搜索结果：Journal of biomedical materials research. Part A

S. aureus plays a central role in chronic rhinosinusitis (CRS), contributing to acute exacerbations and persistent infections through biofilm formation. With rising antibiotic resistance, bioactive glasses such as F18 and 45S5 have emerged as potential alternative antimicrobial agents. To evaluate the antimicrobial effects of F18 and 45S5 on S. aureus isolates from CRS patients, focusing on planktonic growth, biofilm formation, and mechanisms of action. Clinical S. aureus isolates were exposed to F18 and 45S5 (0-512 μg/mL) using a modified Calgary Biofilm Device. Biofilm biomass was quantified by crystal violet staining and spectrophotometry. A pH-controlled assay was performed to determine whether alkalinization mediated antibiofilm effects. Inductively coupled plasma analysis characterized F18 ion-release kinetics. Expression of biofilm-related genes (icaA, icaB, icaD, agrA, agrC) was quantified, and biofilm morphology was examined by scanning electron microscopy. Both bioglasses inhibited biofilm formation at concentrations ≥ 128 μg/mL but did not eradicate mature biofilms. At 512 μg/mL, F18 and 45S5 reduced the biofilm optical density by 78% and 67%, respectively. Although pH elevation occurred, biofilm inhibition was independent of pH variation. F18 exposure downregulated ica operon genes but not agr genes. Ion analysis demonstrated concentration-dependent release of Ca and Si, with no evidence of apatite formation. SEM showed reduced extracellular matrix and altered bacterial organization. F18 and 45S5 inhibit S. aureus biofilm formation through pH-independent mechanisms associated with ion release and suppression of matrix-related genes, supporting their potential as adjunctive strategies in CRS management.

Chronic wounds and bacterial infections present significant challenges in tissue regeneration, demanding the development of advanced bioactive materials that balance biocompatibility, antimicrobial activity, and tunable physical properties. This study explores the multifunctional role of phytic acid (PA) when incorporated into biopolymer films based on konjac glucomannan (KG) and hyaluronic acid (HA), focusing on how the matrix composition modulates PA's effects on film properties relevant to biomedical applications. PA incorporation significantly influenced water uptake, mechanical strength, and surface characteristics in a matrix-dependent manner. In HA-based films, PA promoted matrix compaction, reduced water content, and enhanced antioxidant activity, whereas in KG-based films, PA induced an increase in water retention and less pronounced antioxidant effects. Surface energy and wettability were favorably altered by PA in both systems, supporting potential improvements in cell-material interactions. Cytocompatibility assays confirmed the nontoxic nature of the films, with KG-based formulations demonstrating higher metabolic compatibility. Notably, PA incorporation suppressed bacterial metabolic activity in Pseudomonas aeruginosa and Escherichia coli, especially in HA-based matrices, while Staphylococcus aureus remained largely unaffected. These results underscore the potential of PA as a tunable additive and natural crosslinking agent and highlight the importance of polymer selection in optimizing film functionality. Finally, this work offers valuable insights into the development of sustainable, bioactive materials suitable for tissue engineering such as wound healing.

Mesoporous silica particles (MSPs) are widely investigated in biomaterials due to their high surface area, tunable porosity, and potential for chemical functionalization. In this study, MSPs were modified with different anionic functional groups (carboxyl, phosphate, and sulfonate) and incorporated into Type I collagen hydrogels to evaluate their structural, biological, and drug-loading behavior in the context of bone tissue engineering. A comprehensive set of analyses including FTIR, SEM/EDS, zeta potential, porosity, drug incorporation, cytocompatibility, in vitro mineralization, and short-term in vivo response was conducted. While calcium phosphate deposition was not observed in functionalized composites, the study reveals key insights into how the surface chemistry of MSPs modulates particle-collagen interactions, drug loading efficiency, and biological responses. Phosphate-modified MSPs showed higher cytotoxicity and interfered with collagen self-assembly, whereas MSPs bearing hydroxyl or carboxyl groups maintained better cytocompatibility and distribution within the matrix. Interestingly, MSPs functionalized with sulfonate groups exhibited enhanced simvastatin loading, likely due to their reduced surface polarity resulting from the formation of siloxane bridges in the oxidation process. In vivo implantation of unloaded composites in a rat tibial defect model confirmed good biocompatibility without evidence of acute inflammation. However, no significant bone formation or biomineralization was detected after 14 days. These findings suggest that excessive negative surface charge may impair ion-mediated mineralization and that the interplay between MSP chemistry and the biological environment must be carefully balanced. This work contributes to understanding the structure-function relationships in hybrid silica-collagen systems and identifies key parameters to optimize in future designs of osteoinductive and drug-eluting scaffolds.

