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The relationships between adhesion and cohesion. The relationships between adhesion and cohesion can be grouped as: A, Using the same functional groups for cohesion and adhesion including (a) phenol groups, (b) NHS-ester, (c) aldehyde groups and (d) cyanoacrylate-derivatives-based strategies; B, Using extra strategy with functional groups for adhesion including (e) click chemistry, (f) photo-crosslinking, (g) phase transition (h) hydrophobic interactions and (i) dopingbased strategies; C, Using a different strategy for cohesion including (c) aldehyde groups, (e) click chemistry, (f) Photo-crosslinking, (h) hydrophobic interactions, (j) hydrogen bonds and (k) self-assembly-based strategies.

The relationships between adhesion and cohesion. The relationships between adhesion and cohesion can be grouped as: A, Using the same functional groups for cohesion and adhesion including (a) phenol groups, (b) NHS-ester, (c) aldehyde groups and (d) cyanoacrylate-derivatives-based strategies; B, Using extra strategy with functional groups for adhesion including (e) click chemistry, (f) photo-crosslinking, (g) phase transition (h) hydrophobic interactions and (i) dopingbased strategies; C, Using a different strategy for cohesion including (c) aldehyde groups, (e) click chemistry, (f) Photo-crosslinking, (h) hydrophobic interactions, (j) hydrogen bonds and (k) self-assembly-based strategies.

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Due to the nature of non-invasive wound closure, the ability to close different forms of leaks, and the potential to immobilize various devices, bioadhesives are altering clinical practices. As one of the vital factors, bioadhesives' strength is determined by adhesion and cohesion mechanisms. As well as being essential for adhesion strength, the co...

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... the relationship between adhesion and cohesion will help in the design of bioadhesives, finally facilitating the translation. According to the authors' understanding of bioadhesives, the relationship between cohesion and adhesion can be grouped into three categories: 1) Using the same functional groups for cohesion as those for adhesion (Fig. 3A); 2) using extra functional groups for cohesion in addition to groups to adhesion (Fig. 3B); 3) Using different strategies for cohesion (Fig. 3C). The commonly used cohesion strategies (covalent and non-covalent ones) have also been grouped according to the main mechanisms of different bioadhesive ...
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... finally facilitating the translation. According to the authors' understanding of bioadhesives, the relationship between cohesion and adhesion can be grouped into three categories: 1) Using the same functional groups for cohesion as those for adhesion (Fig. 3A); 2) using extra functional groups for cohesion in addition to groups to adhesion (Fig. 3B); 3) Using different strategies for cohesion (Fig. 3C). The commonly used cohesion strategies (covalent and non-covalent ones) have also been grouped according to the main mechanisms of different bioadhesive ...
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... to the authors' understanding of bioadhesives, the relationship between cohesion and adhesion can be grouped into three categories: 1) Using the same functional groups for cohesion as those for adhesion (Fig. 3A); 2) using extra functional groups for cohesion in addition to groups to adhesion (Fig. 3B); 3) Using different strategies for cohesion (Fig. 3C). The commonly used cohesion strategies (covalent and non-covalent ones) have also been grouped according to the main mechanisms of different bioadhesive ...
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... of the bioadhesives' adhesion relies on the interactions between FGA and tissues. Those FGA are reactive, so they also self-crosslink or crosslink with certain crosslinkers to form the bulk network of the bioadhesives (Fig. 3A). Most of the bioadhesives using phenol groups, NHSester, aldehyde and cyanoacrylate for cohesion can be grouped in this category. For example, phenol groups are sticky because they interact with tissues through covalent or non-covalent crosslinking. Meanwhile, irreversible and reversible strategies, including oxidation and ...
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... which quickly leads to adhesion failure [18,19]. Cohesion reinforcement has been considered when bioadhesives are explored further in load-bearing tissues or elastic and soft tissues, where they must withstand pressure and stress [17,111]. To reinforce the cohesion, some bioadhesives use combinational approaches together with FGA for cohesion (Fig. 3B), which falls into this category [17,127,128]. In this case, the extra force will have little influence on the adhesion mechanism but strengthen the cohesion by offering extra interactions. Generally, the additional force includes covalent and non-covalent strategies (Fig. ...
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... use combinational approaches together with FGA for cohesion (Fig. 3B), which falls into this category [17,127,128]. In this case, the extra force will have little influence on the adhesion mechanism but strengthen the cohesion by offering extra interactions. Generally, the additional force includes covalent and non-covalent strategies (Fig. ...
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... addition to FGA, there are many other strategies to fabricate hydrogel systems with proper bulk mechanical strength. By using these strategies, the competition between adhesion and cohesion can be directly avoided (Fig. 3C) [129]. Properties of cohesion can be purposely designed by selecting the relevant ...
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... contrast, in other conditions, a large swelling ratio is good for nutrient exchange and metabolic waste transfer (Fig. 4B2). Meanwhile, the swelling ratio of the adhesives is always calculated by the weight change of the adhesives in the medium compared with that of the initial weight and there are three kinds of initial weight as summarized in Fig. 4B3, which are dry weight obtained by freeze-drying or vacuum drying and initial wet weight. Since it is reported that vacuum drying will lead to a smaller swelling ratio than that resulting from the freezedrying method, choosing the right initial weight according to how exactly the bioadhesives are applied is essential [141]. Regarding ...
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... out to test the influence of these parts on the cells. 2. Leaching solution coincubation (Fig. 4D2): After the bioadhesives contact body liquids, the uncrosslinked/not fully-crosslinked parts will be released into the surrounding tissues, and the experiment can be used to evaluate their influences on biocompatibility. 3. Degradation products (Fig. 4D3): Degradation is very important for bioadhesives in certain applications, and coincubation of the degradation products of bioadhesives with cells can test their influences on cells after degradation. 4. Cell growth on the surface of the bioadhesives (Fig. 4D4). This is generally used when the bioadhesives are designed to support cell ...
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... the cells inside the network. According to ISO 10993-5, more than 70% of cell viability is nontoxic. In papers, MTT, MTS, CCk-8, AlamarBlue®/PrestoBlue, photomicroscopy and Live&dead assays (Fig. 4E1 to E6) were used to assess the outcome of the testing. Among them, depending on the core molecules, MTT, MTS and CCK-8 are tetrazolium-based assays (Fig. 4E1 to E3) while AlamarBlue® and PrestoBlue® are tetrazolium-based (Fig. 4E4). Their concepts are that tetrazolium/resazurin compounds will be reduced because of the active metabolism of cells [148]. However, there is a chance that the bioadhesives can influence the result by interacting with the tetrazolium/resazurin compounds through ...

