Publications by authors named "Amir A Zadpoor"

94 Publications

3D-Printed Submicron Patterns Reveal the Interrelation between Cell Adhesion, Cell Mechanics, and Osteogenesis.

ACS Appl Mater Interfaces 2021 Jul 12;13(29):33767-33781. Epub 2021 Jul 12.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD Delft, The Netherlands.

The surface topography of implantable devices is of crucial importance for guiding the cascade of events that starts from the initial contact of the cells with the surface and continues until the complete integration of the device in its immediate environment. There is, however, limited quantitative information available regarding the relationships between the different stages of such cascade(s) and how the design of surface topography influences them. We, therefore, used direct laser writing to 3D-print submicron pillars with precisely controlled dimensions and spatial arrangements to perform a systematic study of such relationships. Using single-cell force spectroscopy, we measured the adhesion force and the work of adhesion of the preosteoblast cells residing on the different types of surfaces. Not only the adhesion parameters (after 2-60 s) but also the formation of focal adhesions was strongly dependent on the geometry and arrangement of the pillars: sufficiently tall and dense pillars enhanced both adhesion parameters and the formation of focal adhesions. Our morphological study of the cells (after 24 h) showed that those enhancements were associated with a specific way of cell settlement onto the surface (i.e., "top state"). The cells interacting with tall and dense pillars were also characterized by numerous thick actin stress fibers in the perinuclear region and possibly high internal stresses. Furthermore, living cells with highly organized cytoskeletal networks exhibited greater values of the elastic modulus. The early responses of the cells predicted their late response including matrix mineralization: tall and dense submicron pillars significantly upregulated the expression of osteopontin after 21 days of culture under both osteogenic and nonosteogenic conditions. Our findings paint a detailed picture of at least one possible cascade of events that starts from initial cell adhesion and continues to subsequent cellular functions and eventual matrix mineralization. These observations could inform the future developments of instructive surfaces for medical devices based on physical surface cues and early markers.
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http://dx.doi.org/10.1021/acsami.1c03687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323101PMC
July 2021

Patient-specific 3D-printed shelf implant for the treatment of hip dysplasia: Anatomical and biomechanical outcomes in a canine model.

J Orthop Res 2021 Jun 30. Epub 2021 Jun 30.

Department of Orthopedics, University Medical Center Utrecht, Utrecht, The Netherlands.

A solution for challenging hip dysplasia surgery could be a patient-specific 3D-printed shelf implant that is positioned extra-articular and restores the dysplastic acetabular rim to normal anatomical dimensions. The anatomical correction and biomechanical stability of this concept were tested in a canine model that, like humans, also suffers from hip dysplasia. Using 3D reconstructed computed tomography images the 3D shelf implant was designed to restore the radiological dysplastic hip parameters to healthy parameters. It was tested ex vivo on three dog cadavers (six hips) with hip dysplasia. Each hip was subjected to a biomechanical subluxation test, first without and then with the 3D shelf implant in place. Subsequently, an implant failure test was performed to test the primary implant fixation. At baseline, the dysplastic hips had an average Norberg angle of 88 ± 3° and acetabular coverage of 47 ± 2% and subluxated at an average of 83 ± 2° of femoral adduction. After adding the patient-specific shelf implants the dysplastic hips had an average Norberg angle of 122 ± 2° and acetabular coverage of 67 ± 3% and subluxated at an average of 117 ± 2° of femoral adduction. Implant failure after primary implant fixation occurred at an average of 1330 ± 320 Newton. This showed that the patient-specific shelf implants significantly improved the coverage and stability of dysplastic hips in a canine model with naturally occurring hip dysplasia. The 3D shelf is a promising concept for treating residual hip dysplasia with a straightforward technology-driven approach; however, the clinical safety needs to be further investigated in an experimental proof-of-concept animal study.
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http://dx.doi.org/10.1002/jor.25133DOI Listing
June 2021

The local and global geometry of trabecular bone.

Acta Biomater 2021 08 12;130:343-361. Epub 2021 Jun 12.

Department of Biomechanical Engineering, TU Delft, Mekelweg 2, Delft 2628CD, the Netherlands.

The organization and shape of the microstructural elements of trabecular bone govern its physical properties, are implicated in bone disease, and serve as blueprints for biomaterial design. To devise fundamental structure-property relationships and design truly bone-mimicking biomaterials, it is essential to characterize trabecular bone structure from the perspective of geometry, the mathematical study of shape. Using micro-CT images from 70 donors at five different sites, we analyze the local and global geometry of human trabecular bone in detail, respectively by quantifying surface curvatures and Minkowski functionals. We find that curvature density maps provide distinct and sensitive shape fingerprints for bone from different sites. Contrary to a common assumption, these curvature maps also show that bone morphology does not approximate a minimal surface but exhibits a much more intricate curvature landscape. At the global (or integral) perspective, our Minkowski analysis illustrates that trabecular bone exhibits other types of anisotropy/ellipticity beyond interfacial orientation, and that anisotropy varies substantially within the trabecular structure. Moreover, we show that the Minkowski functionals unify several traditional morphometric indices. Our geometric approach to trabecular morphometry provides a fundamental language of shape that could be useful for bone failure prediction, understanding geometry-driven tissue growth, and the design of bone-mimicking tissue scaffolds. STATEMENT OF SIGNIFICANCE: The architecture of trabecular bone is key in determining bone properties, and is often a starting point for the design of bone-substitutes. Despite the substantial history of bone morphometry, a fundamental characterization of trabecular bone geometry is still lacking. Therefore, we introduce a robust framework to quantify local and global trabecular bone geometry, which we apply to hundreds of micro-CT scans. Our approach relies on quantifying surface curvatures and Minkowski functionals, which are the most fundamental local and global shape quantifiers. Our results show that these shape metrics are sensitive to differences between bone types and unify traditional metrics within a single mathematical framework. This geometrical framework could also be useful to design bone-mimicking scaffolds and understand geometry-driven tissue growth.
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http://dx.doi.org/10.1016/j.actbio.2021.06.013DOI Listing
August 2021

Curvature Induced by Deflection in Thick Meta-Plates.

Adv Mater 2021 Jul 13;33(30):e2008082. Epub 2021 Jun 13.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, Delft, 2628 CD, The Netherlands.

