Scaffolds For Applications Research Articles

Biological scaffold as potential platforms for stem cells: Current development and applications in wound healing.

Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

Reconstructing Critical-Sized Mandibular Defects in a Rabbit Model: Enhancing Angiogenesis and Facilitating Bone Regeneration via a Cell-Loaded 3D-Printed Hydrogel-Ceramic Scaffold Application.

In this study, we propose a spatially patterned 3D-printed nanohydroxyapatite (nHA)/beta-tricalcium phosphate (β-TCP)/collagen composite scaffold incorporating human dental pulp-derived mesenchymal stem cells (hDP-MSCs) for bone regeneration in critical-sized defects. We investigated angiogenesis and osteogenesis in a rabbit critical-sized mandibular defect model treated with this engineered construct. The critical and synergistic role of collagen coating and incorporation of stem cells in the regeneration process was confirmed by including a cell-free uncoated 3D-printed nHA/β-TCP scaffold, a stem cell-loaded 3D-printed nHA/β-TCP scaffold, and a cell-free collagen-coated 3D-printed nHA/β-TCP scaffold in the experimental design, in addition to an empty defect. Posteuthanasia evaluations through X-ray analysis, histological assessments, immunohistochemistry staining, histomorphometry, and reverse transcription-polymerase chain reaction (RT-PCR) suggest the formation of substantial woven and lamellar bone in the cell-loaded collagen-coated 3D-printed nHA/β-TCP scaffolds. Histomorphometric analysis demonstrated a significant increase in osteoblasts, osteocytes, osteoclasts, bone area, and vascularization compared to that observed in the control group. Conversely, a significant decrease in fibroblasts/fibrocytes and connective tissue was observed in this group compared to that in the control group. RT-PCR indicated a significant upregulation in the expression of osteogenesis-related genes, including BMP2, ALPL, SOX9, Runx2, and SPP1. The findings suggest that the hDP-MSC-loaded 3D-printed nHA/β-TCP/collagen composite scaffold is promising for bone regeneration in critical-sized defects.

Synthesis, Characterization, and Evaluation of the Antimicrobial Effects and Cytotoxicity of a Novel Nanocomposite Based on Polyamide 6 and Trimetaphosphate Nanoparticles Decorated with Silver Nanoparticles.

This study aimed to develop a polymeric matrix of polyamide-6 (P6) impregnated with trimetaphosphate (TMP) nanoparticles and silver nanoparticles (AgNPs), and to evaluate its antimicrobial activity, surface free energy, TMP and Ag+ release, and cytotoxicity for use as a support in dental tissue. The data were subjected to statistical analysis (p < 0.05). P6 can be incorporated into TMP without altering its properties. In the first three hours, Ag+ was released for all groups decorated with AgNPs, and for TMP, the release only occurred for the P6-TMP-5% and P6-TMP-10% groups. In the inhibition zones, the AgNPs showed activity against both microorganisms. The P6-TMP-2.5%-Ag and P6-TMP-5%-Ag groups with AgNPs showed a greater reduction in CFU for S. mutans. For C. albicans, all groups showed a reduction in CFU. The P6-TMP groups showed higher cell viability, regardless of time (p < 0.05). The developed P6 polymeric matrix impregnated with TMP and AgNPs demonstrated promising antimicrobial properties against the tested microorganisms, making it a potential material for applications in scaffolds in dental tissues.

Sustainable highly stretchable and tough gelatin-alkali lignin hydrogels for scaffolding and 3D printing applications

Hydrogels and bioinks obtained from gelatin (Gel) generally present poor mechanical properties and require a series of time-consuming and stepwise chemical processes to exhibit improved elasticity and resistance to fatigue. Alkali lignin (AL) is an underutilized by-product of the paper and pulp industry. It is a widely available and inexpensive biomaterial that presents enormous potential for high-value applications owing to its ease of chemical modification and unique naturally occurring polyaromatic structure. This work aims to develop different GelAL hydrogel formulations with a single-step method that are innovative and sustainable. The results obtained from the mechanical, rheological, and degradation studies of the developed GelAL hydrogels demonstrated that their properties can be easily modified and tuned using straightforward processing techniques, allowing these stretchable and tough hydrogels to be used as bioinks in 3D printing. The modulation of mechanical properties through hydrogel formulations is a result of interactions between the Gel and AL which can be associated with the interplay of anionic sulfonates in AL and the arginine and lysine residues from Gel. The tensile stress at the break for the Gel20AL10 formulation was 32% higher than the value for Gel20AL5 and 157% higher than that of Gel10AL10. The elongation at break also decreased as it averaged 659 ± 149% for the Gel20AL10 formulation, which is 20% more than that of Gel20AL5 and 55% more than the average elongation at break of Gel10AL10. Further zeta potential measurements and quartz crystal microbalance with energy dissipation studies demonstrated that Gel and AL seem to form neutral complexes when mixed. These assays support the idea that AL and Gel are readily bound through weak interactions, and chemical crosslinking strategies need to be considered when degradability and mechanical properties tuning are envisioned. Altogether, these high-performance GelAL hydrogels display mechanical properties similar to soft tissues with high elasticity beyond that of natural hydrogels and fulfill the requirements of a broad range of biomedical and tissue engineering scaffolding applications.

