Native Tissue Research Articles

Laparoscopic Shull Technique for Uterine Prolapse and Risk of Recurrences: A Retrospective Comparison with Vaginal Hysterectomy.

The objective was to compare the vaginal and laparoscopic approaches with natural tissue vaginal repair of pelvic organ prolapse (POP) in terms of recurrence rate and complete remission rate (CRR) of symptoms. This retrospective cohort study analyzed women who underwent hysterectomy for uterine prolapse at two Italian hospitals between October 2021 and March 2023. Group A included 89 patients who received vaginal hysterectomy and colposuspension (VCH), whereas group B included 58 patients who underwent laparoscopic hysterectomy followed by laparoscopic colposuspension sec Shull (LPSS). The study included 147 patients with comparable baseline characteristics regarding menopausal age and body mass index. Concerning preoperative data, it is worth mentioning that group A had a higher proportion of patients with more than two previous deliveries and, overall, more severe prolapse stages. Concerning postoperative results, the patients undergoing laparoscopic surgery had longer operation times than group A. Moreover, group B had a higher recurrence rate after surgery (5.6% vs 13%, p = 0.057). Kaplan-Meier analysis indicated a lower rate of prolapse-free patients over time in group B. Cox regression showed a higher hazard ratio for recurrence in the LCSS group than in the VCH group.Complete remission rates for urinary symptoms varied, with group B showing higher CRR for stress incontinence (33% vs 71%, p < 0.001). Both VCH and LCSS are effective for POP treatment, with VCH showing better outcomes in terms of symptom remission and shorter operation times. At the same time, LCSS had better CRR for stress incontinence but a higher recurrence rate. Further high-quality prospective studies are needed to confirm these findings and determine the best surgical approach for POP.

Printable and Tunable Bioresin with Strategically Decorated Molecular Structures.

As personalized medicine rapidly evolves, there is a critical demand for advanced biocompatible materials surpassing current additive manufacturing capabilities. This study presents a novel printable bioresin engineered with tunable mechanical, thermal, and biocompatibility properties through strategic molecular modifications. The study introduces a new bioresin comprising methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA), and a photoinitiator, which is further enhanced by incorporating high molecular weight polymethyl methacrylate (PMMA) to improve biostability and mechanical performance. The integration of printable PMMA presents several synthesis and processing challenges, necessitating substantial modifications to the 3D printing process. Additionally, the bioresin is functionalized with antibacterial silver oxide and bone-growth-promoting hydroxyapatite at various weight ratios to extend its application further. The results demonstrate the agile printability of the novel bioresin and its potential for transformative impact in biomedical applications, offering a versatile material platform for additive manufacturing-enabled personalized medicine. This work highlights the adaptability of the novel printable bioresin for real-life applications and its capacity for multiscale structural tailoring, potentially achieving properties comparable to native tissues and extending beyond conventional additive manufacturing techniques.

Properties of Electrospun Fibers That Influence Foreign Body Response Modulation.

Improving the utility of biomedical devices implanted in subcutaneous tissue by modulating the innate immune response common to these implants is of great interest to improve their utility. Uncontrolled, most biomedical devices produce an immune reaction known broadly as the foreign body response (FBR), which ultimately isolates the device from the native tissue. The use of electrospun fibers to create a porous surface that promotes tissue in-growth and regeneration represents a new paradigm in FBR modulation. A vast number of parameters can be adjusted in the electrospinning process to tune the type and quality of the resulting electrospun matrix, which in turn has varying outcomes with respect to the FBR. In this review, the fabrication and utility of electrospun fiber scaffolds for mitigating the FBR are described, with details of how fiber properties and surface modifications alter immune response for specific biomedical applications.