The design of advanced functional devices often requires the use of intrinsically curved geometries that belong to the realm of non-Euclidean geometry and remain a challenge for traditional engineering approaches. Here, it is shown how the simple deflection of thick meta-plates based on hexagonal cellular mesostructures can be used to achieve a wide range of intrinsic (i.e., Gaussian) curvatures, including dome-like and saddle-like shapes. Depending on the unit cell structure, non-auxetic (i.e., positive Poisson ratio) or auxetic (i.e., negative Poisson ratio) plates can be obtained, leading to a negative or positive value of the Gaussian curvature upon bending, respectively. It is found that bending such meta-plates along their longitudinal direction induces a curvature along their transverse direction. Experimentally and numerically, it is shown how the amplitude of this induced curvature is related to the longitudinal bending and the geometry of the meta-plate. The approach proposed here constitutes a general route for the rational design of advanced functional devices with intrinsically curved geometries. To demonstrate the merits of this approach, a scaling relationship is presented, and its validity is demonstrated by applying it to 3D-printed microscale meta-plates. Several applications for adaptive optical devices with adjustable focal length and soft wearable robotics are presented.
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http://dx.doi.org/10.1002/adma.202008082DOI Listing
July 2021

Topographic features of nano-pores within the osteochondral interface and their effects on transport properties -a 3D imaging and modeling study.

J Biomech 2021 06 11;123:110504. Epub 2021 May 11.

Department of Orthopaedics, University Medical Centre Utrecht, Utrecht, the Netherlands; Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, the Netherlands.

Recent insights suggest that the osteochondral interface plays a central role in maintaining healthy articulating joints. Uncovering the underlying transport mechanisms is key to the understanding of the cross-talk between articular cartilage and subchondral bone. Here, we describe the mechanisms that facilitate transport at the osteochondral interface. Using scanning electron microscopy (SEM), we found a continuous transition of mineralization architecture from the non-calcified cartilage towards the calcified cartilage. This refurbishes the classical picture of the so-called tidemark; a well-defined discontinuity at the osteochondral interface. Using focused-ion-beam SEM (FIB-SEM) on one osteochondral plug derived from a human cadaveric knee, we elucidated that the pore structure gradually varies from the calcified cartilage towards the subchondral bone plate. We identified nano-pores with radius of 10.71 ± 6.45 nm in calcified cartilage to 39.1 ± 26.17 nm in the subchondral bone plate. The extracted pore sizes were used to construct 3D pore-scale numerical models to explore the effect of pore sizes and connectivity among different pores. Results indicated that connectivity of nano-pores in calcified cartilage is highly compromised compared to the subchondral bone plate. Flow simulations showed a permeability decrease by about 2000-fold and solute transport simulations using a tracer (iodixanol, 1.5 kDa with a free diffusivity of 2.5 × 10 m/s) showed diffusivity decrease by a factor of 1.5. Taken together, architecture of the nano-pores and the complex mineralization pattern in the osteochondral interface considerably impacts the cross-talk between cartilage and bone.
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http://dx.doi.org/10.1016/j.jbiomech.2021.110504DOI Listing
June 2021

Inorganic Agents for Enhanced Angiogenesis of Orthopedic Biomaterials.

Adv Healthc Mater 2021 06 26;10(12):e2002254. Epub 2021 May 26.

Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Mekelweg 2, Delft, 2628 CD, The Netherlands.

Aseptic loosening of a permanent prosthesis remains one of the most common reasons for bone implant failure. To improve the fixation between implant and bone tissue as well as enhance blood vessel formation, bioactive agents are incorporated into the surface of the biomaterial. This study reviews and compares five bioactive elements (copper, magnesium, silicon, strontium, and zinc) with respect to their effect on the angiogenic behavior of endothelial cells (ECs) when incorporated on the surface of biomaterials. Moreover, it provides an overview of the state-of-the-art methodologies used for the in vitro assessment of the angiogenic properties of these elements. Two databases are searched using keywords containing ECs and copper, magnesium, silicon, strontium, and zinc. After applying the defined inclusion and exclusion criteria, 59 articles are retained for the final assessment. An overview of the angiogenic properties of five bioactive elements and the methods used for assessment of their in vitro angiogenic potential is presented. The findings show that silicon and strontium can effectively enhance osseointegration through the simultaneous promotion of both angiogenesis and osteogenesis. Therefore, their integration onto the surface of biomaterials can ultimately decrease the incidence of implant failure due to aseptic loosening.
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http://dx.doi.org/10.1002/adhm.202002254DOI Listing
June 2021

On the Use of Black Ti as a Bone Substituting Biomaterial: Behind the Scenes of Dual-Functionality.

Small 2021 06 12;17(24):e2100706. Epub 2021 May 12.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Mekelweg 2, Delft, 2628 CD, The Netherlands.

Despite the potential of small-scale pillars of black titanium (bTi) for killing the bacteria and directing the fate of stem cells, not much is known about the effects of the pillars' design parameters on their biological properties. Here, three distinct bTi surfaces are designed and fabricated through dry etching of the titanium, each featuring different pillar designs. The interactions of the surfaces with MC3T3-E1 preosteoblast cells and Staphylococcus aureus bacteria are then investigated. Pillars with different heights and spatial organizations differently influence the morphological characteristics of the cells, including their spreading area, aspect ratio, nucleus area, and cytoskeletal organization. The preferential formation of focal adhesions (FAs) and their size variations also depend on the type of topography. When the pillars are neither fully separated nor extremely tall, the colocalization of actin fibers and FAs as well as an enhanced matrix mineralization are observed. However, the killing efficiency of these pillars against the bacteria is not as high as that of fully separated and tall pillars. This study provides a new perspective on the dual-functionality of bTi surfaces and elucidates how the surface design and fabrication parameters can be used to achieve a surface topography with balanced bactericidal and osteogenic properties.
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http://dx.doi.org/10.1002/smll.202100706DOI Listing
June 2021

Antibacterial Titanium Implants Biofunctionalized by Plasma Electrolytic Oxidation with Silver, Zinc, and Copper: A Systematic Review.

