Scaffolds For Tissue Engineering Research Articles

Photo-Clickable Triazine-Trione Thermosets as Promising 3D Scaffolds for Tissue Engineering Applications.

There is an overwhelming demand for new scaffolding materials for tissue engineering (TE) purposes. Polymeric scaffolds have been explored as TE materials; however, their high glass transition state (Tg) limits their applicability. In this study, a novel materials platform for fabricating TE scaffolds is proposed based on solvent-free two-component heterocyclic triazine-trione (TATO) formulations, which cure at room temperature via thiol-ene/yne photochemistry. Three ester-containing thermosets, TATO-1, TATO-2, and TATO-3, are used for the fabrication of TE scaffolds including rigid discs, elastic films, microporous sponges, and 3D printed objects. After 14 days' incubation the materials covered a wide range of properties, from the soft TATO-2 having a compression modulus of 19.3MPa and a Tg of 30.4°C to the hard TATO-3 having a compression modulus of 411MPa and a Tg of 62.5°C. All materials exhibit micro- and nano-surface morphologies suited for bone tissue engineering, and in vitro studies found them all to be cytocompatible, supporting fast cell proliferation while minimizing cell apoptosis and necrosis. Moreover, bone marrow-derived mesenchymal stem cells on the surface of the materials are successfully differentiated into osteoblasts, adipocytes, and neuronal cells, underlining the broad potential for the biofabrication of TATO materials for TE clinical applications.

Investigating mechanical properties of 3D printed porous titanium scaffolds for bone tissue engineering

Investigating mechanical properties of 3D printed porous titanium scaffolds for bone tissue engineering

Current Perspectives of Protein in Bone Tissue Engineering: Bone Structure, Ideal Scaffolds, Fabrication Techniques, Applications, Scopes, and Future Advances.

In view of their exceptional approach, excellent inherent biocompatibility and biodegradability properties, and interaction with the local extracellular matrix, protein-based polymers have received attention in bone tissue engineering, which is a multidisciplinary field that repairs and regenerates fractured bones. Bone is a multihierarchical complex structure, and it performs several essential biofunctions, including maintaining mineral balance and structural support and protecting soft organs. Protein-based polymers have gained interest in developing ideal scaffolds as emerging biomaterials for bone fractured healing and regeneration, and it is challenging to design ideal bone substitutes as perfect biomaterials. Several protein-based polymers, including collagen, keratin, gelatin, serum albumin, etc., are potential materials due to their inherent cytocompatibility, controlled biodegradability, high biofunctionalization, and tunable mechanical characteristics. While numerous studies have indicated the encouraging possibilities of proteins in BTE, there are still major challenges concerning their biodegradability, stability in physiological conditions, and continuous release of growth factors and bioactive molecules. Robust scaffolds derived from proteins can be used to replace broken or diseased bone with a biocompatible substitute; proteins, being biopolymers, provide excellent scaffolds for bone tissue engineering. Herein, recent developments in protein polymers for cutting-edge bone tissue engineering are addressed in this review within 3-5 years, with a focus on the significant challenges and future perspectives. The first section discusses the structural fundamentals of bone anatomy and ideal scaffolds, and the second section describes the fabrication techniques of scaffolds. The third section highlights the importance of proteins and their applications in BTE. Hence, the recent development of protein polymers for state-of-the-art bone tissue engineering has been discussed, highlighting the significant challenges and future perspectives.

