Publications
2026
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Optical monitoring of inflammatory response in joint explant cultures using near infrared spectroscopy
CONCLUSIONS: This study showed that NIR spectroscopy combined with ML can detect and quantify OA-related spectral signatures in explant media, thereby demonstrating its potential as a non-destructive and rapid method for monitoring inflammatory activity in ex vivo OA models. -
CPNE7-derived peptides CDP4 and UG28 as pro-angiogenic factors for endothelial regeneration
CONCLUSION AND IMPLICATIONS: CPNE7-derived peptides-especially UG28-are potent and safe pro-angiogenic agents with high translational potential, and their compatibility with chitosan supports their applicability in next-generation regenerative therapies targeting endothelial and microvascular repair. -
L-Ascorbic Acid 2-Phosphate-Releasing Poly(trimethylene carbonate) Increases Cell Proliferation and Collagen Production: A Novel Material for Pelvic Organ Prolapse Tissue Engineering
CONCLUSION: Our results indicate that A2P-releasing PTMC is a promising option for enhancing tissue regeneration in applications for POP tissue engineering. -
Corrigendum to "Biomimetic bone calcium phosphate-based scaffolds fabricated via ceramic vat photopolymerization: Effect of porosity, sintering temperature, mineralogical phases and trace elements on the osteogenic potential" [Mater. Today Bio 38 (2026) 103074]
[This corrects the article DOI: 10.1016/j.mtbio.2026.103074.]. -
Corrigendum to "Biomimetic bone calcium phosphate-based scaffolds fabricated via ceramic vat photopolymerization: Effect of porosity, sintering temperature, mineralogical phases and trace elements on the osteogenic potential" [Mater. Today Bio 38 (2026) 103074]
[This corrects the article DOI: 10.1016/j.mtbio.2026.103074.]. -
Effect of 3D-printed co-culture design of mesenchymal stem cells and human umbilical vein endothelial cells on tubular formation
Functional vascularization remains a major challenge in engineered tissues. Multi-material 3D bioprinting enables precise spatial patterning of different cell types, offering new opportunities to design engineered microenvironments that support vascular self-assembly. Here, we compared three bioprinted co-culture configurations of human umbilical vein endothelial cells (HUVEC) and bone marrow-derived mesenchymal stem cells (BMSC) using a fibrin-gelatin bioink: (i) co-printed within the same... -
Biomimetic bone calcium phosphate-based scaffolds fabricated via ceramic vat photopolymerization: Effect of porosity, sintering temperature, mineralogical phases and trace elements on the osteogenic potential
In response to the growing demand for novel approaches in bone repair, scaffolds that mimic natural bone microstructure and mineralogical composition were developed using a ceramic vat photopolymerization (VPP) method. Due to varying reported results regarding appropriate microstructural characteristics, this study aimed to clarify the best pore size distribution and porosity among the tested scaffolds for an efficient osteogenic response. Scaffolds based on hydroxyapatite both support new bone... -
Establishment of human-relevant <em>in vitro</em> models using animal-free serum replacement and recombinant antibodies
The use of animal-derived reagents in biomedical research poses challenges for reproducibility due to batch-to-batch variability and inter-species differences, along with ethical concerns related to their origin. In pursuing a human-relevant in vitro model, an animal-free and defined cell culture process is preferred to improve relevance and reproducibility. We investigated the use of serum replacement (SR) consisting of human hepatocyte-derived proteins in cell culture and recombinant... -
Bilayer Fiber-Reinforced Composite-Hydrogel Scaffolds With Bioactive Glass for Bone Tissue Regeneration
Bone tissue regeneration for large defects presents a significant challenge, demanding scaffolds that combine robust mechanical support alongside a bioactive environment. Hydrogels represent a promising solution for bone regeneration due to their biocompatibility, tunable properties, and crosslinked three-dimensional (3D) networks mimicking the natural extracellular matrix (ECM). However, their mechanical properties remain suboptimal for restoring bone defects effectively. This study introduces... -
In Vivo Evaluation of Injected and Bioprinted Hyaluronic Acid-Based Bioink in Corneal Stromal Pocket
The corneal stroma contains specialized stromal keratocytes (CSKs) that preserve corneal transparency and homogeneity. Stromal scarring and opacities lead to vision loss in millions globally. While corneal transplantation remains the gold standard, it is constrained by donor shortages. Cell-based therapies using primary stromal cells show promise but still depend on donor tissue. Human adipose tissue-derived stem cells (hASCs) offer an abundant alternative, capable of differentiating into CSKs....
