Scaffolds For Delivery Research Articles

Jade powder/PLGA composite microspheres for improved performance as potential bone repair drug carrier

Poly (lactic-co-glycolic acid) (PLGA) has been widely used as drug delivery carrier or scaffold for bone repair due to its good biocompatibility, biodegradability, and degradation rate controllability. However, defects, like acidic degradation by-products, are associated with PLGA and restrict its practical applications. Jade powder, leftover from jade polishing process, is a natural material rich in elements of Ca, Si, and Mg while biocompatible and antibacterial. Herein, jade powder/PLGA composite microspheres with different mass ratios were prepared by emulsion solvent evaporation method under the optimized conditions. Characterization from SEM, EDS, FTIR, and surface water contact angle measurements indicated jade powder was successfully combined with PLGA and improved the surface wettability of the microspheres. Moreover, it was proved, through in vitro simulated body fluid test as well as adipose stem cell osteogenesis analysis, that jade powder addition enhanced the pH buffering capacity of the composite microsphere for simulated body fluid, and promoted the in vitro osteogenic activity of adipose stem cells at a certain amount. This study provides new ideas to employ jade powder, a natural material otherwise thrown away as solid waste, for improvement on PLGA performance in bone repair or potentially other biomedical fields.

A drug-loaded nano chitosan/hyaluronic acid hydrogel system as a cartilage tissue engineering scaffold for drug delivery

Cartilage lesions, especially osteoarthritis (OA), usually arise from aging, trauma, or obesity and require medical intervention due to the damaged site's inflammation and the cartilage tissue's poor self-healing capacity. This study aimed to prepare a drug-loaded nanoparticle hydrogel system with anti-inflammatory and chondroprotective effects to treat OA. First, hyaluronic acid (HA) was oxidized to create aldehyde functional groups and then cross-linked with adipic acid dihydrazide (ADH) to form a hydrogel. Next, chitosan nanoparticles (CS NPs) loaded with an anti-inflammatory molecule (fisetin) and or a chondrogenic and chondroprotective agent (kartogenin) were incorporated into the hyaluronan hydrogel to improve the release profile of the drug and increase its retention time in the joint cavity. Incorporating drug-loaded NPs into the hyaluronan hydrogel provided the hydrogel with controlled release features and improved properties. In addition, the real-time PCR (Polymerase chain reaction) results showed that the hyaluronan hydrogel containing both drug-loaded NPs performed better than either constituent alone on an in vitro model of OA. Finally, based on the results of in vitro evaluation, this drug-loaded nanoparticle hydrogel system can be a promising technique for treating OA by rapidly suppressing inflammation and supporting cartilage regeneration and requires further investigation in an animal model of OA. Meanwhile, this study investigated, for the first time, the effect of the simultaneous use of fisetin and kartogenin together with a nano CS/HA hydrogel system to treat OA.

Glatiramer Acetate Complexes CpG Oligodeoxynucleotides into Nanoparticles and Boosts Their TLR9-Driven Immunity.

Unmethylated cytosine-guanine oligodeoxynucleotides (CpG ODNs) have a storied history as agonists for Toll-like receptor 9 (TLR9). CpG ODNs have shown promising antitumor effects in preclinical studies by inducing potent proinflammatory immune responses. However, clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure to CpG ODNs. We previously identified that glatiramer acetate (GA), an FDA-approved, lysine-rich polypeptide, could complex class B CpG into cationic nanoparticles which persist at the intratumoral injection site while mitigating the induction of systemic proinflammatory cytokines in mouse tumor models. To extend GA applications across subtypes of CpG ODN (class A, B, and C), we evaluated physiochemical properties and identified the immunological signaling of GA and its complexes with different classes of CpG ODNs. We compared the physiochemical characteristics of three types of GA-CpG nanoparticles, followed by assessments of cell uptake efficiency and endolysosomal trafficking. We then performed successive in vitro and in vivo assays to evaluate immunological discrepancies. Complexation with GA preserved the immunological activity of CpG ODN subtypes while encapsulating them into cationic spherical nanoparticles. GA improved the cellular uptake of CpG ODNs, generally increased retention in early endosomes, and amplified immunological responses. A subsequent in vivo experiment confirmed the achievement of potent tumor suppression while mitigating systemic immune-related toxicities. Together, these data help elucidate the noncanonical role of GA to serve as a nucleic acid delivery scaffold that can improve the efficacy and safety of CpG adjuvant for clinical cancer immunotherapy.

