Two novel CHN1 variants identified in Duane retraction syndrome pedigrees disrupt development of ocular motor nerves in zebrafish.

Duane retraction syndrome (DRS) is a rare congenital eye movement disorder causing by the dysplasia of abducens nerve, and has highly variable phenotype. MRI can reveal the endophenotype of DRS. Most DRS cases are sporadical and isolated, while some are familial or accompanied by other ocular disorders and systemic congenital abnormalities. CHN1 was the most common causative gene for familial DRS. Until now, 13 missense variants of CHN1 have been reported. In this study, we enrolled two unrelated pedigrees with DRS. Detailed clinical examinations, MRI, and the whole exome sequencing (WES) were performed to reveal their clinical and genetic characteristics. Patients from pedigree-1 presented with isolated DRS, and a novel heterozygous variant c.650 A > G, p. His217Arg was identified in CHN1 gene. Patients from pedigree-2 presented with classic DRS and abnormalities in auricle morphology, and the pedigree segregated another novel heterozygous CHN1 variant c.637 T > C, p. Phe213Leu. A variety of bioinformatics software predicted that the two variants had deleterious or disease-causing effects. After injecting of two mutant CHN1 mRNAs into zebrafish embryos, the dysplasia of ocular motor nerves (OMN) was observed. Our present findings expanded the phenotypic and genotypic spectrum of CHN1 related DRS, as well as provided new insights into the role of CHN1 in OMN development. Genetic testing is strongly recommended for patients with a DRS family history or accompanying systemic congenital abnormalities.

Rapid Stress Relaxation, Multistimuli-Responsive Elastomer Based on Dual-Dynamic Covalent Bonds and Aniline Trimer.

Covalent adaptable networks (CANs) are an emerging kind of smart materials in which cross-links are reversible upon some stimuli and then provide malleability and a stimuli-responsive ability to the materials. There is a trend to endow CANs with multistimuli-responsive capabilities and rapid stress relaxation to pursue more advanced applications. To integrate these two features into one material, here, dual-dynamic covalent bonds (imines and boronic esters) and aniline trimer (ACAT) were incorporated into the styrene butadiene elastomer as dynamic cross-links. The obtained CANs were demonstrated with rapid stress relaxation and a relatively low activation energy of 36 ± 1 kJ mol-1, resulting from the synergistic effect of dual-dynamic covalent bonds to rearrange the network at a faster rate than for either imines or boronic esters. Because of the dynamic nature of imines or boronic esters, the elastomer can be recycled upon heat. Moreover, the appearance and configuration of the elastomer could also be manipulated by pH and light because of the inclusion of ACAT. All in all, the coupled multistimuli-responsive behavior and rapid stress relaxation in one single elastomer would potentially be applicable for sensors and actuators with good recyclability.

Self-assembled nanoplatforms with ZIF-8 as a framework for FRET-based glutathione sensing in biological samples.

A glutathione (GSH) optical sensor with high sensitivity and exceptional selectivity was established for the first time. Zeolitic imidazolate framework-8 (ZIF-8) as a model was used for the first time to entrap Mn2+:ZnS quantum dots (QDs) and a rhodamine B derivative (RBD) by self-assembly. Benefiting from the confinement effect of ZIF-8, the loaded QDs and RBD can be brought into close proximity for energy transfer to occur. In the presence of GSH, the fluorescence resonance energy transfer (FRET) process from the QDs to RBD can be initiated, rendering the fluorescent nanoprobe to exhibit a response to GSH. The fluorescence intensity of Mn2+:ZnS@ZIF-8@RBD decreased with an increase in the GSH concentration in the linear range of 5-120 µM and a detection limit of 1.5 µM. This finding leads to a method for the fluorescence detection of GSH with excellent selectivity over other reactive thiols. Moreover, because of its good accuracy and excellent recovery, the nanoplatform can be applied for GSH sensing in real human serum and urine samples. Hence, the developing probe may be extended to other optical sensing domains or drug carriers and has tremendous potential in the field of biomedicine.

Two cases of Duane retraction syndrome with abnormal orbital structures.

