Porosity Of Scaffolds Research Articles

Design and optimization of tamarind seed polysaccharide-based scaffold for tissue engineering applications using statistical modeling and machine learning, and it's in-vitro validation.

This study explores the development and optimization of a novel biomaterial scaffold for tissue engineering, composed of Tamarind seed polysaccharide (TSP), Hydroxypropyl methylcellulose (HPMC), Chitosan (CS), and Sodium alginate (ALG). Scaffold properties, including swelling, degradation, porosity, mechanical strength, conductivity, and surface wettability, were analyzed. Using Response Surface Methodology (RSM) and Artificial Neural Network (ANN) modeling, the optimal scaffold (THAC) composition was determined to be 30.12% TSP, 21.69% HPMC, 12.05% ALG, and 36.14% CS. The ANN model outperformed RSM in predictive accuracy (R2>0.9). Mechanical testing demonstrated a Young's modulus of 0.905±0.103MPa and a compression strength of 0.398±0.028MPa, indicative of its resilience for cartilage engineering. Conductivity analysis revealed enhanced ionic conductance in wet conditions, highlighting its electrolyte-responsive behavior. Surface wettability tests showed a hydrophilic nature, with a contact angle of 58.08±6.84°, enabling superior water absorption. SEM analysis confirmed a uniform porous structure, while cytocompatibility studies with HeLa, MG -63 and ES-E14TG2a cells showed significant cell proliferation and attachment. These results underscore THAC's potential for applications in regenerative medicine, with the combination of RSM and ANN enabling precise tuning of scaffold properties for optimal performance in tissue engineering.

Enhancing Osteogenesis and Mechanical Properties through Scaffold Design in 3D Printed Bone Substitutes.

In the context of regenerative medicine, the design of scaffolds to possess excellent osteogenesis and appropriate mechanical properties has gained significant attention in bone tissue engineering. In this review, we categorized materials into metallic, inorganic, nonmetallic, organic polymer, and composite materials. This review provides a more integrated and multidimensional analysis of scaffold design for bone tissue engineering. Unlike previous works that often focus on single aspects, such as material type or fabrication technique, our review takes a broader approach. It analyzes the interaction between scaffold materials, 3D printing techniques, scaffold structural designs, modification methods, porosities, and pore sizes, and the composition of materials (particularly composite materials). Meanwhile, it focuses on their impacts on scaffolds' osteogenic potential and mechanical performance. This review also provides suggested ranges for porosity and pore size for different materials and outlines recommended surface modification methods. This approach not only consolidates current knowledge but also highlights the interdependencies among various factors affecting scaffold efficacy, offering deeper insights into optimization strategies tailored for specific clinical conditions. Furthermore, we introduce recent advancements in innovative 3D printing techniques and novel composite materials, which are rarely addressed in previous reviews, thereby providing a forward-looking perspective that informs future research directions and clinical applications.

Osteochondral Tissue Engineering: Scaffold Materials, Fabrication Techniques and Applications.

Osteochondral damage, caused by trauma, tumors, or degenerative diseases, presents a major challenge due to the limited self-repair capacity of the tissue. Traditional treatments often result in significant trauma and unpredictable outcomes. Recent advances in bone/cartilage tissue engineering, particularly in scaffold materials and fabrication technologies, offer promising solutions for osteochondral regeneration. This review highlights the selection and design of scaffolds using natural and synthetic materials such as collagen, chitosan (Cs), and polylactic acid (PLA), alongside inorganic components like bioactive glass and nano-hydroxyapatite (nHAp). Key fabrication techniques-freeze-drying, electrospinning, and 3D printing-have improved scaffold porosity and mechanical properties. Special focus is placed on the design of multiphasic scaffolds that mimic natural tissue structures, promoting cell adhesion and differentiation and supporting the regeneration of cartilage and subchondral bone. In addition, the current obstacles and future directions for regenerating damaged osteochondral tissues will be discussed.

A Simplified Mathematical Model for Cell Proliferation in a Tissue-Engineering Scaffold.

