3D Scaffolds Research Articles

Space-Efficient 3D Microalgae Farming with Optimized Resource Utilization for Regenerative Food.

Photosynthetic microalgae produce valuable metabolites and are a source of sustainable food that supports life without compromising arable land. However, the light self-shading, excessive water supply, and insufficient space utilization in microalgae farming have limited its potential in the inland areas most in need of regenerative food solutions. Herein, this work develops a 3D polysaccharide-based hydrogel scaffold for vertically farming microalgae without needing liquid media. This liquid-free strategy is compatible with diverse microalgal species and enables the design of living microalgal frameworks with customizable architectures that enhance light and water utilization. This approach significantly increases microalgae yield per unit water consumption, with an 8.8-fold increase compared to traditional methods. Furthermore, the dehydrated hydrogels demonstrate a reduced size and weight (≈70% reduction), but readily recover their vitality upon rehydration. Importantly, valuable natural products can be produced in this system including proteins, carbohydrates, lipids, and carotenoids. This study streamlines microalgae regenerative farming for low-carbon biomanufacturing by minimizing light self-shading, relieving water supply, and reducing physical footprints, and democratizing access to efficient aquatic food production.

Optimizing the Delivery of mRNA to Mesenchymal Stem Cells for Tissue Engineering Applications.

Messenger RNA (mRNA) represents a promising therapeutic tool in the field of tissue engineering for the fast and transient production of growth factors to support new tissue regeneration. However, one of the main challenges to optimizing its use is achieving efficient uptake and delivery to mesenchymal stem cells (MSCs), which have been long reported as difficult-to-transfect. The aim of this study was to systematically screen a range of nonviral vectors to identify optimal transfection conditions for mRNA delivery to MSCs. Furthermore, for the first time, we wanted to directly compare the protein expression profile from three different types of mRNA, namely, unmodified mRNA (uRNA), base-modified mRNA (modRNA), and self-amplifying mRNA (saRNA) in MSCs. A range of polymer- and lipid-based vectors were used to encapsulate mRNA and directly compared in terms of physicochemical properties as well as transfection efficiency and cytotoxicity in MSCs. We found that both lipid- and polymer-based materials were able to successfully condense and encapsulate mRNA into nanosized particles (<200 nm). The overall charge and encapsulation efficiency of the nanoparticles was dependent on the vector type as well as the vector:mRNA ratio. When screened in vitro, lipid-based vectors proved to be superior in terms of mRNA delivery to MSCs cultured in a 2D monolayer and from a 3D collagen-based scaffold with minimal effects on cell viability, thus opening the potential for scaffold-based mRNA delivery. Modified mRNA consistently showed the highest levels of protein expression in MSCs, demonstrating 1.2-fold and 5.6-fold increases versus uRNA and saRNA, respectively. In summary, we have fully optimized the nonviral delivery of mRNA to MSCs, determined the importance of careful selection of the mRNA type used, and highlighted the strong potential of mRNA for tissue engineering applications.

Multi-modal imaging for dynamic visualization of osteogenesis and implant degradation in 3D bioprinted scaffolds

In situ monitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters. However, an existing gap exists in the availability of effective methodologies for continuous and dynamic monitoring of the bone tissue regeneration process, encompassing the concurrent visualization of bone formation and implant degradation. Here, we present an integrated scaffold designed to facilitate real-time monitoring of both bone formation and implant degradation during the repair of bone defects. Laponite (Lap), CyP-loaded mesoporous silica (CyP@MSNs) and ultrasmall superparamagnetic iron oxide nanoparticles (USPIO@SiO2) were incorporated into a bioink containing bone marrow mesenchymal stem cells (BMSCs) to fabricate functional scaffolds denoted as C@M/GLU using 3D bioprinting technology. In both in vivo and in vitro experiments, the composite scaffold has demonstrated a significant enhancement of bone regeneration through the controlled release of silicon (Si) and magnesium (Mg) ions. Employing near-infrared fluorescence (NIR-FL) imaging, the composite scaffold facilitates the monitoring of alkaline phosphate (ALP) expression, providing an accurate reflection of the scaffold's initial osteogenic activity. Meanwhile, the degradation of scaffolds was monitored by tracking the changes in the magnetic resonance (MR) signals at various time points. These findings indicate that the designed scaffold holds potential as an in situ bone implant for combined visualization of osteogenesis and implant degradation throughout the bone repair process.