Int J Mol Sci 2021 Apr 6;22(7). Epub 2021 Apr 6.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, 2628 CD Delft, The Netherlands.

Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the treatment of IAI. The focus has, therefore, shifted towards the development of implants with intrinsic antibacterial activity to prevent the occurrence of infection. The use of Ag, Cu, and Zn has gained momentum as these elements display strong antibacterial behavior and target a wide spectrum of bacteria. In order to incorporate these elements into the surface of titanium-based bone implants, plasma electrolytic oxidation (PEO) has been widely investigated as a single-step process that can biofunctionalize these (highly porous) implant surfaces. Here, we present a systematic review of the studies published between 2009 until 2020 on the biomaterial properties, antibacterial behavior, and biocompatibility of titanium implants biofunctionalized by PEO using Ag, Cu, and Zn. We observed that 100% of surfaces bearing Ag (Ag-surfaces), 93% of surfaces bearing Cu (Cu-surfaces), 73% of surfaces bearing Zn (Zn-surfaces), and 100% of surfaces combining Ag, Cu, and Zn resulted in a significant (i.e., >50%) reduction of bacterial load, while 13% of Ag-surfaces, 10% of Cu-surfaces, and none of Zn or combined Ag, Cu, and Zn surfaces reported cytotoxicity against osteoblasts, stem cells, and immune cells. A majority of the studies investigated the antibacterial activity against . Important areas for future research include the biofunctionalization of additively manufactured porous implants and surfaces combining Ag, Cu, and Zn. Furthermore, the antibacterial activity of such implants should be determined in assays focused on prevention, rather than the treatment of IAIs. These implants should be tested using appropriate in vivo bone infection models capable of assessing whether titanium implants biofunctionalized by PEO with Ag, Cu, and Zn can contribute to protect patients against IAI.
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http://dx.doi.org/10.3390/ijms22073800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038786PMC
April 2021

The three-dimensional shape symmetry of the lunate and its implications.

J Hand Surg Eur Vol 2021 Jul 30;46(6):587-593. Epub 2021 Mar 30.

Department of Biomechanical Engineering, Delft University of Technology (TU Delft), Delft, The Netherlands.

We studied the three-dimensional (3-D) shape variations and symmetry of the lunate to evaluate whether a contralateral shape-based approach to design patient-specific implants for treatment of Kienböck's disease is accurate. A 3-D statistical shape model of the lunate was built using the computed tomography scans of 54 lunate pairs and shape symmetry was evaluated based on an intraclass correlation analysis. The lunate shape was not bilaterally symmetrical in (1) the angle scaphoid surface - radius-ulna surface, (2) the dorsal side and the length of the side adjacent to the triquetrum, (3) the orientation of the volar surface, (4) the width of the side adjacent to the scaphoid, (5) the skewness in the coronal plane and (6) the curvature of bone articulating with the hamate and capitate. These findings suggest that using the contralateral lunate to design patient-specific lunate implants may not be as accurate as it is intended.
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http://dx.doi.org/10.1177/17531934211004080DOI Listing
July 2021

Surface-treated 3D printed Ti-6Al-4V scaffolds with enhanced bone regeneration performance: an study.

Ann Transl Med 2021 Jan;9(1):39

Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang, China.

Background: Given their highly adjustable and predictable properties, three-dimensional(3D) printed geometrically ordered porous biomaterials offer unique opportunities as orthopedic implants. The performance of such biomaterials is, however, as much a result of the surface properties of the struts as it is of the 3D porous structure. In our previous study, we have investigated the performances of selective laser melted (SLM) Ti-6Al-4V scaffolds which are surface modified by the bioactive glass (BG) and mesoporous bioactive glass (MBG), respectively. The results demonstrated that such modification enhanced the attachment, proliferation, and differentiation of human bone marrow stromal cells (hBMSC). Here, we take the next step by assessing the therapeutic potential of 3D printed Ti-6Al-4V scaffolds with BG and MBG surface modifications for bone regeneration in a rabbit bone defect model.

Methods: 3D printed Ti-6Al-4V scaffolds with BG and MBG surface modifications were implanted into the femoral condyle of the rabbits, the Ti-6Al-4V scaffolds without surface modification were used as the control. At week 3, 6, and 9 after the implantation, micro-computed tomography (micro-CT) imaging, fluorescence double-labeling to determine the mineral apposition rate (MAR), and histological analysis of non-decalcified sections were performed.

Results: We found significantly higher volumes of regenerated bone, significantly higher values of the relevant bone morphometric parameters, clear signs of bone matrix apposition and maturation, and the evidence of progressed angiogenesis and blood vessel formation in the groups where the bioactive glass was added as a coating, particularly the MGB group.

Conclusions: The MBG coating resulted in enhanced osteoconduction and vascularization in bone defect healing, which was attributed to the release of silicon and calcium ions and the presence of a nano-mesoporous structure on the surface of the MBG specimens.
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http://dx.doi.org/10.21037/atm-20-3829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859759PMC
January 2021

Osteogenic and antibacterial surfaces on additively manufactured porous Ti-6Al-4V implants: Combining silver nanoparticles with hydrothermally synthesized HA nanocrystals.

Mater Sci Eng C Mater Biol Appl 2021 Jan 26;120:111745. Epub 2020 Nov 26.

Department of Biomechanical Engineering, Delft University of Technology, Mekelweg 2, 2628 CD Delft, the Netherlands.