While the effects of external factors like fluid mechanical forces and scaffold geometry on tissue growth have been extensively studied, the influence of cell behavior-particularly nutrient consumption and depletion within the scaffold-has received less attention. Incorporating such factors into mathematical models allows for a more comprehensive understanding of tissue-engineering processes. This work presents a comprehensive continuum model for cell proliferation within two-dimensional tissue-engineering scaffolds. Through mathematical modeling and asymptotic analysis based on the small aspect ratio of the scaffolds, the study aims to reduce computational burdens and solve mathematical models for tissue growth within porous scaffolds. The model incorporates fluid dynamics of nutrient feed flow, nutrient transport, cell concentration, and tissue growth, considering the evolving scaffold porosity due to cell proliferation, with the crux of the work establishing the ideal pore shape for channels within the tissue-engineering scaffold to obtain the maximum tissue growth. We investigate scaffolds with specific two-dimensional initial porosity profiles, and our results show that scaffolds which are uniformly graded in porosity throughout their depth promote more tissue growth.

3D Printing of Polyester Scaffolds for Bone Tissue Engineering: Advancements and Challenges

AbstractPolyesters have garnered significant attention in bone tissue engineering (BTE) due to their tunable degradation rates, biocompatibility, and convenient processing. This review focuses on recent advancements and challenges in the 3D printing of polyester‐based scaffolds for BTE. Various 3D printing techniques, such as fused deposition modeling (FDM), selective laser sintering (SLS), vat photopolymerization (VP), and Wet‐spun additive manufacturing, are explored, emphasizing their ability to construct scaffolds with precise architectural control. The main challenges in 3D printed polyester scaffolds are their limited mechanical properties, lack of inherent bioactivity, and the release of acidic byproducts during biodegradation. Strategies to enhance scaffold performance, such as incorporating bioactive ceramics and growth factors, are discussed, focusing on improving osteoconductivity, osteoinductivity, and mechanical strength. Recent studies on integrating these components into polyester scaffolds and techniques to optimize scaffold porosity and biodegradability are presented. Finally, the review addresses ongoing issues, such as the difficulty of incorporating some biomolecules and bioceramics during 3D printing and improved clinical translation. This comprehensive overview aims to provide insight into the future directions and potential solutions for overcoming the limitations of 3D‐printed polyester‐based scaffolds in BTE.

Ion‐Permeable Electrospun Scaffolds Enable Controlled In‐Vitro Electrostimulation Assay of Myoblasts

AbstractIn‐vitro models are fundamental for studying muscular cell contractility and for wide‐screening of therapeutic candidates targeting skeletal muscle diseases, owing to their scalability, reproducibility, and circumvention of ethical concerns. However, in‐vitro assays permitting reliable electrical stimulation of cell contractile activity still require technological development. Here, a novel approach to electrically stimulate differentiated muscular cell contractility is reported exploiting the ionic conductivity and mechanical flexibility of 3D nanofibrous scaffolds. The electrospun poly(L‐lactide‐co‐caprolactone) scaffold allowed for C2C12 murine myoblasts horizontal elongation and myotubes formation. Scaffold porosity enables high ionic conductivity and strong electric field generation, orthogonally oriented to the scaffold surface. Electrically induced cell contractility is determined with atomic force microscopy (AFM) enabling real‐time monitoring of scaffold vibrations in liquid environment. Differentiated cell actuation is found to be linearly correlated to current amplitude and number of current stimuli. Integrating the 3D nanofibrous scaffolds with real‐time AFM monitoring provides highly accurate in‐vitro assays for biomedical research. The induction of electric fields orthogonal to the scaffold surface allows for accurately mimicking the excitation‐contraction coupling mechanism observed in native skeletal muscle tissue. This work paves the way for the quantitative study of muscular cell dynamic behavior and physiology, further evaluating therapy effectiveness for muscular pathologies.

Magnetic hydrogel scaffold based on hyaluronic acid/chitosan and gelatin natural polymers

