabricate dental and orthopedic implants. However, their usage is limited as they fail due to low fracture toughness. To overcome this issue, ceramic coatings on metallic implants is attempted to have a combined effect of ceramics and metallic materials. This paper reports on the microstructure, phase analysis, mechanical properties, osseointegration and antibacterial activity of three different wear-resistant coatings developed on Ti-6Al-4V alloy which is used widely as orthopedic and dental implants. The powders of following compositions, i. Nanostructured Al2O3 + 13 wt% TiO2/µ-TiO2 BL coating (S1), ii. µ-Al2O3 + 13 wt% nanostructured TiO2/µ-TiO2 BL coating (S2), iii. Nanostructured Al2O3 + 13 wt% TiO2/µ-YSZ BL coating (S3), were sprayed using atmospheric plasma spray process onto Ti-6Al-4V alloy. The coatings were characterized using X-ray diffraction (XRD), Scanning electron microscope (SEM), Profilometer and gonieometer to determine their phases, microstructure, surface roughness and contact angle. In addition, micro indentation hardness and scratch resistance were also evaluated. Amongst the three coatings, S2 exhibited higher hardness value with higher scratch resistance. The antibacterial activity was studied using colony formation on all three coatings. The antibacterial efficiency of S1 as well as S3 coatings was higher as seen from less number of bacterial colonies on the surface. The results of in-vitro studies on the biocompatibility of nano/micron alumina and zirconia ceramic coatings which were analyzed with hMSC's, reveals that S1 is cytotoxic with less number of cell attachment when compared to S2 and S3.

Molecularly Imprinted Polymers: Shaping the Future of Early-Stage Bone Loss Detection-A Review.

Osteoporosis is the deterioration of bone mineral density (BMD) because of an imbalance between bone resorption and formation, which might happen due to lots of factors like age, hormonal imbalance, and several others. While this occurrence is prevalent in both genders, it is more common in women, especially postmenopausal women. It is an asymptomatic disease that is underlying until the first incidence of a fracture. The bone is weakened, making it more susceptible to fracture. Even a low trauma can result in a fracture, making osteoporosis an even more alarming disease. These fractures can sometimes be fatal or can make the patient bedridden. Osteoporosis is an understudied disease, and there are certain limitations in diagnosing and early-stage detection of this condition. The standard method of dual X-ray absorptiometry can be used to some extent and can be detected in standard radiographs after the deterioration of a significant amount of bone mass. Clinically assessing osteoporosis using biomarkers can still be challenging, as clinical tests can be expensive and cannot be accessed by most of the general population. In addition, manufacturing antibodies specific to these biomarkers can be a challenging, time-consuming, and expensive method. As an alternative to these antibodies, molecularly imprinted polymers (MIPs) can be used in the detection of these biomarkers. This Review provides a comprehensive exploration of bone formation, resorption, and remodeling processes, linking them to the pathophysiology of osteoporosis. It details biomarker-based detection and diagnosis methods, with a focus on MIPs for sensing CTX-1, NTX-1, and other biomarkers. The discussion compares traditional clinical practices with MIP-based sensors, revealing comparable sensitivity with identified limitations. Additionally, the Review contrasts antibody-functionalized sensors with MIPs. Finally, our Review concludes by highlighting the potential of MIPs in future early-stage osteoporosis detection.

In situ production of low-modulus Ti-Nb alloys by selective laser melting and their functional assessment toward orthopedic applications.

This work aimed to manufacture Ti-28.5Nb and Ti-40.0Nb (wt%) alloys in situ via selective laser melting (SLM) from Ti and Nb elemental powders. X-ray diffraction analysis revealed complete ß-phase (cubic) in Ti-40.0Nb and a mixture of (α'' orthorhombic + ß cubic) phases in Ti-28.5Nb were formed, whereas few of the Nb particles remained only partially fused during manufacturing. The fraction of partially melted Nb particles was determined as ∼2 and ∼18% in Ti-28.5Nb and Ti-40Nb, respectively. Mechanical characterization revealed higher hardness and more strength in Ti-28.5Nb than in Ti-40.0Nb due to the presence of the α'' phase in the former. Tribocorrosion tests reveal a significantly better wear-corrosion resistance for Ti-40.0Nb, as determined from a lower total volume loss in Ti-40.0Nb (∼2 × 10-4 mm-3) than in Ti-28.5Nb (∼13 × 10-2 mm-3). The lower volume loss and better corrosion resistance behavior are attributed to the ß phase, which was dominant in Ti-40.0Nb. Cell studies reveal no toxicity for up to 7 days. Both the alloys were better at supporting cell proliferation than wrought Ti6Al4V. This study presents a route to preparing Ti-Nb alloys in situ by SLM that are promising candidates for biomedical applications.