The recently developed additively manufacturing techniques have enabled the fabrication of porous biomaterials that mimic the characteristics of the native bone, thereby avoiding stress shielding and facilitating bony ingrowth. However, aseptic loosening and bacterial infection, as the leading causes of implant failure, need to be further addressed through surface biofunctionalization. Here, we used a combination of (1) plasma electrolytic oxidation (PEO) using Ca-, P-, and silver nanoparticle-rich electrolytes and (2) post-PEO hydrothermal treatments (HT) to furnish additively manufactured Ti-6Al-4V porous implants with a multi-functional surface. The applied HT led to the formation of hydroxyapatite (HA) nanocrystals throughout the oxide layer. This process was controlled by the supersaturation of Ca and PO during the hydrothermal process. Initially, the high local supersaturation resulted in homogenous nucleation of spindle-like nanocrystals throughout the surface. As the process continued, the depletion of reactant ions in the outermost surface layer led to a remarkable decrease in the supersaturation degrees. High aspect-ratio nanorods and hexagonal nanopillars were, therefore, created. The unique hierarchical structure of the microporous PEO layer (pore size < 3 μm) and spindle-like HA nanocrystals (<150 nm) on the surface of macro-porous additively manufactured Ti-6Al-4V implants provided a favorable substrate for the anchorage of cytoplasmic extensions assisting cell attachment and migration on the surface. The results of our in vitro assays clearly showed the important benefits of the HT and the spindle-like HA nanocrystals including a significantly stronger and much more sustained antibacterial activity, significantly higher levels of pre-osteoblasts metabolic activity, and significantly higher levels of alkaline phosphatase activity as compared to similar PEO-treated implants lacking the HT.
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http://dx.doi.org/10.1016/j.msec.2020.111745DOI Listing
January 2021

The morphological variation of acetabular defects in revision total hip arthroplasty-A statistical shape modeling approach.

J Orthop Res 2021 Jan 25. Epub 2021 Jan 25.

Department of Development and Regeneration, Faculty of Medicine, Institute for Orthopaedic Research and Training (IORT), KU Leuven, Leuven, Belgium.

Classification and evaluation of acetabular defects remain challenging and are primarily based on qualitative classification methods. That is because quantitative techniques describing variations of acetabular defects and accompanying bone loss volume are not available. This study introduces a new method based on statistical shape models (SSMs) to quantitively describe acetabular defects. This method is then applied to 87 acetabular defects to objectively describe the variations in acetabular defects typically encountered during revision total hip arthroplasty. The absolute bone loss volume, relative bone loss volume, and relative bone loss surface area with respect to the SSM-based pre-diseased anatomy were used to quantify the acetabular bone defects in different segments of the acetabular surface. The absolute bone loss volume of the average defect shape was equal to 37.0 cm . The first three principal modes, accounting for 62% of the total shape variation, were found to represent variations in acetabular defect morphology. The first, second, and third principal modes described, respectively, the size of the bone defects, the difference between superomedially and superolaterally migrated defects, and the degree of involvement of the posterior or anterior column. The developed SSM and the introduced approach could be used to create automated and unbiased classification methods based on quantitative data. Moreover, the proposed model and the underlying data provide the basis for a quantitative design approach where the shape and size of new acetabular implants are determined according to clinical variation present in acetabular defects.
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http://dx.doi.org/10.1002/jor.24995DOI Listing
January 2021

Design of a 3D-printed hand prosthesis featuring articulated bio-inspired fingers.

Proc Inst Mech Eng H 2021 Mar 8;235(3):336-345. Epub 2020 Dec 8.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands.

Various upper-limb prostheses have been designed for 3D printing but only a few of them are based on bio-inspired design principles and many anatomical details are not typically incorporated even though 3D printing offers advantages that facilitate the application of such design principles. We therefore aimed to apply a bio-inspired approach to the design and fabrication of articulated fingers for a new type of 3D printed hand prosthesis that is body-powered and complies with basic user requirements. We first studied the biological structure of human fingers and their movement control mechanisms in order to devise the transmission and actuation system. A number of working principles were established and various simplifications were made to fabricate the hand prosthesis using a fused deposition modelling (FDM) 3D printer with dual material extrusion. We then evaluated the mechanical performance of the prosthetic device by measuring its ability to exert pinch forces and the energy dissipated during each operational cycle. We fabricated our prototypes using three polymeric materials including PLA, TPU, and Nylon. The total weight of the prosthesis was 92 g with a total material cost of 12 US dollars. The energy dissipated during each cycle was 0.380 Nm with a pinch force of ≈16 N corresponding to an input force of 100 N. The hand is actuated by a conventional pulling cable used in BP prostheses. It is connected to a shoulder strap at one end and to the coupling of the whiffle tree mechanism at the other end. The whiffle tree mechanism distributes the force to the four tendons, which bend all fingers simultaneously when pulled. The design described in this manuscript demonstrates several bio-inspired design features and is capable of performing different grasping patterns due to the adaptive grasping provided by the articulated fingers. The pinch force obtained is superior to other fully 3D printed body-powered hand prostheses, but still below that of conventional body powered hand prostheses. We present a 3D printed bio-inspired prosthetic hand that is body-powered and includes all of the following characteristics: adaptive grasping, articulated fingers, and minimized post-printing assembly. Additionally, the low cost and low weight make this prosthetic hand a worthy option mainly in locations where state-of-the-art prosthetic workshops are absent.
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http://dx.doi.org/10.1177/0954411920980889DOI Listing
March 2021

Morphometric and Mechanical Analyses of Calcifications and Fibrous Plaque Tissue in Carotid Arteries for Plaque Rupture Risk Assessment.

IEEE Trans Biomed Eng 2021 04 18;68(4):1429-1438. Epub 2021 Mar 18.

Objective: Atherosclerotic plaque rupture in carotid arteries is a major source of cerebrovascular events. Calcifications are highly prevalent in carotid plaques, but their role in plaque rupture remains poorly understood. This work studied the morphometric features of calcifications in carotid plaques and their effect on the stress distribution in the fibrous plaque tissue at the calcification interface, as a potential source of plaque rupture and clinical events.

Methods: A comprehensive morphometric analysis of 65 histology cross-sections from 16 carotid plaques was performed to identify the morphology (size and shape) and location of plaque calcifications, and the fibrous tissue fiber organization around them. Calcification-specific finite element models were constructed to examine the fibrous plaque tissue stresses at the calcification interface. Statistical correlation analysis was performed to elucidate the impact of calcification morphology and fibrous tissue organization on interface stresses.

Results: Hundred-seventy-one calcifications were identified on the histology cross-sections, which showed great variation in morphology. Four distinct patterns of fiber organization in the plaque tissue were observed around the calcification. They were termed as attached, pushed-aside, encircling and random patterns. The stress analyses showed that calcifications are correlated with high interface stresses, which might be comparable to or even above the plaque strength. The stress levels depended on the calcification morphology and fiber organization. Thicker calcification with a circumferential slender shape, located close to the lumen were correlated most prominently to high interface stresses.