2025
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Ascorbic acid 2-phosphate-releasing poly-l-lactide-co-epsilon-caprolactone membranes enhance tissue regeneration: first <em>in vivo</em> insights for pelvic organ prolapse
Pelvic organ prolapse (POP) significantly impacts women's health and quality of life. There is a critical need for alternative biomaterials for surgical POP repair, driven by complications associated with conventional non-absorbable vaginal meshes. As ascorbic acid 2-phosphate (A2P) has been demonstrated to enhance collagen production and cell proliferation in vitro, this study investigated absorbable A2P-releasing poly-l-lactide-co-epsilon-caprolactone (PLCL) membranes in the first in vivo... -
Human induced pluripotent stem cell-derived neurons and coculture conditions regulate the adipogenic differentiation and functionality of human adipose stromal/stem cells
CONCLUSIONS: This research provides a novel human cell-based 3D in vitro model to study adipose tissue innervation and neuro-adipose interactions. Here, the novel human cell-based coculture model holds great potential for future mechanistic studies of neuro-adipose regulation. -
Non-destructive monitoring of cartilage tissue engineering via near-infrared (NIR) spectroscopic assessment of culture medium
Degenerative joint diseases are major contributors to pain, impaired mobility, and an increasing socioeconomic burden in aging populations. Tissue Engineering (TE) offers alternative solutions to restore joint functions. However, current TE approaches often fail to produce biocompatible, patient-specific cartilage. This could be due to the lack of a rapid, non-destructive assessment for monitoring tissue growth. Biological markers such as hyaluronan, lactate, and collagen are released in culture... -
Effects of Bariatric Surgery-Related Weight Loss on the Characteristics, Metabolism, and Immunomodulation of Adipose Stromal/Stem Cells in a Follow-Up Study
Background: The success of adipose stromal/stem cell (ASC)-based therapies may depend on donor characteristics such as body mass index (BMI). A high BMI may negatively impact the therapeutic potential of ASCs, but the effects of weight loss on ASC-mediated immunoregulation have not been extensively studied. Methods: ASCs were obtained from donors with obesity (obASCs) undergoing bariatric surgery and from the same donors after weight loss (wlASCs). Plasma samples, adipose tissue histology, and... -
Systematic development and bioprinting of novel nanostructured multi-material bioinks for bone tissue engineering
A functional bioink with potential in bone tissue engineering must be subjected to critical investigation throughout its intended lifespan. The aim of this study was to develop alginate-gelatin-based (Alg-Gel) multicomponent bioinks systematically and to assess the short- and long-term exposure responses of human bone marrow stromal cells (hBMSCs) printed within these bioinks with and without crosslinking.The first generation of bioinkswas established by incorporating a range of cellulose...
2024
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Ionic Dissolution Products of Lithium-, Strontium-, and Boron-Substituted Silicate Glasses Influence the Viability and Proliferation of Adipose Stromal Cells, Fibroblasts, Urothelial and Endothelial Cells
While bioactive glasses (BaGs) have been studied mainly for bone applications, studies have also shown their potential for soft tissue engineering. Incorporating therapeutic ions, such as lithium (Li^(+)), strontium (Sr^(2+)), and boron (B^(3+)) into the BaGs, has been found to promote angiogenesis and wound healing. However, a systematic study on the impact of Li^(+), Sr^(2+), B^(3+), and the other ions in the BaGs, has not been conducted on a wide range of cells. Although the interactions... -
Borosilicate bioactive glasses with added Mg/Sr enhances human adipose-derived stem cells osteogenic commitment and angiogenic properties
Bioactive glasses are one of the most promising materials for applications in bone tissue engineering. In this study, the focus was on borosilicate bioactive glasses with composition 47.12 SiO(2) - 6.73 B(2)O(3) - 21.77-x-y CaO - 22.65 Na(2)O - 1.72 P(2)O(5) - x MgO - y SrO (mol%). These compositions are based on silicate S53P4 bioactive glass, from where 12.5% of SiO(2) is replaced with B(2)O(3), and additionally, part of CaO is substituted for MgO and/or SrO. The impact of ion release, both as... -
Barrier-free, open-top microfluidic chip for generating two distinct, interconnected 3D microvascular networks