Effect of nanodiamonds surface deposition on hydrophilicity, bulk degradation and in-vitro cell adhesion of 3D-printed polycaprolactone scaffolds for bone tissue engineering

This study was designed to deposit nanodiamonds (NDs) on 3D-printed poly-ϵ-caprolactone (PCL) scaffolds and evaluate their effect on the surface topography, hydrophilicity, degradation, andin-vitrocell adhesion compared to untreated PCL scaffolds. The PCL scaffold specimens were 3D-printed by fused deposition modeling (FDM) technique with specific porosity parameters. The 3D-printed specimens' surfaces were modified by NDs deposition followed by oxygen plasma post-treatment using a plasma focus device and a non-thermal atmospheric plasma jet, respectively. Specimens were evaluated through morphological characterization by field emission scanning electron microscope (FESEM), microstructure characterization by Raman spectroscopy, chemical characterization by Fourier transform infrared (FTIR) spectroscopy, hydrophilicity degree by contact angle and water uptake measurements, andin-vitrodegradation measurements (n= 6). In addition,in-vitrobone marrow mesenchymal stem cells adhesion was evaluated quantitatively by confocal microscopy and qualitatively by FESEM at different time intervals after cell seeding (n= 6). The statistical significance level was set atp⩽ 0.05. The FESEM micrographs, the Raman, and FTIR spectra confirmed the successful surface deposition of NDs on scaffold specimens. The NDs treated specimens showed nano-scale features distributed homogeneously across the surface compared to the untreated ones. Also, the NDs treated specimens revealed a statistically significant smaller contact angle (17.45 ± 1.34 degrees), higher water uptake percentage after 24 h immersion in phosphate buffer saline (PBS) (21.56% ± 1.73), and higher degradation rate after six months of immersion in PBS (43.92 ± 0.77%). Moreover, enhanced cell adhesion at all different time intervals was observed in NDs treated specimens with higher nuclei area fraction percentage (69.87 ± 3.97%) compared to the untreated specimens (11.46 ± 1.34%). Surface deposition of NDs with oxygen-containing functional groups on 3D-printed PCL scaffolds increased their hydrophilicity and degradation rate with significant enhancement of thein-vitrocell adhesion compared to untreated PCL scaffolds.

Fabrication of chitin-fibrin hydrogels to construct the 3D artificial extracellular matrix scaffold for vascular regeneration and cardiac tissue engineering.

As the cornerstone of tissue engineering and regeneration medicine research, developing a cost-effective and bionic extracellular matrix (ECM) that can precisely modulate cellular behavior and form functional tissue remains challenging. An artificial ECM combining polysaccharides and fibrillar proteins to mimic the structure and composition of natural ECM provides a promising solution for cardiac tissue regeneration. In this study, we developed a bionic hydrogel scaffold by combining a quaternized β-chitin derivative (QC) and fibrin-matrigel (FM) in different ratios to mimic a natural ECM. We evaluated the stiffness of those composite hydrogels with different mixing ratios and their effects on the growth of human umbilical vein endothelial cells (HUVECs). The optimal hydrogels, QCFM1 hydrogels were further applied to load HUVECs into nude mice for in vivo angiogenesis. Besides, we encapsulated human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) into QCFM hydrogels and employed 3D bioprinting to achieve batch fabrication of human-engineered heart tissue (hEHT). Finally, the myocardial structure and electrophysiological function of hEHT were evaluated by immunofluorescence and optical mapping. Designed artificial ECM has a tunable modulus (220-1380 Pa), which determines the different cellular behavior of HUVECs when encapsulated in these. QCFM1 composite hydrogels with optimal stiffness (800 Pa) and porous architecture were finally identified, which could adapt for in vitro cell spreading and in vivo angiogenesis of HUVECs. Moreover, QCFM1 hydrogels were applied in 3D bioprinting successfully to achieve batch fabrication of both ring-shaped and patch-shaped hEHT. These QCFM1 hydrogels-based hEHTs possess organized sarcomeres and advanced function characteristics comparable to reported hEHTs. The chitin-derived hydrogels are first used for cardiac tissue engineering and achieve the batch fabrication of functionalized artificial myocardium. Specifically, these novel QCFM1 hydrogels provided a reliable and economical choice serving as ideal ECM for application in tissue engineering and regeneration medicine.

Chondroitin Sulfate and Hyaluronic Acid-Based PolyHIPE Scaffolds for Improved Osteogenesis and Chondrogenesis In Vitro.