Conclusion: Depending on its morphology and the fiber organization around it, a calcification in an atherosclerotic plaque can act as a stress riser and cause high interface stresses.

Significance: This study demonstrated the potential of calcifications in atherosclerotic plaques to cause elevated stresses in plaque tissue and provided a biomechanical explanation for the histopathological findings of calcification-associated plaque rupture.
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http://dx.doi.org/10.1109/TBME.2020.3038038DOI Listing
April 2021

Spiral Honeycomb Microstructured Bacterial Cellulose for Increased Strength and Toughness.

ACS Appl Mater Interfaces 2020 Nov 28;12(45):50748-50755. Epub 2020 Oct 28.

Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands.

Natural materials, such as nacre and silk, exhibit both high strength and toughness due to their hierarchical structures highly organized at the nano-, micro-, and macroscales. Bacterial cellulose (BC) presents a hierarchical fibril structure at the nanoscale. At the microscale, however, BC nanofibers are distributed randomly. Here, BC self-assembles into a highly organized spiral honeycomb microstructure giving rise to a high tensile strength (315 MPa) and a high toughness value (17.8 MJ m), with pull-out and de-spiral morphologies observed during failure. Both experiments and finite-element simulations indicate improved mechanical properties resulting from the honeycomb structure. The mild fabrication process consists of an fermentation step utilizing poly(vinyl alcohol), followed by a post-treatment including freezing-thawing and boiling. This simple self-assembly production process is highly scalable, does not require any toxic chemicals, and enables the fabrication of light, strong, and tough hierarchical composite materials with tunable shape and size.
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http://dx.doi.org/10.1021/acsami.0c15886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662910PMC
November 2020

Quantitative mechanics of 3D printed nanopillars interacting with bacterial cells.

Nanoscale 2020 Nov;12(43):21988-22001

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Mekelweg 2, 2628CD, Delft, The Netherlands.

One of the methods to create sub-10 nm resolution metal-composed 3D nanopillars is electron beam-induced deposition (EBID). Surface nanotopographies (e.g., nanopillars) could play an important role in the design and fabrication of implantable medical devices by preventing the infections that are caused by the bacterial colonization of the implant surface. The mechanical properties of such nanoscale structures can influence their bactericidal efficiency. In addition, these properties are key factors in determining the fate of stem cells. In this study, we quantified the relevant mechanical properties of EBID nanopillars interacting with Staphylococcus aureus (S. aureus) using atomic force microscopy (AFM). We first determined the elastic modulus (17.7 GPa) and the fracture stress (3.0 ± 0.3 GPa) of the nanopillars using the quantitative imaging (QI) mode and contact mode (CM) of AFM. The displacement of the nanopillars interacting with the bacteria cells was measured by scanning electron microscopy (50.3 ± 9.0 nm). Finite element method based simulations were then applied to obtain the force-displacement curve of the nanopillars (considering the specified dimensions and the measured value of the elastic modulus) based on which an interaction force of 88.7 ± 36.1 nN was determined. The maximum von Mises stress of the nanopillars subjected to these forces was also determined (3.2 ± 0.3 GPa). These values were close to the maximum (i.e., fracture) stress of the pillars as measured by AFM, indicating that the nanopillars were close to their breaking point while interacting with S. aureus. These findings reveal unique quantitative data regarding the mechanical properties of nanopillars interacting with bacterial cells and highlight the possibilities of enhancing the bactericidal activity of the investigated EBID nanopillars by adjusting both their geometry and mechanical properties.
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http://dx.doi.org/10.1039/d0nr05984fDOI Listing
November 2020

Natural Architectures for Tissue Engineering and Regenerative Medicine.

J Funct Biomater 2020 Jul 7;11(3). Epub 2020 Jul 7.

Biomaterials and Tissue Biomechanics Section, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, 2628 CD Delft, The Netherlands.

The ability to control the interactions between functional biomaterials and biological systems is of great importance for tissue engineering and regenerative medicine. However, the underlying mechanisms defining the interplay between biomaterial properties and the human body are complex. Therefore, a key challenge is to design biomaterials that mimic the in vivo microenvironment. Over millions of years, nature has produced a wide variety of biological materials optimised for distinct functions, ranging from the extracellular matrix (ECM) for structural and biochemical support of cells to the holy lotus with special wettability for self-cleaning effects. Many of these systems found in biology possess unique surface properties recognised to regulate cell behaviour. Integration of such natural surface properties in biomaterials can bring about novel cell responses in vitro and provide greater insights into the processes occurring at the cell-biomaterial interface. Using natural surfaces as templates for bioinspired design can stimulate progress in the field of regenerative medicine, tissue engineering and biomaterials science. This literature review aims to combine the state-of-the-art knowledge in natural and nature-inspired surfaces, with an emphasis on material properties known to affect cell behaviour.
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http://dx.doi.org/10.3390/jfb11030047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565607PMC
July 2020

Mechanical properties and cytocompatibility of dense and porous Zn produced by laser powder bed fusion for biodegradable implant applications.

Acta Biomater 2020 07 27;110:289-302. Epub 2020 Apr 27.

Department of Materials Engineering, KU Leuven, Kasteelpark Arenberg 44, Heverlee 3001, Belgium.

In this work, the macrotexture of dense Zn produced by laser powder bed fusion (LPBF) was studied and the mechanical properties for different tensile bar orientations were measured. The compressive strength of LPBF Zn scaffolds with five different unit cells was measured for a relative density of 20-51%. In addition, the response of mesenchymal stem cells to the LPBF Zn scaffolds was studied. The elastic modulus and yield strength of dense LPBF Zn were 110.0 ± 0.2 GPa and 78.0 ± 0.4 MPa, respectively in the vertical and 81.0 ± 0.4 GPa and 55.0 ± 0.7 MPa in the horizontal direction. This could be explained by the preferential orientation of the 〈0001〉 direction in the building plane. For LPBF Zn scaffolds, the plateau stress for the different unit cells varied between 8 and 33 MPa for a 30% relative density. Calcein staining, lactate production and DNA measurements over a 13-day period showed that mesenchymal stem cell viability was low for Zn scaffolds. This work forms a basis for further research into the LPBF texture formation of metals with hexagonal crystal structure, guides implant designers in scaffold unit cell and relative density selection and motivates further research into the cytocompatibility of LPBF Zn. STATEMENT OF SIGNIFICANCE: Laser powder bed fusion (LPBF) is a manufacturing technology which allows the seamless combination of porous and non-porous volumes in a metallic implant and is used in the orthopedic manufacturing industry today. The production of highly dense Zn with LPBF has been described earlier, but the mechanical properties of the resulting material have not been studied in detail yet. This study is the first to report on (i) the influence of different scanning strategies on the macrotexture of dense LPBF Zn and the resulting anisotropy of its mechanical properties, (ii) the relationship between the relative density and strength for LPBF Zn scaffolds with five different unit cells and (iii) the in vitro response of mesenchymal stem cells to these scaffolds.
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http://dx.doi.org/10.1016/j.actbio.2020.04.006DOI Listing
July 2020

