Oxidative stress modulating nanomaterials and their biochemical roles in nanomedicine.

Many pathological conditions are predominantly associated with oxidative stress, arising from reactive oxygen species (ROS); therefore, the modulation of redox activities has been a key strategy to restore normal tissue functions. Current approaches involve establishing a favorable cellular redox environment through the administration of therapeutic drugs and redox-active nanomaterials (RANs). In particular, RANs not only provide a stable and reliable means of therapeutic delivery but also possess the capacity to finely tune various interconnected components, including radicals, enzymes, proteins, transcription factors, and metabolites. Here, we discuss the roles that engineered RANs play in a spectrum of pathological conditions, such as cancer, neurodegenerative diseases, infections, and inflammation. We visualize the dual functions of RANs as both generator and scavenger of ROS, emphasizing their profound impact on diverse cellular functions. The focus of this review is solely on inorganic redox-active nanomaterials (inorganic RANs). Additionally, we deliberate on the challenges associated with current RANs-based approaches and propose potential research directions for their future clinical translation.

Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification.

Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m-1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural-tissue-like low conductivity (0.02-0.1 S m-1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m-1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic-transcription-factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural-tissue-like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.

Stereoselective Access to Diverse Alkaloid-Like Scaffolds via an Oxidation/Double-Mannich Reaction Sequence.

Sequential oxidative cleavage and double-Mannich reactions enable the stereoselective conversion of simple norbornenes into complex alkaloid-like structures. The products undergo a wide range of derivatization reactions, including regioselective enol triflate formation/cross-coupling sequences and highly efficient conversion to an unusual tricyclic 8,5,5-fused lactam. Overall, the process represents a formal one-atom aza-ring expansion with concomitant bridging annulation, making it of interest for the broader derivatization of alkene feedstocks.

The biological and therapeutic assessment of a P(3HB-co-4HB)-bioactive glass-graphene composite biomaterial for tissue regeneration.

An ideal wound dressing should create a healing environment that relieves pain, protects against infections, maintains moisture, removes debris, and speeds up wound closure and repair. However, conventional options like gauze often fall short in fulfilling these requirements, especially for chronic or nonhealing wounds. Hence there is a critical need for inventive formulations that offer efficient, cost-effective, and eco-friendly alternatives. This study focuses on assessing the innovative formulation based on a microbial-derived copolymer known as poly(3-hydroxybutyrate-co-4-hydroxybutyrate), P(3HB-co-4HB) bioactive glass and graphene particles, and exploring their biological response in vitro and in vivo-to find the best combination that promotes cell adhesion and enhances wound healing. The formulation optimized at concentration of bioactive glass (1 w/w%) and graphene (0.01 w/w%) showed accelerated degradation and enhanced blood vessel formation. Meanwhile biocompatibility was evaluated using murine osteoblasts, human dermal fibroblasts, and standard cell culture assays, demonstrating no adverse effects after 7 days of culture and well-regulated inflammatory kinetics. Whole thickness skin defect using mice indicated the feasibility of the biocomposites for a faster wound closure and reduced inflammation. Overall, this biocomposite appears promising as an ideal wound dressing material and positively influencing wound healing rates.

In Vitro Evaluation of Remineralization Potential of Five Toothpastes on Soft Drink-Eroded Human Enamel and Dentine.

OBJECTIVE: The purpose of this in vitro study was to evaluate the potential remineralization of enamel and dentine erosion lesions after the application of five different toothpastes. METHODOLOGY: A total of 104 enamel and dentine samples were prepared from maxillary third molars. Each group was divided according to the toothpaste application mode (topical = 56; brushing = 48) and the toothpaste used seven topical groups and six brushing groups (n = 8). The groups included negative control (NC), positive control (PC), Sensodyne Pronamel (SP), Regenerate (R), Regenerate with boosting serum (R+), Colgate Duraphat 5000 (CD), and tooth mousse (TM). RESULTS: The statistical analysis showed significant surface microhardness (SMH) change. All enamel groups showed a significant decrease in SMH compared to NC for both application modes. However, no significance was recorded between test groups. Similar results were observed between dentine groups and their relevant controls for both application modes, except brushed R and R+ groups, which were insignificant to their NC. For topical groups, TM showed a significant increase in SMH. While R and R+ showed lower loss than SP and CD. CONCLUSIONS: All tested agents offered a degree of remineralization in both enamel and dentine with no significant difference between agents in enamel groups while R, R+, and TM offered better results in dentine groups. CLINICAL SIGNIFICANCE:  For dentine groups, similar findings were observed with superior tooth surface protection with the application of TM over other agents. Tooth surface remineralization was achieved when agents were either applied topically or brushed over the surface.

