Search Results (9,741)

Bone tissue exhibits self-healing properties; however, not all defects can be repaired without surgical intervention. Bone tissue engineering offers artificial scaffolds, which can act as a temporary matrix for bone regeneration. The aim of this study was to manufacture scaffolds made of poly(lactic acid), poly(ε-caprolactone), poly(propylene fumarate), and poly(ethylene glycol) modified with bioglass, beta tricalcium phosphate (TCP), and/or wollastonite (W) particles. The scaffolds were fabricated using a gel-casting method and observed with optical and scanning electron microscopes. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), thermogravimetry (TG), wettability, and degradation tests were conducted. The highest content of TCP without W in the composition caused the highest hydrophilicity (water contact angle of 61.9 ± 6.3°), the fastest degradation rate (7% mass loss within 28 days), moderate ability to precipitate CaP after incubation in PBS, and no cytotoxicity for L929 cells. The highest content of W without TCP caused the highest hydrophobicity (water contact angle of 83.4 ± 1.7°), the lowest thermal stability, slower degradation (3% mass loss within 28 days), and did not evoke CaP precipitation. Moreover, some signs of cytotoxicity on day 1 were observed. The samples with both TCP and W showed moderate properties and the best cytocompatibility on day 4. Interestingly, they were covered with typical cauliflower-like hydroxyapatite deposits after incubation in phosphate-buffered saline (PBS), which might be a sign of their excellent bioactivity.  Full article

Spinal cord injury (SCI) can lead to significant bone loss below the level of the lesion increasing the risk of fracture and increased morbidity. Body-weight-supported treadmill training (BWSTT) and transplantation strategies using neurotrophins have been shown to improve motor function after SCI. While rehabilitation training including BWSTT has also been effective in reducing bone loss post-SCI, the effects of transplantation therapies in bone restoration are not fully understood. Furthermore, the effects of a combinational treatment strategy on bone post-SCI also remain unknown. The aim of this study was to determine the effect of a combination therapy including transplantation of scaffold-releasing neurotrophins and BWSTT on the forelimb and hindlimb bones of a T9-T10 contused SCI animals. Humerus and tibia bones were harvested for Micro-CT scanning and a three-point bending test from four animal groups, namely injury, BWSTT (injury with BWSTT), scaffold (injury with scaffold-releasing neurotrophins), and combinational (injury treated with scaffold-releasing neurotrophins and BWSTT). BWSTT and combinational groups reported higher biomechanical properties in the tibial bone (below injury level) and lower biomechanical properties in the humerus bone (above injury level) when compared to the injury and scaffold groups. Studied structural parameters, including the cortical thickness and bone volume/tissue volume (BV/TV) were also higher in the tibia and lower in the humerus bones of BWSTT and combinational groups when compared to the injury and scaffold groups. While no significant differences were observed, this study is the first to report the effects of a combinational treatment strategy on bone loss in contused SCI animals and can help guide future interventions. Full article

Personalized orthopedic devices are increasingly favored for their potential to enhance long-term treatment success. Despite significant advancements across various disciplines, the seamless integration and full automation of personalized orthopedic treatments remain elusive. This paper identifies key interdisciplinary gaps in integrating and automating advanced technologies for personalized orthopedic treatment. It begins by outlining the standard clinical practices in orthopedic treatments and the extent of personalization achievable. The paper then explores recent innovations in artificial intelligence, biomaterials, genomic and proteomic analyses, lab-on-a-chip, medical imaging, image-based biomechanical finite element modeling, biomimicry, 3D printing and bioprinting, and implantable sensors, emphasizing their contributions to personalized treatments. Tentative strategies or solutions are proposed to address the interdisciplinary gaps by utilizing innovative technologies. The key findings highlight the need for the non-invasive quantitative assessment of bone quality, patient-specific biocompatibility, and device designs that address individual biological and mechanical conditions. This comprehensive review underscores the transformative potential of these technologies and the importance of multidisciplinary collaboration to integrate and automate them into a cohesive, intelligent system for personalized orthopedic treatments. Full article