Surface nanocrystallization enhances the biomedical performance of additively manufactured stainless steel.

Additive manufacturing enables the fabrication of patient-specific implants of complex geometries. Although selective laser melting (SLM) of 316L stainless steel (SS) is well established, post-processing is essential to preparing high-performance biomedical implants. The goal of this study was to investigate surface mechanical attrition treatment (SMAT) as a means to enhance the electrochemical, biomechanical, and biological performances of 316L SS fabricated by SLM in devices for the repair of bone tissues. The SMAT conditions were optimized to induce surface nanocrystallization on the additively manufactured samples. SMAT resulted in a thicker oxide layer, which provided corrosion resistance by forming a passive layer. The fretting wear results showed that the rate of wear decreased after SMAT owing to the formation of a harder nanostructured layer. Surface modification of the alloy by SMAT enhanced its ability to support the attachment and proliferation of pre-osteoblasts in vitro. The study of the response in vivo to the additively manufactured alloy in a critical-sized cranial defect murine model revealed enhanced interactions with the cellular components after the alloy was subjected to SMAT without inducing any adverse immune response. Taken together, the results of this work establish SMAT of additively manufactured metallic implants as an effective strategy for engineering next-generation, high-performance medical devices for orthopedics and craniomaxillofacial applications.

Anisotropy of Additively Manufactured Co-28Cr-6Mo Influences Mechanical Properties and Biomedical Performance.

Additive manufacturing (AM) of biomedical alloys such as Co-Cr-Mo alloys holds immense potential for fabricating implants with complex geometry and tailored to meet patient-specific needs. However, layer-by-layer fabrication in AM processes results in undesired anisotropy due to the solidification texture and grain morphology. The present study aimed to investigate the effect of build orientation on the mechanical properties and functional performance, including tribocorrosion behavior and cytocompatibility of an orthopedic Co-28Cr-6Mo alloy manufactured by selective laser melting. Although the fabricated alloy showed weak crystallographic texture due to the rotational scanning strategy, significant anisotropy was found in the tensile properties due to the grain size and morphology. The presence of larger, elongated grains along the build direction as compared to smaller, equiaxed grains perpendicular to the build direction imparted the observed tensile anisotropy. Quantitative analysis based on current models for strengthening mechanisms is insufficient to explain the observed anisotropy, which is ascribed to the possible role of the cellular dendrites and stacking fault strengthening in Co-Cr alloys. Unlike the electrochemical behavior, which was largely independent of the build orientation, the bio-tribocorrosion studies revealed an anisotropic wear rate under fretting conditions. Osteoblast attachment and proliferation were found to be higher on the plane perpendicular to the build direction, owing to the differences in grain size. This work provides novel insights into the role of the manufacturing parameters in a selective-laser-melted Co-Cr alloy and its potential application in engineering load-bearing orthopedic implants.

Influence of Graphene Nanoplatelets on the Performance of Axial Suspension Plasma-Sprayed Hydroxyapatite Coatings.

Axial suspension plasma spraying (ASPS) is an alternative technique to atmospheric plasma spraying (APS), which uses a suspension of much finer powders (<5-micron particle size) as the feedstock. It can produce more refined microstructures than APS for biomedical implants. This paper highlights the influence of incorporated graphene nanoplatelets (GNPs) on the behavior of ASPS hydroxyapatite (HAp) coatings. The characterization of the ASPS coatings (HAp + varying GNP contents) was carried out using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), confocal Raman microscopy (CRM), white light interferometry (WLI), and contact angle measurements. The evaluation of the mechanical properties such as the hardness, roughness, adhesion strength, and porosity was carried out, along with a fretting wear performance. Additionally, the biocompatibility of the Hap + GNP coatings was evaluated using cytotoxicity testing which revealed a decrease in the cell viability from 92.7% to 85.4%, with an increase in the GNP wt.%. The visualization of the cell's components was carried out using SEM and Laser Scanning Microscopy. Furthermore, the changes in the genetic expression of the various cellular markers were assessed to analyze the epigenetic changes in human mesenchymal stem cells. The gene expression changes suggested that GNPs upregulated the proliferation marker and downregulated the pluripotent markers by a minimum of three folds.

An overview of bio-actuation in collagen hydrogels: a mechanobiological phenomenon.