Effect of angular variation and in vitro degradation on mechanical properties of PBAT 3D scaffolds

AbstractThe customization of polymeric prototypes is available to meet the specific needs of individual patients, considering tissue location and patient‐specific characteristics. Poly (butylene adipate‐co‐terephthalate) (PBAT) has shown great promise among various polymers in this scenario due to its biodegradability and processability properties. However, the effect of geometry changes on the mechanical properties of PBAT 3D scaffolds and their mechanical stability after in vitro degradation are crucial to determining the final application. This study focuses on the structural, morphological, and mechanical characterization of PBAT prototypes with different architectures and evaluating their mechanical properties before and after in vitro degradation. Three‐dimensional structures were 3D printed with rectilinear deposition angles of 15°, 30°, 45°, 60°, 75°, and 90°. Mechanical tests revealed that the prototype architecture influenced the stiffness, elongation, and maximum tension, where a greater resistance was observed for filaments containing the lowest angles. The thermal stability of PBAT remained unaffected either by reprocessing or hydrolytic degradation; however, in vitro degradation affected the mechanical behavior by increasing the stiffness and decreasing the elongation of the scaffold. Biological assays have demonstrated the nontoxic nature of PBAT and its potential to promote cell viability at a rate of 95%. These findings underscore the possibility of optimizing the PBAT design and structure to tune the mechanical properties and contribute to advancing tissue engineering strategies.

Decoupling stiffness and toughness of self-healing hydrogels for complex tissue regeneration via 3D bioprinting

Although polysaccharides are attractive biocompatible materials compared with synthetic polymers, most polysaccharide-based hydrogels exhibit suboptimal mechanical properties. In this study, we fabricated a hyaluronate (HA)-based self-healing hydrogel with enhanced toughness that can be used as a 3D bioink for complex tissue regeneration. We hypothesized that the incorporation of oxidation, aimed at minimizing the reduction in the molecular weight of HA, along with the introduction of a double network to the hydrogel, could facilitate the construction of 3D structures with decoupled stiffness and toughness. Various physicochemical properties of hydrogels comprising oxidized and hydrazide-modified HAs for potential use as bioinks were assessed. Bilayered constructs containing primary chondrocytes and osteoblasts were designed and fabricated using 3D printing to mimic the growth plate structure. Transplantation of the 3D-printed construct into a mouse model revealed the controlled differentiation stages of chondrocytes. This strategy for tailoring 3D scaffolds and addressing the limitations of polysaccharide-based hydrogels may hold promise for applications in the biomedical field, including the regeneration of complex tissues and organs.

A Novel Homoconjugated Propellane Triimide: Synthesis, Structural Analyses, and Gas Separation.

Rigid three-dimensional (3D) polycyclic propellanes have garnered interest due to their unique conformational spaces, which display great potential use in selectivity, separation and as models to study through-space electronic interactions. Herein we report the synthesis of a novel rigid propellane, trinaphtho[3.3.3]propellane triimide, which comprises three imide groups embedded on a trinaphtho[3.3.3]propellane. This propellane triimide exhibits large bathochromic shift, amplified molar absorptivity, enhanced fluorescence, and lower reduction potential when compared to the subunits. Computational and experimental studies reveal that the effective through-space π-orbitals interacting (homoconjugation) occurs between the subunits. Single-crystal XRD analysis reveals that the propellane triimide has a highly quasi-D3h symmetric skeleton and readily crystallizes into different superstructures by changing alkyl chains at the imide positions. In particular, the porous 3D superstructure with S-shaped channels is promising for taking up ethane (C2H6) with very good selectivity over ethylene (C2H4), which can purify C2H4 from C2H6/C2H4 in a single separation step. This work showcases a new class of rare 3D polycyclic propellane with intriguing electronic and supramolecular properties.