The Chitinous Skeleton of Ianthella basta Marine Demosponge as a Renewable Scaffold-Based Carrier of Antiseptics

The chitinous skeleton of the marine demosponge Ianthella basta exhibits a unique network-like 3D architecture, excellent capillary properties, and chemical inertness, making it highly suitable for interdisciplinary research, especially in biomedical applications. This study investigates the potential of renewable I. basta chitinous scaffolds for drug delivery and wound dressing. The scaffolds, characterized by a microtubular structure, were impregnated with selected commercially available antiseptics, including solutions with hydrophilic and hydrophobic properties. Evaluations against selected clinical strains of bacteria, as well as fungi, demonstrated significant zones of growth inhibition with antiseptics such as brilliant green, gentian violet, decamethoxine, and polyhexanide. Notably, the antibacterial properties of these antiseptic-treated chitin matrices persisted for over 72 h, effectively inhibiting microbial growth in fresh cultures. These findings highlight the considerable potential of I. basta chitin scaffolds as sustainable, innovative biomaterials for controlled drug release and wound dressing applications.

3D-printed chitosan-pectin-sodium alginate scaffolds for post-surgical peritoneal wound dressing and sustained delivery of oxaliplatin

3D-printed chitosan-pectin-sodium alginate scaffolds for post-surgical peritoneal wound dressing and sustained delivery of oxaliplatin

Characterization of pentenoate-functionalized hyaluronic acid and pentenoate-functionalized gelatin hydrogels for printing and future surgical placement in regenerative medicine applications

Injectable hydrogels with in situ crosslinking may be more suitable than pre-fabricated scaffolds for surgical delivery to clinical injuries. However, low viscosity hydrogel precursors may be challenging to surgically place into an injury if the precursor leaks or is washed out. The biomaterials field for extrusion bioprinting is a fertile ground for discovering biomaterials with injectable and paste-like precursor rheology with in situ gelation capabilities, which may promote better material retention in clinical injuries. We previously developed and evaluated one formulation of a pentenoate-functionalized hyaluronic acid (PHA) / pentenoate-functionalized gelatin (PGel) hydrogel with a paste-like, printable precursor and rapid photocrosslinking in a spinal cord injury application. Further characterization of the material and cell response to PHA/PGel hydrogel formulations is needed to expand the bioprinting and other regenerative medicine opportunities for PHA/PGel hydrogels. In the current study, we utilized 2D NMR methods (i.e., 1H–1H TOCSY) to confirm and quantify a high degree of pentenoate functionalization of PGel and PHA. We characterized the stiffness, swelling, and cell viability using varying formulations of PGel or PHA/PGel hydrogels. For compression testing, a straightforward application of the Ogden model enabled evaluation of the full stress-strain range for improved moduli comparisons. We identified two formulations that best supported cell viability (i.e., 3%/10% and 4%/5% PHA/PGel). Furthermore, one of the identified formulations (4%/5% PHA/PGel) had superior printability compared to the other. With better printability and potentially better clinical surgical placement, the new PHA/PGel hydrogel formulations may be more widely applied in the bioprinting and regenerative medicine fields.