Duane retraction syndrome (DRS) is a rare congenital nonprogressive restrictive strabismus. The absence/hypoplasia of the abducens nerve and the aberrant innervation of the lateral rectus muscle by the oculomotor nerve have been hypothesized as causes of DRS, although the phenomenon of globe retraction can also occur in the setting of mechanical factors, such as congenital abnormal orbital structures or orbital trauma. We present the cases of 2 DRS patients with absent abducens nerve and abnormal muscular bands connecting the superior rectus and inferior rectus muscles on the temporal side of the optic nerve.

Construction of smartphone-adapted signal visualization platform for dual-mode detection of H2S based on integrated metal-organic framework nanoprobes.

Hydrogen sulfide (H2S) is a toxic contaminant and has great influence on many physiological processes. Due to various pathophysiological roles and environmental pollution problems, it is necessary to construct and develop simple and portable monitoring sensors for the precise detection of H2S. Herein, we developed a smartphone-adapted dual-mode detection platform by integrating the colorimetric and photothermal imaging analysis into a metal-organic framework-based chip (ZIF-8/Cu). Due to the nanoconfinement effect of ZIF-8, small-sized plasmonic CuS could be in-situ formed during the detection procedure of H2S and endowed the chips with excellent photothermal properties. By constructing a smartphone-adapted photothermal imager, the metal-organic framework-based chip could achieve a portable photothermal imaging analysis of H2S. Moreover, as the formed CuS was a good peroxidase-like nanozyme, the chips could also be used to trigger the enzymic catalytic reaction toward the chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB)-H2O2, thus providing another colorimetric sensing mode by using a smartphone App. In this smartphone-adapted visualization platform, the portable chemosensors could simultaneously achieve double detection modes at one electrode, which provided a new pathway for the accurate detection of H2S and circumvented the false-positive or negative errors during the detection process. Besides, by using the finite difference time domain (FDTD) simulation method, the in-depth mechanism, including the plasmonic effect and spatial electromagnetic field distribution, was explored to provide a possible reason for the excellent sensing performance of the dual-mode visualization platform. This work provides a new insight into the construction of the accurate, portable and smart sensing platform in the visual screening of H2S.

Fabrication and nano-engineering of non-/noble metal-coupled plasmonic heterostructures for ultrasensitive photoelectrochemical immunoassays.

To achieve reliable and ultrasensitive detection for disease markers in PEC bioanalysis, constructing and nano-engineering of ideal photoelectrodes and signal transduction strategies are of vital importance. Herein, a non-/noble metal coupled plasmonic nanostructure (TiO2/r-STO/Au) was tactically designed with high-efficient PEC performance. Evidenced by the DFT and FDTD calculations, the reduced SrTiO3 (r-STO) was found to support the localized surface plasmon resonance due to the sufficiently increased and delocalized local charge in r-STO. Under the synergistic coupling of plasmonic r-STO and AuNPs, the PEC performance of TiO2/r-STO/Au was found remarkably promoted with reduced onset potential. This merit supported TiO2/r-STO/Au as a self-powered immunoassay via a proposed oxygen-evolution-reaction mediated signal transduction strategy. With the increase of the target biomolecules (PSA), the catalytic active sites of TiO2/r-STO/Au would be blocked and result in the decrease of the oxygen evaluation reaction. Under optimal conditions, the immunoassays exhibited an excellent detection performance with a LOD as low as 1.1 fg/mL. This work proposed a new type of plasmonic nanomaterial for ultrasensitive PEC bioanalysis.

Clinical and genetic characteristics of Chinese patients with congenital cranial dysinnervation disorders.