A Novel Homoconjugated Propellane Triimide: Synthesis, Structural Analyses, and Gas Separation

AbstractRigid three‐dimensional (3D) polycyclic propellanes have garnered interest due to their unique conformational spaces, which display great potential use in selectivity, separation and as models to study through‐space electronic interactions. Herein we report the synthesis of a novel rigid propellane, trinaphtho[3.3.3]propellane triimide, which comprises three imide groups embedded on a trinaphtho[3.3.3]propellane. This propellane triimide exhibits large bathochromic shift, amplified molar absorptivity, enhanced fluorescence, and lower reduction potential when compared to the subunits. Computational and experimental studies reveal that the effective through‐space π‐orbitals interacting (homoconjugation) occurs between the subunits. Single‐crystal XRD analysis reveals that the propellane triimide has a highly quasi‐D3h symmetric skeleton and readily crystallizes into different superstructures by changing alkyl chains at the imide positions. In particular, the porous 3D superstructure with S‐shaped channels is promising for taking up ethane (C2H6) with very good selectivity over ethylene (C2H4), which can purify C2H4 from C2H6/C2H4 in a single separation step. This work showcases a new class of rare 3D polycyclic propellane with intriguing electronic and supramolecular properties.

Simvastatin-loaded 3D aerogel scaffolds promote bone regeneration.

It is imperative to design a suitable material for bone regeneration that emulates the microstructure and compositional framework of natural bone while mitigating the shortcomings of current repair materials. The aim of the study is to synthesize a 3D aerogel scaffold composed of PLCL/gelatin electro-spun nanofiber loaded with Simvastatin and investigate its biocompatibility as well as its performance in cell proliferation and ossification differentiation. PLCL/gelatin nanofibers were fabricated in coaxial electrospinning with simvastatin added. Fibers were fragmented, pipetted into molds, frozen, and dried. The morphology of fibers and contact angles in 4 groups of PLCL, PLCL@S, 3D-PLCL, and 3D-PLCL@S was observed and compared. MC3T3-E1 cells were planted at the four materials to observe cell growth status, and ALP and ARS tests were conducted to compare the ossification of cells. TEM scanning showed the coaxial fiber of the inner PLCL and outer gelatin. The mean diameter of the PLCL/gelatin fibers is 561 ± 95nm and 631 ± 103nm after the drug loading. SEM showed the fibers in the 3D-PLCL@S group were more curled and loose with more space interlaced. The contact angle in this group was 27.1°, the smallest one. Drug release test demonstrated that simvastatin concentration in the 3D-PLCL@S could remain at a relatively high level compared to the control group. The cell proliferation test showed that MC3T3-EI cells could embed into the scaffold deeply and exhibit higher viability in the 3D-PLCL@S group than other groups. The ossification tests of ALP and ARS also inferred that the 3D-PLCL@S scaffold could offer a better osteogenic differentiation matrix. The PLCL/gelatin aerogel scaffold, when loaded with Simvastatin, demonstrates a more pronounced potential in enhancing osteoblast proliferation and osteogenic differentiation. We hypothesize that this scaffold could serve as a promising material for addressing bone defects.

Assessing the efficacy of curcumin-loaded alginate hydrogel on skin wound healing: A gene expression analysis.

Skin tissue engineering has gained significant attention as a promising alternative to traditional treatments for skin injuries. In this study, we developed 3D hydrogel-based scaffolds, Alginate, incorporating different concentrations of Curcumin and evaluated their properties, including morphology, swelling behavior, weight loss, as well as hemo- and cytocompatibility. Furthermore, we investigated the therapeutic potential of Alginate hydrogel containing different amounts of Curcumin using an in vitro wound healing model. The prepared hydrogels exhibited remarkable characteristics, SEM showed that the pore size of hydrogels was 134.64μm with interconnected pores, making it conducive for cellular infiltration and nutrient exchange. Moreover, hydrogels demonstrated excellent biodegradability, losing 63.5% of its weight over 14 days. In addition, the prepared hydrogels had a stable release of curcumin for 3days. The results also show the hemocompatibility of prepared hydrogels and a low amount of blood clotting. To assess the efficacy of the developed hydrogels, 3T3 fibroblast growth was examined during various incubation times. The results indicated that the inclusion of Curcumin at a concentration of 0.1mg/mL positively influenced cellular behavior. The animal study showed that Alginate hydrogel containing 0.1mg/mL curcumin had high wound closure(more than 80%) after 14 days. In addition, it showed up-regulation of essential wound healing genes, including TGFβ1 and VEGF, promoting tissue repair and angiogenesis. Furthermore, the treated group exhibited down-regulation of MMP9 gene expression, indicating a reduction in matrix degradation and inflammation. The observed cellular responses and gene expression changes substantiate the therapeutic efficacy of prepared hydrogels. Consequently, our study showed the healing effect of alginate-based hydrogel containing Curcumin on skin injuries.