Owing to their native extracellular matrix-like features, magnetic hydrogels have been proven to be promising biomaterials as tissue engineering templates In the present work, magnetic hydrogels scaffold based on chitosan, gelatin, hyaluronic acid, containing Fe3O4 as magnetic nanoparticles (IONPs) were prepared. The prepared hydrogels were loaded with ciprofloxacin hydrochloride as a model drug. The magnetic hydrogel was prepared using different volumes of chitosan, 1%, gelatin, 10%, and hyaluronic acid, 1% in glutaraldehyde as the crosslinking agent and Fe3O4 as magnetic nanoparticles. The hydrogel scaffold and magnetic scaffold hydrogel samples were characterized by scanning electron microscopy (SEM), vibrating sample magnetometry (VSM), and Fourier-transform infrared spectroscopy (FTIR). The porosity, mechanical properties, swelling degree, and antibacterial activity of the hydrogel scaffold were also determined as well as the drug release profiles of the hydrogels. SEM imaging revealed that the magnetic hydrogel scaffold showed a relatively rough morphology with an irregular surface. The data obtained indicated that the hydrogel surface has three-dimensional porous microstructures and the porosity varied depending on the hydrogel formulation. The breaking load of the hydrogel scaffold increased from 1.361 Kgf to 4.98 Kgf by increasing the glutaraldehyde concentration from 0.2 mL to 0.8 mL. Swelling degree values in water were from 250 to 2000% after 24 h. The antibacterial activity of the hydrogel scaffold ranged from 54% to about 97% for Gram-positive bacteria (S. aureus) and from about 26–92% for Gram-negative bacteria (E. coli). The ciprofloxacin hydrochloride loaded hydrogel has a sustained release of ciprofloxacin hydrochloride over 10 h. The presence of IONPs gave a faster release of ciprofloxacin hydrochloride.

Determining the Permeability of Porous Bioceramic Scaffolds: Significance, Overview of Current Methods and Challenges Ahead.

The "architectural suitability" of scaffolds for bone tissue engineering is commonly evaluated by assessing the pore volume and the mean pore size (or pore size distribution, if possible) and comparing these values with the reference ranges of human cancellous bone. However, these two parameters cannot precisely describe the complex architecture of bone scaffolds and just provide a preliminary comparative criterion. Permeability is suggested as a more comprehensive and significant parameter to characterize scaffold architecture and mass transport capability, being also related to bone in-growth and, thus, functional properties. However, assessing the permeability of bioactive ceramics and glass scaffolds is a complex task from both methodological and experimental viewpoints. After providing an overview of the fundamentals about porosity in scaffolds, this review explores the different experimental and numerical approaches used to determine the permeability of porous bioceramics, describing the methodologies used (pump-based, gravity-based, acoustic and computational methods) and highlighting advantages and limitations to overcome (e.g., reliability issues and need for better standardization of the experimental procedures).

Optimizing scaffold pore size for tissue engineering: insights across various tissue types.

Scaffold porosity is a critical factor in replicating the complex in vivo microenvironment, directly influencing cellular interactions, migration, nutrient transfer, vascularization, and the formation of functional tissues. For optimal tissue formation, scaffold design must account for various parameters, including material composition, morphology, mechanical properties, and cellular compatibility. This review highlights the importance of interconnected porosity and pore size, emphasizing their impact on cellular behavior and tissue formation across several tissue engineering domains, such as skin, bone, cardiovascular, and lung tissues. Specific pore size ranges enhance scaffold functionality for different tissues: small pores (∼1-2µm) aid epidermal cell attachment in skin regeneration, moderate pores (∼2-12µm) support dermal migration, and larger pores (∼40-100µm) facilitate vascular structures. For bone tissue engineering, multi-layered scaffolds with smaller pores (50-100µm) foster cell attachment, while larger pores (200-400µm) enhance nutrient diffusion and angiogenesis. Cardiovascular and lung tissues benefit from moderate pore sizes (∼25-60µm) to balance cell integration and nutrient diffusion. By addressing critical design challenges and optimizing pore size distributions, this review provides insights into scaffold innovations, ultimately advancing tissue regeneration strategies.

Tailoring Cell Attachment onto Melt Electrowritten Scaffolds via a Phase Separated Hydrogel Coating with Peptide Functionalization

AbstractHighly porous scaffolds with a high surface area can be designed and fabricated via melt electrowriting (MEW). Here, the study introduces morphological features onto the MEW microfibers via a hydrogel coating of phase‐separated poly(2‐hydroxyethyl methacrylate) (pHEMA). This coating is achieved by capturing phase‐separated droplets of pHEMA onto poly(ε‐caprolactone) (PCL) microfibers via dip‐coating, resulting in a hydrogel coating with webbed structures across pores of the MEW scaffold. Excess pHEMA droplets are removed and phase separation is quenched by washing in water, and then functionalized by dipping the pHEMA coated scaffold into a buffered peptide solution. It is demonstrated that a cysteine‐terminated peptide sequence (Cys‐Gly‐Arg‐Gly‐Asp‐Ser‐Gly (CG‐RGD‐SG)) promotes fibroblast adhesion on the hydrogel‐coated MEW scaffolds compared to unmodified pHEMA and compared to scrambled peptide sequence. Due to the protein‐resistant nature of pHEMA, the hydrogel‐coated scaffolds show less cell attachment than non‐coated PCL scaffolds, while RGD‐functionalized pHEMA scaffolds achieve 2.8‐fold increase in cell attachment (p = 0.02) when compared to non‐functionalized pHEMA. The study therefore presents a platform that combines PCL scaffolds of microscale fibers with a phase‐separated pHEMA hydrogel coating that maintains the high porosity of MEW scaffolds yet increases surface area and, importantly, introduces the capability for tailoring cell attachment via peptide functionalization.