Pathologically altered articular cartilage attracts intense chondrocyte invasion into the extracellular matrix: in vitro pilot study

BackgroundDue to non-vascularized and aneural structure, articular cartilage has limited self-repairing capacity. The aim of this study was to investigate the revitalization of inflammatory injured articular cartilage matrices by human nasal chondrocytes (hNC).Materials and methodsCartilage matrix was prepared by devitalization of articular cartilage samples obtained intraoperatively from an adult patient undergoing knee joint replacement. hNC were obtained from native tissues by enzymatic digestion with further expansion over two passages. The obtained nasal chondrocytes were used to seed decellularized scaffolds, which were then cultured in vitro for 7, 14, or 21 days in chondrogenic medium. Migration was observed by histologic staining with fast green, safranin-O, and hematoxylin and scanning electron microscopy. Biochemical analysis was performed to determine the glycosaminoglycan (GAG) and DNA content of the cartilage using dimethylmethylene blue and CyQuant Cell Proliferation Assay Kit.ResultsWe seeded healthy and inflamed cartilage with nasal chondrocytes and found that the cells actively invade mainly pathologically altered cartilage. The results of biochemical quantitative analysis showed that the amount of DNA significantly increased by day 7 and decreased by day 14, while the quantitative values of GAGs had the opposite trend. Histological staining showed that cartilage formation occurred on day 7, intercellular spaces were filled with de novo synthesized cartilage matrix with significantly low GAG content on day 14, and newly formed GAG-rich cartilage was observed on day 21. The obtained data on cartilage regeneration were confirmed by scanning electron microscopy.ConclusionsOur preliminary results showed that human nasal chondrocytes are capable of infiltrating the pathologically altered extracellular matrix of articular cartilage damaged by arthritis, thereby promoting its repair to a physiologically relevant state.Graphical

Rabbit Heart Bioartificial Tissue: Perfusion Decellularization and Characterization.

Despite new approaches in the treatment of cardiovascular disease (CVD) such as percutaneous coronary intervention, coronary artery bypass graft, and left ventricular assist devices, which cannot fully compensate for the effectiveness of the original heart, heart transplantation still remains as the most effective solution. &#xD;A growing body of literature recognizes the importance of developing a whole heart constructed from living tissues to provide an alternative option for patients suffering from diseases of the cardiovascular system. A potential solution that shows a promise is to generate cell-free, i.e., decellularized, scaffolds using native heart tissue to be later cellularized and transplanted. This study reports the decellularization process and efficiency in an effort to create a whole heart scaffold. The hearts harvested from rabbits were perfused and the final bioartificial scaffolds were characterized for the efficiency of decellularization in terms of DNA content, collagen, and glycosaminoglycan. The compressive biomechanical properties of decellularized and native hearts were also determined and compared. Findings revealed that the DNA content of decellularized hearts was significantly reduced while keeping collagen and GAG content unchanged. Biomechanical properties of the hearth became inferior upon removal of the nuclear material. Decellularized hearts have significant importance in treating CVD as they serve as bioartificial hearts, providing a more clinically relevant model for potential human use.&#xD;Future work will focus on the recellularization of the heart using induced pluripotent or embryonic stem cells to test its functionality.

Preparation and characterisation of zirconia/hydroxyapatite bioactive composites as potential dental implants

In dental implants, zirconia is well-known as a crown material due to its excellent acid and base resistances and appearance close to natural teeth. In addition, its extraordinary mechanical properties render zirconia to be a potential candidate as an implant component of a whole implanted tooth, if its biocompatibility can be improved to promote adhesion to natural hard tissues. This study aims to enhance the bioactivity of zirconia with the aim of improving its integration with gum bone. Hydroxyapatite is the major component of natural bone and is thus selected as the modifier to improve the bioactivity of zirconia. A series of zirconia/hydroxyapatite composites with varied compositions were prepared under different conditions in order to find the optimal composites for the target application. Various analytical technologies and mechanical tests are employed to characterise the structure and properties of resultant composites. Results show that the component ratio and sintering temperature have a significant influence on the composite properties. An increase in hydroxyapatite component tends to enhance bioactivity but decline mechanical strength. Composites containing 10 wt% of hydroxyapatite maintain sufficient mechanical strength under the optimal sintering conditions whilst possessing excellent bioactivity, demonstrating that hydroxyapatite-modified zirconia has the potential as dental implant materials. Sintering results suggest that mechanical strength is obtained at 1400 °C for 2 h for the composite containing 10 wt% of hydroxyapatite.

