Biomaterial Degradation Research Articles

Mechanisms of Degradation of Collagen or Gelatin Materials (Hemostatic Sponges) in Oral Surgery: A Systematic Review

Objective: The goal of this systematic review was to identify the mechanisms associated with the enzymatic degradation of collagen and gelatin biomaterials and the possible associated flaws. Methods: Four databases (PubMed, B-On, Cochrane Library, and ResearchGate) were used for the bibliographic search of articles. The research question was formulated using the PCC method, (P): collagen or gelatin sponges, hydrogels, and scaffolds; concept (C): enzymatic degradation of collagen or gelatin sponges, hydrogels, and scaffolds; and context (C): effect of enzymatic action on degradation time of collagen or gelatin sponges, hydrogels, and scaffolds. The search was contextualized according to PRISMA recommendations. The identification and exclusion of evidence followed the PRISMA criteria, with specific inclusion and exclusion factors being stipulated for the selection of articles. The risk of bias assessment was performed using the QUIN Scale. Results: The initial search was composed of 13,830 articles after removing duplicates; 56 articles followed for the full-text reading; 45 were excluded; then, 11 articles were obtained, constituting the results of this systematic review. All studies evaluated the materials using gravimetric analysis, and collagenases were the proteases used for the degradation solution. The materials tested were as follows: human-like collagen (HLC) hydrogel with microbial transglutaminase (MTGase), gelatin sponges subjected to different types of crosslinking, and collagen scaffolds with different types of crosslinking. The period of analysis varied between 0.25 h and 35 days. It was possible to highlight the lack of uniformity in the protocols used, which varied largely, thus influencing the degradation times. The risk of bias was low in nine studies and medium in two studies. Conclusions: This systematic review identified a gap in the literature, highlighting the absence of in vitro studies using human saliva and a collagenase concentration close to the physiological levels to simulate oral dynamics. However, based on existing literature, the mechanisms associated with collagen enzymatic degradation in collagen and gelatin biomaterials were comprehensively understood, answering the first research question postulated. In response to the second research question, the main shortcomings identified in the laboratory evaluation of mechanisms associated with collagen enzymatic degradation in collagen and gelatin biomaterials included the lack of standardization in degradation test protocols; this limited inter-study comparisons, which increased heterogeneity. Additionally, variations in collagenase concentrations and types influenced collagen degradation rates, and inappropriate evaluation intervals hindered the identification of total degradation time.

Effect of Gentamicin Sulfate and Polymeric Polyethylene Glycol Coating on the Degradation and Cytotoxicity of Iron-Based Biomaterials.

The work is focused on the degradation, cytotoxicity, and antibacterial properties, of iron-based biomaterials with a bioactive coating layer. The foam and the compact iron samples were coated with a polyethylene glycol (PEG) polymer layer without and with gentamicin sulfate (PEG + Ge). The corrosion properties of coated and uncoated samples were studied using the degradation testing in Hanks' solution at 37 °C. The electrochemical and static immersion corrosion tests revealed that the PEG-coated samples corroded faster than samples with the bioactive PEG + Ge coating and uncoated samples. The foam samples corroded faster compared with the compact samples. To determine the cytotoxicity, cell viability was monitored in the presence of porous foam and compact iron samples. The antibacterial activity of the samples with PEG and PEG + Ge against Escherichia coli CCM 3954 and Staphylococcus aureus CCM 4223 strains was also tested. Tested PEG + Ge samples showed significant antibacterial activity against both bacterial strains. Therefore, the biodegradable iron-based materials with a bioactive coating could be a suitable successor to the metal materials studied thus far as well as the materials used in the field of medicine.

Dynamic monitoring soft tissue healing via visualized Gd-crosslinked double network MRI microspheres

By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K2 (SL)6 K2 (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.

Cellular and microenvironmental cues that promote macrophage fusion and foreign body response.

