Biomaterials with the ability to self-heal and recover their structural integrity offer many advantages for applications in biomedicine. The past decade has witnessed the rapid emergence of a new ...class of self-healing biomaterials commonly termed injectable, or printable in the context of 3D printing. These self-healing injectable biomaterials, mostly hydrogels and other soft condensed matter based on reversible chemistry, are able to temporarily fluidize under shear stress and subsequently recover their original mechanical properties. Self-healing injectable hydrogels offer distinct advantages compared to traditional biomaterials. Most notably, they can be administered in a locally targeted and minimally invasive manner through a narrow syringe without the need for invasive surgery. Their moldability allows for a patient-specific intervention and shows great prospects for personalized medicine. Injected hydrogels can facilitate tissue regeneration in multiple ways owing to their viscoelastic and diffusive nature, ranging from simple mechanical support, spatiotemporally controlled delivery of cells or therapeutics, to local recruitment and modulation of host cells to promote tissue regeneration. Consequently, self-healing injectable hydrogels have been at the forefront of many cutting-edge tissue regeneration strategies. This study provides a critical review of the current state of self-healing injectable hydrogels for tissue regeneration. As key challenges toward further maturation of this exciting research field, we identify (i) the trade-off between the self-healing and injectability of hydrogels vs their physical stability, (ii) the lack of consensus on rheological characterization and quantitative benchmarks for self-healing injectable hydrogels, particularly regarding the capillary flow in syringes, and (iii) practical limitations regarding translation toward therapeutically effective formulations for regeneration of specific tissues. Hence, here we (i) review chemical and physical design strategies for self-healing injectable hydrogels, (ii) provide a practical guide for their rheological analysis, and (iii) showcase their applicability for regeneration of various tissues and 3D printing of complex tissues and organoids.
Composite colloidal gels are formed by the pH‐induced electrostatic assembly of silica and gelatin nanoparticles. These injectable and moldable colloidal gels are able to withstand substantial ...compressive and tensile loads, and exhibit a remarkable self‐healing efficiency. This study provides new, critical insight into the structural and mechanical properties of composite colloidal gels and opens up new avenues for practical application of colloidal gels.
ABSTRACT
Mass-loss rates and terminal wind velocities are key parameters that determine the kinetic wind energy and momenta of massive stars. Furthermore, accurate mass-loss rates determine the mass ...and rotational velocity evolution of mass stars, and their fates as neutron stars and black holes in function of metallicity (Z). Here, we update our Monte Carlo mass-loss Recipe with new dynamically consistent computations of the terminal wind velocity – as a function of Z. These predictions are particularly timely as the Hubble Space Telescope Ultraviolet Legacy Library of Young Stars as Essential Standards (ULLYSES) project will observe ultraviolet spectra with blue-shifted P Cygni lines of hundreds of massive stars in the low-Z Large and Small Magellanic Clouds (SMC), as well as sub-SMC metallicity hosts. Around 35 000 K, we uncover a weak-wind ‘dip’ and we present diagnostics to investigate its physics with ULLYSES and X-Shooter data. We discuss how the dip may provide important information on wind-driving physics, and how this is of key relevance towards finding a new gold-standard for OB star mass-loss rates. For B supergiants below the Fe iv to iii bi-stability jump, the terminal velocity is found to be independent of Z and M, while the mass-loss rate still varies as $\dot{M} \propto Z^{0.85}$. For O-type stars above the bi-stability jump we, find a terminal-velocity dependence of $\mbox{$v _{\infty }$}\propto Z^{0.19}$ and the Z-dependence of the mass-loss rate is found to be as shallow as $\dot{M} \propto Z^{0.42}$, implying that to reproduce the ‘heavy’ black holes from LIGO/Virgo, the ‘low Z’ requirement becomes even more stringent than was previously anticipated.
This paper reviews current physicochemical and biochemical coating techniques that are investigated to enhance bone regeneration at the interface of titanium implant materials. By applying coatings ...onto titanium surfaces that mimic the organic and inorganic components of living bone tissue, a physiological transition between the non-physiological titanium surface and surrounding bone tissue can be established. In this way, the coated titanium implants stimulate bone formation from the implant surface, thereby enhancing early and strong fixation of bone-substituting implants. As such, a continuous transition from bone tissue to implant surface is induced. This review presents an overview of various techniques that can be used to this end, and that are inspired by either inorganic (calcium phosphate) or organic (extracellular matrix components, growth factors, enzymes, etc.) components of natural bone tissue. The combination, however, of both organic and inorganic constituents is expected to result into truly bone-resembling coatings, and as such to a new generation of surface-modified titanium implants with improved functionality and biological efficacy.
Abstract
Background
Blood-based biomarkers for Alzheimer’s disease (AD) might facilitate identification of participants for clinical trials targeting amyloid beta (Abeta) accumulation, and aid in AD ...diagnostics. We examined the potential of plasma markers Abeta
(1-42/1-40)
, glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) to identify cerebral amyloidosis and/or disease severity.