A nanofibrous polycaprolactone/collagen neural guidance channel filled with sciatic allogeneic schwann cells and platelet-rich plasma for sciatic nerve repair.

Sciatic nerve damage, a common condition affecting approximately 2.8% of the US population, can lead to significant disability due to impaired nerve signal transmission, resulting in loss of sensation and motor function in the lower extremities. In this study, a neural guidance channel was developed by rolling a nanofibrous scaffold produced via electrospinning. The scaffold's microstructure, biocompatibility, biodegradation rate, porosity, mechanical properties, and hemocompatibility were evaluated. Platelet-rich plasma (PRP) activated with 30,000 allogeneic Schwann cells (SCs) was injected into the lumen of the channels following implantation into a rat model of sciatic nerve injury. Recovery of motor function, sensory function, and muscle re-innervation was assessed using the sciatic function index (SFI), hot plate latency time, and gastrocnemius muscle wet weight loss. Results showed mean hot plate latency times of Autograft: 7.03, PCL/collagen scaffolds loaded with PRP and SCs (PCLCOLPRPSCs): 8.34, polymer-only scaffolds (PCLCOL): 10.66, and untreated animals (Negative Control): 12.00. The mean SFI values at week eight were Autograft: -49.30, PCLCOLPRPSCs: -64.29, PCLCOL: -75.62, and Negative Control: -77.14. The PCLCOLPRPSCs group showed a more negative SFI compared to the Autograft group but performed better than both the PCLCOL and Negative Control groups. These findings suggest that the developed strategy enhanced sensory and functional recovery compared to the negative control and polymer-only scaffold groups.

Impact of Porosity and Stiffness of 3D Printed Polycaprolactone Scaffolds on Osteogenic Differentiation of Human Mesenchymal Stromal Cells and Activation of Dendritic Cells.

Despite the potential of extrusion-based printing of thermoplastic polymers in bone tissue engineering, the inherent nonporous stiff nature of the printed filaments may elicit immune responses that influence bone regeneration. In this study, bone scaffolds made of polycaprolactone (PCL) filaments with different internal microporosity and stiffness was 3D-printed. It was achieved by combining three fabrication techniques, salt leaching and 3D printing at either low or high temperatures (LT/HT) with or without nonsolvent induced phase separation (NIPS). Printing PCL at HT resulted in stiff scaffolds (modulus of elasticity (E): 403 ± 19 MPa and strain: 6.6 ± 0.1%), while NIPS-based printing at LT produced less stiff and highly flexible scaffolds (E: 53 ± 10 MPa and strain: 435 ± 105%). Moreover, the introduction of porosity by salt leaching in the printed filaments significantly changed the mechanical properties and degradation rate of the scaffolds. Furthermore, this study aimed to show how these variations influence proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSC) and the maturation and activation of human monocyte-derived dendritic cells (Mo-DC). The cytocompatibility of the printed scaffolds was confirmed by live-dead imaging, metabolic activity measurement, and the continuous proliferation of hBMSC over 14 days. While all scaffolds facilitated the expression of osteogenic markers (RUNX2 and Collagen I) from hBMSC as detected through immunofluorescence staining, the variation in porosity and stiffness notably influenced the early and late mineralization. Furthermore, the flexible LT scaffolds, with porosity induced by NIPS and salt leaching, stimulated Mo-DC to adopt a pro-inflammatory phenotype marked by a significant increase in the expression of IL1B and TNF genes, alongside decreased expression of anti-inflammatory markers, IL10 and TGF1B. Altogether, the results of the current study demonstrate the importance of tailoring porosity and stiffness of PCL scaffolds to direct their biological performance toward a more immune-mediated bone healing process.