Developing microphysiological cell culture platforms with a three-dimensional (3D) microenvironment has been a significant advancement from traditional monolayer cultures. Still, most of the current microphysiological platforms are limited in closed designs, i.e. are not accessible after 3D cell culture loading. Here, we report an open-top microfluidic chip which enables the generation of two sequentially loaded 3D cell cultures without physical barriers restricting the nurture, gas exchange and... -
Boron substitution in silicate bioactive glass scaffolds to enhance bone differentiation and regeneration
Commercially available bioactive glasses (BAGs) are exclusively used in powder form, due to their tendency to crystallize. Silicate BAG 1393 was developed to allow fiber drawing and scaffold sintering, but its slow degradation limits its potential. To enable scaffold manufacturing while maintaining glass dissolution rate close to that of commercially available BAGs, the borosilicate glass 1393B20 was developed. This study investigates the potential of 1393B20 scaffolds to support bone... -
Gellan gum-gelatin based cardiac models support formation of cellular networks and functional cardiomyocytes
Cardiovascular diseases remain as the most common cause of death worldwide. To reveal the underlying mechanisms in varying cardiovascular diseases, in vitro models with cells and supportive biomaterial can be designed to recapitulate the essential components of human heart. In this study, we analyzed whether 3D co-culture of cardiomyocytes (CM) with vascular network and with adipose tissue-derived mesenchymal stem/stromal cells (ASC) can support CM functionality. CM were cultured with either... -
Promoting cell proliferation and collagen production with ascorbic acid 2-phosphate-releasing poly(l-lactide-co-ε-caprolactone) membranes for treating pelvic organ prolapse
Pelvic organ prolapse (POP) afflicts millions of women globally. In POP, the weakened support of the pelvic floor results in the descent of pelvic organs into the vagina, causing a feeling of bulging, problems in urination, defaecation and/or sexual function. However, the existing surgical repair methods for relapsed POP remain insufficient, highlighting the urgent need for more effective alternatives. Collagen is an essential component in pelvic floor tissues, providing structural support, and... -
Cornea-Specific Human Adipose Stem Cell-Derived Extracellular Matrix for Corneal Stroma Tissue Engineering
Utilizing tissue-specific extracellular matrices (ECMs) is vital for replicating the composition of native tissues and developing biologically relevant biomaterials. Human- or animal-derived donor tissues and organs are the current gold standard for the source of these ECMs. To overcome the several limitations related to these ECM sources, including the highly limited availability of donor tissues, cell-derived ECM offers an alternative approach for engineering tissue-specific biomaterials, such... -
Pore graded borosilicate bioactive glass scaffolds: in vitro dissolution and cytocompatibility
3D borosilicate bioactive glass (1393B20 and B12.5MgSr) scaffolds were prepared by robocasting, with and without a dense layer at the top. Pore graded scaffolds are promising as they allow for membrane deposition and could limit the risk of soft tissue infiltration. In vitro dissolution was studied in tris(hydroxymethyl)aminomethane (TRIS) and Simulated Body Fluid (SBF). 1393B20 scaffolds dissolved faster than B12.5MgSr in TRIS whereas they dissolved slower in SBF. The difference in dissolution... -
Designing patient-oriented combination therapies for acute myeloid leukemia based on efficacy/toxicity integration and bipartite network modeling
Acute myeloid leukemia (AML), a heterogeneous and aggressive blood cancer, does not respond well to single-drug therapy. A combination of drugs is required to effectively treat this disease. Computational models are critical for combination therapy discovery due to the tens of thousands of two-drug combinations, even with approved drugs. While predicting synergistic drugs is the focus of current methods, few consider drug efficacy and potential toxicity, which are crucial for treatment success.... -
Novel strategy for multi-material 3D bioprinting of human stem cell based corneal stroma with heterogenous design
Three-dimensional (3D) bioprinting offers an automated, customizable solution to manufacture highly detailed 3D tissue constructs and holds great promise for regenerative medicine to solve the severe global shortage of donor tissues and organs. However, uni-material 3D bioprinting is not sufficient for manufacturing heterogenous 3D constructs with native-like microstructures and thus, innovative multi-material solutions are required. Here, we developed a novel multi-material 3D bioprinting...