Additive manufacturing (AM) can create orthopedic devices with integrated porosity that enables bone fixation post-implantation. While porosity is key in promoting bone ingrowth and long-term fixation, the device must provide adequate mechanical strength and functionality. Since AM process parameters dictate the final mechanical performance of printed parts, identifying key process parameter levels that preserve or improve such behavior in load-bearing devices with integrated porosity is essential. Using a Taguchi design of experiments, gyroid-structured polyether-ether-ketone (PEEK) and polyether-ketone-ketone (PEKK) specimens were fabricated via fused filament fabrication (FFF) AM to examine the impact of nozzle temperature (TN), chamber temperature (TCh), and layer height (LH) on their compressive mechanical behavior. In addition to compression testing, the printed specimens were analyzed using optical microscopy, scanning electron microscopy, and micro-computed tomography. Elevated processing conditions, specifically high TCh combined with thick LH, can enhance heat retention, slow crystallization, increase strut thickness, and improve bonding at strut junctions, enabling porous PEEK and PEKK to withstand higher compressive loads. The elastic moduli of all the porous specimens were more sensitive to variations in processing conditions than their yield strength. Notably, the more amorphous PEKK specimens achieved over 87%-88% of PEEK's calculated elastic modulus in this study and 87%-90% of the yield strength without undergoing annealing. These results are promising, considering that, like PEEK, the elastic modulus of the porous PEKK fell within the range of trabecular bone, while its yield strength surpassed that of trabecular bone.

Common polymeric surgical biomaterials are susceptible to dysregulated fibrous encapsulation, which contributes to failure in 10% of implantable medical devices. While biomaterial factors influencing the underlying foreign body response have been extensively studied, the role of the implantation site-specifically the tissue microenvironment-remains poorly understood. Here, we explore the tissue-specificity of the foreign body response by evaluating fibrous encapsulation around clinically-relevant synthetic non-biodegradable polymers across distinct tissue microenvironments. We first characterize the physicochemical properties of PDMS, PP, PTFE, HDPE and nylon, and develop a mouse model that enables direct within-animal comparisons of fibrous capsule formation next to skin, bone, fat, fascia and muscle. Using this model and these biomaterials, we histologically assess the extent and quality of fibrous encapsulation at 7 and 28 days for all biomaterial-tissue combinations. At 7 days, capsules adjacent to muscle are the thickest, but-at 28 days-capsules in contact with bone and fascia reach comparable thicknesses, which are significantly greater than those of capsules adjacent to skin. Although PTFE and nylon elicit less fibrous encapsulation at 28 days than some of the other biomaterials, adjacent tissue type has a substantially greater influence on fibrous encapsulation than stiffness, roughness or wettability. Interestingly, more vascularized tissues (i.e., skin and muscle) do not show significant differences in capsule thickness over time, suggesting that they may promote a more rapid initiation and stabilization of the foreign body response. Together, these findings identify adjacent tissue type as a dominant predictor of fibrous encapsulation for common polymeric surgical biomaterials.