BACKGROUND: Congenital cranial dysinnervation disorders (CCDDs) are a group of diseases with high clinical and genetic heterogeneity. Clinical examinations combined with Magnetic resonance imaging (MRI) and whole exome sequencing (WES) were performed to reveal the phenotypic and genotypic characteristics in a cohort of Chinese CCDDs patients. RESULTS: A total of 122 CCDDs patients from 96 families were enrolled. All patients showed restrictive eye movements, and 46 patients from 46 families (47.9%, 46/96) were accompanied by multiple congenital malformations. Multi-positional high-resolution MRI was performed in 94 patients from 88 families, of which, all patients had hypoplasia of the cranial nerves except HGPPS patients and 15 patients from 15 families (17.0%,15/88) were accompanied by other craniocerebral malformations. WES was performed in 122 CCDDs patients. Ten pathogenic variants were detected in KIF21A, TUBB3, and CHN1 genes in 43 families. Three variants were unreported, including KIF21A (c.1064T > C, p.F355S), TUBB3 (c.232T > A, p.S78T) and CHN1 (c.650A > G, p.H217R). Of the 43 probands harboring pathogenic variants, 42 were diagnosed with Congenital Fibrosis of Extraocular Muscles (CFEOM) and one was Duane Retraction Syndrome (DRS). No definite pathogenic variants in known candidate genes of CCDDs were found in sporadic DRS, Möbius Syndrome (MBS) and Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) patients. The CFEOM patients harboring R380C, E410K and R262H variants in TUBB3 gene and F355S variant in KIF21A gene exhibited syndromic phenotypes. CONCLUSIONS: This study broadened the phenotypic and genotypic spectrums of CCDDs, and it was the largest clinical and genetic investigation for CCDDs patients from China. KIF21A and TUBB3 were the common pathogenic genes in Chinese CFEOM. MRI coupled with WES can provide a supportive diagnosis in patients with clinically suspected CCDDs.

The Interaction Between Intracellular Energy Metabolism and Signaling Pathways During Osteogenesis.

Osteoblasts primarily mediate bone formation, maintain bone structure, and regulate bone mineralization, which plays an important role in bone remodeling. In the past decades, the roles of cytokines, signaling proteins, and transcription factors in osteoblasts have been widely studied. However, whether the energy metabolism of cells can be regulated by these factors to affect the differentiation and functioning of osteoblasts has not been explored in depth. In addition, the signaling and energy metabolism pathways are not independent but closely connected. Although energy metabolism is mediated by signaling pathways, some intermediates of energy metabolism can participate in protein post-translational modification. The content of intermediates, such as acetyl coenzyme A (acetyl CoA) and uridine diphosphate N-acetylglucosamine (UDP-N-acetylglucosamine), determines the degree of acetylation and glycosylation in terms of the availability of energy-producing substrates. The utilization of intracellular metabolic resources and cell survival, proliferation, and differentiation are all related to the integration of metabolic and signaling pathways. In this paper, the interaction between the energy metabolism pathway and osteogenic signaling pathway in osteoblasts and bone marrow mesenchymal stem cells (BMSCs) will be discussed.

Optimization of imaging parameters in chest CT for COVID-19 patients: an experimental phantom study.

BACKGROUND: With the global outbreak of coronavirus disease 2019 (COVID-19), chest computed tomography (CT) is vital for diagnosis and follow-up. The increasing contribution of CT to the population-collected dose has become a topic of interest. Radiation dose optimization for chest CT of COVID-19 patients is of importance in clinical practice. The present study aimed to investigate the factors affecting the detection of ground-glass nodules and exudative lesions in chest CT among COVID-19 patients and to find an appropriate combination of imaging parameters that optimize detection while effectively reducing the radiation dose. METHODS: The anthropomorphic thorax phantom, with 9 spherical nodules of different diameters and CT values of -800, -630, and 100 HU, was used to simulate the lesions of COVID-19 patients. Four custom-simulated lesions of porcine fat and ethanol were also scanned at 3 tube potentials (120, 100, and 80 kV) and corresponding milliampere-seconds (mAs) (ranging from 10 to 100). Separate scans were performed at pitches of 0.6, 0.8, 1.0, 1.15, and 1.49, and at collimations of 10, 20, 40, and 80 mm at 80 kV and 100 mAs. CT values and standard deviations of simulated nodules and lesions were measured, and radiation dose quantity (volume CT dose index; CTDIvol) was collected. Contrast-to-noise ratio (CNR) and figure of merit (FOM) were calculated. All images were subjectively evaluated by 2 radiologists to determine whether the nodules were detectable and if the overall image quality met diagnostic requirements. RESULTS: All simulated lesions, except -800 HU nodules, were detected at all scanning conditions. At a fixed voltage of 120 or 100 kV, with increasing mAs, image noise tended to decrease, and the CNR tended to increase (F=9.694 and P=0.033 for 120 kV; F=9.028 and P=0.034 for 100 kV). The FOM trend was the same as that of CNR (F=2.768 and P=0.174 for 120 kV; F=1.915 and P=0.255 for 100 kV). At 80 kV, the CNRs and FOMs had no significant change with increasing mAs (F=4.522 and P=0.114 for CNRs; F=1.212 and P=0.351 for FOMs). For the 4 nodules of -800 and -630 HU, CNRs had no statistical differences at each of the 5 pitches (F=0.673, P=0.476). The CNRs and FOMs at each of the 4 collimations had no statistical differences (F=2.509 and P=0.125 for CNRs; F=1.485 and P=0.309 for FOMs) for each nodule. CNRs and subjective evaluation scores increased with increasing parameter values for each imaging iteration. The CNRs of 4 -800 HU nodules in the qualified images at the thresholds of scanning parameters of 120 kV/20 mAs, 100 kV/40 mAs, and 80 kV/80 mAs, had statistical differences (P=0.038), but the FOMs had no statistical differences (P=0.085). Under the 3 threshold conditions, the CNRs and FOMs of the 4 nodules were highest at 100 kV and 40 mAs (1.6 mGy CTDIvol). CONCLUSIONS: For chest CT among COVID-19 patients, it is recommended that 100 kV/40 mAs is used for average patients; the radiation dose can be reduced to 1.6 mGy with qualified images to detect ground-glass nodules and exudation lesions.