Bone defects are a global health concern; bone tissue engineering (BTE) is the most promising alternative to reduce patient morbidity and overcome the inherent drawbacks of autograft and allograft bone. Three-dimensional scaffolds are pivotal in this field due to their potential to provide structural support and mimic the natural bone microenvironment. Following an already published protocol, a 3D porous structure consisting of alginate and hydroxyapatite was prepared after a gelation step and a freezing-drying step. Despite the frequent use of alginate in tissue regeneration, the biological inertness of this polysaccharide hampers proper cell colonization and proliferation. Therefore, the purpose of this work was to enhance the biological properties by promoting the interaction and adhesion between cells and biomaterial with the use of Fibronectin. This extracellular matrix protein was physically adsorbed on the scaffold, and its presence was evaluated with environmental scanning electron microscopy (eSEM) and the Micro-Bicinchoninic Acid (μBCA) protein assay. The MG-63 cell line was used for both static and dynamic (i.e., in bioreactor) 3D cell culturing on the scaffolds. The use of the bioreactor allowed for a better exchange of nutrients and oxygen and a better removal of cell catabolites from the inner portion of the construct, mimicking the physiological environment. The functionalized scaffolds showed an improvement in cell proliferation and colonization compared to non-functionalized ones; the effect of the addition of Fibronectin was more evident in the dynamic culturing conditions, where the cells clearly adhered on the surface of functionalized scaffolds. Full article

Skin is the largest protective tissue of the body and is at risk of damage. Hence, the design and development of wound dressing materials is key for tissue repair and regeneration. Although silk fibroin is a known biopolymer in tissue engineering, its degradation rate is not correlated with wound closure rate. To address this disadvantage, we mimicked the hierarchical structure of skin and also provided antibacterial properties; a hydrogel with globular structure consisting of silk fibroin, pluronic F127, and curcumin was developed. In this regard, the effect of pluronic and curcumin on the structural and mechanical properties of the hydrogel was studied. The results showed that curcumin affected the particle size, crystallinity, and ultimate elongation of the hydrogels. In vitro assays confirmed that the hydrogel containing curcumin is not cytotoxic while the diffused curcumin and pluronic provided a considerable bactericidal property against Methicillin-resistant Staphylococcus aureus. Interestingly, presence of pluronic caused more than a 99% reduction in planktonic and adherent bacteria in the curcumin-free hydrogel groups. Moreover, curcumin improved this number further and inhibited bacteria adhesion to prevent biofilm formation. Overall, the developed hydrogel showed the potential to be used for skin tissue regeneration. Full article

A high level of EpCAM overexpression in lung cancer makes this protein a promising target for targeted therapy. Radionuclide visualization of EpCAM expression would facilitate the selection of patients potentially benefiting from such treatment. Single-photon computed tomography (SPECT) using ^99mTc-labeled engineered scaffold protein DARPin Ec1 has shown its effectiveness in imaging tumors with overexpression of EpCAM in preclinical studies, providing high contrast just a few hours after injection. This first-in-human study aimed to evaluate the safety and distribution of [^99mTc]Tc(CO)₃-(HE)₃-Ec1 in patients with primary lung cancer. Twelve lung cancer patients were injected with 300.7 ± 103.2 MBq of [^99mTc]Tc(CO)₃-(HE)₃-Ec1. Whole-body planar imaging (at 2, 4, 6 and 24 h after injection) and SPECT/CT of the lung (at 2, 4, and 6 h) were performed. The patients’ vital signs and possible side effects were monitored up to 7 days after injection. The patients tolerated the injection of [^99mTc]Tc(CO)₃-(HE)₃-Ec1 well, and their somatic condition remained normal during the entire follow-up period. There were no abnormalities in blood and urine tests after injection of [^99mTc]Tc(CO)₃-(HE)₃-Ec1. The highest absorbed doses were in the kidneys, liver, pancreas, thyroid, gallbladder wall, and adrenals. There was also a relatively high accumulation of [^99mTc]Tc(CO)₃-(HE)₃-Ec1 in the small and large intestines, pancreas and thyroid. According to the SPECT/CT, accumulation of [^99mTc]Tc(CO)₃-(HE)₃-Ec1 in the lung tumor was found in all patients included in the study. Intensive accumulation of [^99mTc]Tc(CO)₃-(HE)₃-Ec1 was also noted in regional metastases. [^99mTc]Tc(CO)₃-(HE)₃-Ec1 can potentially be considered a diagnostic tracer for imaging EpCAM expression in lung cancer patients and other tumors with overexpression of EpCAM. Full article