Development of multi-layered three-dimensional printed scaffold for sequential delivery of biomolecules

Spatiotemporal control of exogenous growth factors plays a crucial role in the sequential repair of damaged tissues. However, traditional therapeutic trials have mostly relied on the delivery of a single molecule because of the limitations of rapid diffusion and the instability of biomolecules. In this study, we developed a novel strategy using a composite of gelatin and silica as an alternative for the stable and sequential release of biomolecules. Two biomolecules, basic fibroblast growth factor and bone morphogenetic protein-2, were incorporated into two separate composites and sequentially layered onto the activated polymer surface. Each molecule was sequentially released from each layer of the scaffold and the silica composite prevented rapid diffusion owing to its nano-porous structure. The adhesion, proliferation, and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells were significantly enhanced in the double-layered group containing separately delivered dual molecules compared with the control or single groups. Our developed gelatin–silica composite was successfully placed in double layers on polymer scaffolds, and cellular responses were promoted in this manner. These results demonstrated that our scaffolding system has potential as a therapeutic strategy for the delivery of dual or multiple biomolecules in regenerative medicine.  

Composite Polycaprolactone/Gelatin Nanofiber Membrane Scaffolds for Mesothelial Cell Culture and Delivery in Mesothelium Repair.

To repair damaged mesothelium tissue, which lines internal organs and cavities, a tissue engineering approach with mesothelial cells seeded to a functional nanostructured scaffold is a promising approach. Therefore, this study explored the uses of electrospun nanofiber membrane scaffolds (NMSs) as scaffolds for mesothelial cell culture and transplantation. We fabricated a composite NMS through electrospinning by blending polycaprolactone (PCL) with gelatin. The addition of gelatin enhanced the membrane's hydrophilicity while maintaining its mechanical strength and promoted cell attachment. The in vitro study demonstrated enhanced adhesion of mesothelial cells to the scaffold with improved morphology and increased phenotypic expression of key marker proteins calretinin and E-cadherin in PCL/gelatin compared to pure PCL NMSs. In vivo studies in rats revealed that only cell-seeded PCL/gelatin NMS constructs fostered mesothelial healing. Implantation of these constructs leads to the regeneration of new mesothelium tissue. The neo-mesothelium is similar to native mesothelium from hematoxylin and eosin (H&E) and immunohistochemical staining. Taken together, the PCL/gelatin NMSs can be a promising scaffold for mesothelial cell attachment, proliferation, and differentiation, and the cell/scaffold construct can be used in therapeutic applications to reconstruct a mesothelium layer.

Electromagnetic-responsive targeted delivery scaffold technology has better potential to repair injured peripheral nerves: a narrative review

Peripheral nerve injury with long size defects has been an urgent clinical challenge. With the development of bioengineering, nanotechnology and additive manufacturing technologies, biologic delivery systems have gradually shown great potential for the treatment of peripheral nerve injury. The main problem of general biologic delivery systems is that the loading capacity of biologics is positively correlated with the release rate, and it is more difficult to achieve long-term stable release of high biologics-loaded scaffolds; thus, it is not possible to carry out full-cycle targeted therapy for peripheral nerve injury sites. To solve these problems, the mechanisms of common neurotrophic factors, bioelectrical signals and biomagnetic signals for repairing peripheral nerve injury are discussed in this paper. Moreover, this review summarizes the mechanism of electroactive and magnetoresponsive materials that have significant ability to repair peripheral nerve injury to promote nerve regeneration and provides an overview of the biologic delivery mechanism for repairing peripheral nerve injury in different structural dimensions. It was finally concluded that electromagnetic responsive targeted delivery scaffolds (four-dimensional scaffolds) have good peripheral nerve repair ability, which provides guidance for the clinical application of targeted therapy for peripheral nerve injury.

3D printed spiral tube-like cellulose scaffold for oral delivery of probiotics.