Erythrocyte-derived carriers have emerged as effective biomimetic platforms for the delivery of therapeutic and imaging cargos. However, clearance by the mononuclear phagocytic system (MPS) limits their utility. Towards development of standardized methods for increased bioavailability, we have developed an approach that lowers the externalization of phosphatidylserine (PS), a biomarker for MPS clearance, to the outer leaflet of the membrane. Specifically, this approach minimizes the hypotonic treatment of erythrocytes to a single cycle for depleting the hemoglobin while enriching the membrane bilayer with cholesterol during depletion, and in the subsequent cargo loading step, using indocyanine green (ICG), a fluorescent probe as an illustrative cargo. Using this strategy, PS externalization remains limited to ~16% and 9% of the carrier system with and without the encapsulated ICG, respectively, compared to ~46%-99% following multiple hypotonic cycles without cholesterol enrichment. Carriers engineered using this method exhibit significantly reduced macrophage uptake in vitro. In vivo biodistribution studies in healthy mice show ~2.7-fold increase in blood-associated fluorescence, and ~3.3-fold decrease in splenic accumulation after intravascular injection relative to carriers formed by multiple cycles of hypotonic treatment and without cholesterol enrichment. This method provides an effective approach to improve the circulatory retention of erythrocyte-based carriers.

Glycosaminoglycans (GAGs) like chondroitin sulfate (CS) influence both mechanical properties and biological signals within the tissue microenvironment. CS modifications have been prevalent in a range of biomaterial design strategies, particularly those with a focus on wound healing. Here, we investigate the impact of CS incorporation within a thiolated gelatin (Gel-SH) hydrogel previously established as a promising biomaterial for tendon-to-bone entheseal repair, reporting a dual biological and mechanical effect. We show that CS inclusion increases mesenchymal stem cell metabolic activity and osteo-tendinous differentiation patterns in the Gel-SH biomaterial. Additionally, we demonstrate that inclusion of CS into a Gel-SH hydrogel insertional zone used to link dissimilar tendon and bone specific collagen scaffolds induces favorable local changes in stress-strain behavior. We further show that the mode of incorporation, free incorporation of CS versus covalent tethering of oxidized CS (CSO), clearly impacts these observed effects. Overall, these results highlight promising new motifs to modulate Gel-SH hydrogels for greater promotion of enthesis-associated behavior in resident hMSCs; further, they offer broad insight into design strategies and key considerations for modification of multicompartment materials, namely in consideration of incorporation methods and on the interplay of mechanical and biological properties.

Multidrug-resistant bacterial infections pose a significant challenge in bone tissue engineering, primarily due to the formation of biofilms on implant surfaces, which can impede osteointegration. KR-12, a cationic antimicrobial peptide (AMP) with dual osteoinductive and biofilm-inhibitory properties, represents a promising strategy to address this issue. Poly(lactic-co-glycolic acid) (PLGA) electrospun nanofiber (NF) scaffolds offer biocompatibility, tunable morphology, and support for cell adhesion and proliferation, making them ideal for bone regeneration. While cold atmospheric plasma (CAP) treatment has been explored to enhance peptide functionalization, covalent conjugation of KR-12 to PLGA electrospun NFs has not yet been reported. In this study, KR-12 was incorporated into electrospun PLGA NFs to create a dual-functional scaffold that promotes osteogenic differentiation while inhibiting biofilm formation. Scaffold surface properties were characterized by scanning electron microscopy (SEM) and contact angle measurements, and peptide incorporation was confirmed via fluorescein isothiocyanate (FITC) labeling and FTIR spectroscopy. Human bone marrow-derived mesenchymal stem cells cultured on KR-12-functionalized NFs exhibited enhanced alkaline phosphatase (ALP) activity, calcium and collagen deposition, and upregulated expression of collagen type I (COL1), osteopontin (OPN), and osteocalcin (OCN), as well as positive immunofluorescence staining. Antibacterial and biofilm formation inhibition activities were evaluated against multidrug-resistant MRSA and P. aeruginosa, as well as non-MDR E. coli and S. aureus, demonstrating potent inhibition of biofilm formation. KR-12-functionalized PLGA NFs thus provide a dual-functional platform for infection-resistant bone tissue regeneration, combining osteogenic support with potent inhibition of biofilm formation.

