Search Results (52)

Background: Postoperative abdominal adhesions are a common and serious complication following abdominal surgery, often leading to chronic pain, bowel obstruction, or infertility. This study aimed to evaluate the efficacy of the new starch-based absorbable hemostatic agent and dressing, BioSight, in comparison with a predicate device (4DryField^® PH) for the prevention of abdominal adhesions in a rat model. Methods: A total of 90 Sprague–Dawley rats were used to establish an intra-abdominal adhesion model and assigned to the BioSight, 4DryField^® PH, or control group. Standardized injuries were created on the cecum and parietal peritoneum, followed by application of the designated materials. Animals were sacrificed at 2, 4, and 12 weeks for macroscopic adhesion scoring and histopathological evaluation. Adhesion area, adhesion strength, and tissue thickness were assessed using established scoring systems, and local healing was examined by H&E staining. All quantitative data were analyzed using one-way ANOVA. Conclusions: In a rat peritoneal adhesion model, BioSight exhibited pronounced anti-adhesion efficacy comparable to 4DryField^® PH. Macroscopic evaluation showed consistently low adhesion scores (≤0.4) across all time points up to 12 weeks, while histological analysis confirmed reduced adhesion thickness, with BioSight displaying numerically lower values, particularly at early stages (251.3 ± 137.4 µm vs. 323.2 ± 174.6 µm at Week 2). This performance is attributed to rapid in situ hydrogel formation that provides effective temporary tissue separation, limits early fibrin deposition and inflammatory cell infiltration, and supports hemostasis. Importantly, the starch-based hydrogel exhibits a balanced biodegradation profile—persisting long enough to protect injured tissues during the critical inflammatory and fibroproliferative phases, yet undergoing complete enzymatic resorption thereafter without adverse tissue reactions. Collectively, these results highlight the anti-adhesion functionality of BioSight and support the clinical potential of plant-derived starch-based bioresorbable surgical adjuncts. Full article

Articular cartilage possesses limited intrinsic healing capacity due to its avascular and aneural nature, posing a significant challenge for treating focal chondral defects. While regenerative strategies employing biomaterials and stem cells have progressed, their mechanistic evaluation is hindered by the lack of physiologically relevant in vitro models. This study aimed to establish and characterize a human ex vivo osteochondral explant model to assess cellular and extracellular matrix responses to cartilage repair strategies. Osteochondral explants (10 mm diameter, n = 61) were harvested from femoral condyles of patients undergoing knee arthroplasty. Standardized full-thickness chondral defects (4 mm) were created and assigned to six treatment groups: native control, untreated defect, fibrin glue, collagen type I hydrogel (ChondroFiller^®), fibrin glue + MSCs, and ChondroFiller^® + MSCs. Explants were cultured for 7, 14, or 21 days, followed by metabolic, biochemical, and histological assessments. Explants remained viable for 21 days. Notably, the ChondroFiller^® group showed a 2.4-fold increase in DNA content by day 14, while MSC-treated groups enhanced collagen deposition and GAG production. Significant correlations between DNA and collagen levels were observed in scaffold-based treatments. This ex vivo model offers a reproducible and translational platform to investigate cartilage regeneration with temporal resolution, supporting preclinical testing of emerging therapeutic approaches. Full article

Dural tear (DT) and cerebrospinal fluid (CSF) leakage, though uncommon complications, represent a potentially serious risk of anterior cervical spine surgery, particularly in patients with ossification of the posterior longitudinal ligament (OPLL). While the incidence in routine anterior cervical discectomy and fusion (ACDF) or corpectomy (ACCF) is typically below 0.5%, it rises sharply to 4–32% in OPLL cases. Furthermore, it exceeds 60% when dural ossification (DO) is present. Adhesion and ossification obliterate the normal epidural plane, creating a fragile osteofibrotic interface that is highly susceptible to tearing during decompression. This review synthesizes current evidence on the pathophysiology of DT and CSF leakage in anterior cervical spine surgery, provides a framework for risk stratification, and outlines evolving techniques for successful repair and management. Intraoperative management has shifted from direct resection toward dura-preserving floating decompression and biologically reinforced multilayer repair using fascia, collagen matrix, fibrin adhesives, and polyethylene glycol (PEG) hydrogel sealants. Postoperative care emphasizes controlled CSF pressure regulation, sterile wound management, and early ambulation. Most DTs achieve successful closure with timely recognition and standardized treatment. However, persistent leakage may require escalation to composite reconstruction, epidural blood patch, or vascularized flap reinforcement. Emerging technologies such as bioactive hydrogels, 3D-printed dural scaffolds, and artificial intelligence–assisted imaging offer potential future improvements, although clinical adoption remains limited. This review summarizes current evidence on the mechanisms, risk factors, diagnostic predictors, repair strategies, and postoperative management of DT and CSF leakage, with specific attention to OPLL-related DO. A more apparent distinction between established clinical practice and emerging investigational technologies is provided to guide evidence-based decision-making. Full article