Osteochondral damage, affecting the articular cartilage and the underlying subchondral bone, presents significant challenges in clinical treatment. Such defects, commonly seen in knee and ankle joints, vary from small localized lesions to larger defects. Current medical therapies encounter several challenges, such as donor shortages, drug side effects, high costs, and rejection problems, often resulting in only temporary relief. Highly porous emulsion-templated polymers (polyHIPEs) offer numerous potential benefits in the fabrication of scaffolds for tissue engineering and regenerative medicine. Polymeric scaffolds synthesized using a high internal phase emulsion (HIPE) technique, called PolyHIPEs, involve polymerizing a continuous phase surrounding a dispersed internal phase to form a solid, foam-like structure. A dense, porous design encourages cell ingrowth, nutrient delivery, and waste disposal from the scaffold, mimicking the cells' natural microenvironment. This study used hydroxyethyl methacrylate (HEMA) and acrylamide (AAM) polyHIPE scaffolds combined with extracellular matrix (ECM) components of the tissue, such as methacrylated hyaluronic acid (MHA) and methacrylated chondroitin sulfate (MCS), to prepare polyHIPE scaffolds. The mouse preosteoblast MC3T3-E1 cells and primary rat chondrocytes (harvested from male Wistar rats) were seeded on the scaffolds and cultured for 21 days to assess the osteogenesis and chondrogenesis in vitro. When compared to the AAM-MHA and AAM-MCS groups at day 21, scaffold groups HEMA-MHA and HEMA-MCS showed a significant rise in alkaline phosphatase (ALP) and calcium content. Chondrogenic markers such as glycosaminoglycan (GAG) and hydroxyproline were also assessed over a 21-day time point. On day 21, it was found that GAG and hydroxyproline production were considerably higher in the HEMA-MHA and HEMA-MCS scaffolds than in the AAM-MHA and AAM-MCS scaffolds. The overall studies showed that polyHIPE monolith scaffolds could favor cell adherence, survival ability, proliferation, differentiation, and ECM formation over 21 days. Thus, incorporating ECM components enhanced osteogenesis and chondrogenesis in vitro and can be further used as tissue repair models.

A practical machine learning approach for predicting the quality of 3D (bio)printed scaffolds.

3D (Bio)printing is a highly effective method for fabricating tissue engineering scaffolds, renowned for their exceptional precision and control. Artificial intelligence (AI) has become a crucial technology in this field, capable of learning and replicating complex patterns that surpass human capabilities. However, the integration of AI in tissue engineering is often hampered by the lack of comprehensive and reliable data. This study addresses these challenges by providing one of the most extensive datasets on 3D-printed scaffolds. It provides the most comprehensive open-source dataset and employs various AI techniques, from unsupervised to supervised learning. This dataset includes detailed information on 1,171 scaffolds, featuring a variety of biomaterials and concentrations-including 60 biomaterials such as natural and synthesized biomaterials, crosslinkers, enzymes, etc.-along with 49 cell lines, cell densities, and different printing conditions. We used over 40 machine learning and deep learning algorithms, tuning their hyperparameters to reveal hidden patterns and predict cell response, printability, and scaffold quality. The clustering analysis using KMeans identified five distinct ones. In classification tasks, algorithms such as XGBoost, Gradient Boosting, Extra Trees Classifier, Random Forest Classifier, and LightGBM demonstrated superior performance, achieving higher accuracy and F1 scores. A fully connected neural network with six hidden layers from scratch was developed, precisely tuning its hyperparameters for accurate predictions. To promote future research, the developed dataset and the associated code are publicly available on www.github.com/saeedrafieyan/MLATE.&#xD.