Schwann cells (SC) are the principal glia in the peripheral nervous system, supporting normal peripheral nerve function, particularly in the myelination of motor and sensory axons of the peripheral nerves. In Neurofibromatosis Type 1 (NF1), disruptions in normal SC function can lead to decreased motor function, sensory capability, and neuropathic pain. There is no cure for NF1 and any available treatments are for symptom management such as surgical removal and drug therapies that do not always have consistent or favorable outcomes. As a result, there has been an increased interest in understanding SC behavior in NF1. This study focuses on characterizing SC response to material topography and material mechanics in an NF1 model. Based on previous studies conducted on other aberrant cells, we hypothesized that material topography, rather than mechanics alone, would have a significant impact on key behaviors such as elongation, migration, proliferation, and nerve growth factor release (NGF). We also investigated the effect of mechanics by using methacrylated hyaluronic Acid (MeHA) in this study to alter its mechanical properties through photocrosslinking (2.5-33.6 kPa). MeHA was fabricated into gels and aligned electrospun nanofibers to alter its topography. Plexiform neurofibroma Schwann cells (pNF-SCs) were cultured and cell elongation, migration, proliferation, and nerve growth factor (NGF) release were observed. Elongation was greater on nanofibers; however, migration and proliferation increased significantly on hydrogels. NGF release was the greatest on 30% substitution nanofibers. The results of this study offer further characterization of pNF-SC behavior, which can be utilized for the development of a more refined in vitro model of NF1.

Decellularized extracellular matrix (dECM) has emerged as a promising material for tissue engineering and regenerative medicine (TERM), particularly for hydrogel development. Although dECM offers unmatched biochemical complexity compared to collagen type I (Coll-I), the most abundant protein in dECM and widely used in TERM, it is often reported that extraction processing-particularly pepsin digestion-compromises protein integrity and functional performance. Digestion protocols typically use 1 mg/mL pepsin and a 10:1 dECM/pepsin weight ratio, potentially leading to excessive degradation of structural proteins and diminished biological performance. This study investigated the effects of reduced pepsin concentrations (0.75 and 0.5 mg/mL) on structural, physico-chemical, mechanical, and biological features of porcine pericardium dECM hydrogels (10 mg/mL), compared to Coll-I. Compared to the standard digestion protocol, lower pepsin levels significantly improved the preservation of collagen's secondary structure and thermal stability (from 317°C ± 4°C to 324°C ± 1°C). Hydrogels digested with 0.5 mg/mL pepsin exhibited an elastic modulus of 119 ± 12 kPa, 2-3 times higher than standard dECM (65 ± 6 kPa) and Coll-I (41 ± 2 kPa), and a storage modulus of 1.5 ± 0.1 kPa, approximately twice that of the standard dECM (0.8 ± 0.1 kPa) and Coll-I (0.7 ± 0.1 kPa) hydrogels. Human dermal fibroblasts showed enhanced adhesion and over twice the viability on these optimized hydrogels. Despite dECM's intrinsic compositional advantages, its performance can be diminished by harsh digestion. Our findings highlight pepsin concentration as a critical and tunable parameter that governs the mechanical integrity and cellular responses of dECM hydrogels. Optimizing this variable enables the development of more robust, bioactive, and scalable dECM hydrogels tailored for TERM applications.