Introducing specific strains of probiotics into the gut microbiome is a promising way to modulate the intestinal microbiome to treat various health conditions clinically. However, oral probiotics typically have a temporary or limited impact on the gut microbiome and overall health benefits. Here, we reported a 3D printed cellulose-derived spiral tube-like scaffold that enabled high efficacy of the oral delivery of probiotics. Benefiting from the unique surface pattern, this system can effectively extend the retention time of loaded probiotics in the gut without invading nearby tissues, provide a favorable environment for the survival and long-term colonization of loaded probiotics, and influence the intestinal ecosystem as a dietary fiber after degradation. We demonstrate Roseburia intestinalis-loaded scaffold exerts noticeable impacts on the regulation of the gut microbiome to treat various gut-related diseases, including obesity and inflammatory bowel disease; thus, we provide a universal platform for oral delivery of probiotics.

Cell-Material Interactions in Covalent Adaptable Thioester Hydrogels.

Covalent adaptable networks (CANs) are polymeric networks with cross-links that can break and reform in response to external stimuli, including pH, shear, and temperature, making them potential materials for use as injectable cell delivery vehicles. In the native niche, cells rearrange the extracellular matrix (ECM) to undergo basic functions including migration, spreading, and proliferation. Bond rearrangement enables these hydrogels to mimic viscoelastic properties of the native ECM which promote migration and delivery from the material to the native tissue. In this work, we characterize thioester CANs to inform their design as effective cell delivery vehicles. Using bulk rheology, we characterize the rearrangement of these networks when they are subjected to strain, which mimics the strain applied by a syringe, and using multiple particle tracking microrheology (MPT) we measure cell-mediated remodeling of the pericellular region. Thioester networks are formed by photopolymerizing 8-arm poly(ethylene glycol) (PEG)-thiol and PEG-thioester norbornene. Bulk rheology measures scaffold properties during low and high strain and demonstrates that thioester scaffolds can recover rheological properties after high strain is applied. We then 3D encapsulated human mesenchymal stem cells (hMSCs) in thioester scaffolds. Using MPT, we characterize degradation in the pericellular region. Encapsulated hMSCs degrade these scaffolds within ≈4 days post-encapsulation. We hypothesize that this degradation is mainly due to cytoskeletal tension that cells apply to the matrix, causing adaptable thioester bonds to rearrange, leading to degradation. To verify this, we inhibited cytoskeletal tension using blebbistatin, a myosin-II inhibitor. Blebbistatin-treated cells can degrade these networks only by secreting enzymes including esterases. Esterases hydrolyze thioester bonds, which generate free thiols, leading to bond exchange. Around treated cells, we measure a decrease in the extent of pericellular degradation. We also compare cell area, eccentricity, and speed of untreated and treated cells. Inhibiting cytoskeletal tension results in significantly smaller cell area, more rounded cells, and lower cell speeds when compared to untreated cells. Overall, this work shows that cytoskeletal tension plays a major role in hMSC-mediated degradation of thioester networks. Cytoskeletal tension is also important for the spreading and motility of hMSCs in these networks. This work informs the design of thioester scaffolds for tissue regeneration and cell delivery.

The LINGO-1-deficient neural stem cell-derived neural tissueoid showed enhanced retention and neuronal relay in the transected spinal cord

Neural stem cell (NSC)-derived neural tissueoids are a promising option to model spinal cord development and repair; however, the survival and integration ability with the host in vivo need to be improved. We aimed to determine if genetically engineered neural tissueoids in a NT-3 delivery scaffold exhibited increased retention and relay properties and to explore the underlying mechanisms. Gene expression screening of tissue and single-nucleus RNA sequencing revealed that leucine rich repeat and immunoglobin-like domain-containing protein 1 (LINGO-1) was significantly increased in neurons following spinal cord injury. The LINGO-1 protein accelerated cell death by increasing cleaved caspase-3 and interacting with TrkC to decrease NT-3-mediated phosphorylation of the PI3K/AKT/CREB axis, resulting in synaptic degradation. Subsequently, we seeded LINGO-1-deficient NSCs on a NT-3 delivery scaffold to construct an apoptosis resistant neural tissueoids, which was transplanted into a T9 complete spinal cord injury (SCI) rat model. The LINGO-1-deficient neural tissueoid was retained in the graft area, dramatically facilitated ascending and descending nerve fiber regeneration and connection, restored relay from brain to the caudal spinal cord, and improved the hindlimb movement function. This study demonstrates that transplantation of a LINGO-1-deficient tissueoid is an efficient pro-survival and neurogenesis strategy for the treatment of SCI.

