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.

Improvement of Biological Effects of Root-Filling Materials for Primary Teeth by Incorporating Sodium Iodide.

Therapeutic iodoform (CHI3) is commonly used as a root-filling material for primary teeth; however, the side effects of iodoform-containing materials, including early root resorption, have been reported. To overcome this problem, a water-soluble iodide (NaI)-incorporated root-filling material was developed. Calcium hydroxide, silicone oil, and NaI were incorporated in different weight proportions (30:30:X), and the resulting material was denoted DX (D5~D30), indicating the NaI content. As a control, iodoform instead of NaI was incorporated at a ratio of 30:30:30, and the material was denoted I30. The physicochemical (flow, film thickness, radiopacity, viscosity, water absorption, solubility, and ion releases) and biological (cytotoxicity, TRAP, ARS, and analysis of osteoclastic markers) properties were determined. The amount of iodine, sodium, and calcium ion releases and the pH were higher in D30 than I30, and the highest level of unknown extracted molecules was detected in I30. In the cell viability test, all groups except 100% D30 showed no cytotoxicity. In the 50% nontoxic extract, D30 showed decreased osteoclast formation compared with I30. In summary, NaI-incorporated materials showed adequate physicochemical properties and low osteoclast formation compared to their iodoform-counterpart. Thus, NaI-incorporated materials may be used as a substitute for iodoform-counterparts in root-filling materials after further (pre)clinical investigation.

Enhancing Distraction Osteogenesis With Carbon Fiber Reinforced Polyether Ether Ketone Bone Pins and a Three-Dimensional Printed Transfer Device to Permit Artifact-Free Three-Dimensional Magnetic Resonance Imaging.

OBJECTIVES: To: (1) design an artifact-free 3D-printed MR-safe temporary transfer device, (2) engineer bone-pins from carbon fiber reinforced polyether ether ketone (CFR-PEEK), (3) evaluate the imaging artifacts of CFR-PEEK, and (4) confirm the osteointegration potential of CFR-PEEK, thus enhancing 3D-planning of bony advancements in hemifacial microsomia using sequential magnetic resonance imaging (MRI). STUDY DESIGN: Engineered CRF-PEEK bone pins and a 3D printed ex-fix device were implanted into a sheep head and imaged with MRI and computed tomography . The osseointegration and bony compatibility potential of CFR-PEEK was assessed with scanning electron microscopy images of MC3T3 preosteoblast cells on the surface of the material. RESULTS: The CFR-PEEK pins resulted in a signal void equivalent to the dimension of the pin, with no adjacent areas of MR-signal loss or computed tomography artifact. MCT3 cells adhered and proliferated on the surface of the discs by forming a monolayer of cells, confirming compatibility and osseointegration potential. CONCLUSION: A 3D printed transfer device could be utilized temporarily during MRI to permit artifact-free 3D planning. CFR-PEEK pins eliminate imaging artifact permitting sequential MRI examination. In combination, this has the potential to enhance distraction osteogenesis, by permitting accurate three-dimensional planning without ionizing radiation.

Controlled Delivery of Pan-PAD-Inhibitor Cl-Amidine Using Poly(3-Hydroxybutyrate) Microspheres.

This study deals with the process of optimization and synthesis of Poly(3-hydroxybutyrate) microspheres with encapsulated Cl-amidine. Cl-amidine is an inhibitor of peptidylarginine deiminases (PADs), a group of calcium-dependent enzymes, which play critical roles in a number of pathologies, including autoimmune and neurodegenerative diseases, as well as cancer. While Cl-amidine application has been assessed in a number of in vitro and in vivo models; methods of controlled release delivery remain to be investigated. P(3HB) microspheres have proven to be an effective delivery system for several compounds applied in antimicrobial, wound healing, cancer, and cardiovascular and regenerative disease models. In the current study, P(3HB) microspheres with encapsulated Cl-amidine were produced in a size ranging from ~4-5 µm and characterized for surface morphology, porosity, hydrophobicity and protein adsorption, in comparison with empty P(3HB) microspheres. Cl-amidine encapsulation in P(3HB) microspheres was optimized, and these were found to be less hydrophobic, compared with the empty microspheres, and subsequently adsorbed a lower amount of protein on their surface. The release kinetics of Cl-amidine from the microspheres were assessed in vitro and expressed as a function of encapsulation efficiency. There was a burst release of ~50% Cl-amidine in the first 24 h and a zero order release from that point up to 16 days, at which time point ~93% of the drug had been released. As Cl-amidine has been associated with anti-cancer effects, the Cl-amidine encapsulated microspheres were assessed for the inhibition of vascular endothelial growth factor (VEGF) expression in the mammalian breast cancer cell line SK-BR-3, including in the presence of the anti-proliferative drug rapamycin. The cytotoxicity of the combinatorial effect of rapamycin with Cl-amidine encapsulated P(3HB) microspheres was found to be 3.5% more effective within a 24 h period. The cells treated with Cl-amidine encapsulated microspheres alone, were found to have 36.5% reduction in VEGF expression when compared with untreated SK-BR-3 cells. This indicates that controlled release of Cl-amidine from P(3HB) microspheres may be effective in anti-cancer treatment, including in synergy with chemotherapeutic agents. Using controlled drug-delivery of Cl-amidine encapsulated in Poly(3-hydroxybutyrate) microspheres may be a promising novel strategy for application in PAD-associated pathologies.