A novel ternary magnetic nanobiocomposite based on tragacanth-silk fibroin hydrogel for hyperthermia and biological properties.

This study involves the development of a new nanocomposite material for use in biological applications. The nanocomposite was based on tragacanth hydrogel (TG), which was formed through cross-linking of Ca2+ ions with TG polymer chains. The utilization of TG hydrogel and silk fibroin as natural compounds has enhanced the biocompatibility, biodegradability, adhesion, and cell growth properties of the nanobiocomposite. This advancement makes the nanobiocomposite suitable for various biological applications, including drug delivery, wound healing, and tissue engineering. Additionally, Fe3O4 magnetic nanoparticles were synthesized in situ within the nanocomposite to enhance its hyperthermia efficiency. The presence of hydrophilic groups in all components of the nanobiocomposite allowed for good dispersion in water, which is an important factor in increasing the effectiveness of hyperthermia cancer therapy. Hemolysis and 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays were conducted to evaluate the safety and efficacy of the nanobiocomposite for in-vivo applications. Results showed that even at high concentrations, the nanobiocomposite had minimal hemolytic effects. Finally, the hyperthermia application of the hybrid scaffold was evaluated, with a maximum SAR value of 41.2W/g measured in the first interval.

Biomimetic Mineralized 3D-Printed Polycaprolactone Scaffold Induced by Self-Adaptive Nanotopology to Accelerate Bone Regeneration.

Three-dimensional (3D)-printed biodegradable polymer scaffolds are at the forefront of personalized constructs for bone tissue engineering. However, it remains challenging to create a biological microenvironment for bone growth. Herein, we developed a novel yet feasible approach to facilitate biomimetic mineralization via self-adaptive nanotopography, which overcomes difficulties in the surface biofunctionalization of 3D-printed polycaprolactone (PCL) scaffolds. The building blocks of self-adaptive nanotopography were PCL lamellae that formed on the 3D-printed PCL scaffold via surface-directed epitaxial crystallization and acted as a linker to nucleate and generate hydroxyapatite crystals. Accordingly, a uniform and robust mineralized layer was immobilized throughout the scaffolds, which strongly bound to the strands and had no effect on the mechanical properties of the scaffolds. In vitro cell culture experiments revealed that the resulting scaffold was biocompatible and enhanced the proliferation and osteogenic differentiation of mouse embryolous osteoblast cells. Furthermore, we demonstrated that the resulting scaffold showed a strong capability to accelerate in vivo bone regeneration using a rabbit bone defect model. This study provides valuable opportunities to enhance the application of 3D-printed scaffolds in bone repair, paving the way for translation to other orthopedic implants.

Therapeutic applications of biological macromolecules and scaffolds for skeletal muscle regeneration: A review

Skeletal muscle (SM) mass and strength maintenance are important requirements for human well-being. SM regeneration to repair minor injuries depends upon the myogenic activities of muscle satellite (stem) cells. However, losses of regenerative properties following volumetric muscle loss or severe trauma or due to congenital muscular abnormalities are not self-restorable, and thus, these conditions have major healthcare implications and pose clinical challenges. In this context, tissue engineering based on different types of biomaterials and scaffolds provides an encouraging means of structural and functional SM reconstruction. In particular, biomimetic (able to transmit biological signals) and several porous scaffolds are rapidly evolving. Several biological macromolecules/biomaterials (collagen, gelatin, alginate, chitosan, and fibrin etc.) are being widely used for SM regeneration. However, available alternatives for SM regeneration must be redesigned to make them more user-friendly and economically feasible with longer shelf lives. This review aimed to explore the biological aspects of SM regeneration and the roles played by several biological macromolecules and scaffolds in SM regeneration in cases of volumetric muscle loss.