Bio-mechanical analysis of porous Ti-6Al-4V scaffold: a comprehensive review on unit cell structures in orthopaedic application.

A scaffold is a three-dimensional porous structure that is used as a template to provide structural support for cell adhesion and the formation of new cells. Metallic cellular scaffolds are a good choice as a replacement for human bones in orthopaedic implants, which enhances the quality and longevity of human life. In contrast to conventional methods that produce irregular pore distributions, 3D printing, or additive manufacturing, is characterized by high precision and controlled manufacturing processes. AM processes can precisely control the scaffold's porosity, which makes it possible to produce patient specific implants and achieve regular pore distribution. This review paper explores the potential of Ti-6Al-4V scaffolds produced via the SLM method as a bone substitute. A state-of-the-art review on the effect of design parameters, material, and surface modification on biological and mechanical properties is presented. The desired features of the human tibia and femur bones are compared to bulk and porous Ti6Al4V scaffold. Furthermore, the properties of various porous scaffolds with varying unit cell structures and design parameters are compared to find out the designs that can mimic human bone properties. Porosity up to 65% and pore size of 600 μm was found to give optimum trade-off between mechanical and biological properties. Current manufacturing constraints, biocompatibility of Ti-6Al-4V material, influence of various factors on bio-mechanical properties, and complex interrelation between design parameters are discussed herein. Finally, the most appropriate combination of design parameters that offers a good trade-off between mechanical strength and cell ingrowth are summarized.

Microstructure, Mechanical Properties, and Corrosion Resistance of Porous Bio Mg Alloy Scaffolds Prepared via a Novel Method

Mg alloy scaffolds can be used as repair materials for human bone defects. Herein, porous Mg–1Zn–1Ca–0.5Mn alloy scaffolds with different pore sizes of the primitive model are prepared by combining 3D‐printed pure Ti templates and infiltration casting Mg alloy method. The results exhibit that the scaffold porosity ranges from 58.8 ± 1.4% to 63.3 ± 5.3% and the surface quality is good. Complete connectivity inside the scaffolds and the precise control of the pore structure are realized simultaneously. The mechanical properties of the scaffolds increase with increasing pore size; therefore, the LP scaffold displays the best mechanical performance with a yield strength of 9.88 ± 0.33 MPa. The simulation results are in good consistent with the experimental results. The reticular second phase provides a barrier to the Mg matrix during corrosion, which improves the corrosion resistance of the scaffolds as the increase of pore size. Therefore, the corrosion rate of the LP scaffolds is only 2.35 ± 1.28 mm year−1 after 200 h of immersion. Furthermore, MC‐3T3 cells adhere on the surface of Mg–1Zn–1Ca–0.5Mn alloy scaffolds, indicating that Mg–1Zn–1Ca–0.5Mn alloy scaffolds have excellent biocompatibility.

Galectin-3/Gelatin Electrospun Scaffolds Modulate Collagen Synthesis in Skin Healing but Do Not Improve Wound Closure Kinetics.

Chronic wounds remain trapped in a pro-inflammatory state, with strategies targeted at inducing re-epithelialization and the proliferative phase of healing desirable. As a member of the lectin family, galectin-3 is implicated in the regulation of macrophage phenotype and epithelial migration. We investigated if local delivery of galectin-3 enhanced skin healing in a full-thickness excisional C57BL/6 mouse model. An electrospun gelatin scaffold loaded with galectin-3 was developed and compared to topical delivery of galectin-3. Electrospun gelatin/galectin-3 scaffolds had an average fiber diameter of 200 nm, with 83% scaffold porosity approximately and an average pore diameter of 1.15 μm. The developed scaffolds supported dermal fibroblast adhesion, matrix deposition, and proliferation in vitro. In vivo treatment of 6 mm full-thickness excisional wounds with gelatin/galectin-3 scaffolds did not influence wound closure, re-epithelialization, or macrophage phenotypes, but increased collagen synthesis. In comparison, topical delivery of galectin-3 [6.7 µg/mL] significantly increased arginase-I cell density at day 7 versus untreated and gelatin/galectin-3 scaffolds (p < 0.05). A preliminary assessment of increasing the concentration of topical galectin-3 demonstrated that at day 7, galectin-3 [12.5 µg/mL] significantly increased both epithelial migration and collagen content in a concentration-dependent manner. In conclusion, local delivery of galectin 3 shows potential efficacy in modulating skin healing in a concentration-dependent manner.