Biosynthesis and characterization of a novel, biocompatible medium chain length polyhydroxyalkanoate by Pseudomonas mendocina CH50 using coconut oil as the carbon source.

This study validated the utilization of triacylglycerides (TAGs) by Pseudomonas mendocina CH50, a wild type strain, resulting in the production of novel mcl-PHAs with unique physical properties. A PHA yield of 58% dcw was obtained using 20 g/L of coconut oil. Chemical and structural characterisation confirmed that the mcl-PHA produced was a terpolymer comprising of three different repeating monomer units, 3-hydroxyoctanoate, 3-hydroxydecanoate and 3-hydroxydodecanoate or P(3HO-3HD-3HDD). Bearing in mind the potential of P(3HO-3HD-3HDD) in biomedical research, especially in neural tissue engineering, in vitro biocompatibility studies were carried out using NG108-15 (neuronal) cells. Cell viability data confirmed that P(3HO-3HD-3HDD) supported the attachment and proliferation of NG108-15 and was therefore confirmed to be biocompatible in nature and suitable for neural regeneration.

Biospectroscopy of Nanodiamond-Induced Alterations in Conformation of Intra- and Extracellular Proteins: A Nanoscale IR Study.

The toxicity of nanomaterials raises major concerns because of the impact that nanomaterials may have on health, which remains poorly understood. We need to explore the fate of individual nanoparticles in cells at nano and molecular levels to establish their safety. Conformational changes in secondary protein structures are one of the main indicators of impaired biological function, and hence, the ability to identify these changes at a nanoscale level offers unique insights into the nanotoxicity of materials. Here, we used nanoscale infrared spectroscopy and demonstrated for the first time that nanodiamond-induced alterations in both extra- and intracellular secondary protein structures lead to the formation of antiparallel ß-sheet, ß-turns, intermolecular ß-sheet, and aggregation of proteins. These conformational changes of the protein structure may result in the loss of functionality of proteins and in turn lead to adverse effects.

Electrohydrodynamic encapsulation of cisplatin in poly (lactic-co-glycolic acid) nanoparticles for controlled drug delivery.

Targeted delivery of potent, toxic chemotherapy drugs, such as cisplatin, is a significant area of research in cancer treatment. In this study, cisplatin was successfully encapsulated with high efficiency (>70%) in poly (lactic-co-glycolic acid) polymeric nanoparticles by using electrohydrodynamic atomization (EHDA) where applied voltage and solution flow rate as well as the concentration of cisplatin and polymer were varied to control the size of the particles. Thus, nanoparticles were produced with three different drug:polymer ratios (2.5, 5 and 10wt% cisplatin). It was shown that smaller nanoparticles were produced with 10wt% cisplatin. Furthermore, these demonstrated the best sustained release (smallest burst release). By fitting the experimental data with various kinetic models it was concluded that the release is dependent upon the particle morphology and the drug concentration. Thus, these particles have significant potential for cisplatin delivery with controlled dosage and release period that are crucial chemotherapy parameters.

Degradation of zinc containing phosphate-based glass as a material for orthopedic tissue engineering.

Phosphate-based glasses have been examined in many studies as a potential biomaterial for bone repair because of its degradation properties, which can be controlled and allow the release of various elements to promote osteogenic tissue growth. However most of these experiments studied either tertiary or quaternary glass systems. This study investigated a qinternary system that included titanium dioxide for degradation rate control and zinc that is considered to have a role in bone formation. Zinc and titanium phosphate glass discs of different compositions were melt synthesized and samples of each composition was tested for different physical, chemical and biological characteristics via density measurement, X-ray diffraction, differential thermal analysis, mass loss, ion release, scanning electron microscopy, biocompatibility studies via live/dead assays at three time points (day 1, 4, and 7). The results showed that the glass was amorphous and that the all thermal variables decreased as zinc oxide amount raised, mass loss as well as ion release increased as zinc oxide increased, and the maximum rise was with ZnO15. The cellular studies showed that all the formulation showed similar cytocompatibility properties with MG63 except ZnO15, which displayed cytotoxic properties and this was confirmed also by the scanning electron microscope images. In conclusion, replacing calcium oxide with zinc oxide in proportion less than 10 % can have a positive effect on bone forming cells.

Calcium Phosphonate Frameworks for Treating Bone Tissue Disorders.