Due to their congruity with the native extracellular matrix and their ability to assist in soft tissue repair, hydrogels have been touted as a matrix mimicking biomaterial. Hydrogels are one of the prevalent scaffolds used for 3D cell culture. They can exhibit actuation in response to various stimuli like a magnetic field, electric field, mechanical force, temperature, or pH. In 3D cell culture, the traction exerted by cells on hydrogel can induce non-periodic mechanobiological movements (shrinking or folding) called 'bio-actuation'. Interestingly, this hydrogel 'tropism' phenomenon in 3D cell cultures can be exploited to devise hydrogel-cell-based actuators for tissue engineering. This review briefs about the discrepancies in 2D vs. 3D cell culturing on hydrogels and discusses on different types of cell migration occurring inside the hydrogel matrix. It substantiates the role of mechanical stimuli (such as stiffness) exhibited by the collagen-based hydrogel used for 3D cell culture and its influence in governing the lineage commitment of stem cells. Lastly, the review also audits the cytoskeleton proteins present in cells responsible for influencing the actuation of collagen hydrogel and also elaborates on the cellular signaling pathways responsible for actuation of collagen hydrogels.

Tailoring biocompatible Ti-Zr-Nb-Hf-Si metallic glasses based on high-entropy alloys design approach.

Present work unveils novel magnetic resonance imaging (MRI) compatible glassy Ti-Zr-Nb-Hf-Si alloys designed based on a high entropy alloys approach, by exploring the central region of multi-component alloy phase space. Phase analysis has revealed the amorphous structure of developed alloys, with a higher thermal stability than the conventional metallic glasses. The alloys exhibit excellent corrosion properties in simulated body fluid. Most importantly, the weak paramagnetic nature (ultralow magnetic susceptibility) and superior radiopacity (high X-ray attenuation coefficients) offer compatibility with medical diagnostic imaging systems thereby opening unexplored realms for biomedical applications.

A Critical Review on Polymeric Biomaterials for Biomedical Applications.

Natural and synthetic polymers have been explored for many years in the field of tissue engineering and regeneration. Researchers have developed many new strategies to design successful advanced polymeric biomaterials. In this review, we summarized the recent notable advancements in the preparation of smart polymeric biomaterials with self-healing and shape memory properties. We also discussed novel approaches used to develop different forms of polymeric biomaterials such as films, hydrogels and 3D printable biomaterials. In each part, the applications of the biomaterials in soft and hard tissue engineering with their in vitro and in vivo effects are underlined. The future direction of the polymeric biomaterials that could pave a path towards successful clinical implications is also underlined in this review.

A Review on Development of Bio-Inspired Implants Using 3D Printing.

Biomimetics is an emerging field of science that adapts the working principles from nature to fine-tune the engineering design aspects to mimic biological structure and functions. The application mainly focuses on the development of medical implants for hard and soft tissue replacements. Additive manufacturing or 3D printing is an established processing norm with a superior resolution and control over process parameters than conventional methods and has allowed the incessant amalgamation of biomimetics into material manufacturing, thereby improving the adaptation of biomaterials and implants into the human body. The conventional manufacturing practices had design restrictions that prevented mimicking the natural architecture of human tissues into material manufacturing. However, with additive manufacturing, the material construction happens layer-by-layer over multiple axes simultaneously, thus enabling finer control over material placement, thereby overcoming the design challenge that prevented developing complex human architectures. This review substantiates the dexterity of additive manufacturing in utilizing biomimetics to 3D print ceramic, polymer, and metal implants with excellent resemblance to natural tissue. It also cites some clinical references of experimental and commercial approaches employing biomimetic 3D printing of implants.

Enhanced Biocorrosion Resistance and Cellular Response of a Dual-Phase High Entropy Alloy through Reduced Elemental Heterogeneity.

The leaching out of toxic elements from metallic bioimplants has serious repercussions, including allergies, peripheral neuritis, cancer, and Alzheimer's disease, leading to revision or replacement surgeries. The development of advanced structural materials with excellent biocompatibility and superior corrosion resistance in the physiological environment holds great significance. High entropy alloys (HEAs) with a huge compositional design space and outstanding mechanical and functional properties can be promising for bioimplant applications. However, microstructural heterogeneity arising from elemental segregation in these multiprinciple alloy systems is the Achilles heel in the development of next-generation HEAs. Here, we demonstrate a pathway to homogenize the microstructure of a biocompatible dual-phase HEA, comprising refractory elements, namely, MoNbTaTiZr, through severe surface deformation using stationary friction processing (SFP). The strain and temperature field during processing homogenized the elemental distribution, which was otherwise unresponsive to conventional annealing treatments. Nearly 15 min of the SFP treatment resulted in a significant elemental homogenization across dendritic and interdendritic regions, similar to a week-long annealing treatment at 1275 K. The SFP processed alloy showed a nearly six times higher biocorrosion resistance compared to its as-cast counterpart. X-ray photoelectron spectroscopy was used to investigate the nature of the oxide layer formed on the specimens. Superior corrosion behavior of the processed alloy was attributed to the formation of a stable passive layer with zirconium oxide as the primary constituent and higher hydrophobicity. Biocompatibility studies performed using the human mesenchymal stem cell line, showed higher viability for the processed HEA compared to its as-cast counterpart as well as conventional metallic biomaterials including stainless steel (SS316L) and titanium alloy (Ti6Al4V).