Lysophosphatidic Acid/Polydopamine-Modified nHA Composite Scaffolds for Enhanced Osteogenesis via Upregulating the Wnt/Beta-Catenin Pathway.

Guided bone regeneration (GBR) technology has been widely used for the regeneration of periodontal bone defects. However, the limited mechanical properties and bone regeneration potential of the currently available GBR membranes often limit their repair effectiveness. In this paper, serum-derived growth factor lysophosphatidic acid (LPA) nanoparticles and dopamine-decorative nanohydroxyapatite (pDA/nHA) particles were double-loaded into polylactic-glycolic acid/polycaprolactone (PLGA/PCL) scaffolds as an organic/inorganic biphase delivery system, namely, PP-pDA/nHA-LPA scaffolds. Physicochemical properties and osteogenic ability in vitro and in vivo were performed. Scanning electron microscopy and mechanical tests showed that the PP-pDA/nHA-LPA scaffolds had a 3D bionic scaffold structure with improved mechanical properties. In vitro cell experiments demonstrated that the PP-pDA/nHA-LPA scaffolds could significantly enhance the attachment, proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. In vivo, the PP-pDA/nHA-LPA scaffolds exhibited great cytocompatibility and cell recruitment ability in 2- and 4-week subcutaneous implantation experiments and significantly promoted bone regeneration in the periodontal defect scaffold implantation experiment. Moreover, LPA-loaded scaffolds were confirmed to enhance osteogenic activities by upregulating the expression of β-catenin and further activating the Wnt/β-catenin pathway. These results demonstrate that the biphase PP-pDA/nHA-LPA delivery system is a promising material for the GBR.

The role of poly(3‐hydroxybutyrate)‐based derivatives in skin, nerve, cartilage, and bone tissue engineering applications—An updated review

AbstractPoly(3‐hydroxybutyrate) (PHB) has gained significant attention in the realm of medical applications in recent years. This acceptability is rooted in its bioactive properties and remarkable biocompatibility, as the degradation products exhibit negligible cytotoxicity. PHB boasts commendable mechanical resilience, distinguishing it from other polymers commonly used in tissue engineering. Using PHB in fabricating 3D scaffolds serves various objectives, often involving a combination with other polymers, ceramics, fibers, or regenerative factors. This distinctive approach sets it apart, leading to the creation of composite biomaterials. These incorporated materials enhance characteristics such as brittleness, hydrophobicity, degradation rate, and biocompatibility, within the composite. This review delves into the diverse roles that PHB, its alloys, and its compounds play in the engineering of skin, nerve, cartilage, and bone tissues. We explain these roles by highlighting key methodologies for crafting 3D tissue scaffolds with widely adopted techniques, including polymeric sponges, electrospinning, and salt leaching.

Dual-Sensitive Fluorescent Nanoprobes for Simultaneously Monitoring In Situ Changes in pH and Matrix Metalloproteinase Expression in Stiffness-Tunable Three-Dimensional In Vitro Scaffolds.