Repairing Transected Peripheral Nerve Using a Biomimetic Nerve Guidance Conduit Containing Intraluminal Sponge Fillers.

Nerve guide conduits (NGCs) with geometric design have shown significant advantages in guidance of nerve reinnervation across the defect of injured peripheral nerves. It is realized that intraluminal fillers with distinctive structure can effectively provide an inner guidance for sprouting of axons and improve the permeability of NGC. In this work, a poly(lactic-co-glycolic acid) (PLGA) NGC is prepared containing intraluminal sponge fillers (labeled as ISF-NGC) and used for reconstruction of a rat sciatic nerve with a 10 mm gap. For comparison, the same procedure is applied to a single hollow PLGA NGC (labeled as H-NGC) and an autologous nerve. As evidenced by significantly improved nerve morphology and function, the ISF-NGC achieves a superior nerve repair effect over H-NGC, which is comparable to autologous nerve grafting. It is likely that the H-NGC only provides a protected tunnel for nerve fiber regrowth and axonal extension, while ISF-NGC offers an extracellular matrix-mimetic architecture as autograft to provide contact guidance for nerve reinnervation. This newly developed ISF-NGC is a promising candidate to aid nerve reinnervation across longer gaps commonly encountered in clinical cases.

Large-scale and fast synthesis of nano-hydroxyapatite powder by a microwave-hydrothermal method.

A microwave-hydrothermal (M-H) method assisted with ultrasonic atomization precipitation was developed for large-scale and fast synthesis of nano-hydroxyapatite (nano-HAP) powder. This technology combines the uniform mixing effect of ultrasonic atomization precipitation at high concentration with the rapid and uniform heating effect of the M-H method, aiming to obtain a high quality product with low agglomeration, homogeneous size distribution, accurate stoichiometry, and high purity while improving the yield. The influences of reaction temperature, reaction time and reactant concentration on the formation of nano-HAP were investigated. The results show that the crystallinity increases significantly and the diameter of nano-HAP increases to some extent, but the length does not change obviously while the reaction temperature increase from 60 °C to 160 °C and the reaction time increases from 1 minute to 40 minutes respectively. The crystallinity, dispersion and crystal size of nano-HAP do not change obviously while the concentration of Na2HPO4·12H2O increases from 0.06 mol L-1 to 0.4 mol L-1. When the reaction temperature is 160 °C, the reaction time is 40 min, and the concentration of Na2HPO4·12H2O is 0.4 mol L-1, the yield of nano-HAP powder achieved a maximum yield (0.033 kg L-1). The obtained nano-HAP powder exhibits a uniform size and good dispersibility, with a size of 87.62 ± 22.44 nm and crystallinity of 0.92, respectively. This study indicates that the M-H method assisted with ultrasonic atomization precipitation is a facile one-pot method for the rapid and large-scale synthesis of highly crystalline, dispersible nano-HAP particles.