2023
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Ascorbic Acid 2-Phosphate-Releasing Supercritical Carbon Dioxide-Foamed Poly(L-Lactide-Co-epsilon-Caprolactone) Scaffolds Support Urothelial Cell Growth and Enhance Human Adipose-Derived Stromal Cell Proliferation and Collagen Production
Tissue engineering can provide a novel approach for the reconstruction of large urethral defects, which currently lacks optimal repair methods. Cell-seeded scaffolds aim to prevent urethral stricture and scarring, as effective urothelium and stromal tissue regeneration is important in urethral repair. In this study, the aim was to evaluate the effect of the novel porous ascorbic acid 2-phosphate (A2P)-releasing supercritical carbon dioxide-foamed poly(L-lactide-co-ε-caprolactone) (PLCL)... -
Novel strategy for multi-material 3D bioprinting of human stem cell based corneal stroma with heterogenous design
Three-dimensional (3D) bioprinting offers an automated, customizable solution to manufacture highly detailed 3D tissue constructs and holds great promise for regenerative medicine to solve the severe global shortage of donor tissues and organs. However, uni-material 3D bioprinting is not sufficient for manufacturing heterogenous 3D constructs with native-like microstructures and thus, innovative multi-material solutions are required. Here, we developed a novel multi-material 3D bioprinting... -
Robust scoring of selective drug responses for patient-tailored therapy selection
Most patients with advanced malignancies are treated with severely toxic, first-line chemotherapies. Personalized treatment strategies have led to improved patient outcomes and could replace one-size-fits-all therapies, yet they need to be tailored by testing of a range of targeted drugs in primary patient cells. Most functional precision medicine studies use simple drug-response metrics, which cannot quantify the selective effects of drugs (i.e., the differential responses of cancer cells and... -
Ascorbic Acid 2-Phosphate Releasing Supercritically Foamed Porous Poly-L-Lactide-Co-ε-Caprolactone Scaffold Enhances the Collagen Production of Human Vaginal Stromal Cells: A New Approach for Vaginal Tissue Engineering
CONCLUSION: This is the first study evaluating the effect of A2P on vaginal tissue engineering, and the results are highly encouraging, indicating that scPLCL(A2P) has potential as a scaffold for vaginal tissue engineering. -
Improvements in Maturity and Stability of 3D iPSC-Derived Hepatocyte-like Cell Cultures
Induced pluripotent stem cell (iPSC) technology enables differentiation of human hepatocytes or hepatocyte-like cells (iPSC-HLCs). Advances in 3D culturing platforms enable the development of more in vivo-like liver models that recapitulate the complex liver architecture and functionality better than traditional 2D monocultures. Moreover, within the liver, non-parenchymal cells (NPCs) are critically involved in the regulation and maintenance of hepatocyte metabolic function. Thus, models... -
Simultaneous induction of vasculature and neuronal network formation on a chip reveals a dynamic interrelationship between cell types
CONCLUSIONS: Overall, our study provides a novel human neurovascular network model that is applicable for creating in vivo-like tissue models with intrinsic neurovascular interactions. The 3D neurovascular network model on chip forms an initial platform for the development of vascularized and innervated organ-on-chip and further body-on-chip concepts and offers the possibility for mechanistic studies on neurovascular communication both under healthy and in disease conditions. Video Abstract. -
In vitro biocompatibility of polylactide and polybutylene succinate blends for urethral tissue engineering
Surgical treatment of urothelial defects with autologous genital or extragenital tissue grafts is susceptible to complications. Tissue engineering utilizing novel biomaterials and cells such as human urothelial cells (hUC) for epithelial regeneration and adipose stromal cells (hASC) for smooth muscle restoration might offer new treatment options for urothelial defects. Previously, polylactide (PLA) has been studied for urethral tissue engineering, however, as such, it is too stiff and rigid for... -
Immunomodulatory Functions of Adipose Mesenchymal Stromal/Stem Cell Derived From Donors With Type 2 Diabetes and Obesity on CD4 T Cells
For adipose stromal/stem cell (ASCs)-based immunomodulatory therapies, it is important to study how donor characteristics, such as obesity and type 2 diabetes (T2D), influence ASCs efficacy. Here, ASCs were obtained from 2 groups, donors with T2D and obesity (dASCs) or nondiabetic donors with normal-weight (ndASCs), and then cultured with anti-CD3/CD28-stimulated allogeneic CD4 T cells. ASCs were studied for the expression of the immunomodulators CD54, CD274, and indoleamine 2, 3 dioxygenase 1... -
Heat Shock Protein 27 Is Involved in the Bioactive Glass Induced Osteogenic Response of Human Mesenchymal Stem Cells
Bioactive glass (BaG) materials are increasingly used in clinics, but their regulatory mechanisms on osteogenic differentiation remain understudied. In this study, we elucidated the currently unknown role of the p38 MAPK downstream target heat shock protein 27 (HSP27), in the osteogenic commitment of human mesenchymal stem cells (hMSCs), derived from adipose tissue (hASCs) and bone marrow (hBMSCs). Osteogenesis was induced with ionic extract of an experimental BaG in osteogenic medium (OM). Our...