A tumor microenvironment often presents altered physicochemical characteristics of the extracellular matrix (ECM) including changes in matrix composition, stiffness, protein expression, pH, temperature, or the presence of certain stromal and immune cells. Of these, overexpression of matrix metalloproteinases (MMPs) and extracellular acidosis are the two major hallmarks of cancer that can be exploited for tumor detection. The change in matrix stiffness and the release of certain cytokines (TNF-α) in the tumor microenvironment play major roles in inducing MMP-9 expression in cancerous cells. This study highlights the role of mechanical cues in upregulating MMP-9 expression in cancerous cells using stiffness-tunable matrix compositions and dual-sensitive fluorescent nanoprobes. Ionically cross-linked 3D alginate/gelatin (AG) scaffolds with three stiffnesses were chosen to reflect the ECM stiffnesses corresponding to healthy and pathological tissues. Moreover, a dual-sensitive nanoprobe, an MMP-sensitive peptide conjugated to carbon nanoparticles with intrinsic pH fluorescence properties, was utilized for in situ monitoring of the two cancer hallmarks in the 3D scaffolds. This platform was further utilized for designing a 3D core-shell platform for spatially mapping tumor margins and for visualizing TNF-α-induced MMP-9 expression in cancerous cells.

Harvesting decellularized liver extracellular matrix from rodents for 3D scaffold fabrication

Decellularization is a process to harvest the decellularized extra cellular matrix (dECM) that helps develop 3D scaffolds which mimic the native tissue composition. The decellularized tissues retain the structural and functional properties of the extracellular matrix (ECM) by an efficient decellularization process that retains tissue-specific biochemical and biophysical cues for tissue regeneration. In this study, we report an injection-based decellularization method, without perfusion setup. This study also compares the efficiency of the proposed protocol in the two animal models viz rat and mice. This method harvests rat and mice liver dECM using ethylenediamine tetra acetic acid (EDTA) and sodium dodecyl sulphate (SDS) within 08 h and 02 h respectively and preserved significant amount of ECM proteins. We reported that the harvested mice decellularized extracellular matrix (mdECM) and rat decellularized extracellular matrix (rdECM) had significant reduction in their DNA content (∼97%) and retained structural architecture resembling their native tissue counterparts. The total protein content retained in mdECM was ∼39% while that retained in rdECM was ∼65%. It was also found that the sGAG (sulphated glycosaminoglycan) content showed a no List of Figures.

Fused Deposition Modeling 3D-Printed Scaffolds for Bone Tissue Engineering Applications: A Review.

The emergence of bone tissue engineering as a trend in regenerative medicine is forcing scientists to create highly functional materials and scaffold construction techniques. Bone tissue engineering uses 3D bio-printed scaffolds that allow and stimulate the attachment and proliferation of osteoinductive cells on their surfaces. Bone grafting is necessary to expedite the patient's condition because the natural healing process of bones is slow. Fused deposition modeling (FDM) is therefore suggested as a technique for the production process due to its simplicity, ability to create intricate components and movable forms, and low running costs. 3D-printed scaffolds can repair bone defects in vivo and in vitro. For 3D printing, variousmaterials including metals, polymers, and ceramics are often employed but polymeric biofilaments are promising candidates for replacing non-biodegradable materials due to their adaptabilityand environment friendliness. This review paper majorly focuses on the fused deposition modeling approach for the fabrication of 3D scaffolds. In addition, it also provides information on biofilaments used in FDM 3D printing, applications, and commercial aspects of scaffolds in bone tissue engineering.

Is Silver Addition to Scaffolds Based on Polycaprolactone Blended with Calcium Phosphates Able to Inhibit Candida albicans and Candida auris Adhesion and Biofilm Formation?

Candida spp. periprosthetic joint infections are rare but difficult-to-treat events, with a slow onset, unspecific symptoms or signs, and a significant relapse risk. Treatment with antifungals meets with little success, whereas prosthesis removal improves the outcome. In fact, Candida spp. adhere to orthopedic devices and grow forming biofilms that contribute to the persistence of this infection and relapse, and there is insufficient evidence that the use of antifungals has additional benefits for anti-biofilm activity. To date, studies on the direct antifungal activity of silver against Candida spp. are still scanty. Additionally, polycaprolactone (PCL), either pure or blended with calcium phosphate, could be a good candidate for the design of 3D scaffolds as engineered bone graft substitutes. Thus, the present research aimed to assess the antifungal and anti-biofilm activity of PCL-based constructs by the addition of antimicrobials, for instance, silver, against C. albicans and C. auris. The appearance of an inhibition halo around silver-functionalized PCL scaffolds for both C. albicans and C. auris was revealed, and a significant decrease in both adherent and planktonic yeasts further demonstrated the release of Ag+ from the 3D constructs. Due to the combined antifungal, osteoproliferative, and biodegradable properties, PCL-based 3D scaffolds enriched with silver showed good potential for bone tissue engineering and offer a promising strategy as an ideal anti-adhesive and anti-biofilm tool for the reduction in prosthetic joints of infections caused by Candida spp. by using antimicrobial molecule-targeted delivery.