Applications of a biocompatible alginate/pericardial fluid-based hydrogel for the production of a bioink in tissue engineering.

Enhancing the biocompatibility of biomaterials is a critical aspect of tissue engineering and regenerative medicine. Advances in 3D bioprinting technology, blending natural and synthetic materials for the production of bioink, offer new opportunities to develop highly biocompatible materials that can closely mimic the native tissue environment. In this study, we used pericardial fluid structure (PFS)-based material together with alginate to mimic the extracellular matrix (ECM) and produce a bioink material. Thus, blended alginate with PFS material and MC3T3-E1 pre-osteoblast cell-laden hydrogels characterized by comparing each other, especially alginate hydrogels, and evaluated in terms of biocompatibility for tissue engineering applications. According to the rheological analysis results, all hydrogel groups A, A-PFS (150mg), and A-PFS (1:1) had viscoelastic properties. Mechanical tests showed that the A-PFS (1:1) hydrogel had the most strength properties. Additionally, the viscosity values of the hydrogel solutions were in an applicable range for use in 3D bioprinters. It was also found out that PFS increased the biocompatibility of alginate-based bioink, in terms of cell proliferation and differentiation. Overall, these findings suggest that alginate and pericardial fluid-based materials can be successfully used for bioink production. The resulting hydrogels exhibit viscoelastic properties, appropriate viscosity for 3D bioprinting, and support cell viability, proliferation, and osteogenic differentiation. This research has the potential not only to produce bioink but also to produce injectable hydrogels and drug delivery systems, which can become biocompatible materials that can be used for tissue engineering and regenerative medicine applications.

FRESH 3D Bioprinting of Collagen Types I, II, and III.

Collagens play a vital role in the mechanical integrity of tissues as well as in physical and chemical signaling throughout the body. As such, collagens are widely used biomaterials in tissue engineering; however, most 3D fabrication methods use only collagen type I and are restricted to simple cast or molded geometries that are not representative of native tissue. Freeform reversible embedding of suspended hydrogel (FRESH) 3D bioprinting has emerged as a method to fabricate complex 3D scaffolds from collagen I but has yet to be leveraged for other collagen isoforms. Here, we developed collagen type II, collagen type III, and combination bioinks for FRESH 3D bioprinting of millimeter-sized scaffolds with micrometer scale features with fidelity comparable to scaffolds fabricated with the established collagen I bioink. At the microscale, single filament extrusions were similar across all collagen bioinks with a nominal diameter of ∼100 μm using a 34-gauge needle. Scaffolds as large as 10 × 10 × 2 mm were also fabricated and showed similar overall resolution and fidelity across collagen bioinks. Finally, cell adhesion and growth on the different collagen bioinks as either cast or FRESH 3D bioprinted scaffolds were compared and found to support similar growth behaviors. In total, our results expand the range of collagen isoform bioinks that can be 3D bioprinted and demonstrate that collagen types I, II, III, and combinations thereof can all be FRESH printed with high fidelity and comparable biological response. This serves to expand the toolkit for the fabrication of tailored collagen scaffolds that can better recapitulate the extracellular matrix properties of specific tissue types.