Biofabrication of aminated nanocellulose reinforced polyvinyl alcohol/chitosan nanofibrous scaffold for sustained release of diltiazem hydrochloride

In the modern environment conscious era, there has been a huge demand for the effective green method to fabricate biomaterials for sustained transdermal release of diltiazem hydrochloride to treat hypertension and cardiac failure. In this vein, the present study explores the amination of waste jute sourced nanocellulose (ANC) and its effect as a reinforcing filler to design electrospun polyvinyl alcohol (PVA)/chitosan based polymeric nanofibrous scaffold for drug delivery. The characterization results of FTIR (Fourier Transform Infrared Spectroscopy) confirm the successful chemical modification of nanocellulose (NCC). SEM (Scanning Electron Microscopy) results indicate the morphological modifications in ANC due to grafting. ANC enhances the mechanical properties of scaffold and sustains the release of the loaded drug to 67.89±3.39% as compared to the pure PVA/chitosan scaffold of 92.63±4.63% over a period of 72 h as shown by the results of in-vitro drug release study. Moreover, the incorporation of 0.5 % ANC improves the anti-bacterial activity against both gram-positive (97.4±4.87%, reduction in viable cells count) and gram-negative bacteria (98.5±4.93%, reduction in viable cells count). Further, the skin irritation and MTT assay authenticate the biocompatibility of the developed scaffold. The overall findings hence prove the efficacy of the engineered scaffold as a potential transdermal patch for sustained drug delivery applications.

Cellulose-based aerogels, films, and fibers for advanced biomedical applications

Cellulose possesses hydrophilicity, high water retention capacity, excellent mechanical properties, and biocompatibility, making it a promising candidate material for biomedical applications. As a substrate and dispersant used in the preparation of aerogels, films, and fibers, it improves their moisturizing ability, water absorption, drug utilization and slows down the rate of drug release, demonstrating outstanding therapeutic effects in biomedical research. This review summarizes and discusses the latest advancements in the application of cellulose-based aerogels, films, and fibers in the biomedical field. First, the properties of cellulose and its application principles in biomedical materials are analyzed. Second, the methods for preparing cellulose-based aerogels, films, and fibers are summarized, along with their advantages and disadvantages. Then, the latest research progress of cellulose-based aerogels, films, and fibers in drug delivery, wound dressings, and tissue engineering scaffolds is reviewed. Finally, the review concludes with a summary and provides future development directions for the field.

Magneto-mechanically derived diffusion processes in ultra-soft biological hydrogels

Magneto-active hydrogels (MAHs) consist of a polymeric network doped with magnetic particles that enable the material to mechanically respond to magnetic stimuli. This multifunctionality allows for modulation of mechanical properties in a remote and dynamic manner. These characteristics combined with the biocompatibility of hydrogels, make MAHs excellent for drug delivery and biological scaffolds. In this work, ultra-soft biological MAHs with strong magnetostriction are fabricated from human blood plasma (∼20 Pa). The material is experimentally tested using a novel in-house device that allows for a precise control of magnetic actuation conditions, enabling the hydrogel modulation in terms of mechanical deformation and stiffness. We study the impact of magnetic actuation on the solvent expulsion and diffusion dynamics within the polymeric network. To further elucidate the mechanisms driving solvent diffusion processes, a computational framework for modeling the diffusion process of two different species within a magneto-responsive material is proposed. These experimental and computational outcomes open exciting new opportunities for the use of ultra-soft MAHs in bioengineering applications.