Correction: Large-scale and fast synthesis of nano-hydroxyapatite powder by a microwave-hydrothermal method.

[This corrects the article DOI: 10.1039/C9RA00091G.].

Development of a novel morphological paclitaxel-loaded PLGA microspheres for effective cancer therapy: in vitro and in vivo evaluations.

Sustained release of therapeutic agents into tumor cells is a potential approach to improve therapeutic efficacy, decrease side effects, and the drug administration frequency. Herein, we used the modified double-emulsion solvent evaporation (DSE) method to prepare a novel morphological paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) microspheres (MS). The prepared rough PTX-PLGA-MS possessed microporous surface and highly porous internal structures, which significantly influenced the drug entrapment and release behaviors. The rough MS with an average particle size of 53.47 ± 2.87 µm achieved high drug loading (15.63%) and encapsulation efficiency (92.82%), and provided a favorable sustained drug release. The in vitro antitumor tests of flow cytometry and fluoroimmunoassay revealed that the rough PTX-PLGA-MS displayed effective anti-gliomas activity and enhanced the cellular PTX uptake through adsorptive endocytosis. Both in vitro and in vivo antitumor results demonstrated that the sustained-release PTX could induce the microtubules assembly and the over-expression of Bax and Cyclin B1 proteins, resulting in the microtubule dynamics disruption, G2/M phase arrest, and cell apoptosis accordingly. Furthermore, as the rough PTX-PLGA-MS could disperse and adhere throughout the tumor sites and cause extensive tumor cell apoptosis with one therapeutic course (12 days), they could reduce the system toxicity and drug administration frequency, thus achieving significant tumor inhibitory effects with rapid sustained drug release. In conclusion, our results verified that the rough PTX-PLGA-MS drug release system could serve as a promising treatment to malignant glioma.

Development and biocompatibility evaluation of biodegradable bacterial cellulose as a novel peripheral nerve scaffold.

Peripheral nerve injury is a serious medical problem and severely affects normal life of patient. Bacterial cellulose (BC) is considered as a novel promising biomaterial for tissue engineering, but the poor biodegradability limits its application. In this study, biodegradable bacterial cellulose scaffolds were prepared with different oxidation degrees (O.Ds.) using sodium periodate, evaluating their potential application in peripheral nerve repair. The chemical structure and surface morphology of the oxidized bacterial cellulose (OBC) scaffolds were characterized using Fourier transform infrared spectroscopy, Wide angle X-ray diffraction, and Scanning electron microscope. The porosity, mechanical properties, and degradation behavior of the OBC series scaffolds were extensively examined. Cellular viability and blood compatibility of OBC scaffolds were studied by MTT assay and hemolytic test using Schwann cells (SCs) and red blood cells (RBCs), respectively. The results demonstrated that the biodegradability of OBC scaffolds was improved significantly. OBC scaffolds with lower O.Ds. displayed high porosity with interconnected pores, suitable mechanical property, and biodegradability for peripheral nerve repair. In vitro cytotoxicity and hemolysis test analysis indicated that OBC0.05/3 scaffold is cellular and blood compatible, demonstrating its potential application as a good candidate for peripheral nerve repair. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1288-1298, 2018.

Paclitaxel-loaded PLGA microspheres with a novel morphology to facilitate drug delivery and antitumor efficiency.

The aim of this study was to develop a novel morphological paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) microspheres (MS) delivery system to enhance drug delivery and antitumor efficiency as well as reduce drug administration frequency. Therefore, different morphological types of PTX-PLGA-MS were prepared using a modified solvent evaporation technique. Morphology analysis confirmed the successful preparation of the smooth PTX-PLGA-MS with internal sporadic porosity, and the novel rough PTX-PLGA-MS with microporous surface and porous internal structures. The PTX drugs were distributed in the readily bioavailable state (amorphous) in PTX-loaded MS, which allowed fast drug release from MS following intratumoral administration. The drug entrapment and release behaviors indicated that the rough MS could provide enough hydrophobic space for PTX-loading and deep surface folds for fast matrices degradation, thus achieving a higher drug-loading efficiency (17.8%) and a rapid sustained drug release effect. Furthermore, the rough MS showed strengthened in vitro anti-hepatoma efficiency than that of free PTX and smooth MS. The in vivo studies indicated remarkable antitumor activity of rough MS (tumor inhibition rate = 58.33%) for at least 13 days after a single injection, which was because the rapid sustained-release drugs could induce the pro-apoptosis gene and protein expressions, cause extensive tumor cell apoptosis, and reduce the toxicity to normal tissues. In conclusion, the rough PTX-PLGA-MS drug delivery system with outstanding tumor growth inhibition effect could serve as a promising treatment for liver tumor.