Durotaxis and Topotaxis Orchestrated Guidance on Cell Migration in 3D Printed Scaffold/Hydrogel Composite

Printing three-dimensional (3D) scaffolds with suitable mechanical cues is an effective strategy for guiding tissue regeneration by inducing cell migration and growth. Nevertheless, many studies considered only one type of cue for 3D tissue engineering scaffold fabrication, such as topological cues, which is insufficient. To realize durotaxis- and topotaxis-orchestrated guidance on cell migration, a 3D printed scaffold/hydrogel composite was fabricated in this study. The porous scaffold provided a topological cue (topotaxis), and the combined hydrogel provided a compliance cue (durotaxis). The results indicated that the thin fibers of the scaffold induced cell migration, and the larger pore size and directed fiber number of the scaffold led to more uniform cell orientation (topotaxis). Furthermore, when collagen was cured to cover the scaffold to result in a compliance change, the cells in the collagen still sensed the scaffold topological cue and migrated along it (durotaxis). Collagen also provides a living space and nutrition for cells, thereby significantly increasing their number. The effects of durotaxis and topotaxis synthesis provide a promising solution for tissue engineering scaffold applications.

Applications of Scaffolds in Tissue Engineering: Current Utilization and Future Prospective.

Current regenerative medicine tactics focus on regenerating tissue structures pathologically modified by cell transplantation in combination with supporting scaffolds and biomolecules. Natural and synthetic polymers, bioresorbable inorganic and hybrid materials, and tissue decellularized were deemed biomaterials scaffolding because of their improved structural, mechanical, and biological abilities.Various biomaterials, existing treatment methodologies and emerging technologies in the field of Three-dimensional (3D) and hydrogel processing, and the unique fabric concerns for tissue engineering. A scaffold that acts as a transient matrix for cell proliferation and extracellular matrix deposition, with subsequent expansion, is needed to restore or regenerate the tissue. Diverse technologies are combined to produce porous tissue regenerative and tailored release of bioactive substances in applications of tissue engineering. Tissue engineering scaffolds are crucial ingredients. This paper discusses an overview of the various scaffold kinds and their material features and applications. Tabulation of the manufacturing technologies for fabric engineering and equipment, encompassing the latest fundamental and standard procedures.

Potential Application of Polysaccharide-based Aerogel Scaffolds for Bone Tissue Engineering

Potential Application of Polysaccharide-based Aerogel Scaffolds for Bone Tissue Engineering

Fabrication and application of salicin-polycaprolactone 3D-printed scaffold in the healing of femur bone defects

Polycaprolactone (PCL) is a suitable material for bone repair due to good biocompatibility and mechanical properties. However, low bioactivity and hydrophobicity pose major challenges for its biomedical applications. To overcome these limitations, PCL-based scaffolds loaded with bioactive agents have been developed. Salicin (Sal) is an anti-inflammatory and analgesic herbal glycoside with osteogenic potential. In the present study, we aimed to produce a Sal-laden PCL (PCL–Sal) scaffold for bone healing applications. Three-dimensional scaffolds were produced and their biocompatibility, and physical-chemical characteristics were determined. The osteogenic potential of the PCL (PCL) and PCL–Sal scaffolds was evaluated using bone marrow mesenchymal stem cells (BMSCs). Scaffolds were implanted into a 5 mm bone defect created in the femur of adult rats, and the new bone fraction was determined using micro-computed tomography scanning at one-month follow-up. PCL–Sal scaffold had a structure, porosity, and fiber diameter suitable for bone construction. It also possessed a higher rate of hydrophilicity and bioactivity compared to the PCL, providing a suitable surface for the proliferation and bone differentiation of BMSCs. Furthermore, PCL–Sal scaffolds showed a higher capacity to scavenge free radicals compared to PCL. The improved bone healing potential of the PCL–Sal scaffold was also confirmed according to in vivo implantation results. Our findings revealed that the Sal-laden implant could be considered for bone repair due to desirable characteristics of Sal such as hydrophilicity, surface modification for cell attachment, and antioxidant properties.

Application of hydrogel scaffolds as a cell substrate for cartilage tissue regeneration

Cell therapy or tissue engineering is currently one of the potentially effective strategies for repairing cartilage defects. Mesenchymal stromal cells and autologous and allogeneic chondrocytes obtained from cartilage biopsies from patients undergoing arthroscopic surgery are the most commonly used cells for tissue engineering. Matrices (scaffolds) often used during cell implantation can facilitate successful cell implantation. These can be static supporting or plastic hydrogel substances obtained by various methods from natural or synthetic materials, allowing cells to be delivered to the site damaged by injection. Significant advantages of biocompatible hydrogels in cartilage injury therapy are determined based on the properties of the natural extracellular matrix and the high plasticity required for adapting to irregular surfaces of the tissue defect and allowing injectable cell delivery. These characteristics make injectable hydrogels a promising tool for cartilage bioengineering.&#x0D; This study highlights the progress in injectable hydrogels as carriers of different cells in the repair of cartilage tissue defects, as well as the current requirements and unresolved issues related to the use of such therapeutic approaches.