Tau pathology is a defining hallmark of Alzheimer’s disease (AD), closely associated with cognitive decline. Antisense oligonucleotides targeting the tau-encoding gene MAPT (MAPT-ASO) have shown promise in clinical trials, but their therapeutic potential is limited by poor delivery across the blood–brain barrier (BBB). In this study, we developed transferrin (TF)-functionalized liposomes encapsulating MAPT-ASOs and evaluated their transport across a 3D self-assembled microvascular BBB model composed of human brain microvascular endothelial cells, astrocytes, and pericytes embedded in a fibrin hydrogel. Following confirmation of MAPT-ASO efficacy in reducing tau levels and protecting against glutamate-induced axonal degeneration, we observed significantly enhanced extravascular accumulation and sustained delivery of MAPT-ASOs with TF-functionalized liposomes over 24 h, compared to non-functionalized control liposomes. This study presents a novel delivery strategy for a functionally effective tau-targeting anti-sense oligonucleotide (ASO), potentially enabling systemic delivery rather than intrathecal administration. In addition, this study demonstrates the utility of the 3D in vitro BBB model for screening and optimizing brain delivery of nucleic acid-based therapeutics. Full article

Secondary osteonecrosis (ON) is a common complication in paediatric cancer survivors. Combining multipotent mesenchymal stromal cells (MSCs) with core decompression surgery halts disease progression and stimulates bone regeneration. However, the success of advanced therapy medicinal products (ATMPs) requires versatile “off-the-shelf” tissue engineering products (TEPs). This study evaluated the safety and efficacy of TEPs loaded with allogeneic MSCs from Wharton’s jelly (WJ-MSCs) in a large-animal model of bone regeneration to support a paediatric investigational plan for ON patients. WJ-MSC-laden fibrin-based hydrogels combined with a synthetic bone substitute (PRO-DENSE^TM) were tested in 16 juvenile sheep (8 males and 8 females) distributed in four experimental groups. Each animal received four cylindrical bone defects in the femoral and tibial epiphyses and was assessed at 6 and 12 weeks. Safety was confirmed, and bone regeneration was observed across all groups. A combination of WJ-MSCs with PRO-DENSE^TM led to improved histological scores, osteogenesis, and construct integration. Trabecular bone volume also increased more in cellular groups over time. However, effects were inconsistent across groups, reflecting the variability seen in clinical trials and highlighting the significant impact of factors such as immunogenetic compatibility, MSC batch potency, and interaction with the recipient’s microenvironment on the therapeutic effectiveness and successful clinical translation of allogeneic ATMPs. Full article

Regenerative medicine is a challenging field in current research and development, whilst translating the findings of novel tissue regenerative agents into clinical application. Protein-based hydrogels are derived from various sources, with animal-derived products being primarily utilized to deliver cells and promote cell genesis and proliferation, thereby aiding in numerous indications, including bone tissue regeneration, cartilage regeneration, spinal cord injury, and wound healing. As biocompatible and biodegradable systems, they are tolerated by the human body, allowing them to exert their beneficial effects in many indications. In this review article, multiple types of animal-derived proteins (e.g., collagen, gelatin, serum albumin, fibrin) were described, and a selection of the recent literature was collected to support the claims behind these innovative systems. During the literature review, special indications were found when applying these hydrogels, including the therapeutic option to treat post-myocardial infarct sites, glaucoma, and others. Maintaining their structure and mechanical integrity is still challenging. It is usually solved by adding (semi)synthetic polymers or small molecules to strengthen or loosen the mechanical stress in the hydrogel’s structure. All in all, this review points out the potential application of value-added delivery systems in regenerative medicine. Full article

Background: Traditional root canal therapy (RCT) effectively removes diseased or necrotic pulp tissue and replaces it with inorganic materials. Regenerative endodontics is an alternative to conventional RCT by using biologically based approaches to restore the pulp–dentin complex. This review explores emerging techniques, including autogenic and allogenic pulp transplantation, platelet-rich fibrin, human amniotic membrane scaffolds, specialized pro-resolving mediators, nanofibrous and bioceramic scaffolds, injectable hydrogels, dentin matrix proteins, and cell-homing strategies. These methods utilize stem cells, growth factors, and biomaterials to regenerate vascularized, functional pulp tissue. Methods: A narrative review was conducted using PubMed, Scopus, and Embase to identify studies published between 2010 and 2023. In vitro, animal, and clinical studies focusing on innovative regenerative endodontic techniques were analyzed. Conclusions: Although regenerative endodontics demonstrates great potential, challenges remain in standardizing protocols, addressing biological variability, and achieving consistent clinical outcomes. Future research must focus on refining these techniques to ensure their safety, efficacy, and accessibility in routine practice. By addressing current limitations, regenerative endodontics could redefine the management of pulpitis, offering biologically based treatments that enhance tooth vitality, structural integrity, and long-term prognosis. Full article