Tunable gelatin methacrylate polyethylene glycol diacrylate hydrogels for cell mechanosensing applications

Three-dimensional (3D) tissue-engineered scaffolds mimic the physiological environment of cells by providing essential structural support, biochemical cues, and the mechanical strength needed for cell adhesion, proliferation, migration, and differentiation. Hydrogels like polyethylene glycol diacrylate (PEGDA) are commonly used biomaterials for cell culture due to their affordability, tunable stiffness, and ability to efficiently transport nutrients and gases. However, PEGDA lacks cell adhesion sites essential for cell proliferation and migration and has limited degradability. Methacrylated gelatin (GelMA) produced from denatured bovine collagen, crosslinks under ultraviolet light (UV) resulting in a degradable hydrogel with cell adhesion sites. Here, we synthesized GelMA with variable degree of methacrylation and crosslinked it with PEGDA to produce cell scaffolds with independently tunable mechanical and biochemical properties by varying the ratios of the two polymers. We determined polymer ratios that resulted in scaffolds with different mechanical properties but the same gelatin concentrations (providing cell adhesion and degradation sites) as well as different gelatin concentrations but the same mechanical properties. With the developed scaffold library, we further used a design of experiments approach to probe the parameter space and perform detailed analysis on chemical composition-scaffold properties as well as scaffold properties-cell behavior correlations. Our findings showed that hydrogel properties such as modulus, swelling, pore size, and permeability, strongly depended on total polymer concentration and not on the GelMA fraction. GelMA significantly influenced cell spreading, while addition of any amount of PEGDA delayed cell spreading significantly. We suggest that such analysis will broaden the utility of the GelMA/PEGDA hydrogels, presenting a versatile platform for mechanosensing research in 3D environments.

Cartilage lacuna-biomimetic hydrogel microspheres endowed with integrated biological signal boost endogenous articular cartilage regeneration

Despite numerous studies on chondrogenesis, the repair of cartilage—particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited. In this study, we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals, enabling sequential immunomodulation and endogenous articular cartilage regeneration. We first integrated the chondrogenic growth factor transforming growth factor-β3 (TGF-β3) into mesoporous silica nanoparticles (MSNs). Then, TGF-β3@MSNs and insulin-like growth factor 1 (IGF-1) were encapsulated within microspheres made of polydopamine (pDA). In the final step, growth factor-loaded MSN@pDA and a chitosan (CS) hydrogel containing platelet-derived growth factor-BB (PDGF-BB) were blended to produce growth factors loaded composite microspheres (GFs@μS) using microfluidic technology. The presence of pDA reduced the initial acute inflammatory response, and the early, robust release of PDGF-BB aided in attracting endogenous stem cells. Over the subsequent weeks, the continuous release of IGF-1 and TGF-β3 amplified chondrogenesis and matrix formation. μS were incorporated into an acellular cartilage extracellular matrix (ACECM) and combined with a polydopamine-modified polycaprolactone (PCL) structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix, resulting in enhanced cartilage repair and patellar cartilage protection. This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling, leading to efficient articular cartilage regeneration.

Impact of Composition and Autoclave Sterilization on the Mechanical and Biological Properties of ECM-Mimicking Cryogels

Cryogels represent a valid strategy as scaffolds for tissue engineering. In order to adequately support adhesion and proliferation of anchorage-dependent cells, different polymers need to be combined within the same scaffold trying to mimic the complex features of a natural extracellular matrix (ECM). For this reason, in this work, gelatin (Gel) and chondroitin sulfate (CS), both functionalized with methacrylic groups to produce CSMA and GelMA derivatives, were selected to prepare cryogel networks. Both homopolymer and heteropolymer cryogels were produced, via radical crosslinking reactions carried out at −12 °C for 2 h. All the scaffolds were characterized for their mechanical, swelling and morphological properties, before and after autoclave sterilization. Moreover, they were evaluated for their biocompatibility and ability to support the adhesion of human gingival fibroblasts and tenocytes. GelMA-based homopolymer networks better withstood the autoclave sterilization process, compared to CSMA cryogels. Indeed, GelMA cryogels showed a decrease in stiffness of approximately 30%, whereas CSMA cryogels of approximately 80%. When GelMA and CSMA were blended in the same network, an intermediate outcome was observed. However, the hybrid scaffolds showed a general worsening of the biological performance. Indeed, despite their ability to withstand autoclave sterilization with limited modification of the mechanical and morphological properties, the hybrid cryogels exhibited poor cell adhesion and high LDH leakage. Therefore, not only do network components need to be properly selected, but also their combination and ability to withstand effective sterilization process should be carefully evaluated for the development of efficient scaffolds designed for tissue engineering purposes.