Background: Tissue engineering represents a promising field in regenerative medicine, with bioresorbable polymers such as polycaprolactone (PCL) playing a crucial role as scaffolds. These scaffolds support the growth and repair of tissues by mimicking the extracellular matrix. Objective: This study aimed to assess the in vivo performance of three-dimensional PCL scaffolds by evaluating their effects on bone repair in rat calvaria and the tissue reaction in subcutaneous implant sites, as well as their impact on major organs such as the kidneys, lungs, and liver. Methods: Three-dimensional scaffolds made of PCL were implanted in the subcutaneous tissue of rats’ backs and calvaria. Histological analyses were conducted to observe the bone repair process in calvaria and the tissue response in subcutaneous implant sites. Additionally, the kidneys, lungs, and livers of the animals were examined for any adverse tissue alterations. Results: The histological analysis of the bone repair in calvaria revealed newly formed bone growing towards the center of the defects. In subcutaneous tissues, a thin fibrous capsule with collagenous fibers enveloping the implant was observed in all animals, indicating a positive tissue response. Importantly, no harmful alterations or signs of inflammation, hyperplasia, metaplasia, dysplasia, or hemorrhage were detected in the kidneys, lungs, and liver. Conclusions: The findings demonstrate that PCL scaffolds produced through additive manufacturing are biocompatible, non-cytotoxic, and bioresorbable, promoting osteoconduction without adverse effects on major organs. Hence, PCL is confirmed as a suitable biomaterial for further studies in tissue engineering and regenerative medicine. Full article

Vitronectin is a glycoprotein present in plasma and the extracellular matrix that is implicated in cell migration. The high amount of vitronectin found in neuroblastoma biopsies has been associated with poor prognosis. Moreover, increased vitronectin levels have been described in the plasma of patients with different cancers. Our aim was to assess vitronectin as a potential circulating biomarker of neuroblastoma prognosis. Vitronectin concentration was quantified using ELISA in culture media of four neuroblastoma cell lines grown in a monolayer and in 3D models, and in the plasma of 114 neuroblastoma patients. Three of the neuroblastoma cell lines secreted vitronectin to culture media when cultured in a monolayer and 3D models. Vitronectin release was higher by neuroblastoma cells cultured in 3D models than in the monolayer and was still elevated when cells were grown in 3D scaffolds with cross-linked vitronectin. Vitronectin secretion occurred independently of cell numbers in cultures. Its concentration in the plasma of neuroblastoma patients ranged between 52.4 and 870 µg/mL (median, 218 µg/mL). A ROC curve was used to establish a cutoff of 361 µg/mL, above which patients over 18 months old had worse prognosis (p = 0.0018). Vitronectin could be considered a new plasma prognostic biomarker in neuroblastoma and warrants confirmation in collaborative studies. Drugs inhibiting vitronectin interactions with cells and/or the extracellular matrix could represent a significant improvement in survival for neuroblastoma patients. Full article

Reconstructive and regenerative medicine are critical disciplines dedicated to restoring tissues and organs affected by injury, disease, or congenital anomalies. These fields rely on biomaterials like synthetic polymers, metals, ceramics, and biological tissues to create substitutes that integrate seamlessly with the body. Personalized implants and prosthetics, designed using advanced imaging and computer-assisted techniques, ensure optimal functionality and fit. Regenerative medicine focuses on stimulating natural healing mechanisms through cellular therapies and biomaterial scaffolds, enhancing tissue regeneration. In bone repair, addressing defects requires advanced solutions such as bone grafts, essential in medical and dental practices worldwide. Bovine bone scaffolds offer advantages over autogenous grafts, reducing surgical risks and costs. Incorporating antimicrobial properties into bone substitutes, particularly with metals like zinc, copper, and silver, shows promise in preventing infections associated with graft procedures. Silver nanoparticles exhibit robust antimicrobial efficacy, while zinc nanoparticles aid in infection prevention and support bone healing; 3D printing technology facilitates the production of customized implants and scaffolds, revolutionizing treatment approaches across medical disciplines. In this review, we discuss the primary biomaterials and their association with antimicrobial agents. Full article