Knee cartilage has limited natural healing capacity, complicating the development of effective treatment plans. Current non-cell-based therapies (e.g., microfracture) result in poor repair cartilage mechanical properties, low durability, and suboptimal tissue integration. Advanced treatments, such as autologous chondrocyte implantation, face challenges including cell leakage and inhomogeneous distribution. Successful cell therapy relies on prolonged retention of therapeutic biologicals at the implantation site, yet the optimal integration of implanted material into the surrounding healthy tissue remains an unmet need. This study evaluated the effectiveness of a newly developed photo-curable adhesive hydrogel for cartilage repair, focusing on adhesion properties, integration performance, and ability to support tissue regeneration. The proposed hydrogel design exhibited significant adhesion strength, outperforming commercial adhesives such as fibrin-based glues. An in vivo goat model was used to evaluate the hydrogels’ adhesion properties and long-term integration into full-thickness cartilage defects over six months. Results showed that cell-free hydrogel-treated defects achieved superior integration with surrounding tissue and enhanced cartilage repair, with notable lateral integration. In vitro results further demonstrated high cell viability, robust matrix production, and successful cell encapsulation within the hydrogel matrix. These findings highlight the potential of adhesive hydrogel formulations to improve the efficacy of cell-based therapies, offering a potentially superior treatment for knee cartilage defects. Full article

As one of the biomarkers of coagulation system-related diseases, the detection of thrombin is of practical importance. Thus, this study developed a portable biosensor based on a personal glucometer for rapid detection of thrombin activity. Fibrinogen was used for the detection of thrombin, and the assay principle was inspired by the blood coagulation process, where thrombin hydrolyzes fibrinogen to produce a fibrin hydrogel, and the amount of invertase encapsulated in the fibrin hydrogel fluctuates in accordance with the activity of thrombin in the sample solution. The quantitative assay is conducted by measuring the amount of unencapsulated invertase available to hydrolyze the substrate sucrose, and the signal readout is recorded using a personal glucometer. A linear detection range of 0–0.8 U/mL of thrombin with a limit of detection of 0.04 U/mL was obtained based on the personal glucometer sensing platform. The results of the selectivity and interference experiments showed that the developed personal glucometer sensing platform is highly selective and accurate for thrombin activity. Finally, the reliability of the portable glucometer method for rapid thrombin detection in serum samples was investigated by measuring the recovery rate, which ranged from 92.8% to 107.7%. In summary, the fibrin hydrogel sensing platform proposed in this study offers a portable and versatile means for detecting thrombin using a personal glucometer. This approach not only simplifies the detection process, but also eliminates the need for large instruments and skilled operators, and substantially reduces detection costs. Full article

This study focuses on enhancing controllable fibrin-based hydrogels for tissue engineering, addressing existing weaknesses. By integrating a novel copolymer, we improved the foundation for cell-based angiogenesis with adaptable structural features. Tissue engineering often faces challenges like waste disposal and nutrient supply beyond the 200 µm diffusion limit. Angiogenesis breaks through this limitation, allowing the construction of larger constructs. Our innovative scaffold combination significantly boosts angiogenesis, resulting in longer branches and more capillary network junctions. The copolymer attached to fibrin fibers enables precise adjustment of hydrogel mechanical dynamic properties for specific applications. Our material proves effective for angiogenesis, even under suppression factors like suramin. In our study, we prepared fibrin-based hydrogels with and without the copolymer PVP12400-co-GMA10mol%. Using a co-culture system of human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), we analyzed angiogenetic behavior on and within the modified hydrogels. Capillary-like structures were reproducibly formed on different surfaces, demonstrating the general feasibility of three-dimensional endothelial cell networks in fibrin-based hydrogels. This highlights the biomaterial’s suitability for in vitro pre-vascularization of biohybrid implants. Full article

Three-dimensional (3D) neuronal cultures grown in hydrogels are promising platforms to design brain-like neuronal networks in vitro. However, the optimal properties of such cultures must be tuned to ensure a hydrogel matrix sufficiently porous to promote healthy development but also sufficiently rigid for structural support. Such an optimization is difficult since it implies the exploration of different hydrogel compositions and, at the same time, a functional analysis to validate neuronal culture viability. To advance in this quest, here we present a combination of a rheological protocol and a network-based functional analysis to investigate PEGylated fibrin hydrogel networks with gradually higher stiffness, achieved by increasing the concentration of thrombin. We observed that moderate thrombin concentrations of 10% and 25% in volume shaped healthy networks, although the functional traits depended on the hydrogel stiffness, which was much higher for the latter concentration. Thrombin concentrations of 65% or higher led to networks that did not survive. Our results illustrate the difficulties and limitations in preparing 3D neuronal networks, and stress the importance of combining a mechano-structural characterization of a biomaterial with a functional one. Full article