Multi-parameter design of triply periodic minimal surface scaffolds: from geometry optimization to biomechanical simulation

This study introduces a multi-parameter design methodology to create triply periodic minimal surface (TPMS) scaffolds with predefined geometric characteristics. The level-set constant and unit cell lengths are systematically correlated with targeted porosity and minimum pore sizes. Network and sheet scaffolds featuring diamond, gyroid, and primitive level-set structures are generated. Three radially graded schemes are applied to each of the six scaffold type, accommodating radial variations in porosity and pore sizes. Computer simulations are conducted to assess the biomechanical performance of 18 scaffold models. Results disclose that diamond and gyroid scaffolds exhibit more expansive design ranges than primitive counterparts. While primitive scaffolds display the highest Young’s modulus and permeability, their lower yield strength and mesenchymal stem cell (MSC) adhesion render them unsuitable for bone scaffolds. Gyroid scaffolds demonstrate superior mechanical and permeability performances, albeit with slightly lower MSC adhesion than diamond scaffolds. Sheet scaffolds, characterized by more uniform material distribution, exhibit superior mechanical performance in various directions, despite slightly lower permeability. The higher specific surface area of sheet scaffolds contributes to elevated MSC adhesion. The stimulus factor analysis also revealed the superior differentiation potential of sheet scaffolds over network ones. The diamond sheet type demonstrated the optimal differentiation. Introducing radial gradations enhances axial mechanical performance at the expense of radial mechanical performance. Radially decreasing porosity displays the highest permeability, MSC adhesion, and differentiation capability, aligning with the structural characteristics of human bones. This study underscores the crucial need to balance diverse biomechanical properties of TPMS scaffolds for bone tissue engineering.

Centrifugally spun hydroxyapatite/carbon composite nanofiber scaffolds for bone tissue engineering

In recent years, advancements in tissue engineering have demonstrated the potential to expedite bone matrix formation, leading to shorter recovery times and decreased clinical challenges compared to conventional methods. Therefore, this study aims to develop composite carbon nanofibers (CNFs) integrated with nano-hydroxyapatite (nHA) particles as scaffolds for bone tissue engineering applications. A key strategy in achieving this objective involves harnessing nanofibrous structures, which offer a high surface area, coupled with nHA particles expected to accelerate bone regeneration and enhance biological activity. To realize this, polyacrylonitrile (PAN)/nHA nanofibers were fabricated using the centrifugal spinning (C-Spin) technique and subsequently carbonized to yield CNF/nHA composite structures. Scanning Electron Microscopy (SEM) confirmed C-Spin as a suitable method for PAN and CNF nanofiber production, with nHA particles uniformly dispersed throughout the nanofibrous structure. Carbonization resulted in reduced fiber diameter due to thermal decomposition and shrinkage of PAN molecules during the process. Furthermore, the incorporation of nHA particles into PAN lowered the stabilization temperature (by 5 °C–20 °C). Tensile tests revealed that PAN samples experienced an approximately 80% increase in ultimate tensile strength and a 187% increase in modulus with a 5 wt.% nHA loading. However, following carbonization, CNF samples exhibited a 50% decrease in strength compared to PAN samples. Additionally, the addition of nHA into CNF improved the graphitic structure. The incorporation of nHA particles into the spinning solution represents a viable strategy for enhancing CNF bioactivity.