Porous Mg–Zn–Ca scaffolds for bone repair: a study on microstructure, mechanical properties and in vitro degradation behavior

Biodegradable porous Mg scaffolds are a promising approach to bone repair. In this work, 3D-spherical porous Mg–1.5Zn–0.2Ca (wt.%) scaffolds were prepared by vacuum infiltration casting technology, and MgF2 and fluorapatite coatings were designed to control the degradation behavior of Mg-based scaffolds. The results showed that the pores in Mg-based scaffolds were composed of the main spherical pores (450–600 μm) and interconnected pores (150–200 μm), and the porosity was up to 74.97%. Mg-based porous scaffolds exhibited sufficient mechanical properties with a compressive yield strength of about 4.04 MPa and elastic modulus of appropriately 0.23 GPa. Besides, both MgF2 coating and fluorapatite coating could effectively improve the corrosion resistance of porous Mg-based scaffolds. In conclusion, this research would provide data support and theoretical guidance for the application of biodegradable porous Mg-based scaffolds in bone tissue engineering.Graphical

Horsetail-inspired lattice structures for bone scaffold applications

A well-design bone scaffold is critical for facilitating post in vivo implantation recovery. Key factors, such as elastic moduli matching to alleviate stress shielding, anisotropic characteristics, and sufficient porosity for cell ingrowth, shape the design consideration for bone scaffolds. Herein, we propose a novel body-centered cubic (BCC) lattice with modified horsetail inspired cross-section strut members as the building block for synthetic bone scaffold application. We demonstrated that geometrical parameters can be varied to attain expected desirable mechanical properties. We also successfully matched the performance of the physical compression tests of Ti-6Al-4V-based samples manufactured using selective laser melting to that of the simulation environment to facilitate design. Through our work, we created Ti-6Al-4V-based lattices, which match the mechanical performance of native bone in terms of elastic moduli and yield strength. Biologically, the lattices provide in-strut pore dimensions that facilitate bone cell ingrowth as well as yield point that is beyond the strain required to promote secondary healing. The good energy absorption capability of our lattices also adds resilience to accidental damage when applied for use in bone scaffold design. We also discovered that the isotropy characteristic is decoupled from the outer radius of the designed lattice; this avoids convolution that would otherwise increase design difficulties. Through this novel design, the tuning of the mechanical properties to attain the key considerations with geometrical variations is made possible. &amp;nbsp;

A Transparent and Injectable Biomaterial Prepared by Mixing Collagen and Anti-Cancer Platinum Derivatives.

This study presents the synthesis of a cross-linked collagen material, named platinum-containing collagen gel (PCG), which is achieved by simply mixing collagen and derivatives of an anti-cancer platinum complex. The cross-linking reagents are derivatives of cisplatin or transplatin, generated through a ligand exchange with dimethyl sulfoxide. PCG exhibits superior physical strength and transparency compared with the native collagen gel formed through spontaneous fibril formation. The versatility of PCG as a cell culture scaffold, applicable to both 2D and 3D models, with low cytotoxicity is demonstrated. Furthermore, PCG exhibits pH-responsive gel-forming properties. This enables the removal of free cross-linker by dialysis in an acidic solution and subsequent gel formation upon neutralization. This material holds promise for application in cell culture scaffolds and medical injections.

Bone Marrow-Derived Mesenchymal Stem Cell-Laden Nanocomposite Scaffolds Enhance Bone Regeneration in Rabbit Critical-Size Segmental Bone Defect Model.