Systematic analysis of the fate of hydrogel nanoparticles after in vivo administration is essential for their clinical translation. Biodegradable, disulfide-crosslinked synthetic nanogels are a promising platform for the delivery of therapeutic molecules, but their biodistribution and clearance profiles remain underexplored compared to other solid nanoparticles. In this study, we investigated the safety, pharmacokinetics, tissue, and cellular distribution profiles of poly(acrylamide-co-methacrylic acid) (P(AAm-co-MAA)) nanogels following a single intravenous or intraperitoneal injection. The nanogels exhibited rapid clearance from plasma, followed by early distribution primarily to the kidneys, liver, and small intestine. Within the liver, the nanogels showed preferential uptake by endothelial cells and resident macrophages. We further revealed organ-specific differences in nanogel retention and clearance, with highly perfused organs demonstrating parallel clearance behavior with plasma, while organs such as the kidneys and small intestine served as sites of longer nanogel retention. Single injections of P(AAm-co-MAA) nanogel suspension did not induce any systemic innate immune activation nor organ-specific toxicity, demonstrating a promising safety profile. These findings provide new insights into the in vivo behavior of redox-responsive nanogels and provide a framework for their rational design and clinical translation.

Diseases of the back of the eye such as neovascular age-related macular degeneration (nAMD) are vision threatening and treatment is burdensome for patients, often requiring ocular injections every other month. Injection risks and logistics lower patient compliance; however, even patients receiving optimal treatment can deteriorate. Gene silencing has shown great potential as a therapeutic alternative but is often limited by instability of the genetic payload, reducing efficacy. In the current work, a cationic block co-polymer was developed and investigated as a delivery system for an antisense oligonucleotide (ASO) to the posterior segment of the eye. This work details the synthesis, characterization, in vitro, and ex vivo testing of the polymer and the subsequent polyplexes formed between the polymer and ASO. pH-dependent polyplexes were formed which fully complexed the ASO at 1:1 and 10:1 ratios of polymer amine groups to ASO phosphate groups (N/P ratio). Neither formulation displayed a significant reduction in the viability of human retinal pigment epithelial (ARPE-19) cells. The polyplexes were under 150 nm in diameter, with a slightly negative zeta potential. In comparison to the naked ASO, the 10:1 polyplexes achieved superior transfection into ARPE-19 cells. After 24 h, the ASO delivered by the 10:1 polyplexes displayed significant knockdown of the target protein. Polyplexes were well distributed throughout the vitreous humor, retina, and choroid within 4 h of intravitreal administration in an ex vivo porcine eye. These materials show potential for gene delivery in the treatment of various posterior segment conditions including nAMD.

Most of the orthopedic implants are nowadays manufactured using titanium or titanium alloy materials due to their mechanical properties and good compatibility with human tissues. Still, implant rejections frequently occur and are related to a loss of the osteointegration, which in turn is strongly linked to the implant surface's features. In particular, an increase in the roughness or functionalization with bioactive groups of the surface of a Ti implant demonstrates an enhanced osteointegration. In this study, we analyze the osteointegration of a femoral implant made of Ti alloy (TA6V) with high roughness (≈3.5 μm) and functionalized with polyvinyl benzyl phosphonic acid bioactive polymers (p(VBP)). The TA6V sample surfaces were sandblasted to increase their surface roughness and then followed a two-step UV-induced grating polymerization process to covalently link p(VBP) polymers to their surfaces. The prepared surfaces were characterized at each step using scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS), Fourier-transform infrared spectroscopy (FTIR), water contact angle measurement (WCA), and colorimetry (TB assay). Then, samples were incubated with MC3T3-E1 osteoblast cells, and cell viability, cell morphology, alkaline phosphatase activity, and formed calcium ions were evaluated. Finally, an in vivo study was carried out by integrating the grafted femoral implants in rabbits for 6 and 12 weeks, followed by quantitative ultrasound measurements (QUS) of the bone/implant interface. Successful grafting of p(VBP) is demonstrated on the rough TA6V surfaces, and in vitro results show an enhanced integration and activity of the osteoblastic cell.