During the foreign body response (FBR), macrophages fuse to form foreign body giant cells (FBGCs). Modulation of FBGC formation can prevent biomaterial degradation and loss of therapeutic efficacy. However, the microenvironmental cues that dictate FBGC formation are poorly understood with conflicting reports. Here, we identified molecular and cellular factors involved in driving FBGC formation in vitro. Macrophages demonstrated distinct fusion competencies dependent on monocyte differentiation. The transition from a proinflammatory to a reparative microenvironment, characterised by specific cytokine and growth factor programmes, accompanied FBGC formation. Toll-like receptor signalling licensed the formation of FBGCs containing more than 10 nuclei but was not essential for cell-cell fusion to occur. Moreover, the fibroblast-macrophage crosstalk influenced FBGC development, with the fibroblast secretome inducing macrophages to secrete more PDGF, which enhanced large FBGC formation. These findings advance our understanding as to how a specific and timely combination of cellular and microenvironmental factors is required for an effective FBR, with monocyte differentiation and fibroblasts being key players.

Development of an integrated device utilizing exosome-hyaluronic acid-based hydrogel and investigation of its osteogenic and angiogenic characteristics

Tissue engineering (TE) has been widely proposed as a potential solution to the global shortage of donor organs for transplantation. Organic and biocompatible materials have been explored as potential candidates to mimic natural extracellular matrices for regenerative applications. Biomimetic environments have been created using these materials, and hydrogels have shown promise in tissue regeneration due to their rapid gel-forming ability and excellent biocompatibility. Therefore, achieving comparisons between studies utilizing identical materials can prove arduous, as variations in material concentrations, sample preparation techniques, and laboratory conditions significantly influence the physicochemical characteristics of hydrogel systems. To ensure their promotion for clinical purposes, stable variables are crucial. In this regard, we have created an amalgamated and simplified device to assist in hydrogel-based systems using hyaluronic acid and alginate-loaded exosomes for regenerative medicine. The objective of this study is to examine the porosity, injectability, release of loaded exosomes, mechanical properties, and the rate of dissolution and degradation of well-known biomaterials, including alginate and hyaluronic acid, at different concentrations in a stable and controlled setting provided by a simplified integrated device. Furthermore, it aims to comprehensively assess their ex vivo and in vivo osteogenesis and vascularity-related metrics.

Effects of glass-ceramic produced by the sol-gel route in macrophages recruitment and polarization into bone tissue regeneration.

Effective bone substitute biomaterials remain an important challenge in patients with large bone defects. Glass ceramics produced by different synthesis routes may result in changes in the material physicochemical properties and consequently affect the success or failure of the bone healing response. To investigate the differences in the orchestration of the inflammatory and healing process in bone grafting and repair using different glass-ceramic routes production. Thirty male Wistar rats underwent surgical unilateral parietal defects filled with silicate glass-ceramic produced by distinct routes: BS - particulate glass-ceramic produced via the fusion/solidification route, and BG - particulate glass-ceramic produced via the sol-gel route. After 7, 14, and 21 days from biomaterial grafting, parietal bones were removed to be analyzed under H&E and Massons' Trichome staining, and immunohistochemistry for CD206, iNOS, and TGF-β. Our findings demonstrated that the density of lymphocytes and plasma cells was significantly higher in the BS group at 45, and 7 days compared to the BG group, respectively. Furthermore, a significant increase of foreign body giant cells (FBGCs) in the BG group at day 7, compared to BS was found, demonstrating early efficient recruitment of FBGCs against sol-gel-derived glass-ceramic particulate (BS group). According to macrophage profiles, CD206+ macrophages enhanced at the final periods of both groups, being significantly higher at 45 days of BS compared to the BG group. On the other hand, the density of transformation growth factor beta (TGF-β) positive cells on 21 days were the highest in BG, and the lowest in the BS group, demonstrating a differential synergy among groups. Noteworthy, TGF-β+ cells were significantly higher at 21 days of BG compared to the BS group. Glass-ceramic biomaterials can act differently in the biological process of bone remodeling due to their route production, being the sol-gel route more efficient to activate M2 macrophages and specific FBGCs compared to the traditional route. Altogether, these features lead to a better understanding of the effectiveness of inflammatory response for biomaterial degradation and provide new insights for further preclinical and clinical studies involved in bone healing.

Hydrogel degradation promotes angiogenic and regenerative potential of cell spheroids for wound healing.