Lignin‐based polyurethane composites enhanced with hydroxyapatite for controlled drug delivery and potential cellular scaffold applications

AbstractPolymer technology has rapidly advanced across diverse domains, particularly in biomedical applications. Among various polymers, polyurethane (PU) hold great potential in developing biomaterials such as biomedical scaffold and drug delivery. In this study, we have innovatively engineered eco‐friendly polyurethane using lignin, a sustainable bio‐polyol derived from oil palm empty fruit bunches. To enhance the physicochemical properties of the PU, we have incorporated hydroxyapatite (HA) into the composites. The inclusion of HA has led to notable improvements in crucial properties such as density, porosity, and water absorption, making these composites ideal candidates for tissue regeneration scaffolds. Furthermore, to assess their biomedical applicability in drug delivery and cell scaffolding, we have employed the quercetin drug model. The results revealed a sustained kinetic release behavior within the polyurethane/hydroxyapatite (PU/HA) composites, showcasing their potential for controlled drug delivery applications. Moreover, cytotoxicity assays conducted using neuro‐2a cell models demonstrated the non‐cytotoxic nature of both PU and PU/HA composites. This finding holds significant implications for biomedical applications, indicating that these composites offer biocompatible platforms for tissue engineering and regenerative medicine endeavors. The ability of these composites to support cell viability underscores their potential for a wide range of biomedical applications, including neural tissue engineering and drug delivery systems targeting brain diseases. These findings pave the way for the development of innovative and sustainable biomaterials with diverse biomedical applications.Highlights An eco‐friendly polyurethane has been engineered by harnessing liginin‐derived oil palm empty fruit bunches. Incorporation of hydroxyapaptite enhance the physical properties of polyurethane. Controlled kinetic drug release is one of polyurethane/hydroxyapatite (PU/HA) composites features. The PU/HA composites has low cytotoxicity against neuro‐2a cells.

DNA Tetrahedron Delivering miR-21-5p Promotes Senescent Bone Defects Repair through Synergistic Regulation of Osteogenesis and Angiogenesis.

Compromised osteogenesis and angiogenesis is the character of stem cell senescence, which brought difficulties for bone defects repairing in senescent microenvironment. As the most abundant bone-related miRNA, miRNA-21-5p plays a crucial role in inducing osteogenic and angiogenic differentiation. However, highly efficient miR-21-5p delivery still confronts challenges including poor cellular uptake and easy degradation. Herein, TDN-miR-21-5p nanocomplex is constructed based on DNA tetrahedral (TDN) and has great potential in promoting osteogenesis and alleviating senescence of senescent bone marrow stem cells (O-BMSCs), simultaneously enhancing angiogenic capacity of senescent endothelial progenitor cells (O-EPCs). Of note, the activation of AKT and Erk signaling pathway may direct regulatory mechanism of TDN-miR-21-5p mediated osteogenesis and senescence of O-BMSCs. Also, TDN-miR-21-5p can indirectly mediate osteogenesis and senescence of O-BMSCs through pro-angiogenic growth factors secreted from O-EPCs. In addition, gelatin methacryloyl (GelMA) hydrogels are mixed with TDN and TDN-miR-21-5p to fabricate delivery scaffolds. TDN-miR-21-5p@GelMA scaffold exhibits greater bone repair with increased expression of osteogenic- and angiogenic-related markers in senescent critical-size cranial defects in vivo. Collectively, TDN-miR-21-5p can alleviate senescence and induce osteogenesis and angiogenesis in senescent microenvironment, which provides a novel candidate strategy for senescent bone repair and widen clinical application of TDNs-based gene therapy.