Bone Regeneration in Critical-Sized Bone Defects Treated with Additively Manufactured Porous Metallic Biomaterials: The Effects of Inelastic Mechanical Properties.

Materials (Basel) 2020 Apr 24;13(8). Epub 2020 Apr 24.

Department of Orthopaedics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands.

Additively manufactured (AM) porous metallic biomaterials, in general, and AM porous titanium, in particular, have recently emerged as promising candidates for bone substitution. The porous design of such materials allows for mimicking the elastic mechanical properties of native bone tissue and showed to be effective in improving bone regeneration. It is, however, not clear what role the other mechanical properties of the bulk material such as ductility play in the performance of such biomaterials. In this study, we compared the bone tissue regeneration performance of AM porous biomaterials made from the commonly used titanium alloy Ti6Al4V-ELI with that of commercially pure titanium (CP-Ti). CP-Ti was selected because of its high ductility as compared to Ti6Al4V-ELI. Critical-sized (6 mm diameter) femoral defects in rats were treated with implants made from both Ti6Al4V-ELI and CP-Ti. Bone regeneration was assessed up to 11 weeks using micro-CT scanning. The regenerated bone volume was assessed ex vivo followed by histology and biomechanical testing to assess osseointegration of the implants. The bony defects treated with AM CP-Ti implants generally showed higher volumes of regenerated bone as compared to those treated with AM Ti6Al4V-ELI. The torsional strength of the two titanium groups were similar however, and both considerably lower than those measured for intact bony tissue. These findings show the importance of material type and ductility of the bulk material in the ability for bone tissue regeneration of AM porous biomaterials.
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http://dx.doi.org/10.3390/ma13081992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215733PMC
April 2020

Degradable Poly(Methyl Methacrylate)-co-Methacrylic Acid Nanoparticles for Controlled Delivery of Growth Factors for Bone Regeneration.

Tissue Eng Part A 2020 12 14;26(23-24):1226-1242. Epub 2020 Apr 14.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas, USA.

Bone tissue engineering strategies have been developed to address the limitations of the current gold standard treatment options for bone-related disorders. These systems consist of an engineered scaffold that mimics the extracellular matrix and provides an architecture to guide the natural bone regeneration process, and incorporated growth factors that enhance cell recruitment and ingress into the scaffold and promote the osteogenic differentiation of stem cells and angiogenesis. In particular, the osteogenic growth factor bone morphogenetic protein 2 (BMP-2) has been widely studied as a potent agent to improve bone regeneration. A key challenge in growth factor delivery is that the growth factors must reach their target sites without losing bioactivity and remain in the location for an extended period to effectively aid in the formation of new bone. Protein incorporation into nanoparticles can both protect protein bioactivity and enable its sustained release. In this study, a poly(methyl methacrylate-co-methacrylic acid) nanoparticle-based system was synthesized incorporating a custom poly(ethylene glycol) dimethacrylate crosslinker. It was demonstrated that the nanoparticle degradation rate can be controlled by tuning the number of hydrolytically degradable ester units along the crosslinker. We also showed that the nanoparticles had high affinity for a model protein for BMP-2, and optimal conditions for maximum protein loading efficiency were elucidated. Ultimately, the proposed system and its high degree of tunability can be applied to a wide range of growth factors and tissue engineering applications. Impact Statement In this study, we developed a novel method of synthesizing nanoparticles with tunable degradation rates through the incorporation of a custom synthesized, hydrolytically degradable crosslinker. In addition, we demonstrated the affinity of the synthesized nanoparticles for a model protein for bone morphogenetic protein 2 (BMP-2). The tunability of these nanoparticles can be used to develop complex tissue engineering systems, for example, for the delivery of multiple growth factors involved at different stages of the bone regeneration process.
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http://dx.doi.org/10.1089/ten.tea.2020.0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757707PMC
December 2020

On bone fatigue and its relevance for the design of architected materials.

Authors:
Amir A Zadpoor

Proc Natl Acad Sci U S A 2020 03 3;117(13):6985. Epub 2020 Mar 3.

Department of Biomechanical Engineering, Delft University of Technology, 2628CD Delft, The Netherlands

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http://dx.doi.org/10.1073/pnas.1922857117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132290PMC
March 2020

Deciphering the Roles of Interspace and Controlled Disorder in the Bactericidal Properties of Nanopatterns against .

Nanomaterials (Basel) 2020 Feb 18;10(2). Epub 2020 Feb 18.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, 2628CD Delft, The Netherlands.

Recent progress in nano-/micro-fabrication techniques has paved the way for the emergence of synthetic bactericidal patterned surfaces that are capable of killing the bacteria via mechanical mechanisms. Different design parameters are known to affect the bactericidal activity of nanopatterns. Evaluating the effects of each parameter, isolated from the others, requires systematic studies. Here, we systematically assessed the effects of the interspacing and disordered arrangement of nanopillars on the bactericidal properties of nanopatterned surfaces. Electron beam induced deposition (EBID) was used to additively manufacture nanopatterns with precisely controlled dimensions (i.e., a height of 190 nm, a diameter of 80 nm, and interspaces of 100, 170, 300, and 500 nm) as well as disordered versions of them. The killing efficiency of the nanopatterns against Gram-positive bacteria increased by decreasing the interspace, achieving the highest efficiency of 62 ± 23% on the nanopatterns with 100 nm interspacing. By comparison, the disordered nanopatterns did not influence the killing efficiency significantly, as compared to their ordered correspondents. Direct penetration of nanopatterns into the bacterial cell wall was identified as the killing mechanism according to cross-sectional views, which is consistent with previous studies. The findings indicate that future studies aimed at optimizing the design of nanopatterns should focus on the interspacing as an important parameter affecting the bactericidal properties. In combination with controlled disorder, nanopatterns with contrary effects on bacterial and mammalian cells may be developed.
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http://dx.doi.org/10.3390/nano10020347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075137PMC
February 2020

Immobilization of nanocarriers within a porous chitosan scaffold for the sustained delivery of growth factors in bone tissue engineering applications.