Chronic nonhealing wounds are debilitating and diminish one's quality of life, necessitating the development of improved strategies for effective treatment. Biomaterial- and cell-based therapies offer an alternative treatment compared to conventional wound care for regenerating damaged tissues. Cell-based approaches frequently utilize endothelial cells (ECs) to promote vascularization and mesenchymal stromal cells (MSCs) for their potent secretome that promotes host cell recruitment. Spheroids have improved therapeutic potential over monodisperse cells, while degradable scaffolds can influence cellular processes conducive to long-term tissue regeneration. However, the role of biomaterial degradation on the therapeutic potential of heterotypic EC-MSC spheroids for wound healing is largely unknown. We formed poly(ethylene) glycol (PEG) hydrogels with varying ratios of matrix metalloproteinase (MMP)-degradable and non-degradable crosslinkers to develop three distinct constructs - fully degradable, partially degradable, and non-degradable - and interrogate the influence of degradation rate on engineered cell carriers for wound healing. We found that the vulnerability to degradation was critical for cellular proliferation, while inhibition of degradation impaired spheroid metabolic activity. Higher concentrations of degradable crosslinker promoted robust cell spreading, outgrowth, and secretion of proangiogenic cytokines (i.e., VEGF, HGF) that are critical in wound healing. The degree of degradation dictated the unique secretory profile of spheroids. When applied to a clinically relevant full-thickness ex vivo skin model, degradable spheroid-loaded hydrogels restored stratification of the epidermal layer, confirming the efficacy of scaffolds to promote wound healing. These results highlight the importance of matrix remodeling and its essential role in the therapeutic potential of heterotypic spheroids.

Tissue formation and host remodeling of an elastomeric biodegradable scaffold in an ovine pulmonary leaflet replacement model.

In pursuit of a suitable scaffold material for cardiac valve tissue engineering applications, an acellular, electrospun, biodegradable polyester carbonate urethane urea (PECUU) scaffold was evaluated as a pulmonary valve leaflet replacement in vivo. In sheep (n = 8), a single pulmonary valve leaflet was replaced with a PECUU leaflet and followed for 1, 6, and 12 weeks. Implanted leaflet function was assessed in vivo by echocardiography. Explanted samples were studied for gross pathology, microscopic changes in the extracellular matrix, host cellular re-population, and immune responses, and for biomechanical properties. PECUU leaflets showed normal leaflet motion at implant, but decreased leaflet motion and dimensions at 6 weeks. The leaflets accumulated α-SMA and CD45 positive cells, with surfaces covered with endothelial cells (CD31+). New collagen formation occurred (Picrosirius Red). Accumulated tissue thickness correlated with the decrease in leaflet motion. The PECUU scaffolds had histologic evidence of scaffold degradation and an accumulation of pro-inflammatory/M1 and anti-inflammatory/M2 macrophages over time in vivo. The extent of inflammatory cell accumulation correlated with tissue formation and polymer degradation but was also associated with leaflet thickening and decreased leaflet motion. Future studies should explore pre-implant seeding of polymer scaffolds, more advanced polymer fabrication methods able to more closely approximate native tissue structure and function, and other techniques to control and balance the degradation of biomaterials and new tissue formation by modulation of the host immune response.

Polydopamine-Functionalized Bacterial Cellulose as Hydrogel Scaffolds for Skin Tissue Engineering.

Bacterial cellulose (BC) is a natural polysaccharide polymer hydrogel produced sustainably by the strain Gluconacetobacter hansenii under static conditions. Due to their biocompatibility, easy functionalization, and necessary physicochemical and mechanical properties, BC nanocomposites are attracting interest in therapeutic applications. In this study, we functionalized BC hydrogel with polydopamine (PDA) without toxic crosslinkers and used it in skin tissue engineering. The BC nanofibers in the hydrogel had a thickness of 77.8 ± 20.3 nm, and they could be used to produce hydrophilic, adhesive, and cytocompatible composite biomaterials for skin tissue engineering applications using PDA. Characterization techniques, namely Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and Raman spectroscopy, were performed to investigate the formation of polydopamine on the BC nanofibers. The XRD peaks for BC occur at 2θ = 14.65°, 16.69°, and 22.39°, which correspond to the planes of (100), (010), and (110) of cellulose type Iα. Raman spectroscopy confirmed the formation of PDA, as indicated by the presence of bands corresponding to the vibration of aromatic rings and aliphatic C-C and C-O stretching at 1336 and 1567 cm-1, respectively. FTIR confirmed the presence of peaks corresponding to PDA and BC in the BC/PDA hydrogel scaffolds at 3673, 3348, 2900, and 1052 cm-1, indicating the successful interaction of PDA with BC nanofibers, which was further corroborated by the SEM images. The tensile strength, swelling ratio, degradation, and surface wettability characteristics of the composite BC biomaterials were also investigated. The BC/PDA hydrogels with PDA-functionalized BC nanofibers demonstrated excellent tensile strength and water-wetting ability while maintaining the stability of the BC fibers. The enhanced cytocompatibility of the BC/PDA hydrogels was studied using the PrestoBlue assay. Culturing murine NIH/3T3 fibroblasts on BC/PDA hydrogels showed higher metabolic activity and enhanced proliferation. Additionally, it improved cell viability when using BC/PDA hydrogels. Thus, these BC/PDA composite biomaterials can be used as biocompatible natural alternatives to synthetic substitutes for skin tissue engineering and wound-dressing applications.