Bone tissue engineering scaffolds should be biocompatible, match the mechanical properties of native bone, and degrade at a rate that facilitates tissue regeneration. However, most scaffolds will excel in only one or two of these areas while sacrificing the others. This study aims to vary poly( ε $$ \varepsilon $$ -caprolactone) (PCL) molecular weight blend ratios (100:0, 70:30, and 50:50 25 kDa:14 kDa PCL) and nanohydroxyapatite (nHA) ceramic content (0, 30, and 40 wt%) to design 3D-printed scaffolds with tunable mechanical properties and degradation kinetics. Nine different 3D-printing inks were created, all of which exhibited similar thermal properties. While 40 wt% nHA fibers had a homogeneous distribution of nHA, 30 wt% nHA fibers exhibited significant differences in nHA radial distribution, as characterized by micro-computed tomography. PCL with blended molecular weights had the highest compressive moduli, whereas the 0 and 30 wt% nHA groups had the highest stress at yield and peak stress before becoming brittle like the 40 wt% nHA groups. An accelerated degradation study resulted in increased PCL mass loss in the presence of nHA, suggesting nHA promoted accelerated degradation of PCL. These findings demonstrate that blending polymer molecular weights and incorporating ceramic content provides an effective means of tailoring 3D-printing inks to produce scaffolds with application-specific mechanical and degradation properties. In summary, the key novel contributions of the present work are the blending of different PCL molecular weights, the incorporation of relatively high wt% nHA, and the quantification of radial nHA distribution in individual printed fibers.

Poly(ether)urethanes (PEUs) are widely used in long term implanted medical devices. Their susceptibility to oxidative degradation has raised concerns regarding compatibility with vaporized hydrogen peroxide (VH2O2) sterilization. This study investigates the chemical and mechanical stability of PEU80A, a Shore 80A durometer PEU, following exposure to VH2O2 sterilization. Two VH2O2 sterilization conditions were characterized, three times (nominal) and 10 times (extreme) the cycle required for cardiac pacemaker sterilization and compared to two solution-based hydrogen peroxide exposures, with and without cobalt chloride catalyst. Compared to the extreme VH2O2 condition, the solution exposure conditions were four orders of magnitude higher in concentration and 40-fold longer in duration. Comprehensive characterization of PEU80A included molar mass analysis, antioxidant quantification, mechanical testing, free radical profiling, soft segment loss assessment, exhaustive chemical extraction, and evaluations of hemocompatibility and cytotoxicity. The results demonstrated that VH2O2 sterilization did not induce any detectable degradation in PEU80A, even after 3 years of real-time aging post VH2O2 exposure. Only the catalyzed solution exposure resulted in measurable oxidative degradation, evidenced by antioxidant depletion, molar mass reduction, soft segment depletion, and mechanical weakening. Despite these changes, the comprehensive testing for chemical extractables, hemocompatibility, and cytotoxicity, used to evaluate biocompatibility, remained unaffected. These findings demonstrated the continued oxidative stability and biocompatibility of PEU80A after VH2O2 sterilization, supporting its use as a terminal sterilization method for implantable devices comprised of this material. Furthermore, these data suggest that the biostability of a material is impacted long before any changes in biocompatibility can be resolved.