Synthesis of polycarbonate urethane elastomers and effects of the chemical structures on their thermal, mechanical and biocompatibility properties.

In this study, to obtain biomedical polyurethane elastomers with good mechanical properties and biocompatibility, a series of polycarbonate urethanes were synthesized via a two-step solution of polymerization method using the poly(1,6-hexanediol)carbonate diols (PCDL) as the soft segment, 4,4'-methylenebis(cyclohexyl isocyanate) (H12MDI), 1,6-hexamethylene diisocyanate (HDI) and 1,4-butanediol (BDO) as the hard segment with dibutyltin dilaurate as the catalyst. In this article, we illustrated the physical behaviors were obviously influenced by synthetic routes. And their chemical and physical structures were investigated by gel permeation chromatograph (GPC), differential scanning calorimeter (DSC), fourier transform infrared spectrography (FT-IR) and mechanical properties tests. The surface wettability were studied by contact angle measurement (CA). As a kind of short-term implant biomaterial, the results of the hemolysis and platelet adhesive tests were recorded by spectrophotometer and scanning electron microscopy (SEM), indicating the materials have a great potential for developments and applications in biomedical field.

Influence of hydroxyl-terminated polydimethylsiloxane on high-strength biocompatible polycarbonate urethane films.

The present study describes a series of novel polycarbonate urethane films that were fabricated via the solution-casting method from 4,4'-methylenebis(cyclohexyl isocyanate) (H12MDI) and 1,4-butanediol (BDO) chain extender as hard segments, poly(1,6-hexanediol)carbonate diols (PCDL) and hydroxyl-terminated polydimethylsiloxane (PDMS) as soft segments, with dibutyltin dilaurate as the catalyst. Varied molar ratios of PDMS (less than 30%) were utilized to enhance the mechanical properties and biocompatibilities. The microstructure and degrees of phase separation were characterized using atomic force microscopy. The chemical structure and surface morphology of the materials were further confirmed by attenuated total reflectance Fourier transform infrared spectroscopy, 1H NMR and 13C NMR, water droplet contact angle and scanning electron microscopy. Thermal properties were measured by differential scanning calorimetry. MTT assay and hemolytic tests were studied for evaluating cellular viability and hemocompatibility of fabricated films using L929 fibroblast cells and adult rabbit blood. The results demonstrated polyurethane films with soft segments partially replaced by PDMS could remarkably improve the biocompatibility while maintaining relatively stable mechanical behavior, making them exciting potential candidates for artificial vessels or other tissue engineering applications.

A Biomimetic Silk Fibroin/Sodium Alginate Composite Scaffold for Soft Tissue Engineering.

A cytocompatible porous scaffold mimicking the properties of extracellular matrices (ECMs) has great potential in promoting cellular attachment and proliferation for tissue regeneration. A biomimetic scaffold was prepared using silk fibroin (SF)/sodium alginate (SA) in which regular and uniform pore morphology can be formed through a facile freeze-dried method. The scanning electron microscopy (SEM) studies showed the presence of interconnected pores, mostly spread over the entire scaffold with pore diameter around 54~532 µm and porosity 66~94%. With significantly better water stability and high swelling ratios, the blend scaffolds crosslinked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) provided sufficient time for the formation of neo-tissue and ECMs during tissue regeneration. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) results confirmed random coil structure and silk I conformation were maintained in the blend scaffolds. What's more, FI-TR spectra demonstrated crosslinking reactions occurred actually among EDC, SF and SA macromolecules, which kept integrity of the scaffolds under physiological environment. The suitable pore structure and improved equilibrium swelling capacity of this scaffold could imitate biochemical cues of natural skin ECMs for guiding spatial organization and proliferation of cells in vitro, indicating its potential candidate material for soft tissue engineering.