Titanium-doped phosphate glasses containing zinc and strontium applied in bone regeneration.

Phosphate bioactive glass has been studied for its advanced biodegradability and active ion release capability. Our previous research found that phosphate glass containing (P2O5)-(Na2O)-(TiO2)-(CaO)-(SrO) or (ZnO) showed good biocompatibility with MG63 and hMSCs. This study further investigated the application of 5 mol% zinc oxide or 17.5 mol% strontium oxide in titanium-doped phosphate glass for bone tissue engineering. Ti-Ca-Na-Phosphate glasses, incorporating 5% zinc oxide or 17.5% strontium oxide, were made with melting quenching technology. The pre-osteoblast cell line MC3T3-E1 was cultured for indirect contact tests with graded diluted phosphate glass extractions and for direct contact tests by seeding cells on glass disks. The cell viability and cytotoxicity were analysed in vitro over 7 days. In vivo studies utilized the tibial defect model with or without glass implants. The micro-CT analysis was performed after surgery and then at 2, 6, and 12 weeks. Extractions from both zinc and strontium phosphate glasses showed no negative impact on MC3T3-E1 cell viability. Notably, non-diluted Zn-Ti-Ca-Na-phosphate glass extracts significantly increased cell viability by 116.8% (P < 0.01). Furthermore, MC3T3-E1 cells cultured with phosphate glass disks exhibited no increase in LDH release compared with the control group. Micro-CT images revealed that, over 12 weeks, both zinc-doped and strontium-doped phosphate glasses demonstrated good bone incorporation and longevity compared to the no-implant control. Titanium-doped phosphate glasses containing 5 mol% zinc oxide, or 17.5 mol% strontium oxide have promising application potential for bone regeneration research.

3D Porous Binary Composites of Collagen, Elastin, and Fibrin Proteins Orchestrate Adipose Tissue Regeneration.

The objective for this study is to advance the development of a specialized biomaterial that can effectively facilitate the regeneration of adipose tissue. In prior studies, the assessment of collagen (Col), elastin (Ela), and fibrin (Fib) unary scaffolds has been conducted. However, it is important to note that native adipose tissue is comprised of a diverse array of extracellular matrix (ECM) constituents. To mimic this behavior, binary compositions of collagen, elastin, and fibrin are fabricated in a 1:1 ratio, resulting in the formation of Col/Ela, Col/Fib, and Ela/Fib composites through a customized fabrication procedure. The physical properties of these scaffolds are comprehensively analyzed using a range of material characterization techniques. Additionally, the biological properties of the scaffolds are investigated by examining the survival, proliferation, and phenotype of adipose-derived stem cells. Subsequently, the aforementioned binary scaffolds are implanted into a rodent model for 28 days. the explants are analysed through X-ray microtomography, histology, and immunohistochemistry. The findings of the study demonstrate that the utilization of binary combinations of Col/Ela, Col/Fib, and Ela/Fib has a discernible impact on the physical and biological characteristics of the scaffolds. Nevertheless, Ela/Fib exhibits characteristics that make it a suitable candidate for adipogenesis due to its notable upregulation of caveolin-1 expression in both acellular and cellular cohorts. The combination of two natural polymers in this cell-material interaction has significantly enhanced the comprehension of adipogenesis.

In Vivo Osteogenic and Angiogenic Properties of a 3D-Printed Isosorbide-Based Gyroid Scaffold Manufactured via Digital Light Processing.