Vascular graft infection is a rare but life-threatening condition, primarily occurring after 30 days post-surgery. Meta-analysis has shown that antimicrobial coatings on graft materials do not prevent these infections. Moreover, infections still occurs even though studies have shown that there is no bacterial proliferation or bacterial penetration of common vascular graft material. The time frame of infection, meta-analysis, and in situ studies suggest that bacteria present at the suture site are introduced into the surrounding tissue or that systemically circulating bacteria may be surviving, proliferating, diffusing slowly, and evading host immune defense in synthetic vascular grafts. De novo vascular graft materials, such as tissue-engineered vascular graft material and decellularized vasculature may provide an in situ platform for studying survival, proliferation, and diffusion in tissue and tissue-like materials. In this study, we used confocal microscopy to image the penetration depth of bacteria over time as a proxy for the diffusion of Staphylococcus aureus and Escherichia coli into alginate, GelMA, and decellularized porcine vascular tissue. We quantified viable bacteria breakthrough as a function of biomaterial type. We found that the penetration depth over time was similar in all three biomaterials, however E. coli broke through much less from tissue than from engineered materials, while S. aureus had higher breakthrough in the GelMa but otherwise equal rates. These results point to the possibility of interstitial growth control relative to surface coatings as a future target for engineering infection resistance in engineered vascular grafts.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population, with no curative treatment currently available. Current therapies primarily target late-stage symptoms and are limited by their frequent and invasive intravitreal (IVT) injections. To address oxidative stress-induced inflammation mechanisms relevant to early retinal degeneration, we developed a heme-bound human serum albumin (heme-albumin) complex designed to transiently induce heme oxygenase-1 (HO-1), a cytoprotective enzyme with antioxidant and anti-inflammatory effects. Polydopamine nanoparticles (PDA NPs) were selected as a delivery system due to their ability to scavenge reactive oxygen species (ROS) and degrade under oxidative environments. A previous in vitro study demonstrated that heme-albumin-loaded PDA NPs reduce oxidative damage and inflammatory signaling in retinal pigment epithelium (RPE) cells. This study evaluates the in vivo biocompatibility of IVT-administered heme-albumin and unloaded PDA NPs as independent components in a murine model. At the tested doses, both components showed minimal cytotoxicity with preservation of retinal structure, establishing biocompatible dosing for future evaluation in retinal disease models.

Repairing large bone defects is a significant clinical challenge. In this context, cellulose nanomaterials, such as bacterial nanocellulose (BNC), cellulose nanofibrils (CNF), and cellulose nanocrystals (CNC), have emerged as promising alternatives due to their natural origin and mechanical properties. Particularly noteworthy is their chemical malleability, which thereby confers specific functionalities. This comprehensive literature review evaluates the efficacy of nanocellulose scaffolds for the repair of critical bone defects, with a focus on the impact of surface modifications. The effects of inserting bioactive functional groups and adding metal ions are analyzed in vitro and in vivo models. The parameters evaluated include material mineralization (production and precipitation of biogenic apatite, Ca/P ratio), cell adhesion and proliferation, bioadsorption, degradation, and toxicity. The results discussed provide valuable insights into the chemical and biological processes of bone formation, supporting a new paradigm: cellulose is no longer just an "eco-friendly filler" but has become a programmable structural scaffold. The trends highlighted in this review open new avenues for the treatment of bone diseases and tissue regeneration.

A suitable tissue-engineered equivalent is necessary to support cultured cells for cell therapy transplantation, thereby alleviating the increasing demand for donor tissue. A compressed collagen I hydrogel, Real Architecture For 3D Tissue (RAFT), was introduced to substitute native corneal stroma for supporting endothelial cell growth as an extracellular cellular matrix (ECM) tissue equivalent. Here, the RAFT's mechanical properties and transparency were optimized to tailor for designing a corneal endothelium transplantation graft. Meanwhile, the gene and protein expression of ZO-1, Na/K ATPase, and N-Cadherin were used to investigate the impact of mechanical properties on cell behavior. The results showed that increasing the collagen concentration and reducing the initial loading volume could generate a stiffer, thinner, and more transparent RAFT. Staining results showed that porcine corneal endothelial cells (PCECs) remained alive, forming a high cell density monolayer with ZO-1 and Na/K ATPase expressions on various stiffnesses of RAFTs. Gene and protein expression results showed that PCECs could grow on various stiffnesses of RAFTs (elastic modulus ranged from 1.17 ± 0.11 to 2.08 ± 0.14 MPa), expressing ZO-1, Na/K ATPase, and N-Cadherin. In short, RAFTs fabricated with 0.4 of 5 mg/mL collagen I shared similar optical and mechanical properties to the native cornea, with a thickness of 73.67 ± 1.70 μm, a stiffness of 0.40 ± 0.03 MPa, an elastic modulus of 1.17 ± 0.07 MPa, and light transmittance of 60.71% ± 1.17%. This is an ideal tissue-engineered cell carrier suitable for developing a cell-seeded RAFT graft for cell therapy.