In vitro and in vivo dissolution of biocompatible S59 glass scaffolds

Fabrication of porous tissue-engineering scaffolds from bioactive glasses (BAG) is complicated by the tendency of BAG compositions to crystallize in thermal treatments during scaffold manufacture. Here, experimental biocompatible glass S59 (SiO2 59.7 wt%, Na2O 25.5 wt%, CaO 11.0 wt%, P2O5 2.5 wt%, B2O3 1.3 wt%), known to be resistant to crystallization, was used in sintering of glass granules (300–500 µm) into porous scaffolds. The dissolution behavior of the scaffolds was then studied in vivo in rabbit femurs and under continuous flow conditions in vitro (14 days in vitro/56 days in vivo). The scaffolds were osteoconductive in vivo, as bone could grow into the scaffold structure. Still, the scaffolds could not induce sufficiently rapid bone ingrowth to replace the strength lost due to dissolution. The scaffolds lost their structure and strength as the scaffold necks dissolved. In vitro, S59 dissolved congruently throughout the 14-day experiments, resulting in only a slight reaction layer formation. Manufacturing BAG scaffolds from S59 that retain their amorphous structure was thus possible. The relatively rapid and stable dissolution of the scaffold implies that the glass S59 may have the potential to be used in composite implants providing initial strength and stable, predictable release of ions over longer exposure times.Graphical

Graded or random – Effect of pore distribution in 3D titanium scaffolds on corrosion performance and response of hMSCs

Researchers agree that the ideal scaffold for tissue engineering should possess a 3D and highly porous structure, biocompatibility to encourage cell/tissue growth, suitable surface chemistry for cell attachment and differentiation, and mechanical properties that match those of the surrounding tissues. However, there is no consensus on the optimal pore distribution. In this study, we investigated the effect of pore distribution on corrosion resistance and performance of human mesenchymal stem cells (hMSC) using titanium scaffolds fabricated by laser beam powder bed fusion (PBF-LB). We designed two scaffold architectures with the same porosities (i.e., 75 %) but different distribution of pores of three sizes (200, 500, and 700 μm). The pores were either grouped in three zones (graded, GRAD) or distributed randomly (random, RAND). Microfocus X-ray computed tomography revealed that the chemically polished scaffolds had the porosity of 69 ± 4 % (GRAD) and 71 ± 4 % (RAND), and that the GRAD architecture had the higher surface area (1580 ± 101 vs 991 ± 62 mm2) and the thinner struts (221 ± 37 vs 286 ± 14 μm). The electrochemical measurements demonstrated that the apparent corrosion rate of chemically polished GRAD scaffold decreased with the immersion time extension, while that for polished RAND was increased. The RAND architecture outperformed the GRAD one with respect to hMSC proliferation (over two times higher although the GRAD scaffolds had 85 % higher initial cell retention) and migration from a monolayer. Our findings demonstrate that the pore distribution affects the biological properties of the titanium scaffolds for bone tissue engineering.

Graded or random – Effect of pore distribution in 3D titanium scaffolds on corrosion performance and response of hMSCs

Researchers agree that the ideal scaffold for tissue engineering should possess a 3D and highly porous structure, biocompatibility to encourage cell/tissue growth, suitable surface chemistry for cell attachment and differentiation, and mechanical properties that match those of the surrounding tissues. However, there is no consensus on the optimal pore distribution. In this study, we investigated the effect of pore distribution on corrosion resistance and performance of human mesenchymal stem cells (hMSC) using titanium scaffolds fabricated by laser beam powder bed fusion (PBF-LB). We designed two scaffold architectures with the same porosities (i.e., 75 %) but different distribution of pores of three sizes (200, 500, and 700 μm). The pores were either grouped in three zones (graded, GRAD) or distributed randomly (random, RAND). Microfocus X-ray computed tomography revealed that the chemically polished scaffolds had the porosity of 69 ± 4 % (GRAD) and 71 ± 4 % (RAND), and that the GRAD architecture had the higher surface area (1580 ± 101 vs 991 ± 62 mm2) and the thinner struts (221 ± 37 vs 286 ± 14 μm). The electrochemical measurements demonstrated that the apparent corrosion rate of chemically polished GRAD scaffold decreased with the immersion time extension, while that for polished RAND was increased. The RAND architecture outperformed the GRAD one with respect to hMSC proliferation (over two times higher although the GRAD scaffolds had 85 % higher initial cell retention) and migration from a monolayer. Our findings demonstrate that the pore distribution affects the biological properties of the titanium scaffolds for bone tissue engineering.