The skin is crucial for homeostasis and body defense, requiring quick healing to maintain internal balance. Initially used for bone repair, calcium hydroxyapatite (HAp) is now being studied for soft tissue engineering. This literature review investigated HAp’s role in tissue repair through searches on PubMed, Scopus (Elsevier), Science Direct, Springer Link, and Google Scholar databases without time restrictions, using keywords “hydroxyapatite AND skin AND wound” and “hydroxyapatite AND skin repair”. Inclusion criteria encompassed in vivo studies in humans and animals, English publications, full access, and sufficient data on HAp’s role in tissue repair. Exclusions included duplicates, unrelated articles, editor letters, reviews, comments, conference abstracts, dissertations, and theses. Out of the 472 articles initially identified, 139 met the inclusion criteria, with 21 focusing on HAp for tissue repair. Findings indicate that HAp and nano-HAp in skin regeneration are promising, especially when combined with other biomaterials, offering antimicrobial and anti-inflammatory benefits and stimulating angiogenesis. This suggests their potential application in dermatology, surgery, and dentistry, extending HAp’s versatility from hard tissues to enhancing critical properties for soft tissue repair and accelerating healing. Full article

There is an ongoing effort to advance methodologies for culturing functional photoreceptors in vitro for retinal regenerative strategies. To support the formation of functional photoreceptors, a scaffold should replicate the native environment. The aim of this study was to optimize a sodium alginate–gelatin (SA-G) bioink to mimic the retinal properties while ensuring the printing of constructs with high shape fidelity. The optimized bioink was thoroughly characterized in terms of its physical, mechanical, and rheological properties, printability assessment, and preliminary biocompatibility. The material showed a constant degradation rate, which is crucial for effective tissue regeneration as it provides support for cell differentiation and polarization while gradually degrading to allow cell proliferation and matrix deposition. The optimized bioink displayed stiffness comparable to the native photoreceptor layer, potentially providing appropriate mechanical cues for photoreceptor maturation. Additionally, it exhibited shear-thinning behavior, the presence of yield stress, and fast recovery kinetics, which are essential for successful extrusion. The high shape fidelity of 3D-printed constructs suggested the feasibility of printing complex patterns to drive photoreceptor polarization. The preliminary cell results demonstrated homogeneous cell distribution and sustained cell viability over time. Overall, these findings indicate that the optimized bioink can provide the mechanical and topographical cues necessary for cultivating photoreceptors in vitro for retinal regeneration. Full article

Teaching computation in science courses can enhance science education, but doing so requires that teachers expand the vision of their discipline beyond the traditional view of science presented in most curricula. This article describes a design-based research (DBR) program that included collaboration among high school teachers and professional development leaders in physics and computer science education. Through three years of professional development and teacher-led development, field testing, and refinement of integrated curricular resources, we have combined instructional modeling practices, physical lab materials, and computer programming activities. One of the outcomes is a co-created framework for the integration of computational modeling into physics that is sensitive to teachers’ interests and expressed needs in addition to learning goals. This framework merges two evidence-based approaches to teaching: Bootstrap:Algebra, a web-based computing curriculum that emphasizes using multiple representations of functions and scaffolds that make the programming process explicit, and Modeling Instruction in physics, an approach that emphasizes the use of conceptual models, modeling practices and representational tools. In doing so, we uncover the need to balance teachers’ visions for integration opportunities with practical instructional needs and emphasize that frameworks for integration need to reflect teachers’ values and goals. Full article