A calcium sulphate/hydroxyapatite ceramic biomaterial carrier for local delivery of tobramycin in bone infections: Analysis of rheology, drug release and antimicrobial efficacy

Local targeted treatment of bone and joint infections using antibiotic-containing carriers is a common practice today. A recently FDA approved biphasic calcium sulphate/hydroxyapatite (CaS/HA) carrier containing gentamicin has been reported to give a sustained drug release, highly effective in eradicating bone infections. We present the first study evaluating the widely used aminoglycoside tobramycin (TOB) incorporated in the CaS/HA material with or without gentamycin (GEN) or vancomycin (VAN) with focus on rheology, drug release and antibacterial efficacy. In-vitro antibiotic release kinetics and biomaterial degradation were established by immersing the composites in phosphate buffered saline. The anti-bacterial effect of antibiotic containing CaS/HA composites as well as antibiotics release fractions were evaluated by Kirby-Bauer disk diffusion against S. aureus. The CaS/HA + GEN + TOB combination delayed setting to over 30 min whereas TOB + VAN slightly prolonged setting time (25 min vs. 15 min) still with good injectability. TOB was released from CaS/HA continuously for 35 days and during this period, the antibiotic loaded biomaterial could show a continuous anti-bacterial efficacy even at the last time point of day-35. After day-35, the pellets used for antibiotic release were taken out from release medium and broken into a paste. CaS/HA + TOB paste showed the largest ZOI (25 mm) against S. aureus ATCC 25923, while CaS/HA + VAN paste had no ZOI and CaS/HA + VAN + TOB paste had a ZOI of 18 mm. At the same time, the ZOI of CaS/HA + TOB against S. aureus P-3 was 14 mm compared to 0 mm in the other two groups. Adding TOB to CaS/HA containing VAN, extended the antimicrobial effect with a longer time and larger zone of inhibition, while no synergistic effect of the co-delivery was observed. Our in-vitro results indicate that CaS/HA could be used as a carrier for TOB as a local targeted delivery system in the treatment of bone infections.

Hydrolytic hydrogels tune mesenchymal stem cell persistence and immunomodulation for enhanced diabetic cutaneous wound healing

Diabetes is associated with an altered global inflammatory state with impaired wound healing. Mesenchymal stem/stromal cells (MSC) are being explored for treatment of diabetic cutaneous wounds due to their regenerative properties. These cells are commonly delivered by injection, but the need to prolong the retention of MSC at sites of injury has spurred the development of biomaterial-based MSC delivery vehicles. However, controlling biomaterial degradation rates in vivo remains a therapeutic-limiting challenge. Here, we utilize hydrolytically degradable ester linkages to engineer synthetic hydrogels with tunable in vivo degradation kinetics for temporally controlled delivery of MSC. In vivo hydrogel degradation rate can be controlled by altering the ratio of ester to amide linkages in the hydrogel macromers. These hydrolytic hydrogels degrade at rates that enable unencumbered cutaneous wound healing, while enhancing the local persistence MSC compared to widely used protease-degradable hydrogels. Furthermore, hydrogel-based delivery of MSC modulates local immune responses and enhances cutaneous wound repair in diabetic mice. This study introduces a simple strategy for engineering tunable degradation modalities into synthetic biomaterials, overcoming a key barrier to their use as cell delivery vehicles.