INTRODUCTION: Osteogenic and angiogenic properties of synthetic bone grafts play a crucial role in the restoration of bone defects. Angiogenesis is recognised for its support in bone regeneration, particularly in larger defects. The objective of this study is to evaluate the new bone formation and neovascularisation of a 3D-printed isosorbide-based novel CSMA-2 polymer in biomimetic gyroid structures. METHODS: The gyroid scaffolds were fabricated by 3D printing CSMA-2 polymers with different hydroxyapatite (HA) filler concentrations using the digital light processing (DLP) method. A small animal subcutaneous model and a rat calvaria critical-size defect model were performed to analyse tissue compatibility, angiogenesis, and new bone formation. RESULTS: The in vivo results showed good biocompatibility of the 3D-printed gyroid scaffolds with no visible prolonged inflammatory reaction. Blood vessels were found to infiltrate the pores from day 7 of the implantation. New bone formation was confirmed with positive MT staining and BMP-2 expression, particularly on scaffolds with 10% HA. Bone volume was significantly higher in the CSMA-2 10HA group compared to the sham control group. DISCUSSION AND CONCLUSIONS: The results of the subcutaneous model demonstrated a favourable tissue response, including angiogenesis and fibrous tissue, indicative of the early wound healing process. The results from the critical-size defect model showcased new bone formation, as confirmed by micro-CT imaging and immunohistochemistry. The combination of CSMA-2 as the 3D printing material and the gyroid as the 3D structure was found to support essential events in bone healing, specifically angiogenesis and osteogenesis.

Biosubstitutes for dural closure: Unveiling research, application, and future prospects of dura mater alternatives.

The dura mater, as the crucial outermost protective layer of the meninges, plays a vital role in safeguarding the underlying brain tissue. Neurosurgeons face significant challenges in dealing with trauma or large defects in the dura mater, as they must address the potential complications, such as wound infections, pseudomeningocele formation, cerebrospinal fluid leakage, and cerebral herniation. Therefore, the development of dural substitutes for repairing or reconstructing the damaged dura mater holds clinical significance. In this review we highlight the progress in the development of dural substitutes, encompassing autologous, allogeneic, and xenogeneic replacements, as well as the polymeric-based dural substitutes fabricated through various scaffolding techniques. In particular, we explore the development of composite materials that exhibit improved physical and biological properties for advanced dural substitutes. Furthermore, we address the challenges and prospects associated with developing clinically relevant alternatives to the dura mater.

Lithium-loaded GelMA-Phosphate glass fibre constructs: Implications for astrocyte response.

Combinations of different biomaterials with their own advantages as well as functionalization with other components have long been implemented in tissue engineering to improve the performance of the overall material. Biomaterials, particularly hydrogel platforms, have shown great potential for delivering compounds such as drugs, growth factors, and neurotrophic factors, as well as cells, in neural tissue engineering applications. In central the nervous system, astrocyte reactivity and glial scar formation are significant and complex challenges to tackle for neural and functional recovery. GelMA hydrogel-based tissue constructs have been developed in this study and combined with two different formulations of phosphate glass fibers (PGFs) (with Fe3+ or Ti2+ oxide) to impose physical and mechanical cues for modulating astrocyte cell behavior. This study was also aimed at investigating the effects of lithium-loaded GelMA-PGFs hydrogels in alleviating astrocyte reactivity and glial scar formation offering novel perspectives for neural tissue engineering applications. The rationale behind introducing lithium is driven by its long-proven therapeutic benefits in mental disorders, and neuroprotective and pronounced anti-inflammatory properties. The optimal concentrations of lithium and LPS were determined in vitro on primary rat astrocytes. Furthermore, qPCR was conducted for gene expression analysis of GFAP and IL-6 markers on primary astrocytes cultured 3D into GelMA and GelMA-PGFs hydrogels with and without lithium and in vitro stimulated with LPS for astrocyte reactivity. The results suggest that the combination of bioactive phosphate-based glass fibers and lithium loading into GelMA structures may impact GFAP expression and early IL-6 expression. Furthermore, GelMA-PGFs (Fe) constructs have shown improved performance in modulating glial scarring over GFAP regulation.

Normal Ileal Mucus Is Inadequate for Epithelial Protection in Ileal Pouch Mucosa.