J Biomed Mater Res A 2020 05 29;108(5):1122-1135. Epub 2020 Jan 29.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas.

To guide the natural bone regeneration process, bone tissue engineering strategies rely on the development of a scaffold architecture that mimics the extracellular matrix and incorporates important extracellular signaling molecules, which promote fracture healing and bone formation pathways. Incorporation of growth factors into particles embedded within the scaffold can offer both protection of protein bioactivity and a sustained release profile. In this work, a novel method to immobilize carrier nanoparticles within scaffold pores is proposed. A biodegradable, osteoconductive, porous chitosan scaffold was fabricated via the "freeze-drying method," leading to scaffolds with a storage modulus of 8.5 kPa and 300 μm pores, in line with existing bone scaffold properties. Next, poly(methyl methacrylate-co-methacrylic acid) nanoparticles were synthesized and immobilized to the scaffold via carbodiimide-crosslinker chemistry. A fluorescent imaging study confirmed that the conventional methods of protein and nanocarrier incorporation into scaffolds can lead to over 60% diffusion out of the scaffold within the first 5 min of implantation, and total disappearance within 4 weeks. The novel method of nanocarrier immobilization to the scaffold backbone via carbodiimide-crosslinker chemistry allows full retention of particles for up to 4 weeks within the scaffold bulk, with no negative effects on the viability and proliferation of human umbilical vein endothelial cells.
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http://dx.doi.org/10.1002/jbm.a.36887DOI Listing
May 2020

Synthetic Polymers Provide a Robust Substrate for Functional Neuron Culture.

Adv Healthc Mater 2020 02 15;9(4):e1901347. Epub 2020 Jan 15.

Department of Neuroscience, Erasmus MC Rotterdam, Rotterdam, NL-3015 GE, The Netherlands.

Substrates for neuron culture and implantation are required to be both biocompatible and display surface compositions that support cell attachment, growth, differentiation, and neural activity. Laminin, a naturally occurring extracellular matrix protein is the most widely used substrate for neuron culture and fulfills some of these requirements, however, it is expensive, unstable (compared to synthetic materials), and prone to batch-to-batch variation. This study uses a high-throughput polymer screening approach to identify synthetic polymers that supports the in vitro culture of primary mouse cerebellar neurons. This allows the identification of materials that enable primary cell attachment with high viability even under "serum-free" conditions, with materials that support both primary cells and neural progenitor cell attachment with high levels of neuronal biomarker expression, while promoting progenitor cell maturation to neurons.
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http://dx.doi.org/10.1002/adhm.201901347DOI Listing
February 2020

Substrate curvature as a cue to guide spatiotemporal cell and tissue organization.

Biomaterials 2020 02 27;232:119739. Epub 2019 Dec 27.

Department of Biomechanical Engineering, Delft University of Technology (TU Delft), Mekelweg 2, Delft, 2628CD, the Netherlands.

Recent evidence clearly shows that cells respond to various physical cues in their environments, guiding many cellular processes and tissue morphogenesis, pathology, and repair. One aspect that is gaining significant traction is the role of local geometry as an extracellular cue. Elucidating how geometry affects cell and tissue behavior is, indeed, crucial to design artificial scaffolds and understand tissue growth and remodeling. Perhaps the most fundamental descriptor of local geometry is surface curvature, and a growing body of evidence confirms that surface curvature affects the spatiotemporal organization of cells and tissues. While well-defined in differential geometry, curvature remains somewhat ambiguously treated in biological studies. Here, we provide a more formal curvature framework, based on the notions of mean and Gaussian curvature, and summarize the available evidence on curvature guidance at the cell and tissue levels. We discuss the involved mechanisms, highlighting the interplay between tensile forces and substrate curvature that forms the foundation of curvature guidance. Moreover, we show that relatively simple computational models, based on some application of curvature flow, are able to capture experimental tissue growth remarkably well. Since curvature guidance principles could be leveraged for tissue regeneration, the implications for geometrical scaffold design are also discussed. Finally, perspectives on future research opportunities are provided.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119739DOI Listing
February 2020

Reactive ion etching for fabrication of biofunctional titanium nanostructures.

Sci Rep 2019 12 11;9(1):18815. Epub 2019 Dec 11.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Mekelweg 2, 2628 CD, Delft, The Netherlands.

One of the major problems with the bone implant surfaces after surgery is the competition of host and bacterial cells to adhere to the implant surfaces. To keep the implants safe against implant-associated infections, the implant surface may be decorated with bactericidal nanostructures. Therefore, fabrication of nanostructures on biomaterials is of growing interest. Here, we systematically studied the effects of different processing parameters of inductively coupled plasma reactive ion etching (ICP RIE) on the Ti nanostructures. The resultant Ti surfaces were characterized by using scanning electron microscopy and contact angle measurements. The specimens etched using different chamber pressures were chosen for measurement of the mechanical properties using nanoindentation. The etched surfaces revealed various morphologies, from flat porous structures to relatively rough surfaces consisting of nanopillars with diameters between 26.4 ± 7.0 nm and 76.0 ± 24.4 nm and lengths between 0.5 ± 0.1 μm and 5.2 ± 0.3 μm. The wettability of the surfaces widely varied in the entire range of hydrophilicity. The structures obtained at higher chamber pressure showed enhanced mechanical properties. The bactericidal behavior of selected surfaces was assessed against Staphylococcus aureus and Escherichia coli bacteria while their cytocompatibility was evaluated with murine preosteoblasts. The findings indicated the potential of such ICP RIE Ti structures to incorporate both bactericidal and osteogenic activity, and pointed out that optimization of the process conditions is essential to maximize these biofunctionalities.
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http://dx.doi.org/10.1038/s41598-019-55093-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906493PMC
December 2019

Nanomaterials for bone tissue regeneration: updates and future perspectives.