Biomaterial based implants caused remote liver fatty deposition through activated blood-derived macrophages

Understanding the biocompatibility of biomaterials is a prerequisite for the prediction of its clinical application, and the present assessments mainly rely on in vitro cell culture and in situ histopathology. However, remote organs responses after biomaterials implantation is unclear. Here, by leveraging body-wide-transcriptomics data, we performed in-depth systems analysis of biomaterials – remote organs crosstalk after abdominal implantation of polypropylene and silk fibroin using a rodent model, demonstrating local implantation caused remote organs responses dominated by acute-phase responses, immune system responses and lipid metabolism disorders. Of note, liver function was specially disturbed, defined as hepatic lipid deposition. Combining flow cytometry analyses and liver monocyte recruitment inhibition experiments, we proved that blood derived monocyte-derived macrophages in the liver underlying the mechanism of abnormal lipid deposition induced by local biomaterials implantation. Moreover, from the perspective of temporality, the remote organs responses and liver lipid deposition of silk fibroin group faded away with biomaterial degradation and restored to normal at end, which highlighted its superiority of degradability. These findings were further indirectly evidenced by human blood biochemical ALT and AST examination from 141 clinical cases of hernia repair using silk fibroin mesh and polypropylene mesh. In conclusion, this study provided new insights on the crosstalk between local biomaterial implants and remote organs, which is of help for future selecting and evaluating biomaterial implants with the consideration of whole-body response.

User‐Controlled 4D Biomaterial Degradation with Substrate‐Selective Sortase Transpeptidases for Single‐Cell Biology (Adv. Mater. 19/2023)

Multiplexed Cell Capture Harvesting cells from biomaterials for downstream analysis without perturbing their state represents an outstanding challenge in 3D/4D culture and tissue engineering. In article number 2209904, Cole A. DeForest and co-workers demonstrate that engineered sortase transpeptidases can be used to selectively grade and recover single-cell suspensions from specific subvolumes of hydrogel multimaterials, permitting multiplexed cell capture with largely “biologically invisible” cues.

Allogeneic biomaterial: a fibrosis inhibitor in ischemic myocardial damage

Injectable allogeneic decellularized biomaterials are being developed both as scaffolds for delivery of cellular products and as independent pharmacological agents that affect the cascade of tissue reactions during the period of post-ischemic myocardial remodeling. Biomaterial degradation products can affect cellular processes and modulate cytokine effects, thus determining the healing strategy of damaged tissue. In this work, the influence of biomaterial on the expression of key fibrogenic factors by the cells of tissue bed was demonstrated, and the degree of damage to the myocardium during its ischemic damage was experimentally determined. The aim of our study was to determine the area of myocardial scar degeneration and detection of key fibrogenic factors (bFGF-1, TGFb1, MMP-9), as well as TIMP-2 (MMP-9 antagonist) at the acute and subacute stages of myocardial infarction after implantation of allogeneic powder-like biomaterial in an experimental model.In the course of experiments, the left ventricular coronary artery was ligated in male Wistar rats (experimental group). All animals were divided into 3 groups: experimental group I (n = 50), experimental group II (n = 50), and controls (n = 50). In experimental group I, the artery ligation was simultaneously accompanied by intramyocardial administration of powder-like biomaterial suspension (2 mg). In experimental group II, the allogeneic powder-like biomaterial was administered 5 days after coronary occlusion, and only physiological saline was administered in the control group. The animals were withdrawn from experiment on days +3, +7, +14, +30, and +45. Standard histological assessment (hematoxylin and eosin staining, according to Mallory) and immunohistochemical examination (MMP-9, TGFb1, bFGF-1, TIMP-2) were made, and statistical evaluation was performed. The cells with positive staining were counted, and the scar area index was calculated.We have found that administration of dispersed allogeneic biomaterial was followed by a five-fold decrease in the degree of scar degeneration in both experimental groups at the acute and subacute stages of ischemic myocardial damage as compared to the control group. A significantly decreased expression of fibrogenic factors (MMP-9, TGFb1, bFGF-1) by the local cells was found, along with increased activity of metalloproteinase inhibitor (TIMP-2) in connective tissue cells.Decellularized allogeneic powder-like biomaterial serves as a fibrosis inhibitor and promotes cardioprotection during myocardial remodeling at the initial stages after ischemic injury.