A major challenge for future drug development comprises finding alternative models for drug screening. The use of animal models in research is highly controversial, with an ongoing debate on their ethical acceptability. Also, animal models are often poorly predictive of therapeutic outcomes due to the differences between animal and human physiological environments. In this study, we aimed to develop a biomimetic hydrogel that replicates the composition of skin for potential use in in vitro modeling within tissue engineering. The hydrogel was fabricated through the crosslinking of collagen type I, hyaluronic acid, four-arm PEG succinimidyl glutarate (4S-StarPEG), and fibrinogen. Various ratios of these components were systematically optimized to achieve a well-interconnected porosity and desirable rheological properties. To evaluate the hydrogel’s cytocompatibility, fibroblasts were embedded within the matrix. The resulting hydrogel exhibited promising properties as a scaffold, also facilitating the growth of and proliferation of the cells. This biomimetic hydrogel holds great potential for tissue engineering applications, particularly in skin regeneration and cancer research. The study used melanoma spheroids fabricated using the 96-round bottom well plate method as a potential application. The results demonstrate that the developed hydrogels allowed the maintenance of spheroid integrity and viability, meaning it has a promising use as a three-dimensional in vitro model of melanoma for both tissue engineering and drug screening applications. Full article

Atrioventricular block (AVB) is a severe disease for pediatric patients. The repetitive operations needed in the case of the pacemaker implantation to maintain the electrical signal at the atrioventricular node (AVN) affect the patient’s life quality. In this study, we present a method of biofabrication of multi-cell-laden cylindrical fibrin-based fibers that can restore the electrical signal at the AVN. We used human umbilical vein smooth muscle cells (HUVSMCs), human umbilical vein endothelial cells (HUVECs) and induced pluripotent stem cell cardiomyocytes (iPSC-CMs) cultivated either statically or dynamically to mimic the native AVN. We investigated the influence of cell composition, construct diameter and cyclic stretch on the function of the fibrin hydrogels in vitro. Immunohistochemistry analyses showed the maturity of the iPSC-CMs in the constructs through the expression of sarcomeric alpha actinin (SAA) and electrical coupling through Connexin 43 (Cx43) signal. Simultaneously, the beating frequency of the fibrin hydrogels was higher and easy to maintain whereas the concentration of iPSC-CMs was higher compared with the other types of cylindrical constructs. In total, our study highlights that the combination of fibrin with the cell mixture and geometry is offering a feasible biofabrication method for tissue engineering approaches for the treatment of AVB. Full article

Traumatic injuries are a major cause of morbidity and mortality worldwide; however, there is limited research on microvascular traumatic injuries. To address this gap, this research aims to develop and optimise an in vitro construct for traumatic injury research at the microvascular level. Tissue engineering constructs were created using a range of polymers (collagen, fibrin, and gelatine), solvents (PBS, serum-free endothelial media, and MES/NaCl buffer), and concentrations (1–5% w/v). Constructs created from these hydrogels and HUVECs were evaluated to identify the optimal composition in terms of cell proliferation, adhesion, migration rate, viability, hydrogel consistency and shape retention, and tube formation. Gelatine hydrogels were associated with a lower cell adhesion, whereas fibrin and collagen ones displayed similar or better results than the control, and collagen hydrogels exhibited poor shape retention; fibrin scaffolds, particularly at high concentrations, displayed good hydrogel consistency. Based on the multipronged evaluation, fibrin hydrogels in serum-free media at 3 and 5% w/v were selected for further experimental work and enabled the formation of interconnected capillary-like networks. The networks formed in both hydrogels displayed a similar architecture in terms of the number of segments (10.3 ± 3.21 vs. 9.6 ± 3.51) and diameter (8.6446 ± 3.0792 $\mathsf{\mu }$m vs. 7.8599 ± 2.3794 $\mathsf{\mu }$m). Full article

Biopolymers represent a great resource for the development and utilization of new functional materials due to their particular advantages such as biocompatibility, biodegradability and non-toxicity. “Intelligent gels” sensitive to different stimuli (temperature, pH, ionic strength) have different applications in many industries (e.g., pharmacy, biomedicine, food). This review summarizes the research efforts presented in the patent and non-patent literature. A discussion was conducted regarding biopolymer-based hydrogels such as natural proteins (i.e., fibrin, silk fibroin, collagen, keratin, gelatin) and polysaccharides (i.e., chitosan, hyaluronic acid, cellulose, carrageenan, alginate). In this analysis, the latest advances in the modification and characterization of advanced biopolymeric formulations and their state-of-the-art administration in drug delivery, wound healing, tissue engineering and regenerative medicine were addressed. Full article