Properties of scaffolds based on chitosan and collagen with bioglass 45S5.

Scaffolds based on chitosan (CTS), collagen (Coll) and glycosaminoglycans (GAG) mixtures cross-linked by tannic acid (TA) with bioglass 45S5 addition were obtained with the use of the freeze-drying method. The prepared scaffolds were characterised for morphology, mechanical strength and degradation rate. Moreover, cell viability on the obtained scaffolds was measured with and without the presence of ascorbic acid and dexamethasone. The main purpose of the research was to compare the effectiveness of bioglass 45S5 influence on the physicochemical and biological properties of scaffolds. The results demonstrated that the scaffolds based on the blends of biopolymers cross-linked by TA are stable in an aqueous environment. Scanning electron microscope images allowed the observation of a porous scaffold structure with interconnected pores. The addition of bioglass nanoparticles improved the mechanical properties and decreased the degradation rate of composite materials. The biological properties were improved for 20% tannic acid addition compared to 5%. However, the addition of bioglass 45S5 did not change to cells response significantly.

Exosomes in the Oral and Maxillofacial Region.

Exosomes are a type of extracellular vesicles, released from different tissues in a living individual. By virtue of their ability to be released from both the normal and diseased individual, they play an inevitable role in the diagnosis, prognosis, and therapeutic aspect of a disease. With this background, the untapped role of exosomes in the field of oral and maxillofacial region is unveiled.

Surface mechanical attrition treatment of low modulus Ti-Nb-Ta-O alloy for orthopedic applications.

Surface mechanical attrition treatment (SMAT) is recognized as a surface severe plastic deformation (SPD) method that is effective in improving the surface-dependent mechanical and functional properties of conventional metallic biomaterials. In this study, we aimed to systemically investigate the effect of SMAT on the physical, electrochemical, tribological and biological performances of a newly developed low modulus ß Ti-Nb-Ta-O alloy with two different microstructures, namely, single phase ß-treated and dual phase ß + α aged. The microhardness results showed considerable hardening for the ß-treated condition due to formation of deformation substructures; that was associated with increased corrosion resistance resulting from a stronger and denser passive layer on the surface, as revealed by Tafel polarization, impedance studies and Mott-Scottky plots. The wear volume loss during fretting in serum solution was found to decrease by 46% while friction coefficient decreased only marginally, due to presence of a harder and more brittle surface. In the ß + α condition of the alloy, minimal hardening was observed due to coarsening of the precipitates during SMAT. However, this also reduced the number of α-ß interfaces, which in turn minimized the tendency for galvanic corrosion resulting in lower corrosion rate after SMAT. Wear resistance was enhanced after SMAT, with 32% decrease in wear volume loss and 21% decrease in friction coefficient resulted due to improved ductility on the surface. The attachment and growth of osteoblasts on the alloys in vitro were not affected by SMAT and was comparable to that on commercially pure Ti. Taken together, these results provide new insights into the effects of surface SPD of low modulus ß- Ti alloys for orthopedic applications and underscore the importance of the initial microstructure in determining the performance of the alloy.

Biocompatible High Entropy Alloys with Excellent Degradation Resistance in a Simulated Physiological Environment.

Bioimplants are susceptible to simultaneous wear and corrosion degradation in the aggressive physiological environment. High entropy alloys with equimolar proportion of constituent elements represent a unique alloy design strategy for developing bioimplants due to their attractive mechanical properties, superior wear, and corrosion resistance. In this study, the tribo-corrosion behavior of an equiatomic MoNbTaTiZr high entropy alloy consisting of all biocompatible elements was evaluated and compared with 304 stainless steel as a benchmark. The high entropy alloy showed a low wear rate and a friction coefficient as well as quick and stable passivation in simulated body fluid. An increase from room temperature to body temperature showed excellent temperature assisted passivity and nobler surface layer of the high entropy alloy, resulting in four times better wear resistance compared to stainless steel. Stem cells and osteoblast cells displayed proliferation and migratory behavior, indicating in vitro biocompatibility. Several filopodia extensions on the cell periphery indicated early osteogenic commitment, and cell adhesion on the high entropy alloy. These results pave the way for utilizing the unique combination of tribo-corrosion resistance, excellent mechanical properties, and biocompatibility of MoNbTaTiZr high entropy alloy to develop bioimplants with improved service life and lower risk of implant induced cytotoxicity in the host body.