Two new examples of uncommon three-dimensional Ca-bearing metal organic frameworks, [Ca(H2O)3(HPXBP)] (CaP1) and [Ca2(H2O)2(HPXBP)1.5] (CaP2) (PXBP: p-xylylenebisphosphonate), were prepared and their structures characterized by single crystal X-ray diffraction. CaP1 crystallizes in the monoclinic C2/c space group, with three water molecules occupying a half coordination sphere on one side of the Ca atom, while CaP2 crystallizes in the triclinic P1̅ space group, with two crystallographic unique Ca atoms, each coordinated by a single water molecule. In contrast with CaP2, which exhibits very low bioactivity, CaP1 readily precipitates bone-precursor phases (octacalcium phosphate, OCP, and hydroxyapatite) in SBF solutions. Moreover, studies with MG63 osteoblast-like cells indicate that CaP1 is not toxic and stimulates bone mineralization and, thus, holds considerable potential for treating bone diseases, such as osteoporosis.

Hydroxyapatite, fluor-hydroxyapatite and fluorapatite produced via the sol-gel method: dissolution behaviour and biological properties after crystallisation.

Hydroxyapatite (HA), fluor-hydroxyapatite (FHA) with varying levels of fluoride ion substitution and fluorapatite (FA) were synthesised by the sol-gel method as possible implant coating or bone-grafting materials. Calcium nitrate and triethyl phosphite were used as precursors under an ethanol-water based solution. Different amounts of ammonium fluoride were incorporated for the preparation of the FHA and FA sol-gels. After heating and powdering the sol-gels, dissolution behaviour was assessed using ion chromatography to measure Ca(2+) and PO4 (3-) ion release. Biological behaviour was assessed using cellular proliferation with human osteosarcoma cells and alamarBlue™ assay. Statistical analysis was performed with a two way analysis of variance and post hoc testing with a Bonferroni correction. Increasing fluoride substitution into an apatite structure decreased the dissolution rate. Increasing the firing temperature of the HA, FHA and FA sol-gels up to 1,000 °C decreased the dissolution rate. There was significantly higher cellular proliferation on highly substituted FHA and FA than on HA or Titanium. The properties of an implant coating or bone grafting material can be tailored to meet specific requirements by altering the amount of fluoride that is incorporated into the original apatite structure. The dissolution behaviour can further be altered by the temperature at which the sol-gel is fired.

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.

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.

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.

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.

Catalyst-free synthesis of high elongation degradable polyurethanes containing varying ratios of isosorbide and polycaprolactone: physical properties and biocompatibility.

Biocompatible and biodegradable polyurethanes were prepared with fixed aliphatic diisocyanate level and varying ratios of isosorbide, and PCL diol via a simple one-shot polymerization without a catalyst. The successful synthesis of the polyurethanes was confirmed by gel permeation chromatography, (1)H-nuclear magnetic resonance and Fourier transform-infrared spectroscopies and the thermal properties were determined by differential scanning calorimetry and showed glass transition temperatures of around 30-35 °C. The degradation tests were performed at 37 °C in phosphate buffer solution (approx. pH 7.3) and showed a mass loss of around 5 % after 12 weeks, except for the polymer with the highest isosorbide content which showed an initial rapid mass loss. The in vitro cytocompatibility test results following culture of osteoblasts on the polymer surface showed that relative cell number on all of the polyurethane films after 5 days of cultured on polymer films was lower compared to the proliferation rate on the optimized tissue culture plastic. These polymers offer significant promise due to the simplicity of the synthesis and the controlled degradation.

Comparison of mesenchymal stem cell proliferation and differentiation between biomimetic and electrochemical coatings on different topographic surfaces.

The hypothesis for this study was that there is no difference in mesenchymal stem cells (MSCs) proliferation and osteogenic differentiation between calcium-phosphate (CaP) coatings with different crystal size deposited on different topographic surfaces of metal discs. Polished (P) and sand-blasted (SB) tantalum and TiAl6V4 discs were CaP coated by three methods-biomimetic (BioM), electrochemical at 20 mA/cm(2) and at 6.5 mA/cm(2)-and cultured with MSCs. At days 4, 7 and 14, cell proliferation-alamarBlue(®) activity and DNA quantification-and differentiation down the osteogenic lineage-ALP activity normalised per amount of DNA and SEM (morphology)-were analysed. Results showed that MSCs proliferated more when cultured on the nano-sized BioM coatings compared to uncoated and electrochemically coated discs. MSCs also proliferated more on P surfaces than on SB and or electrochemical coatings. All the coatings induced osteogenic differentiation, which was greater on electrochemical coatings and SB discs.

Application of high-strength biodegradable polyurethanes containing different ratios of biobased isomannide and poly (ϵ-caprolactone) diol.

Biodegradable-biocompatible polyurethanes were prepared with fixed hexamethylene diisocyanate and varying ratios of isomannide and poly(ϵ-caprolactone) diol using a simple one-step polymerization without a catalyst. The polyurethane structures were confirmed by 1H-nuclear magnetic resonance, Fourier transform infrared spectroscopy, and gel permeation chromatography. The glass transition temperatures were determined by thermal analysis to be between 25°C and 30°C. Degradation tests performed at 37°C in phosphate buffer produced mass losses of 5%-10% after 8 weeks. After 5 days of culture, using osteoblastic cells, the relative cell number on all the polyurethane films was only slightly lower than that of an optimized tissue culture plastic. These polymers offer significant promise with a simplistic synthesis and controlled degradation.

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.

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.