BACKGROUND: Clinical, nonspecific pouchitis is common after restorative proctocolectomy for ulcerative colitis, but its cause is unknown. A possible lack of protection for the ileal mucosa in its role as a reservoir for colonic-type bacteria may be the missing piece in defining the causes of pouchitis. OBJECTIVE: The study aimed to review the causes of pouchitis and introduce the hypothesis that inadequate mucus protection in the pouch, combined with a predisposition to abnormal inflammation, is the most common cause of nonspecific pouchitis. DATA SOURCES: Review of PubMed and MEDLINE for articles discussing pouchitis and intestinal mucus. STUDY SELECTION: Studies published from 1960 to 2023. The main search terms were "pouchitis," and "intestinal mucus," whereas Boolean operators were used with multiple other terms to refine the search. Duplicates and case reports were excluded. MAIN OUTCOME MEASURES: Current theories about the cause of pouchitis, descriptions of the role of mucus in the physiology of intestinal protection, and evidence of the effects of lack of mucus on mucosal inflammation. RESULTS: The crossreference of "intestinal mucus" with "pouchitis" produced 9 references, none of which discussed the role of mucus in the development of pouchitis. Crossing "intestinal mucus" with "pouch" resulted in 32 articles, combining "pouchitis" with "barrier function" yielded 37 articles, and "pouchitis" with "permeability" yielded only 8 articles. No article discussed the mucus coat as a barrier to bacterial invasion of the epithelium or mentioned inadequate mucus as a factor in pouchitis. However, an ileal pouch produces a colonic environment in the small bowel, and the ileum lacks the mucus protection needed for this sort of environment. This predisposes pouch mucosa to bacterial invasion and chronic microscopic inflammation that may promote clinical pouchitis in patients prone to an autoimmune response. LIMITATIONS: No prior studies address inadequate mucus protection and the origin of proctitis. There is no objective way of measuring the autoimmune tendency in patients with ulcerative colitis. CONCLUSIONS: Studies of intestinal mucus in the ileal pouch and its association with pouchitis are warranted.

Highly porous phosphate-based glasses for controlled delivery of antibacterial Cu ions prepared via sol-gel chemistry.

Mesoporous glasses are a promising class of bioresorbable biomaterials characterized by high surface area and extended porosity in the range of 2 to 50 nm. These peculiar properties make them ideal materials for the controlled release of therapeutic ions and molecules. Whilst mesoporous silicate-based glasses (MSG) have been widely investigated, much less work has been done on mesoporous phosphate-based glasses (MPG). In the present study, MPG in the P2O5-CaO-Na2O system, undoped and doped with 1, 3, and 5 mol% of Cu ions were synthesized via a combination of the sol-gel method and supramolecular templating. The non-ionic triblock copolymer Pluronic P123 was used as a templating agent. The porous structure was studied via a combination of Scanning Electron Microscopy (SEM), Small-Angle X-ray Scattering (SAXS), and N2 adsorption-desorption analysis at 77 K. The structure of the phosphate network was investigated via solid state 31P Magic Angle Spinning Nuclear Magnetic Resonance (31P MAS-NMR) and Fourier Transform Infrared (FTIR) spectroscopy. Degradation studies, performed in water via Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), showed that phosphates, Ca2+, Na+ and Cu ions are released in a controlled manner over a 7 days period. The controlled release of Cu, proportional to the copper loading, imbues antibacterial properties to MPG. A significant statistical reduction of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacterial viability was observed over a 3 days period. E. coli appeared to be more resistant than S. aureus to the antibacterial effect of copper. This study shows that copper doped MPG have great potential as bioresorbable materials for controlled delivery of antibacterial ions.

3D Bioprinting tissue analogs: Current development and translational implications.

Three-dimensional (3D) bioprinting is a promising and rapidly evolving technology in the field of additive manufacturing. It enables the fabrication of living cellular constructs with complex architectures that are suitable for various biomedical applications, such as tissue engineering, disease modeling, drug screening, and precision regenerative medicine. The ultimate goal of bioprinting is to produce stable, anatomically-shaped, human-scale functional organs or tissue substitutes that can be implanted. Although various bioprinting techniques have emerged to develop customized tissue-engineering substitutes over the past decade, several challenges remain in fabricating volumetric tissue constructs with complex shapes and sizes and translating the printed products into clinical practice. Thus, it is crucial to develop a successful strategy for translating research outputs into clinical practice to address the current organ and tissue crises and improve patients' quality of life. This review article discusses the challenges of the existing bioprinting processes in preparing clinically relevant tissue substitutes. It further reviews various strategies and technical feasibility to overcome the challenges that limit the fabrication of volumetric biological constructs and their translational implications. Additionally, the article highlights exciting technological advances in the 3D bioprinting of anatomically shaped tissue substitutes and suggests future research and development directions. This review aims to provide readers with insight into the state-of-the-art 3D bioprinting techniques as powerful tools in engineering functional tissues and organs.

Stereoselective two-carbon ring expansion of allylic amines via electronic control of palladium-promoted equilibria.

General methodologies enabling the two-carbon homologation of pyrrolidine and piperidine systems have yet to be developed. Herein we report that palladium-catalysed allylic amine rearrangements enable efficient two-carbon ring expansion of 2-alkenyl pyrrolidine and piperidines to their azepane and azocane counterparts. Conditions are mild, tolerant of a range of functional groups and the process can occur with high enantioretention. The products formed undergo a range of orthogonal transformations, making them ideal scaffolds for the creation of compound libraries.