Methods
We included individuals with a positive (
n
= 176: 63 ± 7 years, 87 (49%) females) or negative (
n
= 76: 61 ± 9 years, 27 (36%) females) amyloid PET status, with syndrome diagnosis subjective cognitive decline (18 PET+, 25 PET−), mild cognitive impairment (26 PET+, 24 PET−), or AD-dementia (132 PET+). Plasma Abeta
(1-42/1-40)
, GFAP, and NfL were measured by Simoa. We applied two-way ANOVA adjusted for age and sex to investigate the associations of the plasma markers with amyloid PET status and syndrome diagnosis; logistic regression analysis with Wald’s backward selection to identify an optimal panel that identifies amyloid PET positivity; age, sex, and education-adjusted linear regression analysis to investigate associations between the plasma markers and neuropsychological test performance; and Spearman’s correlation analysis to investigate associations between the plasma markers and medial temporal lobe atrophy (MTA).
Results
Abeta
(1-42/1-40)
and GFAP independently associated with amyloid PET status (
p
= 0.009 and
p
< 0.001 respectively), and GFAP and NfL independently associated with syndrome diagnosis (
p
= 0.001 and
p
= 0.048 respectively). The optimal panel identifying a positive amyloid status included Abeta
(1-42/1-40)
and GFAP, alongside age and APOE (AUC = 88% (95% CI 83–93%), 82% sensitivity, 86% specificity), while excluding NfL and sex. GFAP and NfL robustly associated with cognitive performance on global cognition and all major cognitive domains (GFAP: range standardized β (sβ) = − 0.40 to − 0.26; NfL: range sβ = − 0.35 to − 0.18; all:
p
< 0.002), whereas Abeta
(1-42/1-40)
associated with global cognition, memory, attention, and executive functioning (range sβ = 0.22 – 0.11; all:
p
< 0.05) but not language. GFAP and NfL showed moderate positive correlations with MTA (both: Spearman’s rho> 0.33,
p
< 0.001). Abeta
(1-42/1-40)
showed a moderate negative correlation with MTA (Spearman’s rho = − 0.24,
p
= 0.001).
Discussion and conclusions
Combination of plasma Abeta
(1-42/1-40)
and GFAP provides a valuable tool for the identification of amyloid PET status. Furthermore, plasma GFAP and NfL associate with various disease severity measures suggesting potential for disease monitoring.
Objective
We investigated the association of plasma amyloid beta (Abeta)40, Abeta42, and total tau (tTau) with the presence of Alzheimer pathological changes in cognitively normal individuals with ...subjective cognitive decline (SCD).
Methods
We included 248 subjects with SCD (61 ± 9 years, 42% female, Mini‐Mental State Examination = 28 ± 2) from the SCIENCe project and Amsterdam Dementia Cohort. Subjects were dichotomized as amyloid abnormal by cerebrospinal fluid (CSF) and positron emission tomography (PET). Baseline plasma Abeta40, Abeta42, and tTau were measured using Simoa technology. Associations between plasma levels and amyloid status were assessed using logistic regression analyses and receiver operating characteristic analyses. Association of plasma levels with risk of clinical progression to mild cognitive impairment (MCI) or dementia was assessed using Cox proportional hazard models.
Results
Fifty‐seven (23%) subjects were CSF‐amyloid abnormal. Plasma Abeta42/Abeta40 ratio and plasma Abeta42 alone, but not tTau, identified abnormal CSF‐amyloid status (plasma ratio: area under the curve AUC = 77%, 95% confidence interval CI = 69–84%; plasma Abeta42: AUC = 66%, 95% CI: 58–74%). Combining plasma ratio with age and apolipoprotein E resulted in AUC = 83% (95% CI = 77–89%). The Youden cutoff of the plasma ratio gave a sensitivity of 76% and specificity of 75%, and applying this as a prescreener would reduce the number of lumbar punctures by 51%. Using PET as outcome, a comparable reduction in number of PET scans would be achieved when applying the plasma ratio as prescreener. In addition, low plasma ratio was associated with clinical progression to MCI or dementia (hazard ratio = 2.0, 95% CI = 1.4–2.3).
Interpretation
Plasma Abeta42/Abeta40 ratio has potential as a prescreener to identify Alzheimer pathological changes in cognitively normal individuals with SCD. Ann Neurol 2018;84:656–666
The design of bioactive three-dimensional (3D) scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding ...both biological and architectural properties of the scaffolds. This study investigates whether the sustained release of bone morphogenetic protein 2 (BMP-2) influences osteogenicity of tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles (GMPs) was used as a sustained release system, which was dispersed in hydrogel-based constructs and compared to direct inclusion of BMP-2 in alginate or control GMPs. The constructs were supplemented with goat multipotent stromal cells (gMSCs) and biphasic calcium phosphate to study osteogenic differentiation and bone formation respectively. BMP-2 release kinetics and bioactivity showed continuous release for three weeks coinciding with osteogenicity. Osteogenic differentiation and bone formation of bioprinted GMP containing constructs were investigated after subcutaneous implantation in mice or rats. BMP-2 significantly increased bone formation, which was not influenced by the release timing. We showed that 3D printing of controlled release particles is feasible and that the released BMP-2 directs osteogenic differentiation in vitro and in vivo.