Predictive control of pore architecture in ice-templated scaffolds via heat flux density modulation

Replicating the intricate architecture of native tissues remains a significant challenge in tissue engineering. Ice-templated biomimetic scaffolds possess controlled porosity that conveniently resembles the native parenchyma of many tissues. In this study, we investigate the relationship between the porous architecture of lyophilised collagen scaffolds and key processing parameters during production. We establish a predictive model that correlates specific lyophilisation conditions with the resulting pore sizes. Systematic variations in the freeze-drying conditions resulted in scaffolds with average pore sizes ranging from 46 μm to 251 μm, effectively matching the length scale of extracellular matrix features found in native tissues. We introduce the concept of heat flux density (HFD) at equilibrium as a metric for quantifying latent heat extraction efficiency during the freezing process. Our findings reveal a power law relationship between HFD at equilibrium and pore size, with an exponent of −0.44. This approach provides a non-destructive and non-intrusive method for precisely controlling pore architecture, advancing the potential for creating scaffolds that closely emulate the complex structures of native tissues.

Tissue-engineered fibrillar fibronectin matrices are not only lovely, but also functional for regenerative medicines and in vitro model systems

Fibronectin is an ubiquitous extracellular matrix protein which comprises fibrous three-dimensional microenvironments in native tissues. Although its importance and fibrillogenesis in vivo has been considerably investigated, yet current in vitro tissue engineering platforms for fibrillar fibronectin pose major drawbacks such as low scalability, applicability, and reproducibility. Due to such platform limitations, understanding of spatiotemporal mechanobiology between cells and fibrillar fibronectin matrices largely remains unexplored. This article briefly underlines current tissue-engineering platforms and mechanobiological understanding of fibrillar fibronectin as well as suggests potential directions in future fibronectin researches.

In-vitro investigation of chitosan/polyvinyl alcohol/TiO2 composite membranes for wound regeneration

Bacterial infections significantly delay the physiological wound healing process and can cause further damage to the wound region. In the current work, we aim to design titanium dioxide nanoparticles (TiO2 NPs) incorporated with chitosan (Chi) and poly(vinyl alcohol) (PVA) film using the casting method and to study their potential for faster wound healing. The prepared TiO2 NPs were analyzed for physicochemical properties, and TEM results showed an average particle size of 39.6nm. The nanocomposite films were scrutinized by FTIR, XRD, and TGA analyses. The effective incorporation of the nanoparticles and their uniform dispersion within the Chi/PVA matrix was confirmed through SEM analysis. The composite films exhibited excellent hydrophilic properties (64.3º), along with favorable swelling and degradation rates, and mechanical properties similar to native skin tissue, ensuring comfortable interaction with wound beds. The better hemocompatibility, with an erythrocyte lysis percentage of 3.52%, further supports the wound healing properties of these films. Additionally, composite films possess excellent antibacterial activity against wound pathogens such as B. subtilis and E.coli. Furthermore, an in vitro wound closure rate of 92.3% at 48 hours was observed for the TiO2 incorporated film (CPT3) using fibroblast HIH3T3 cells. The results suggest that it could be a promising biomaterial for wound healing application.

Transglutaminase-triggered dual gradients of mechanical and biochemical cues self-assembling peptide hydrogel for guiding MC3T3-E1 cell behaviors

The mechanical properties and bioactive motif densities of extracellular matrix materials play crucial roles in regulating cell behaviors, such as cell adhesion, migration, proliferation, and differentiation. However, current studies on cellular responses to ECM predominantly concentrated on polymer hydrogels featuring a single factor, such as the mechanical strength, the types of bioactive motifs, and the morphology of the polymers. This limited focus may overlook the complex interplay of multiple factors. Here, we developed dual gradient peptide Q3GT-I3K hydrogels with tunable mechanical strength (0.3–4.0 kPa) and different density of bioactive motif (0.45–3.67 mM) by enzymatic crosslinking. These hydrogels can mimic the viscoelasticity of natural soft tissues. The properties of mechanical strength and cell responsive motif density could be controlled by modulating the proportion of the substrates in the enzymatic reaction. MC3T3 cells significantly differentiated into osteoblasts after seeded on the Q3GT-I3K hydrogel (2.8 kPa, 1.83 mM Q3GT) for 21 days, identifying from the elevated expression of alkaline phosphatase and substantial calcium nodule formation. Importantly, the engineered hydrogels exert a synergistic effect on the cell behaviors such as early adhesion, late proliferation, and differentiation of MC3T3-E1 cells. This paper introduces a new strategy for designing tissue engineering scaffold materials with specific functions.