Fabrication of novel 316L stainless steel scaffolds by combining freeze-casting and 3D-printed gyroid templating techniques

Porous metals have been widely investigated as bioimplants to repair cancellous bone defects. Nevertheless, how to endure extreme stress and strike a balance between load-bearing performance, elastic modulus, and permeability are important issues. Freeze-casting is a novel technique for manufacturing micro-scale open-cellular lamellar porous materials. However, the pore size is relatively small because of the inherent constraints of the ice template. On the other hand, the scaffold with gyroid pore structures has been proven to have higher permeability due to its larger and smoother channels. To combine the advantages of both porous structures, the present study aims to develop dual-scale 316L stainless steel (316L SS) porous structures by incorporating the 3D-printed gyroid templates into the freeze-casting to further improve the lightweight, specific strength, energy absorption, and permeability of the porous structures. The results showed that macro-scale gyroid channels were successfully built into the micro-scale open-cellular lamellar porous scaffolds. The porosity of dual-scale scaffolds was 70.1 %–74.4 %, which was higher than that of 53.1 %–66.5 % in the single-scale scaffolds. The elastic moduli of the single-scale scaffolds were higher than that of the dual-scale scaffolds; both were within the range of human cancellous bone, demonstrating their mechanical compatibility. Furthermore, the dual-scale scaffolds presented a prominent rise in permeability compared to the single-scale scaffolds. Notably, the permeability of the 3G series scaffolds was comparable to human cancellous bone. In summary, the hierarchical 316L SS scaffolds with controllable macro-scale gyroid channels exhibit great potential for biomedical applications.

Impact of internal phase volume on the physical, morphological and mechanical characteristics of emulsion templated scaffolds

Objectives: The high porosity of tissue engineering scaffolds is advantageous as they provide a high degree of infiltration of nutrients, enable cell penetration, and support vascularisation. However, the mechanical strength is also critical for providing structural support to the defect site throughout the regeneration process. In this study, we aimed to establish a relationship between internal phase volume and emulsion-templated scaffolds' physical, morphological and mechanical characteristics. Methods: In this work, tetra methacrylate functionalised polycaprolactone (4PCLMA) polymers were synthesised via ring-opening polymerisation followed by methacrylation. 4PCLMA-based emulsion templated matrices with 60%, 75% and 82% internal phase volumes were fabricated (P60, P75, and P82). These scaffolds' densities, porosities, average pore and window sizes, degree of interconnectivity values, and mechanical properties were investigated. Results: Increasing internal phase volume reduced the density of the foams by almost two-fold. No direct correlation was observed between average pore size and internal phase volume. Both the average window sizes and the degree of interconnectivity values increase with increasing internal phase volume. Compression modulus values are calculated as 0.46±0.04 MPa, 0.23±0.02 MPa and 0.14±0.01 MPa for P60, P75, and P82, respectively. Increasing internal phase volume from 60% to 82% caused a more than 2-fold reduction in the stiffness of the emulsion-templated matrices. Conclusions: Accordingly, by reporting on this experimental framework, we established a relationship between internal phase volume and the physical, morphological and mechanical characteristics of 4PCMA-based scaffolds to precisely engineer these characteristics for specific tissue engineering applications.

Optimizing silicon doping levels for enhanced osteogenic and angiogenic properties of 3D-printed biphasic calcium phosphate scaffolds: An in vitro screening and in vivo validation study

Biphasic calcium phosphate (BCP) ceramics are valued for their osteoconductive properties but have limited osteogenic and angiogenic activities, which restricts their clinical utility in bone defect repair. Silicon doping has emerged as an effective strategy to enhance these biological functions of BCP. However, the biological impact of BCP is influenced by the level of silicon doping, necessitating determination of the optimal concentration to maximize efficacy in bone repair. This study investigated the effects of silicon doping on both the physicochemical and biological properties of BCP, with a specific focus on osteogenic and angiogenic potentials. Results indicated that silicon doping exceeding 4 mol.% led to the formation of α-TCP, accelerating BCP degradation, enhancing silicon ion release, and promoting mineralization product formation. Simultaneously, silicon doping increased the porosity of BCP scaffolds, which typically reduces their compressive strength. Nevertheless, scaffolds doped with ≤4 mol.% silicon maintained compressive strengths exceeding 2 MPa. In vitro biological experiments indicated that higher levels of silicon doping (≥6 mol.%) partially inhibited the successful differentiation of stem cells and the vascularization of endothelial cells. Optimal conditions for promoting osteogenic differentiation and angiogenesis were identified between 2 and 4 mol.% silicon doping, with an optimal level of approximately 4 mol.%. Subsequent in vivo experiments confirmed that BCP scaffolds doped with 4 mol.% silicon effectively promoted vascularization and new bone formation, highlighting their potential for clinical bone defect repair.