Bone regeneration poses a significant challenge in the field of tissue engineering, prompting ongoing research to explore innovative strategies for effective bone healing. The integration of stem cells and nanomaterial scaffolds has emerged as a promising approach, offering the potential to enhance regenerative outcomes. This study focuses on the application of a stem cell-laden nanomaterial scaffold designed for bone regeneration in rabbits. The in vivo study was conducted on thirty-six healthy skeletally mature New Zealand white rabbits that were randomly allocated into six groups. Group A was considered the control, wherein a 15 mm critical-sized defect was created and left as such without any treatment. In group B, this defect was filled with a polycaprolactone-hydroxyapatite (PCL + HAP) scaffold, whereas in group C, a PCL + HAP-carboxylated multiwalled carbon nanotube (PCL + HAP + MWCNT-COOH) scaffold was used. In group D, a PCL + HAP + MWCNT-COOH scaffold was used with local injection of bone morphogenetic protein-2 (BMP-2) on postoperative days 30, 45, and 60. The rabbit bone marrow-derived mesenchymal stem cells (rBMSCs) were seeded onto the PCL + HAP + MWCNT-COOH scaffold by the centrifugal method. In group E, an rBMSC-seeded PCL + HAP + MWCNT-COOH scaffold was used along with the local injection of rBMSC on postoperative days 7, 14, and 21. For group F, in addition to the treatment given to group E, BMP-2 was administered locally on postoperative days 30, 45, and 60. Gross observations, radiological observation, scanning electron microscopic assessment, and histological evaluation study showed that group F displayed the best healing properties, followed by group E, group D, group C, and B. Group A showed no healing with ends blunting minimal fibrous tissue. Incorporating growth factor BMP-2 in tissue-engineered rBMSC-loaded nanocomposite PCL + HAP + MWCNT-COOH construct can augment the osteoinductive and osteoconductive properties, thereby enhancing the healing in a critical-sized bone defect. This novel stem cell composite could prove worthy in the treatment of non-union and delayed union fractures in the near future.

Recent Advances in Implantable 3D-Printed Scaffolds for Repair of Spinal Cord Injury.

Spinal cord injury (SCI) is an important factor in sensory and motor disorders that affects thousands of people every year. Currently, despite successes in basic science and clinical research, there are few effective methods in the treatment of chronic and acute spinal cord injuries. In the last decade, the use of 3D printed scaffolds in the treatment of SCI had satisfactory and promising results. By providing a microenvironment around the injury site and in combination with growth factors or cells, 3D printed scaffolds help in axon regeneration as well as neural recovery after SCI. Here, we provide an overview of tissue engineering, 3D printing scaffolds, the different polymers used and their characterization methods. This review highlights the recent encouraging applications of 3D printing scaffolds in developing the novel SCI therapy.

Application of biomimetic three-dimensional scaffolds in bone tissue repairing

Application of biomimetic three-dimensional scaffolds in bone tissue repairing

Evaluation of in vitro corrosion behavior and biocompatibility of poly[xylitol-(1,12-dodecanedioate)](PXDD)-HA coated porous iron for bone scaffolds applications.

The present study evaluates the corrosion behavior of poly[xylitol-(1,12-dodecanedioate)](PXDD)-HA coated porous iron (PXDD140/HA-Fe) and its cell-material interaction aimed for temporary bone scaffold applications. The physicochemical analyses show that the addition of 20wt.% HA into the PXDD polymers leads to a higher crystallinity and lower surface roughness. The corrosion assessments of the PXDD140/HA-Fe evaluated by electrochemical methods and surface chemistry analysis indicate that HA decelerates Fe corrosion due to a lower hydrolysis rate following lower PXDD content and being more crystalline. The cell viability and cell death mode evaluations of the PXDD140/HA-Fe exhibit favorable biocompatibility as compared to bare Fe and PXDD-Fe scaffolds owing to HA's bioactive properties. Thus, the PXDD140/HA-Fe scaffolds possess the potential to be used as a biodegradable bone implant.

Chitosan Poly(vinyl alcohol) Methacrylate Hydrogels for Tissue Engineering Scaffolds.

A major challenge in tissue engineering scaffolds is controlling scaffold degradation rates during healing while maintaining mechanical properties to support tissue formation. Hydrogels are three-dimensional matrices that are widely applied as tissue scaffolds based on their unique properties that can mimic the extracellular matrix. In this study, we develop a hybrid natural/synthetic hydrogel platform to tune the properties for tissue engineering scaffold applications. We modified chitosan and poly(vinyl alcohol) (PVA) with photo-cross-linkable methacrylate functional groups and then synthesized a library of chitosan PVA methacrylate hydrogels (ChiPVAMA) with two different photoinitiators, Irgacure 2959 (I2959) and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). ChiPVAMA hydrogels showed tunability in degradation rates and mechanical properties based on both the polymer content and photoinitiator type. This tunability could enable their application in a range of tissue scaffold applications. In a 2D scratch wound healing assay, all hydrogel samples induced faster wound closure compared to a gauze clinical wound dressing control. NIH/3T3 cells encapsulated in hydrogels showed a high viability (∼92%) over 14 days, demonstrating the capacity of this system as a supportive cell scaffold. In addition, hydrogels containing a higher chitosan content demonstrated a high antibacterial capacity. Overall, ChiPVAMA hydrogels provide a potential tissue engineering scaffold that is tunable, degradable, and suitable for cell growth.