Biomimetic structural design and performance study of 3D-printed graded minimal surface bone scaffolds with enhanced bioactivity

Bone bionics and structural engineering have played a vital role in bone regeneration, with artificial scaffolds generating widespread interest. However, the mechanical properties and bone regeneration potential of biomimetic structures remain unclear. Herein, biodegradable polymer composites based on poly(butylene adipate-co-terephthalate)/poly(lactic acid) (PBAT/PLA) were 3D-printed into lattice structures as tissue engineering scaffolds. For structural design, graded diamond (D) minimal surfaces were proposed and designed to mimic the natural bone structure. The graded topologies were realized by designing gradient thickness either radially from center to edge or vertically from top to bottom. The mechanical performance of these graded samples displayed better load-carrying and energy absorption capacity than the uniform counterparts. No obvious damage was detected in the internal microstructure of the compressed samples using computed tomography. Subsequently, platelet-rich plasma (PRP), containing diverse cytokines, was loaded on the graded scaffolds. The PRP-loaded D-scaffold reported improved in vitro cell proliferation and osteoblast differentiation. Finally, femoral condyle defect repair results indicated that the PRP-loaded D-scaffold effectively promoted early-stage bone regeneration. Overall, this work provides insights into fabricating artificial scaffolds with bioactive factors and biomimetic lattice structures.

The role of glycerol in manufacturing freeze-dried chitosan and cellulose foams for mechanically stable scaffolds in skin tissue engineering

Various strategies have extensively explored enhancing the physical and biological properties of chitosan and cellulose scaffolds for skin tissue engineering. This study presents a straightforward method involving the addition of glycerol into highly porous structures of two polysaccharide complexes: chitosan/carboxymethyl cellulose (Chit/CMC) and chitosan/oxidized cellulose (Chit/OC); during a one-step freeze-drying process. Adding glycerol, especially to Chit/CMC, significantly increased stability, prevented degradation, and improved mechanical strength by nearly 50%. Importantly, after 21 days of incubation in enzymatic medium Chit/CMC scaffold has almost completely decomposed, while foams reinforced with glycerol exhibited only 40% mass loss. It is possible due to differences in multivalent cations and polymer chain contraction, resulting in varied hydrogen bonding and, consequently, distinct physicochemical outcomes. Additionally, the scaffolds with glycerol improved the cellular activities resulting in over 40% higher proliferation of fibroblast after 21 days of incubation. It was achieved by imparting water resistance to the highly absorbent material and aiding in achieving a balance between hydrophilic and hydrophobic properties. This study clearly indicates the possible elimination of additional crosslinkers and multiple fabrication steps that can reduce the cost of scaffold production for skin tissue engineering applications while tailoring mechanical strength and degradation.

In vitro biocompatibility and stem cell regenerative assessment of hollow hydroxyapatite spheres deposited wollastonite/Ca2P6O17/TCP/doped-wollastonite scaffolds