Advancements in textile techniques for cardiovascular tissue replacement and repair.

In cardiovascular therapeutics, procedures such as heart transplants and coronary artery bypass graft are pivotal. However, an acute shortage of organ donors increases waiting times of patients, which is reflected in negative effects on the outcome for the patient. Post-procedural complications such as thrombotic events and atherosclerotic developments may also have grave clinical implications. To address these challenges, tissue engineering is emerging as a solution, using textile technologies to synthesize biomimetic scaffolds resembling natural tissues. This comprehensive analysis explains methodologies including electrospinning, electrostatic flocking, and advanced textile techniques developed from weaving, knitting, and braiding. These techniques are evaluated in the context of fabricating cardiac patches, vascular graft constructs, stent designs, and state-of-the-art wearable sensors. We also closely examine the interaction of distinct process parameters with the biomechanical and morphological attributes of the resultant scaffolds. The research concludes by combining current findings and recommendations for subsequent investigation.

Culturing 3D chitosan/gelatin/nano-hydroxyapatite and bone-derived scaffolds in a dynamic environment enhances osteochondral reconstruction.

Bioreactor can provide a dynamic culture environment for the in vitro construction of osteochondral tissue engineering. They facilitate more efficient exchange of nutrients and provide mechanical and other beneficial stimulation. Previous findings demonstrated that rotary flask (RF) bioreactor, rotary cell culture system (RCCS), or electromagnetic field (EMF) mediated scaffold culture could create a favorable dynamic environment for osteochondral tissue engineering. However, it is still unclear whether there is an optimal bioreactor or if bioreactors under multi-parameter coupling conditions are conducive to osteochondral tissue engineering. Based on this, the application of static T-flask (TF), RF, RCCS, and coupling environment of RCCS and EMF for osteochondral tissue engineering were systematically compared. The results showed that the RCCS/EMF culture system achieved the highest level of cellular proliferation and directed differentiation. Compared with the static culture group, the expression levels of chondrogenic factors of Sox9, Col II, and ACAN and osteogenic factors of Runx2, OCN, and Col I in RCCS/EMF culture system were 2.90±0.10, 3.53±0.05, 3.15±0.08, 7.16±0.15, 5.01±0.21 and 3.99±0.17 folds, respectively. The 'Active osteochondral' constructs (The construct is composed of chitosan/gelatin/nano-hydroxyapatite and bone-derived scaffolds) were prepared under different culture modes in vitro and implanted into the femoral condylar defect of New Zealand rabbits. After 12weeks, all culture modes could effectively promote the repair of osteochondral defects, in which the RCCS/EMF intervention had the best effect on the in vivo in-situ repair of osteochondral tissues. Furthermore, the fabricated cartilage and subchondral bone in the RCCS/EMF treatment group were most similar to the surrounding natural tissues, providing a new therapeutic idea for osteochondral tissue engineering.

Biomimetic tubular materials: from native tissues to a unifying view of new vascular, tracheal, gastrointestinal, oesophageal, and urinary grafts.

Repairing tubular tissues-the trachea, the esophagus, urinary and gastrointestinal tracts, and the circulatory system-from trauma or severe pathologies that require resection, calls for new, more effective graft materials. Currently, the relatively narrow family of materials available for these applications relies on synthetic polymers that fail to reproduce the biological and physical cues found in native tissues. Mimicking the structure and the composition of native tubular tissues to elaborate functional grafts is expected to outperform the materials currently in use, but remains one of the most challenging goals in the field of biomaterials. Despite their apparent diversity, tubular tissues share extensive compositional and structural features. Here, we assess the current state of the art through a dual layer model, reducing each tissue to an inner epithelial layer and an outer muscular layer. Based on this model, we examine the current strategies developed to mimic each layer and we underline how each fabrication method stands in providing a biomimetic material for future clinical translation. The analysis provided here, addressed to materials chemists, biomaterials engineers and clinical staff alike, sets new guidelines to foster the elaboration of new biomimetic materials for effective tubular tissue repair.