Nanomedicine (Lond) 2019 11 29;14(22):2987-3006. Epub 2019 Nov 29.

Precision Health Program & Department of Radiology, Michigan State University, East Lansing, MI 48824, USA.

Joint replacement and bone reconstructive surgeries are on the rise globally. Current strategies for implants and bone regeneration are associated with poor integration and healing resulting in repeated surgeries. A multidisciplinary approach involving basic biological sciences, tissue engineering, regenerative medicine and clinical research is required to overcome this problem. Considering the nanostructured nature of bone, expertise and resources available through recent advancements in nanobiotechnology enable researchers to design and fabricate devices and drug delivery systems at the nanoscale to be more compatible with the bone tissue environment. The focus of this review is to present the recent progress made in the rationale and design of nanomaterials for tissue engineering and drug delivery relevant to bone regeneration.
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http://dx.doi.org/10.2217/nnm-2018-0445DOI Listing
November 2019

Submicron Patterns-on-a-Chip: Fabrication of a Microfluidic Device Incorporating 3D Printed Surface Ornaments.

ACS Biomater Sci Eng 2019 Nov 14;5(11):6127-6136. Epub 2019 Oct 14.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD Delft, The Netherlands.

Manufacturing high throughput in vitro models resembling the tissue microenvironment is highly demanded for studying bone regeneration. Tissues such as bone have complex multiscale architectures inside which cells reside. To this end, engineering a microfluidic platform incorporated with three-dimensional (3D) microscaffolds and submicron/nanoscale topographies can provide a promising model for 3D cell cultures. There are, however, certain challenges associated with this goal, such as the need to decorate large surfaces area with high-fidelity 3D submicron structures. Here, we succeeded in fabricating a microfluidic platform embedded with a large area (mm range) of reproducible submicron pillar-based topographies. Using the two-photon polymerization (2PP) as a 3D printing technique based on direct laser writing, uniform submicron patterns were created through optimization of the process parameters and writing strategy. To demonstrate the multiscale fabrication capabilities of this approach, submicron pillars of various heights were integrated onto the surfaces of a 3D microscaffold in a single-step 2PP process. The created submicron topography was also found to improve the hydrophilicity of the surface while being able to withstand flow rates of up to 8 mL/min. The material (IP-Dip resin) used for patterning did not have cytotoxic effects against human mesenchymal stromal cells after 3 days of dynamic culture in the microfluidic device. This proof-of-principle study, therefore, marks a significant step forward in manufacturing submicron structure-on-a-chip models for bone regeneration studies.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01155DOI Listing
November 2019

Additively manufactured porous metallic biomaterials.

Authors:
Amir A Zadpoor

J Mater Chem B 2019 07;7(26):4088-4117

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft, The Netherlands.

Additively manufactured (AM, =3D printed) porous metallic biomaterials with topologically ordered unit cells have created a lot of excitement and are currently receiving a lot of attention given their great potential for improving bone tissue regeneration and preventing implant-associated infections. This paper presents an overview of the various aspects of design, manufacturing, and bio-functionalization of these materials from a "designer material" viewpoint and discusses how rational design principles could be used to topologically design the underlying lattice structures in such a way that the desired properties including mechanical properties, fatigue behavior, mass transport properties (e.g., permeability, diffusivity), surface area, and geometrical features affecting the rate of tissue regeneration (e.g., surface curvature) are simultaneously optimized. We discuss the different types of topological design including those based on beam-based unit cells, sheet-based unit cells (e.g., triply periodic minimal surfaces), and functional gradients. We also highlight the use of topology optimization algorithms for the rational design of AM porous biomaterials. The topology-property relationships for all of the above-mentioned types of properties are presented as well followed by a discussion of the applicable AM techniques and the pros and cons of different types of base materials (i.e., bioinert and biodegradable metals). Finally, we discuss how the huge (internal) surfaces of AM porous biomaterials and their pore space could be used respectively for surface bio-functionalization and accommodation of drug delivery vehicles so as to enhance their bone tissue regeneration performance and minimize the risk of implant-associated infections. We conclude with a general discussion and by suggesting some possible areas for future research.
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http://dx.doi.org/10.1039/c9tb00420cDOI Listing
July 2019

Meta-biomaterials.

Authors:
Amir A Zadpoor

Biomater Sci 2019 Dec;8(1):18-38

Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Delft University of Technology (TU Delft), Mekelweg 2, Delft 2628 CD, The Netherlands.

Meta-biomaterials are designer biomaterials with unusual and even unprecedented properties that primarily originate from their geometrical designs at different (usually smaller) length scales. This concept has been primarily used in the context of orthopedic biomaterials with the ultimate aim of improving the bone tissue regeneration performance of implants and decreasing the risk of implant-associated infections. In this paper, we review the ways though which geometrical design at the macro-, micro-, and nanoscales combined with advanced additive manufacturing techniques (3D printing) could be used to create the unusual properties of meta-biomaterials. Due to their intended applications in orthopedics, metallic and hard polymeric biomaterials have received the most attention in the literature. However, the reviewed concepts are, at least in principle, applicable to a wide range of biomaterials including ceramics and soft polymers. At the macroscale, we discuss the concepts of patient-specific implants, deployable meta-implants, and shape-morphing implants. At the microscale, we introduce the concept of multi-physics meta-biomaterials while also covering the applications of auxetic meta-biomaterials for improving the longevity of orthopedic implants. At the nanoscale, the different aspects of the geometrical design of surface nanopatterns that simultaneously stimulate the osteogenic differentiation of stem cells and kill bacteria are presented. The concept of origami-based meta-biomaterials and the applications of self-folding mechanisms in the fabrication of meta-biomaterials are addressed next. We conclude with a discussion on the available evidence regarding the superior performance of meta-biomaterials and suggest some possible avenues for future research.
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http://dx.doi.org/10.1039/c9bm01247hDOI Listing
December 2019
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