Physicochemical, Biological, and Antibacterial Properties of Four Bioactive Calcium Silicate-Based Cements.

Calcium silicate-based cement (CSC) is a pharmaceutical agent that is widely used in dentistry. This bioactive material is used for vital pulp treatment due to its excellent biocompatibility, sealing ability, and antibacterial activity. Its drawbacks include a long setting time and poor maneuverability. Hence, the clinical properties of CSC have recently been improved to decrease its setting time. Despite the widespread clinical usage of CSC, there is no research comparing recently developed CSCs. Therefore, the purpose of this study is to compare the physicochemical, biological, and antibacterial properties of four commercial CSCs: two powder-liquid mix types (RetroMTA® [RETM]; Endocem® MTA Zr [ECZR]) and two premixed types (Well-Root™ PT [WRPT]; Endocem® MTA premixed [ECPR]). Each sample was prepared using circular Teflon molds, and tests were conducted after 24 h of setting. The premixed CSCs exhibited a more uniform and less rough surface, higher flowability, and lower film thickness than the powder-liquid mix CSCs. In the pH test, all CSCs showed values between 11.5 and 12.5. In the biological test, cells exposed to ECZR at a concentration of 25% showed greater cell viability, but none of the samples showed a significant difference at low concentration (p > 0.05). Alkaline phosphatase staining revealed that cells exposed to ECZR underwent more odontoblast differentiation than the cells exposed to the other materials; however, no significant difference was observed at a concentration of 12.5% (p > 0.05). In the antibacterial test, the premixed CSCs showed better results than the powder-liquid mix CSCs, and ECPR yielded the best results, followed by WRPT. In conclusion, the premixed CSCs showed improved physical properties, and of the premixed types, ECPR exhibited the highest antibacterial properties. For biological properties, none of these materials showed significant differences at 12.5% dilution. Therefore, ECPR may be a promising material with high antibacterial activity among the four CSCs, but further investigation is needed for clinical situations.

Biodegradable and Sustainable Synthetic Antibodies-A Perspective.

Molecular imprinting technology has been around for almost a century, and we have witnessed dramatic advancements in the overall design and production of molecularly imprinted polymers (MIPs), particularly in terms of possible formats of the final products when it comes to truly resembling antibody substitutes, i.e., MIP nanoparticles (MIP NPs). Nonetheless, the overall technology appears to struggle to keep up with the current global sustainability efforts, as recently elucidated in the latest comprehensive reviews, which introduced the "GREENIFICATION" concept. In this review, we will try to elucidate if these advancements in MIP nanotechnology have indeed resulted in a sustainability amelioration. We will do so by discussing the general production and purification strategies for MIP NPs, specifically from a sustainability and biodegradation perspective, also considering the final intended application and ultimate waste management.

Influence of Gelatin Source and Bloom Number on Gelatin Methacryloyl Hydrogels Mechanical and Biological Properties for Muscle Regeneration.

Approximately half of an adult human's body weight is made up of muscles. Thus, restoring the functionality and aesthetics of lost muscle tissue is critical. The body is usually able to repair minor muscle injuries. However, when volumetric muscle loss occurs due to tumour extraction, for instance, the body will form fibrous tissue instead. Gelatin methacryloyl (GelMA) hydrogels have been applied for drug delivery, tissue adhesive, and various tissue engineering applications due to their tuneable mechanical properties. Here, we have synthesised GelMA from different gelatin sources (i.e., porcine, bovine, and fish) with varying bloom numbers, which refers to the gel strength, and investigated for the influence of the source of gelatin and the bloom number on biological activities and mechanical properties. The results indicated that the source of the gelatin and variable bloom numbers have an impact on GelMA hydrogel properties. Furthermore, our findings established that the bovine-derived gelatin methacryloyl (B-GelMA) has better mechanical properties than the other varieties composed of porcine and fish with 60 kPa, 40 kPa, and 10 kPa in bovine, porcine, and fish, respectively. Additionally, it showed a noticeably greater swelling ratio (SR) ~1100% and a reduced rate of degradation, improving the stability of hydrogels and giving cells adequate time to divide and proliferate to compensate for muscle loss. Furthermore, the bloom number of gelatin was also proven to influence the mechanical properties of GelMA. Interestingly, although GelMA made of fish had the lowest mechanical strength and gel stability, it demonstrated excellent biological properties. Overall, the results emphasise the importance of gelatin source and bloom number, allowing GelMA hydrogels to have a wide range of mechanical and excellent biological properties and making them suitable for various muscle tissue regeneration applications.