2022
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Hyaluronic acid based next generation bioink for 3D bioprinting of human stem cell derived corneal stromal model with innervation
Corneal transplantation remains gold standard for the treatment of severe cornea diseases, however, scarcity of donor cornea is a serious bottleneck. 3D bioprinting holds tremendous potential for cornea tissue engineering (TE). One of the key technological challenges is to design bioink compositions with ideal printability and cytocompatibility. Photo-crosslinking and ionic crosslinking are often used for the stabilization of 3D bioprinted structures, which can possess limitations on biological... -
Bioactivated gellan gum hydrogels affect cellular rearrangement and cell response in vascular co-culture and subcutaneous implant models
Hydrogels are suitable soft tissue mimics and capable of creating pre-vascularized tissues, that are useful for in vitro tissue engineering and in vivo regenerative medicine. The polysaccharide gellan gum (GG) offers an intriguing matrix material but requires bioactivation in order to support cell attachment and transfer of biomechanical cues. Here, four versatile modifications were investigated: Purified NaGG; avidin-modified NaGG combined with biotinylated fibronectin (NaGG-avd); oxidized GG... -
Angiogenic Potential of Human Adipose-Derived Mesenchymal Stromal Cells in Nanofibrillated Cellulose Hydrogel
Adipose-derived mesenchymal stromal cells (ASCs) hold great potential for cellular therapies by having immunomodulatory behavior and tissue regenerative properties. Due to the capability of ASCs to differentiate into endothelial cells (ECs) and other angiogenic cell types, such as pericytes, ASCs are a highly valuable source for stimulating angiogenesis. However, cellular therapies in tissue engineering have faced challenges in poor survival of the cells after transplantation, which is why a... -
Effect of cell culture media on extracellular vesicle secretion from mesenchymal stromal cells and neurons
CONCLUSIONS: We demonstrated successful EV isolation from MSC and neuronal cells using an ultrafiltration-SEC method. The EV yield from MSC and neuronal cultures exhibited a large batch effect, apparently related to the culture media used, highlighting the importance of including NCC as a negative control in all cell culture experiments. -
Growth Response and Differentiation of Bone Marrow-Derived Mesenchymal Stem/Stromal Cells in the Presence of Novel Multiple Myeloma Drug Melflufen
Mesenchymal stem/stromal cells (MSCs) are self-renewing and multipotent progenitors, which constitute the main cellular compartment of the bone marrow stroma. Because MSCs have an important role in the pathogenesis of multiple myeloma, it is essential to know if novel drugs target MSCs. Melflufen is a novel anticancer peptide-drug conjugate compound for patients with relapsed refractory multiple myeloma. Here, we studied the cytotoxicity of melflufen, melphalan and doxorubicin in healthy human... -
Preventing White Adipocyte Browning during Differentiation <em>In Vitro</em>: The Effect of Differentiation Protocols on Metabolic and Mitochondrial Phenotypes
Mitochondrial dysfunction in white adipose tissue is strongly associated with obesity and its metabolic complications, which are important health challenges worldwide. Human adipose-derived stromal/stem cells (hASCs) are a promising tool to investigate the underlying mechanisms of such mitochondrial dysfunction and to subsequently provide knowledge for the development of treatments for obesity-related pathologies. A substantial obstacle in using hASCs is that the key compounds for adipogenic... -
Vasculogenic Potency of Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells Results in Differing Vascular Network Phenotypes in a Microfluidic Chip
The vasculature is an essential, physiological element in virtually all human tissues. Formation of perfusable vasculature is therefore crucial for reliable tissue modeling. Three-dimensional vascular networks can be formed through the co-culture of endothelial cells (ECs) with stromal cells embedded in hydrogel. Mesenchymal stem/stromal cells (MSCs) derived from bone marrow (BMSCs) and adipose tissue (ASCs) are an attractive choice as stromal cells due to their natural perivascular localization...
2021
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Evaluation of the effect of donor weight on adipose stromal/stem cell characteristics by using weight-discordant monozygotic twin pairs
CONCLUSIONS: Our genetically matched data suggest that a higher weight of the donor may have some effect on ASC characteristics, especially on angiogenic and adipogenic potential, which should be considered when ASCs are used clinically. -
Pluronic Micelle-Mediated Tissue Factor Silencing Enhances Hemocompatibility, Stemness, Differentiation Potential, and Paracrine Signaling of Mesenchymal Stem Cells
Mesenchymal stem/stromal cells (MSCs) evoke great excitement for treating different human diseases due to their ability to home inflamed tissues, suppress inflammation, and promote tissue regeneration. Despite great promises, clinical trial results are disappointing as allotransplantation of MSCs trigger thrombotic activity and are damaged by the complement system, compromising their survival and function. To overcome this, a new strategy is presented by the silencing of tissue factor (TF), a... -
Additive Behavioral Improvement after Combined Cell Therapy and Rehabilitation Despite Long-Term Microglia Presence in Stroke Rats
CONCLUSION: Combined cell therapy and rehabilitation additively improved behavioral outcome despite long-term perilesional microglia presence in stroke rats.