Decellularization of fish tissues for tissue engineering and regenerative medicine applications

Abstract Decellularization is the process of obtaining acellular tissues with low immunogenic cellular components from animals or plants while maximizing the retention of the native extracellular matrix structure, mechanical integrity, and bioactivity. The decellularized tissue obtained through the tissue decellularization technique retains the structure and bioactive components of its native tissue; it not only exhibits comparatively strong mechanical properties, low immunogenicity, and good biocompatibility, but also stimulates in situ neovascularization at the implantation site and regulates the polarization process of recruited macrophages, thereby promoting the regeneration of damaged tissue. Consequently, many commercial products have been developed as promising therapeutic strategies for the treatment of different tissue defects and lesions, such as wounds, dura, bone and cartilage defects, nerve injuries, myocardial infarction, urethral strictures, corneal blindness, and other orthopaedic applications. Recently, there has been a growing interest in the decellularization of fish tissues because of the abundance of sources, less religious constraints, and risks of zoonosis transmission between mammals. In this review, we provide a complete overview of the state-of-the-art decellularization of fish tissues, including the organs and methods used to prepare acellular tissues. We enumerated common decellularized fish tissues from various fish organs, such as skin, scale, bladder, cartilage, heart, and brain, and elaborated their different processing methods and tissue engineering applications. Furthermore, we presented the perspectives of (1) the future development direction of fish tissue decellularization technology, (2) expanding the sources of decellularized tissue, and (3) innovating decellularized tissue bio-inks for 3D bioprinting to unleash the great potential of decellularized tissue in tissue engineering and regenerative medicine applications.

High-filler content electrospun fibers from biodegradable polymers and hydroxyapatite: Toward improved scaffolds for tissue engineering.

One of the key challenges in tissue engineering area is the creation of biocompatible scaffolds that support cell growth and mimic the structural and mechanical properties of native tissues. Among various materials used for scaffold fabrication, composite materials based on biodegradable polymers reinforced with bioactive inorganic fillers have attracted significant attention due to their properties. One of the important problems with the preparation of composite electrospun fibers is the low filler content in the fiber. This study aims to select the best composition for electrospun polymer fibers in terms of potential application in tissue engineering. The effect of the viscosity of polymer solution/dispersion and filler content on the structure and properties of the fibers was determined. Morphology and filler content were compared. Series of electrospun composite fibers were fabricated from poly(ĺ-caprolactone) (PCL), poly(L-lactic acid) (PLLA) and hydroxyapatite (HAP), containing from 10 wt% to 40 wt% HAP. The properties of the resulting composites were studied using scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and viscosimetry measurements. The addition of HAP to the polymer solution caused a significant increase in viscosity, but the results showed that it is possible to obtain composite electrospun fibers even with 40 wt% filler content. Scanning electron microscopy analysis shows randomly oriented electrospun fibers with an average diameter in the range of 3.8-8.5 ěm for solution and dispersion with high viscosity (1,210-2,000 mPa·s) and significantly larger diameters (approx. 12 ěm) for the PCL solution (326 mPa·s). It is possible to transform the composite dispersion from biopolymers and HAP into nonwoven fabrics at up to 40 wt% filler content. Due to their unique properties, such materials are promising for application in tissue engineering.