User-Controlled 4D Biomaterial Degradation with Substrate-Selective Sortase Transpeptidases for Single-Cell Biology.

Stimuli-responsive biomaterials show great promise for modeling disease dynamics ex vivo with spatiotemporal control over the cellular microenvironment. However, harvesting cells from such materials for downstream analysis without perturbing their state remains an outstanding challenge in 3/4-dimensional (3D/4D) culture and tissue engineering. In this manuscript, a fully enzymatic strategy for hydrogel degradation that affords spatiotemporal control over cell release while maintaining cytocompatibility is introduced. Exploiting engineered variants of the sortase transpeptidase evolved to recognize and selectively cleave distinct peptide sequences largely absent from the mammalian proteome, many limitations implicit to state-of-the-art methods to liberate cells from gels are sidestepped. It is demonstrated that evolved sortase exposure has minimal impact on the global transcriptome of primary mammalian cells and that proteolytic cleavage proceeds with high specificity; incorporation of substrate sequences within hydrogel crosslinkers permits rapid and selective cell recovery with high viability. In composite multimaterial hydrogels, it is shown that sequential degradation of hydrogel layers enables highly specific retrieval of single-cell suspensions for phenotypic analysis. It is expected that the high bioorthogonality and substrate selectivity of the evolved sortases will lead to their broad adoption as an enzymatic material dissociation cue and that their multiplexed use will enable newfound studies in 4D cell culture.

Long-Term Degradation Assessment of a Polyurethane-Based Surgical Adhesive—Assessment and Critical Consideration of Preclinical In Vitro and In Vivo Testing

Tissue adhesives constitute a great possibility to improve conventional wound closure. In contrast to sutures, they enable nearly immediate hemostasis and can prevent fluid or air leaks. In the present study, a poly(ester)urethane-based adhesive was investigated which already proved to be suitable for different indications, such as reinforcing vascular anastomosis and sealing liver tissue. Using in vitro and in vivo setups, the degradation of the adhesives was monitored over a period of up to 2 years, to evaluate long-term biocompatibility and determine degradation kinetics. For the first time, the complete degradation of the adhesive was documented. In subcutaneous locations, tissue residues were found after 12 months and in intramuscular locations, tissue degradation was complete after about 6 months. A detailed histological evaluation of the local tissue reaction revealed good biocompatibility throughout the different degradation stages. After full degradation, complete remodeling to physiological tissue was observed at the implant locations. In addition, this study critically discusses common issues related to the assessment of biomaterial degradation kinetics in the context of medical device certification. This work highlighted the importance and encouraged the implementation of biologically relevant in vitro degradation models to replace animal studies or at least reduce the number of animals in preclinical testing prior to clinical studies. Moreover, the suitability of frequently used implantation studies based on ISO 10993-6 at standard locations was critically discussed, especially in light of the associated lack of reliable predictions for degradation kinetics at the clinically relevant site of implantation.

Rapid Conductometric Detection of SARS-CoV-2 Proteins and Its Variants Using Molecularly Imprinted Polymer Nanoparticles.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) biosensors have captured more attention than the conventional methodologies for SARS-CoV-2 detection due to having cost-effective platforms and fast detection. However, these reported SARS-CoV-2 biosensors suffer from drawbacks including issues in detection sensitivity, degradation of biomaterials on the sensor's surface, and incapability to reuse the biosensors. To overcome these shortcomings, molecularly imprinted polymer nanoparticles (nanoMIPs) incorporated conductometric biosensor for highly accurate, rapid, and selective detection of two model SARS-CoV-2 proteins: (i) receptor binding domain (RBD) of the spike (S) glycoprotein and (ii) full length trimeric spike protein are introduced. In addition, these biosensors successfully responded to several other SARS-CoV-2 RBD spike protein variants including Alpha, Beta, Gamma, and Delta. Our conductometric biosensor selectively detects the two model proteins and SARS-CoV-2 RBD spike protein variant samples in real-time with sensitivity to a detection limit of 7 pg mL-1 within 10 min of sample incubation. A battery-free, wireless near-field communication (NFC) interface is incorporated with the biosensor for fast and contactless detection of SARS-CoV-2 variants. The smartphone enabled real-time detection and on-screen rapid result for SARS-CoV-2 variants can curve the outbreak due to its ability to alert the user to infection in real time.