This research examines the biological behavior of multilayer ceramic-glass scaffolds for bone tissue engineering. The scaffolds consist of a high-strength core of wollastonite and P6 (Ca2P6O17), with a sequential coating of TCP and wollastonite doped with Na+, K+ and Mg2+ ions to confer bioactivity to the system. Two formulations were investigated: a magnesium-deficient one, which served as a microstructure control, and a magnesium-rich one in which hollow hydroxyapatite (HA) spheres precipitated after one week of immersion in simulated body fluid (SBF). These formulations are denoted as C-Scaffold and HA-Scaffold, respectively. Further exploration and comparison of the physiological effects of both scaffolds is necessary to fully understand their potential as drug release agents and associated therapeutic advantages. The study considered aspects such as protein adhesion, cell morphology, and the inflammatory response. The results showed that the HA-Scaffold had over 34 % more plasma protein adhesion compared to the C-Scaffold. Similarly, cell proliferation assays showed increased cell growth in both HFF-1 fibroblasts and mesenchymal stem cells (MSCs) treated with HA-Scaffold compared to C-Scaffold. This may be attributed to the higher protein adsorption, which acts as a facilitator for cell adhesion. Three-dimensional photography from computerized microtomography confirmed that the scaffolds have a similar morphology and porosity to the intricate structure of trabecular bone in the humeral head. The study shows that the scaffolds made of Wollastonite/Ca2P6O17/TCP/Doped-Wollastonite with HA hollow spheres are highly suitable for use in this bone segment due to their overall porosity of over 86 % and approximate mechanical strength of 1.6 MPa. These findings demonstrate the biocompatibility and enhanced biological properties of the scaffolds, making them an excellent material for bone tissue engineering.

Exploring Squalene's Impact on Epidermal Thickening and Collagen Production: Molecular Docking Insights

Background:: Aging is a progressive deterioration characterized by the gradual buildup of physiological alterations as time passes. The aging phenomenon encompasses various interconnected systems within the body, such as the skin, bones, cartilage, and hair. Objective and Methods: In this study, based on the appropriate properties of squalene, including antioxidant, anti-inflammatory, and skin repair properties, a molecular docking study was designed for the drug squalene and proteins related to the dermis and epidermis pathway and collagen production (including Col3A1, Col1A2, FBN1, Decorin, and HAS2). Results and Discussion:: The docking results indicated that the interaction of squalene with hyaluronan synthetase 2 (HAS2) possessed the highest negative binding free energy value of -10.90 KCal/mol, followed by decorin with a value of -9.99 KCal/mol. Also, the inhibition constant values of squalene- HAS2 and squalene-decorin complexes were equal to 1.61 and 7.51 μM, respectively. It has been stated that decorin (as a small proteoglycan) and HAS2 are involved in controlling the assembly of skin fibrils and the biosynthesis of glucosaminoglycans, respectively. Conclusion:: Considering that proteoglycans and glucosaminoglycans play a role in the skin aging process, squalene may be used as an anti-aging agent to induce these pathways and for different purposes. Squalene may be used as a potential agent alone or in combination with other compounds in tissue engineering scaffolds for cosmetic, anti-aging, wound healing, and tissue repair applications.

Acceleration of chondrogenic differentiation utilizing biphasic core-shell alginate sulfate electrospun nanofibrous scaffold

Engineering new biomedical materials with tailored physicochemical, mechanical and biological virtues in order to differentiate stem cells into chondrocytes for cartilage regeneration has garnered much scientific interest. In this study, core/shell nanofibrous scaffold based on poly(ɛ-caprolactone) (PCL) as a core material and alginate sulfate (AlgS)-poly(vinyl alcohol) (PVA) blend as shell materials (AlgS-PVA/PCL) was fabricated by emulsion electrospinning. In this vein, the influence of AlgS to PVA ratio (30:70, 50:50), organic to aqueous phase ratio (1:2, 1:3 and 1:5) and acid concentration (0, 10, 20, 30, 40 and 50 %) on nanofibers morphology were investigated. SEM images depicted that AlgS to PVA ratio of 30:70 and 50:50, organic to aqueous phase ratio of 1:3 and 1:5 and acid concentration of 30 % led to uniform, bead-free fibrous mats. AlgS-PVA/PCL scaffolds with AlgS to PVA ratio of 30:70 and organic to aqueous phase ratio of 1:3, showed admirable mechanical features, high porosity (>90 %) with desirable swelling ratio in wet condition. In vitro assays indicated that the AlgS-PVA/PCL scaffold surface had desirable interaction with stem cells and promotes cells attachment, proliferation and differentiation. Thus, we envision that this salient structure could be an intriguing construction as a cartilage tissue-engineered scaffold.