Physicochemical, Pre-Clinical, and Biological Evaluation of Viscosity Optimized Sodium Iodide-Incorporated Paste.

This study aimed to investigate the impact of different viscosities of silicone oil on the physicochemical, pre-clinical usability, and biological properties of a sodium iodide paste. Six different paste groups were created by mixing therapeutic molecules, sodium iodide (D30) and iodoform (I30), with calcium hydroxide and one of the three different viscosities of silicone oil (high (H), medium (M), and low (L)). The study evaluated the performance of these groups, including I30H, I30M, I30L, D30H, D30M, and D30L, using multiple parameters such as flow, film thickness, pH, viscosity, and injectability, with statistical analysis (p < 0.05). Remarkably, the D30L group demonstrated superior outcomes compared to the conventional iodoform counterpart, including a significant reduction in osteoclast formation, as examined through TRAP, c-FOS, NFATc1, and Cathepsin K (p < 0.05). Additionally, mRNA sequencing showed that the I30L group exhibited increased expression of inflammatory genes with upregulated cytokines compared to the D30L group. These findings suggest that the optimized viscosity of the sodium iodide paste (D30L) may lead to clinically favorable outcomes, such as slower root resorption, when used in primary teeth. Overall, the results of this study suggest that the D30L group shows the most satisfactory outcomes, which may be a promising root-filling material that could replace conventional iodoform-based pastes.

Materials and extracellular matrix rigidity highlighted in tissue damages and diseases: Implication for biomaterials design and therapeutic targets.

Rigidity (or stiffness) of materials and extracellular matrix has proven to be one of the most significant extracellular physicochemical cues that can control diverse cell behaviors, such as contractility, motility, and spreading, and the resultant pathophysiological phenomena. Many 2D materials engineered with tunable rigidity have enabled researchers to elucidate the roles of matrix biophysical cues in diverse cellular events, including migration, lineage specification, and mechanical memory. Moreover, the recent findings accumulated under 3D environments with viscoelastic and remodeling properties pointed to the importance of dynamically changing rigidity in cell fate control, tissue repair, and disease progression. Thus, here we aim to highlight the works related with material/matrix-rigidity-mediated cell and tissue behaviors, with a brief outlook into the studies on the effects of material/matrix rigidity on cell behaviors in 2D systems, further discussion of the events and considerations in tissue-mimicking 3D conditions, and then examination of the in vivo findings that concern material/matrix rigidity. The current discussion will help understand the material/matrix-rigidity-mediated biological phenomena and further leverage the concepts to find therapeutic targets and to design implantable materials for the treatment of damaged and diseased tissues.

Digital Light Processing 3D Printing of Gyroid Scaffold with Isosorbide-Based Photopolymer for Bone Tissue Engineering.

As one of the most transplanted tissues of the human body, bone has varying architectures, depending on its anatomical location. Therefore, bone defects ideally require bone substitutes with a similar structure and adequate strength comparable to native bones. Light-based three-dimensional (3D) printing methods allow the fabrication of biomimetic scaffolds with high resolution and mechanical properties that exceed the result of commonly used extrusion-based printing. Digital light processing (DLP) is known for its faster and more accurate printing than other 3D printing approaches. However, the development of biocompatible resins for light-based 3D printing is not as rapid as that of bio-inks for extrusion-based printing. In this study, we developed CSMA-2, a photopolymer based on Isosorbide, a renewable sugar derivative monomer. The CSMA-2 showed suitable rheological properties for DLP printing. Gyroid scaffolds with high resolution were successfully printed. The 3D-printed scaffolds also had a compressive modulus within the range of a human cancellous bone modulus. Human adipose-derived stem cells remained viable for up to 21 days of incubation on the scaffolds. A calcium deposition from the cells was also found on the scaffolds. The stem cells expressed osteogenic markers such as RUNX2, OCN, and OPN. These results indicated that the scaffolds supported the osteogenic differentiation of the progenitor cells. In summary, CSMA-2 is a promising material for 3D printing techniques with high resolution that allow the fabrication of complex biomimetic scaffolds for bone regeneration.