2020
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<em>In Vitro</em> Oxygen-Glucose Deprivation-Induced Stroke Models with Human Neuroblastoma Cell- and Induced Pluripotent Stem Cell-Derived Neurons
Stroke is a devastating neurological disorder and one of the leading causes of mortality and disability. To understand the cellular and molecular mechanisms of stroke and to develop novel therapeutic approaches, two different in vitro human cell-based stroke models were established using oxygen-glucose deprivation (OGD) conditions. In addition, the effect of adipose stem cells (ASCs) on OGD-induced injury was studied. In the present study, SH-SY5Y human neuroblastoma cells and human induced... -
Myocardin-Related Transcription Factor A (MRTF-A) Regulates the Balance between Adipogenesis and Osteogenesis of Human Adipose Stem Cells
Previous studies have demonstrated that myocardin-related transcription factor A (MRTF-A) generates a link between the dynamics of the actin cytoskeleton and gene expression with its coregulator, serum response factor (SRF). MRTF-A has also been suggested as a regulator of stem cell differentiation. However, the role of MRTF-A in human mesenchymal stem cell differentiation remains understudied. We aimed to elucidate whether MRTF-A is a potential regulator of human adipose stem cell (hASC)... -
A tube-source X-ray microtomography approach for quantitative 3D microscopy of optically challenging cell-cultured samples
Development and study of cell-cultured constructs, such as tissue-engineering scaffolds or organ-on-a-chip platforms require a comprehensive, representative view on the cells inside the used materials. However, common characteristics of biomedical materials, for example, in porous, fibrous, rough-surfaced, and composite materials, can severely disturb low-energy imaging. In order to image and quantify cell structures in optically challenging samples, we combined labeling, 3D X-ray imaging, and... -
Materials and Orthopedic Applications for Bioresorbable Inductively Coupled Resonance Sensors
Bioresorbable passive resonance sensors based on inductor-capacitor (LC) circuits provide an auspicious sensing technology for temporary battery-free implant applications due to their simplicity, wireless readout, and the ability to be eventually metabolized by the body. In this study, the fabrication and performance of various LC circuit-based sensors are investigated to provide a comprehensive view on different material options and fabrication methods. The study is divided into sections that... -
Evaluation of scaffold microstructure and comparison of cell seeding methods using micro-computed tomography-based tools
Micro-computed tomography (micro-CT) provides a means to analyse and model three-dimensional (3D) tissue engineering scaffolds. This study proposes a set of micro-CT-based tools firstly for evaluating the microstructure of scaffolds and secondly for comparing different cell seeding methods. The pore size, porosity and pore interconnectivity of supercritical CO(2) processed poly(l-lactide-co-ɛ-caprolactone) (PLCL) and PLCL/β-tricalcium phosphate scaffolds were analysed using computational... -
Co-culture of human induced pluripotent stem cell-derived retinal pigment epithelial cells and endothelial cells on double collagen-coated honeycomb films
In vitro cell culture models representing the physiological and pathological features of the outer retina are urgently needed. Artificial tissue replacements for patients suffering from degenerative retinal diseases are similarly in great demand. Here, we developed a co-culture system based solely on the use of human induced pluripotent stem cell (hiPSC)-derived cells. For the first time, hiPSC-derived retinal pigment epithelium (RPE) and endothelial cells (EC) were cultured on opposite sides of... -
Bioactive glass ions for in vitro osteogenesis and microvascularization in gellan gum-collagen hydrogels
Lack of bone grafts appeals for bone augmentation solutions. We aimed at osteogenic differentiation of human adipose stem cells (hASCs) and microvascularization in coculture with human umbilical vein endothelial cells (HUVECs) embedded in three-dimensional (3D) gellan gum (GG) and collagen type I (COL) hydrogel mixture. We compared endothelial growth medium-2 (EGM-2) and bioactive glass extract-based endothelial and osteogenic medium (BaG EM-OM) for vascularized bone-like graft development in... -
Diopside-tricalcium phosphate bioactive ceramics for osteogenic differentiation of human adipose stem cells
Ti scaffolds combined with autologous human adipose-derived mesenchymal stem cells (hASCs) have been successfully applied for regenerative cranio-maxillofacial bone therapies. Future challenges reside in regeneration of larger bone defects and displacement of the permanent Ti structure, thus, advanced resorbable scaffolds are needed. Composites of β-Ca(3) (PO(4) )(2) with 80 and 60 wt % of CaMg(SiO(3) )(2) with improved mechanical properties compared to tricalcium phosphate (TCP) materials are...