Development and characterization of a novel injectable thyroid extracellular matrix hydrogel for enhanced thyroid tissue engineering applications

Hypothyroidism, a condition characterized by decreased synthesis and secretion of thyroid hormones, significantly impacts intellectual development and physical growth. Current treatments, including hormone replacement therapy and thyroid transplantation, have limitations due to issues like hormone dosage control and immune rejection. Tissue engineering presents a potential solution by combining cells and biomaterials to construct engineered thyroid tissue. This study focuses on the development and characterization of a novel 3D injectable hydrogel derived from thyroid extracellular matrix (TEM) for thyroid tissue engineering. TEM hydrogels were prepared through decellularization of rat thyroid tissue, followed by extensive physicochemical and mechanical property evaluations. The TEM hydrogels exhibited properties similar to natural thyroid tissue, including high biocompatibility and a complex 3D ultrastructure. Thyroid hormone-secreting cells cultured in TEM hydrogels demonstrated superior viability, hormone secretion, and thyroid-related gene expression compared to those in traditional type I collagen hydrogels. The study also confirmed the significant retention of key growth factors and ECM proteins within the TEM hydrogels. The results indicate that TEM hydrogels can provide a biomimetic microenvironment, promoting the long-term survival and function of thyroid cells, thus holding great promise for the treatment of hypothyroidism. This research contributes a potential new avenue for thyroid tissue engineering, offering a promising alternative for hypothyroidism treatment.

Engineered Osteochondral Scaffolds with Bioactive Cartilage Zone for Enhanced Articular Cartilage Regeneration.

Despite progress, osteochondral (OC) tissue engineering strategies face limitations in terms of articular cartilage layer development and its integration with the underlying bone tissue. The main objective of this study is to develop a zonal OC scaffold with native biochemical signaling in the cartilage zone to promote articular cartilage development devoid of cells and growth factors. Herein, we report the development and in vivo assessment of a novel gradient and zonal-structured scaffold for OC defect regeneration. The scaffold system is composed of a mechanically supportive 3D-printed template containing decellularized cartilage extracellular matrix (ECM) biomaterial in the cartilage zone that possesses bioactive characteristics, such as chemotactic activity and native tissue biochemical composition. OC scaffolds with a bioactive cartilage zone were implanted in vivo in a rabbit osteochondral defect model and assessed for gross morphology, matrix deposition, cellular distribution, and overall tissue regeneration. The scaffold system supported recruitment and infiltration of host cells into the cartilage zone of the graft, which led to increased ECM deposition and physiologically relevant articular cartilage tissue formation. Semi-quantitative ICRS scoring (overall score double for OC scaffold with bioactive cartilage zone compared to PLA scaffold) further confirm the bioactive scaffold enhanced articular cartilage engineering. This strategy of designing bioactive scaffolds to promote endogenous cellular infiltration can be a much simpler and effective approach for OC tissue repair and regeneration.

Trends and challenges in organoid modeling and expansion with pluripotent stem cells and somatic tissue.

The increasing demand for disease modeling, preclinical drug testing, and long waiting lists for alternative organ substitutes has posed significant challenges to current limitations in organoid technology. Consequently, organoid technology has emerged as a cutting-edge tool capable of accurately recapitulating the complexity of actual organs in physiology and functionality. To bridge the gaps between basic research and pharmaceutical as well as clinical applications, efforts have been made to develop organoids from tissue-derived stem cells or pluripotent stem cells. These developments include optimizing starting cells, refining culture systems, and introducing genetic modifications. With the rapid development of organoid technology, organoid composition has evolved from single-cell to multi-cell types, enhancing their level of biomimicry. Tissue structure has become more refined, and core challenges like vascularization are being addressed actively. These improvements are expected to pave the way for the construction of organoid atlases, automated large-scale cultivation, and universally compatible organoid biobanks. However, major obstacles remain to be overcome before urgently proof-of-concept organoids can be readily converted to practical applications. These obstacles include achieving structural and functional summarily to native tissue, remodeling the microenvironment, and scaling up production. This review aims to summarize the status of organoid development and applications, highlight recent progress, acknowledge existing limitations and challenges, and provide insights into future advancements. It is expected that this will contribute to the establishment of a reliable, scalable, and practical platform for organoid production and translation, further promoting their use in the pharmaceutical industry and regenerative medicine.