Lightweight and high-strength textured fibrous Si3N4 3D scaffold seeded with β-Si3N4 particles prepared via freeze casting

Highly porous Si3N4 ceramics with unidirectionally aligned pore channels are gaining significant attention across various fields due to their outstanding functional capabilities. However, achieving high strength in such unidirectional highly porous Si3N4 ceramics remains challenging. Herein, we design and fabricate a novel β-Si3N4 scaffold composed of directionally aligned lamellar walls with a textured microstructure by directionally freeze casting of α-Si3N4 suspensions with fine elongated β-Si3N4 seeds addition, followed by liquid phase sintering. During the sintering, the scaffold exhibited anisotropic shrinkage, and fibrous β-Si3N4 grains were synthesized through epitaxial growth on the seeds preferentially oriented or the nuclei originated from α-Si3N4 powders, resulting in the grains aligned parallel to lamellar walls and bridged the walls. Seed additions of 7 to 15 wt% were beneficial for the optimized distribution of the two types of β-Si3N4 grains, which contributed to the excellent resistance to bucking-induced fracture for the walls. Compared with other unidirectional porous Si3N4 prepared by freeze-casting in the literature, the Si3N4 scaffold exhibited outstanding compressive strength, ranging from 2.8 to 22.0 MPa, as the porosity decreased from 94.4 % to 88.0 % and the density increased from 175 to 365 mg/cm3. The lightweight and strong Si3N4 scaffolds are promising candidates for engineering applications in harsh environments.

Characterization and In Vitro Evaluation of Porous Polymer-Blended Scaffolds Functionalized with Tricalcium Phosphate.

Bone tissue is one of the most transplanted tissues. The ageing population and bone diseases are the main causes of the growing need for novel treatments offered by bone tissue engineering. Three-dimensional (3D) scaffolds, as artificial structures that fulfil certain characteristics, can be used as a temporary matrix for bone regeneration. In this study, we aimed to fabricate 3D porous polymer scaffolds functionalized with tricalcium phosphate (TCP) particles for applications in bone tissue regeneration. Different combinations of poly(lactic acid) (PLA), poly(ethylene glycol) (PEG with molecular weight of 600 or 2000 Da) and poly(ε-caprolactone) (PCL) with TCP were blended by a gel-casting method combined with rapid heating. Porous composite scaffolds with pore sizes from 100 to 1500 µm were obtained. ATR-FTIR, DSC, and wettability tests were performed to study scaffold composition, thermal properties, and hydrophilicity, respectively. The samples were observed with the use of optical and scanning electron microscopes. The addition of PCL to PLA increased the hydrophobicity of the composite scaffolds and reduced their susceptibility to degradation, whereas the addition of PEG increased the hydrophilicity and degradation rates but concomitantly resulted in enhanced creation of rounded mineral deposits. The scaffolds were not cytotoxic according to an indirect test in L929 fibroblasts, and they supported adhesion and growth of MG-63 cells when cultured in direct contact.

Snail Mucus-Enhanced Adhesion of Human Chondrocytes on 3D Porous Agarose Scaffolds.