Maximum black hole mass across cosmic time Vink, Jorick S; Higgins, Erin R; Sander, Andreas A C ...
Monthly notices of the Royal Astronomical Society,
06/2021, Letnik:
504, Številka:
1
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
At the end of its life, a very massive star is expected to collapse into a black hole (BH). The recent detection of an 85 M⊙ BH from the gravitational wave event GW 190521 appears to ...present a fundamental problem as to how such heavy BHs exist above the approximately 50 M⊙ pair-instability (PI) limit where stars are expected to be blown to pieces with no remnant left. Using mesa, we show that for stellar models with non-extreme assumptions, 90–100 M⊙ stars at reduced metallicity ($Z/\mbox{ $\mathrm{Z}_{\odot }$}\le 0.1$) can produce blue supergiant progenitors with core masses sufficiently small to remain below the fundamental PI limit, yet at the same time lose an amount of mass via stellar winds that is small enough to end up in the range of an ‘impossible’ 85 M⊙ BH. The two key points are the proper consideration of core overshooting and stellar wind physics with an improved scaling of mass-loss with iron (Fe) contents characteristic for the host galaxy metallicity. Our modelling provides a robust scenario that not only doubles the maximum BH mass set by PI, but also allows us to probe the maximum stellar BH mass as a function of metallicity and cosmic time in a physically sound framework.
Viscoelastic properties of hydrogels such as stress relaxation or plasticity have been recognized as important mechanical cues that dictate the migration, proliferation, and differentiation of ...embedded cells. Stress relaxation rates in conventional hydrogels are usually much slower than cellular processes, which impedes rapid cellularization of these elastic networks. Colloidal hydrogels assembled from nanoscale building blocks may provide increased degrees of freedom in the design of viscoelastic hydrogels with accelerated stress relaxation rates due to their strain-sensitive rheology which can be tuned via interparticle interactions. Here, we investigate the stress relaxation of colloidal hydrogels from gelatin nanoparticles in comparison to physical gelatin hydrogels and explore the particle interactions that govern stress relaxation. Colloidal and physical gelatin hydrogels exhibit comparable rheology at small deformations, but colloidal hydrogels fluidize beyond a critical strain while physical gels remain primarily elastic independent of strain. This fluidization facilitates fast exponential stress relaxation in colloidal gels at strain levels that correspond to strains exerted by cells embedded in physiological extracellular matrices (10-50%). Increased attractive particle interactions result in a higher critical strain and slower stress relaxation in colloidal gels. In physical gels, stress relaxation is slower and mostly independent of strain. Hence, colloidal hydrogels offer the possibility to modulate viscoelasticity via interparticle interactions and obtain fast stress relaxation rates at strains relevant for cell activity. These beneficial features render colloidal hydrogels promising alternatives to conventional monolithic hydrogels for tissue engineering and regenerative medicine.
In the endeavor to design biomaterials that favor cell activity, research has long focused on biochemical cues. Recently, the time-, stress-, and strain-dependent mechanical properties, i.e. viscoelasticity, of biomaterials has been recognized as important factor that dictates cell fate. We herein present the viscoelastic stress relaxation of colloidal hydrogels assembled from gelatin nanoparticles, which show a strain-dependent fluidization at strains relevant for cell activity, in contrast to many commonly used monolithic hydrogels with primarily elastic behavior.
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ABSTRACT
The mass-loss rates of massive helium stars are one of the major uncertainties in modern astrophysics. Regardless of whether they were stripped by a binary companion or managed to peel off ...their outer layers by themselves, the influence and final fate of helium stars – in particular the resulting black hole mass – highly depends on their wind mass-loss as stripped-envelope objects. While empirical mass-loss constraints for massive helium stars have improved over the last decades, the resulting recipes are limited to metallicities with the observational ability to sufficiently resolve individual stars. Yet, theoretical efforts have been hampered by the complexity of Wolf–Rayet (WR) winds arising from the more massive helium stars. In an unprecedented effort, we calculate next-generation stellar atmosphere models resembling massive helium main-sequence stars with Fe-bump driven winds up to $500\, \mathrm{M}_\odot$ over a wide metallicity range between 2.0 and $0.02\, \mathrm{Z}_\odot$. We uncover a complex Γe-dependency of WR-type winds and their metallicity-dependent breakdown. The latter can be related to the onset of multiple scattering, requiring higher L/M-ratios at lower metallicity. Based on our findings, we derive the first ever theoretically motivated mass-loss recipe for massive helium stars. We also provide estimates for Lyman continuum and $\rm{He\,{\small II}}$ ionizing fluxes, finding stripped helium stars to contribute considerably at low metallicity. In sharp contrast to OB-star winds, the mass-loss for helium stars scales with the terminal velocity. While limited to the helium main sequence, our study marks a major step towards a better theoretical understanding of helium star evolution.
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