Deferoxamine/magnesium modified β-tricalcium phosphate promotes the bone regeneration in osteoporotic rats.

Recently, Deferoxamine (DFO) and magnesium (Mg) have been identified as critical factors for angiogenesis and bone formation. However, in current research studies, there is a lack of focus on whether DFO plus Mg can affect the regeneration of β-tricalcium phosphate (β-TCP) in osteoporosis and through what biological mechanisms. Therefore, the present work was aimed to preparation and evaluate the effect of Deferoxamine/magnesium modified β-tricalcium phosphate promotes (DFO/Mg-TCP) in ovariectomized rats model and preliminary exploration of possible mechanisms. The MC3T3-E1 cells were co-cultured with the exudate of DFO/Mg-TCP and induced to osteogenesis, and the cell viability, osteogenic activity were observed by Cell Counting Kit-8(CCK-8), Alkaline Phosphatase (ALP) staining, Alizarin Red Staining (RES) and Western Blot. In vitro experiments, CCK-8, ALP and ARS staining results show that the mineralization and osteogenic activity of MC3T3-E1increased significantly after intervention by DFO/Mg-TCP, as well as a higher levels of protein expressions including VEGF, OC, Runx-2 and HIF-1α. In vivo experiment, Micro-CT and Histological analysis evaluation show that DFO/Mg-TCP treatment presented the stronger effect on bone regeneration, bone mineralization and biomaterial degradation, when compared with OVX+Mg-TCP group and OVX+TCP group, as well as a higher VEGF, OC, Runx-2 and HIF-1α gene expression. The present study indicates that treatment with DFO/Mg-TCP was associated with increased regeneration by enhancing the function of osteoblasts in an OVX rat.

The degradation of gelatin/alginate/fibrin hydrogels is cell type dependent and can be modulated by targeting fibrinolysis.

In tissue engineering, cell origin is important to ensure outcome quality. However, the impact of the cell type chosen for seeding in a biocompatible matrix has been less investigated. Here, we investigated the capacity of primary and immortalized fibroblasts of distinct origins to degrade a gelatin/alginate/fibrin (GAF)-based biomaterial. We further established that fibrin was targeted by degradative fibroblasts through the secretion of fibrinolytic matrix-metalloproteinases (MMPs) and urokinase, two types of serine protease. Finally, we demonstrated that besides aprotinin, specific targeting of fibrinolytic MMPs and urokinase led to cell-laden GAF stability for at least forty-eight hours. These results support the use of specific strategies to tune fibrin-based biomaterials degradation over time. It emphasizes the need to choose the right cell type and further bring targeted solutions to avoid the degradation of fibrin-containing hydrogels or bioinks.

Preliminary results of customized bone graft made by robocasting hydroxyapatite and tricalcium phosphates for oral surgery

The objective of this study was to assess the mechanical characteristics and the clinical usefulness of beta-tricalcium phosphate (β-TCP) and hydroxyapatite (HA) bioblocks grafted in edentulous jaws of 12 patients. The scaffolds were produced by robocasting ceramic inks containing 80%/20% β-TCP and HA, respectively, with an overall porosity of 60%, with a macropore size between 300 and 500 μm. The mechanical performance of cylindrical vs conical specimens was compared using a universal testing machine. The clinical study was performed on 12 edentulous patients who received 4 cylindrical bone bioblocks. After 10 to 16 weeks of osseointegration, the bioblocks were explanted with trephine for histologic analysis by Goldner and Von Kossa staining. Conical shapes were significantly stronger (96.4 ± 8.7 MPa) than cylindrical shapes (87.8 ± 12.2 MPa). The overall degree of porosity ranged from 53.4% to 58.1% in the coronal region to 62.5% to 66.9% at the apex. After the maturation period, 41 valid bioblocks (85.4%) were obtained for histologic study. Bone showing some cellularity was found in 68.4% of the samples, indicating biologically active bone, and adequate calcification was found in 31.7% of the samples. In terms of biomaterial degradation, 73.2% of the samples were completely resorbed or showed significant resorption. The 80%/20% β-TCP and HA grafts customized by robocasting appear adequate for regenerating self-contained defects.