2019
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3D Scaffolds of Polycaprolactone/Copper-Doped Bioactive Glass: Architecture Engineering with Additive Manufacturing and Cellular Assessments in a Coculture of Bone Marrow Stem Cells and Endothelial Cells
The local delivery of Cu^(2+) from copper-doped bioactive glass (Cu-BaG) was combined with 3D printing of polycaprolactone (PCL) scaffolds for its potent angiogenic effect in bone tissue engineering. PCL and Cu-BaG were, respectively, dissolved and dispersed in acetone to formulate a moderately homogeneous ink. The PCL/Cu-BaG scaffolds were fabricated via direct ink writing into a cold ethanol bath. The architecture of the printed scaffolds, including strut diameter, strut spacing, and porosity,... -
Co-culture of human induced pluripotent stem cell-derived retinal pigment epithelial cells and endothelial cells on double collagen-coated honeycomb films
In vitro cell culture models representing the physiological and pathological features of the outer retina are urgently needed. Artificial tissue replacements for patients suffering from degenerative retinal diseases are similarly in great demand. Here, we developed a co-culture system based solely on the use of human induced pluripotent stem cell (hiPSC)-derived cells. For the first time, hiPSC-derived retinal pigment epithelium (RPE) and endothelial cells (EC) were cultured on opposite sides of... -
Tissue adhesive hyaluronic acid hydrogels for sutureless stem cell delivery and regeneration of corneal epithelium and stroma
Regeneration of a severely damaged cornea necessitates the delivery of both epithelium-renewing limbal epithelial stem cells (LESCs) and stroma-repairing cells, such as human adipose-derived stem cells (hASCs). Currently, limited strategies exist for the delivery of these therapeutic cells with tissue-like cellular organization. With the added risks related to suturing of corneal implants, there is a pressing need to develop new tissue adhesive biomaterials for corneal regeneration. To address... -
Nanofibrillar cellulose wound dressing supports the growth and characteristics of human mesenchymal stem/stromal cells without cell adhesion coatings
CONCLUSIONS: As a result, NFC wound dressing offers a functional cell culture platform for hASCs to be used further for in vivo wound healing studies in the future. -
Bioactive glass ions for in vitro osteogenesis and microvascularization in gellan gum-collagen hydrogels
Lack of bone grafts appeals for bone augmentation solutions. We aimed at osteogenic differentiation of human adipose stem cells (hASCs) and microvascularization in coculture with human umbilical vein endothelial cells (HUVECs) embedded in three-dimensional (3D) gellan gum (GG) and collagen type I (COL) hydrogel mixture. We compared endothelial growth medium-2 (EGM-2) and bioactive glass extract-based endothelial and osteogenic medium (BaG EM-OM) for vascularized bone-like graft development in... -
Design of modular gellan gum hydrogel functionalized with avidin and biotinylated adhesive ligands for cell culture applications
This article proposes the coupling of the recombinant protein avidin to the polysaccharide gellan gum to create a modular hydrogel substrate for 3D cell culture and tissue engineering. Avidin is capable of binding biotin, and thus biotinylated compounds can be tethered to the polymer network to improve cell response. The avidin is successfully conjugated to gellan gum and remains functional as shown with fluorescence titration and electrophoresis (SDS-PAGE). Self-standing hydrogels were formed... -
Diopside-tricalcium phosphate bioactive ceramics for osteogenic differentiation of human adipose stem cells
Ti scaffolds combined with autologous human adipose-derived mesenchymal stem cells (hASCs) have been successfully applied for regenerative cranio-maxillofacial bone therapies. Future challenges reside in regeneration of larger bone defects and displacement of the permanent Ti structure, thus, advanced resorbable scaffolds are needed. Composites of β-Ca(3) (PO(4) )(2) with 80 and 60 wt % of CaMg(SiO(3) )(2) with improved mechanical properties compared to tricalcium phosphate (TCP) materials are... -
Perspectives for Clinical Translation of Adipose Stromal/Stem Cells
Adipose stromal/stem cells (ASCs) are an ideal cell type for regenerative medicine applications, as they can easily be harvested from adipose tissue in large quantities. ASCs have excellent proliferation, differentiation, and immunoregulatory capacities that have been demonstrated in numerous studies. Great interest and investment have been placed in efforts to exploit the allogeneic use and immunomodulatory and anti-inflammatory effects of ASCs. However, bridging the gap between in vitro and in... -
In-vitro dissolution characteristics and human adipose stem cell response to novel borophosphate glasses
The main drawbacks of traditional silicate bioactive glasses are their narrow hot forming domain and noncongruent dissolution. In this article, we report on new borophosphate glasses [xM(n) O(m) + (100 - x) (47.5P(2) O(5) + 2.5B(2) O(3) + 10Na(2) O + 20CaO + 20SrO)], M(n) O(m) being CuO, Ag(2) O, and CeO(2) , having high thermal processability, hence suitable for fiber drawing and sintering into scaffolds. Furthermore, the glasses dissolve congruently in simulated body fluid (SBF) and TRIS... -
Combined Adipose Tissue-Derived Mesenchymal Stem Cell Therapy and Rehabilitation in Experimental Stroke
Background/Objective: Stroke is a leading global cause of adult disability. As the population ages as well as suffers co-morbidities, it is expected that the stroke burden will increase further. There are no established safe and effective restorative treatments to facilitate a good functional outcome in stroke patients. Cell-based therapies, which have a wide therapeutic window, might benefit a large percentage of patients, especially if combined with different restorative strategies. In this...