This study reports the preparation of a novel porous 3D scaffold from agarose-snail mucus (AGSMu) for cartilage tissue repair applications. AG is reported for its unique thermal and mechanical properties, biocompatibility, and biodegradability, making it suitable for biomedical applications. Still, it lacks the cell adhesion properties required for tissue engineering applications. SMu is a complex substance identified to contain glycosaminoglycans (GAGs) and other bioactive molecules that promote wound healing and reduce cartilage deterioration and inflammation. Hence, porous 3D blend scaffolds containing AG and SMu were prepared by the freeze-drying method, characterized, and investigated for bioactive effects on human chondrocyte (C28/I2) cells. The scaffolds had a microporous structure with an average pore size of 245 μm. FTIR spectroscopy showed that SMu was successfully incorporated into the scaffolds. The SMu increased the mechanical strength of the composite scaffolds by more than 80% compared to the pristine AG scaffold. The scaffolds were found to be biocompatible with tunable degradation. The human chondrocyte cells attached and proliferated well on the 3D scaffolds in a few days, demonstrating a marked improvement in adhesion due to the presence of SMu. Enhanced cell adhesion and mechanical properties of 3D porous AG scaffolds could make them suitable for articular cartilage repair and regeneration.

Photo-Polymerizable Autologous Growth-Factor Loaded Silk-Based Biomaterial-Inks toward 3D Printing-Based Regeneration of Meniscus Tears.

Meniscustears in the avascular region undergoing partial or full meniscectomy lead to knee osteoarthritis and concurrent lifestyle hindrances in the young and aged alike. Here they reported ingenious photo-polymerizable autologous growth factor loaded 3D printed scaffolds to potentially treat meniscal defects . A shear-thinning photo-crosslinkable silk fibroin methacrylate-gelatin methacrylate-polyethylene glycol dimethacrylate biomaterial-ink is formulated and loaded with freeze-dried growth factor rich plasma (GFRP) . The biomaterial-ink exhibits optimal rheological properties and shape fidelity for 3D printing. Initial evaluation revealed that the 3D printed scaffolds mimicmechanical characteristics of meniscus, possess favourable porosity and swelling characteristics, and demonstrate sustained GFRP release. GFRP laden 3D scaffolds are screened with human neo-natal stem cells in vitro and biomaterial-ink comprising of 25mg mL-1 of GFRP (GFRP25) is found to be amicable for meniscus tissue engineering. GFRP25 ink demonstratedrigorous rheological compliance, and printed constructs demonstrated long term degradability (>6 weeks), GFRP release (>5 weeks), and mechanical durability (3 weeks). GFRP25 scaffolds aided in proliferation of seeded human neo-natal stem cellsandtheir meniscus-specific fibrochondrogenic differentiation . GFRP25 constructs show amenable inflammatory response in vitro and in vivo. GFRP25 biomaterial-ink and printed GFRP25 scaffolds could be potential patient-specific treatment modalities for meniscal defects.

2D and 3D PVA electrospun scaffold evaluation for ligament implant replacement: A mechanical testing, modelling and experimental biomechanics approach

The gold standard to characterise anterior cruciate ligament (ACL) implants is through the evaluation of mechanical properties such as Young's modulus or ultimate tensile stress. Currently, no studies have been performed to relate the in-vivo hyper-elastic behaviour of the ACL with the design of tissue engineered ligaments. The aim of this work is to determine the most comparable 2D/3D polyvinyl alcohol (PVA) electrospun structure to the in-vivo mechanical behaviour of the natural ligament. Biomechanics of 12 young participants were captured while daily and high impact activities were performed. A musculoskeletal knee model and kinematic data were used to estimate the in-vivo ACL length and strain. The in-vivo ACL tensile forces were determined with a non-linear force/strain relationship. 2D scaffolds, 1 twisted filament scaffolds, 3 twisted filaments scaffolds and 3 twisted/braided filaments scaffolds were fabricated using electrospinning and characterised morphologically and mechanically using scanning electron microscopy and tensile testing respectively. Cyclic tensile and shear tests were performed in dry and wet conditions to crosslinked and non-crosslinked samples. The hyper-elastic behaviour of our PVA scaffolds was characterised with the Mooney Rivlin model and a non-linear string-based model, and both models compared with the in-vivo mechanical behaviour of the native ACL. Crosslinked 3 twisted/braided filaments scaffolds faithfully mimicked the morphology and the hyper-elastic behaviour of the natural ACL, showed a good resistance to shear loading and remained undegraded in phosphate-buffer saline solution. This study demonstrated, for the first time, that 3 twisted/braided filaments PVA electrospun scaffolds have an excellent potential for ACL replacements.