Localized delivery of metformin via 3D printed GelMA-Nanoclay hydrogel scaffold for enhanced treatment of diabetic bone defects

BackgroundDiabetic bone defects present significant challenges for individuals with diabetes. While metformin has been explored for bone regeneration via local delivery, its application in treating diabetic bone defects remains under-explored. In this study, we aim to leverage 3D printing technology to fabricate a GelMA-Nanoclay hydrogel scaffold loaded with metformin specifically for this purpose. The objective is to assess whether the in situ release of metformin can effectively enhance osteogenesis, angiogenesis, and immunomodulation in the context of diabetic bone defects. Materials and methodsUtilizing 3D printing technology, we constructed a GelMA-Nanoclay-Metformin hydrogel scaffold with optimal physical properties and biocompatibility. The osteogenic, angiogenic, and immunomodulatory characteristics of the hydrogel scaffold were thoroughly investigated through both in vitro and in vivo experiments. ResultsGelMA10%-Nanoclay8%-Metformin5mg/mL was selected as the bioink for 3D printing due to its favorable swelling rate, degradation rate, mechanical strength, and drug release rate. Through in vitro investigations, the hydrogel scaffold extract, enriched with metformin, demonstrated a substantial enhancement in the proliferation and migration of BMSCs within a high-glucose microenvironment. It effectively enhances osteogenesis, angiogenesis, and immunomodulation. In vivo experimental outcomes further underscored the efficacy of the metformin-loaded GelMA-Nanoclay hydrogel scaffold in promoting superior bone regeneration within diabetic bone defects. ConclusionsIn conclusion, while previous studies have explored local delivery of metformin for bone regeneration, our research is pioneering in its application to diabetic bone defects using a 3D printed GelMA-Nanoclay hydrogel scaffold. This localized delivery approach demonstrates significant potential for enhancing bone regeneration in diabetic patients, offering a novel approach for treating diabetic bone defects. The translational potential of this articleOur study demonstrates, for the first time, the successful loading of the systemic antidiabetic drug metformin onto a hydrogel scaffold for localized delivery. This approach exhibits significant efficacy in mending diabetic bone defects, presenting a promising new avenue for the treatment of such conditions.

Biopolymer-Based Biomimetic Aerogel for Biomedical Applications.

Aerogels are lightweight and highly porous materials that have been found to have great potential in biomedical research because of some of their unique properties, such as their high surface area, tunable porosity, and biocompatibility. Researchers have been exploring ways to use aerogels to create biomimetic scaffolds inspired by natural extracellular matrices (ECMs) for various biomedical applications. Aerogel scaffolds can serve as three-dimensional (3D) templates for cell growth and tissue regeneration, promoting wound healing and tissue repair. Additionally, aerogel-based scaffolds have great potential in controlled drug delivery systems, where their high surface area and porosity enable the efficient loading and release of therapeutic agents. In this review, we discuss biopolymer-based biomimetic aerogel scaffolds for tissue engineering, drug delivery, and biosensors. Finally, we also discuss the potential directions in the development of aerogel-based biomimetic scaffolds.

Influence of Substrate Stiffness on iPSC-Derived Retinal Pigmented Epithelial Cells.

Retinal degenerative diseases are a major cause of blindness involving the dysfunction of photoreceptors, retinal pigmented epithelium (RPE), or both. A promising treatment approach involves replacing these cells via surgical transplantation, and previous work has shown that cell delivery scaffolds are vital to ensure sufficient cell survival. Thus, identifying scaffold properties that are conducive to cell viability and maturation (such as suitable material and mechanical properties) is critical to ensuring a successful treatment approach. In this study, we investigated the effect of scaffold stiffness on human RPE attachment, survival, and differentiation, comparing immortalized (ARPE-19) and stem cell-derived RPE (iRPE) cells. Polydimethylsiloxane was used as a model polymer substrate, and varying stiffness (~12 to 800 kPa) was achieved by modulating the cross-link-to-base ratio. Post-attachment changes in gene and protein expression were assessed using qPCR and immunocytochemistry. We found that while ARPE-19 and iRPE exhibited significant differences in morphology and expression of RPE markers, substrate stiffness did not have a substantial impact on cell growth or maturation for either cell type. These results highlight the differences in expression between immortalized and iPSC-derived RPE cells, and also suggest that stiffnesses in this range (~12-800 kPa) may not result in significant differences in RPE growth and maturation, an important consideration in scaffold design.