2018
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Focal Adhesion Kinase and ROCK Signaling Are Switch-Like Regulators of Human Adipose Stem Cell Differentiation towards Osteogenic and Adipogenic Lineages
Adipose tissue is an attractive stem cell source for soft and bone tissue engineering applications and stem cell therapies. The adipose-derived stromal/stem cells (ASCs) have a multilineage differentiation capacity that is regulated through extracellular signals. The cellular events related to cell adhesion and cytoskeleton have been suggested as central regulators of differentiation fate decision. However, the detailed knowledge of these molecular mechanisms in human ASCs remains limited. This... -
Porous poly-l-lactide-co-ɛ-caprolactone scaffold: a novel biomaterial for vaginal tissue engineering
The surgical reconstruction of functional neovagina is challenging and susceptible to complications. Therefore, developing tissue engineering-based treatment methods for vaginal defects is important. Our aim was to develop and test a novel supercritical carbon dioxide foamed poly-l-lactide-co-ɛ-caprolactone (scPLCL) scaffold for vaginal reconstruction. The scaffolds were manufactured and characterized for porosity (65 ± 4%), pore size (350 ± 150 µm) and elastic modulus (2.8 ± 0.4 MPa). Vaginal... -
The effect of S53P4-based borosilicate glasses and glass dissolution products on the osteogenic commitment of human adipose stem cells
Despite the good performance of silicate bioactive glasses in bone regeneration, there is considerable potential to enhance their properties by chemical modifications. In this study, S53P4-based borosilicate glasses were synthesized and their dissolution profile was studied in simulated body fluid by assessing pH change, ion release and conversion to hydroxyapatite. The viability, proliferation, attachment, osteogenesis and endothelial marker expression of human adipose stem cells (hASCs) was... -
Knitted 3D Scaffolds of Polybutylene Succinate Support Human Mesenchymal Stem Cell Growth and Osteogenesis
Polybutylene succinate (PBS) is a biodegradable polyester with better processability and different mechanical properties compared to polylactides (PLAs), the most commonly used synthetic polymers in tissue engineering (TE). Since only few studies have evaluated PBS-containing materials for bone TE, we prepared PLA-PBS blends and analyzed material properties as well as cell attachment, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs) on scaffolds. In addition... -
Monocyte-derived extracellular vesicles stimulate cytokine secretion and gene expression of matrix metalloproteinases by mesenchymal stem/stromal cells
Intercellular communication is essential in bone remodelling to ensure that new bone is formed with only temporary bone loss. Monocytes (MCs) and osteoclasts actively take part in controlling bone remodelling by providing signals that promote osteogenic differentiation of mesenchymal stem/stromal cells (MSCs). Extracellular vesicles (EVs) have attracted attention as regulators of bone remodelling. EVs facilitate intercellular communication by transferring a complex cargo of biologically active... -
Human stem cell based corneal tissue mimicking structures using laser-assisted 3D bioprinting and functional bioinks
There is a high demand for developing methods to produce more native-like 3D corneal structures. In the present study, we produced 3D cornea-mimicking tissues using human stem cells and laser-assisted bioprinting (LaBP). Human embryonic stem cell derived limbal epithelial stem cells (hESC-LESC) were used as a cell source for printing epithelium-mimicking structures, whereas human adipose tissue derived stem cells (hASCs) were used for constructing layered stroma-mimicking structures. The... -
Hydrazone crosslinked hyaluronan-based hydrogels for therapeutic delivery of adipose stem cells to treat corneal defects
Corneal blindness is a worldwide problem, plagued by insufficient amount of high-quality donor tissue. Cell therapy using human adipose stem cells (hASCs) has risen as an alternative to regenerate damaged corneal stromal tissue, the main structural and refractive layer of the cornea. Herein we propose a method to deliver hASCs into corneal defects in hyaluronan (HA)-based hydrogels, which form rapidly in situ by hydrazone crosslinking. We fabricated two different HA-based hydrazone-crosslinked... -
Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model
Anal incontinence is a devastating condition that significantly reduces the quality of life. Our aim was to evaluate the effect of human adipose stem cell (hASC) injections in a rat model for anal sphincter injury, which is the main cause of anal incontinence in humans. Furthermore, we tested if the efficacy of hASCs could be improved by combining them with polyacrylamide hydrogel carrier, Bulkamid. Human ASCs derived from a female donor were culture expanded in DMEM/F12 supplemented with human... -
Comparison of Poly(l-lactide-co-ɛ-caprolactone) and Poly(trimethylene carbonate) Membranes for Urethral Regeneration: An In Vitro and In Vivo Study
Urethral defects are normally reconstructed using a patient's own genital tissue; however, in severe cases, additional grafts are needed. We studied the suitability of poly(l-lactide-co-ɛ-caprolactone) (PLCL) and poly(trimethylene carbonate) (PTMC) membranes for urethral reconstruction in vivo. Further, the compatibility of the materials was evaluated in vitro with human urothelial cells (hUCs). The attachment and viability of hUCs and the expression of different urothelial cell markers...