The wound healing mechanism is dynamic and well-orchestrated; yet, it is a complicated process. The hallmark of wound healing is to promote wound regeneration in less time without invading skin pathogens at the injury site. This study developed a sodium–carboxymethylcellulose (Na-CMC) bilayer scaffold that was later integrated with silver nanoparticles/graphene quantum dot nanoparticles (AgNPs/GQDs) as an acellular skin substitute for future use in diabetic wounds. The bilayer scaffold was prepared by layering the Na-CMC gauze onto the ovine tendon collagen type 1 (OTC-1). The bilayer scaffold was post-crosslinked with 0.1% (w/v) genipin (GNP) as a natural crosslinking agent. The physical and chemical characteristics of the bilayer scaffold were evaluated. The results demonstrate that crosslinked (CL) groups exhibited a high-water absorption capacity (>1000%) and an ideal water vapour evaporation rate (2000 g/m² h) with a lower biodegradation rate and good hydrophilicity, compression, resilience, and porosity than the non-crosslinked (NC) groups. The minimum inhibitory concentration (MIC) of AgNPs/GQDs presented some bactericidal effects against Gram-positive and Gram-negative bacteria. The cytotoxicity tests on bilayer scaffolds demonstrated good cell viability for human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Therefore, the Na-CMC bilayer scaffold could be a potential candidate for future diabetic wound care. Full article

Background: Telocytes are interstitial stromal cells identified in various human organs, including the kidney. Their presence and role in human diabetic kidney disease remain unknown. Methods: To identify and localize telocytes in glomerular and tubule-interstitial compartments, both normal and diabetic human renal tissues were examined using immunohistochemistry, immunofluorescence, and transmission electron microscopy. Results: Renal telocytes are elongated interstitial cells with long, thin telopodes, showing alternating thin and thick segments. They expressed CD34, Nestin, α-SMA, and Vimentin markers. Occasionally, c-Kit expression was observed in some rounded and spindle cells, while no positivity was detected for PDGFR-β and NG2. Telocytes were identified around Bowman’s capsule, tubules, and peritubular capillaries in both normal and diabetic conditions. In diabetic renal samples, there was a significant increase in α-SMA expressing telocytes, leading to periglomerular fibrosis. These telocytes also exhibited a synthetic phenotype with proteoglycan deposition in the extracellular matrix and, in some cases, showed pre-adipocytic differentiation. Conclusions: Telocytes were identified in normal and diabetic human kidneys. These cells form an elastic mechanical scaffold in the interstitium and are present in all renal cortical compartments. In diabetic samples, their increased α-SMA expression and synthetic phenotype suggest their potential role in the pathogenesis of diabetic nephropathy. Full article

The aim of the study was to compare conventional sintering with additive manufacturing techniques for β-TCP bioceramics, focusing on mechanical properties and biocompatibility. A “critical” bone defect requires surgical intervention beyond simple stabilization. Autologous bone grafting is the gold standard treatment for such defects, but it has its limitations. Alloplastic bone grafting with synthetic materials is becoming increasingly popular. The use of bone graft substitutes has increased significantly, and current research has focused on optimizing these substitutes, whereas this study compares two existing manufacturing techniques and the resulting β-TCP implants. The 3D printed β-TCP hybrid structure implant was fabricated from two components, a column structure and a freeze foam, which were sintered together. The conventionally fabricated ceramics were fabricated by casting. Both scaffolds were characterized for porosity, mechanical properties, and biocompatibility. The hybrid structure had an overall porosity of 74.4 ± 0.5%. The microporous β-TCP implants had a porosity of 43.5 ± 2.4%, while the macroporous β-TCP implants had a porosity of 61.81%. Mechanical testing revealed that the hybrid structure had a compressive strength of 10.4 ± 6 MPa, which was significantly lower than the microporous β-TCP implants with 32.9 ± 8.7 MPa. Biocompatibility evaluations showed a steady increase in cell proliferation over time for all the β-TCP implants, with minimal cytotoxicity. This study provides a valuable insight into the potential of additive manufacturing for β-TCP bioceramics in the treatment of bone defects. Full article