(Invited) Organic Electrochemical Bioelectronic Devices Based on 3D Conductive Polymer Scaffolds

The integration of 3D tissue-engineered microporous scaffolds based on conductive polymers (CPs) into bioelectronic devices have led to the possibility of dynamic monitoring of biological phenomena through electrical measurements. The 3D structure and morphology of the porous scaffolds mimics the topographical features of human physiology, while the electrically conductive nature of the polymers allows for electrical measurements for label-free monitoring and live-sensing of cells. 3D scaffolds based on the polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) prepared by the freeze drying process have been the focus of many studies and well integrated into bioelectronic devices such as electrodes[1] and organic electrochemical transistors[2].The influence of the different protocols and freezing rates on the pore size and structure was examined by scanning electron microscopy and micro computed tomography. Pores of circular and elongated ellipses were observed by SEM and a pore size distribution (the longest dimension of the ellipsoid) between 80 µm and 220 µm was measured. It was observed that a higher cooling rate generated larger pores with more elongated pore morphology as well as a wider pore size distribution. The pre-cooling treatment with 0.5°C/min cooling rate was most useful in generating scaffolds with a more homogenous pore structure and a pore size of approximately 100 µm.The different scaffolds were incorporated into electronic devices such as transmembrane electrodes to characterize the electrical properties and evaluate the reproducibility of the scaffolds prior to cell culture. No significant change in the electrochemical impedance spectra was observed despite the large difference in porosity of the different scaffolds. In addition, the different scaffolds were used to host and monitor biological cells like fibroblasts and endothelial cells. Cell growth and proliferation in the different scaffolds was also monitored by immunofluorescence microscopy. It was observed that a pre-cooling protocol and a freezing rate of 0.5°C/min helps to fabricate scaffolds with an optimized, uniform and homogenous pore morphology. This design protocol is highly beneficial in reducing the random artifacts of the nucleation process and generating scaffolds highly conducive to cell growth and survival and to create a versatile bioelectronic platform for studying in-vitro cell models.A new, sophisticated bioelectronic device was constructed with the scaffolds with the operation mode of an electrode and an organic electrochemical transistor. The device operation models an electrochemical cell with two or three electrodes and is used to build different in vitro organ models. In this presentation, I show the use of electrochemical techniques to monitor biological phenomenon based on 3D conducting polymer scaffolds.

Decellularized Extracellular Matrix Scaffolds for Soft Tissue Augmentation: From Host-Scaffold Interactions to Bottlenecks in Clinical Translation.

Along with a paradigm shift in looking at soft tissue fillers from space-filling to bioactive materials, decellularized extracellular matrix (DEM) fillers have gained more attention considering their superior bioactivity. However, the complex mechanisms that govern the interaction between host tissues and DEMs have been partially understood. This review first covers the mechanisms that determine immunogenicity, angiogenesis and vasculogenesis, and recellularization and remodeling after DEM implantation into host tissue, with a particular focus on related findings from filler materials. Accordingly, the review delves into the dual role of macrophages and their M1/M2 polarization paradigm to form both constructive and destructive immune responses to DEM implants. Moreover, the contribution of macrophages in angiogenesis has been elucidated, which includes but is not limited to the secretion of angiogenic growth factors and extracellular matrix (ECM) remodeling. The findings challenge the traditional view of immune cells as solely destructive entities in biomaterials and indicate their multifaceted roles in tissue regeneration. Furthermore, the review discusses how the compositional factors of DEMs, such as the presence of growth factors and matrikines, can influence angiogenesis, cell fate, and differentiation during the recellularization process. It is also shown that the biomechanical properties of DEMs, including tissue stiffness, modulate cell responses through mechanotransduction pathways, and the structural properties of DEMs, such as scaffold porosity, impact cell-cell and cell-ECM interactions. Finally, we pointed out the current clinical applications, the bottlenecks in the clinical translation of DEM biomaterials into soft tissue fillers, as well as the naïve research areas of the field.