Citations

... Polymeric hydrogel-based biosealants have recently emerged as a promising alternative for suturing and stapling because of their sol-gel phase transition, bioactivity, and strong tissue adhesion [22,23]. Therefore, they have been used to prevent gas/ liquid leakage and bleeding and immobilize implantable medical devices on target tissues [24]. Currently, various tissue adhesive biosealants, such as Tisseel, Coseal, Duraseal, Progel, and others, have been successfully approved by the Food and Drug Administration and are widely used in clinics [24]. ...
... Therefore, they have been used to prevent gas/ liquid leakage and bleeding and immobilize implantable medical devices on target tissues [24]. Currently, various tissue adhesive biosealants, such as Tisseel, Coseal, Duraseal, Progel, and others, have been successfully approved by the Food and Drug Administration and are widely used in clinics [24]. However, these commercialized biosealants have relatively lower tissue adhesiveness when applied to myocardial tissue owing to the presence of the body or pericardial fluid and the dynamic pulsation of the heart [20,[25][26][27]. ...
Article
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Myocardial infarction (MI) is treated with stem cell transplantation using various biomaterials and methods, such as stem cell/spheroid injections, cell sheets, and cardiac patches. However, current treatment methods have some limitations, including low stem cell engraftment and poor therapeutic effects. Furthermore, these methods cause secondary damage to heart due to injection and suturing to immobilize them in the heart, inducing side effects. In this study, we developed stem cell spheroid-laden 3-dimensional (3D) patches (S_3DP) with biosealant to treat MI. This 3D patch has dual modules, such as open pockets to directly deliver the spheroids with their paracrine effects and closed pockets to improve the engraft rate by protecting the spheroid from harsh microenvironments. The spheroids formed within S_3DP showed increased viability and expression of angiogenic factors compared to 2-dimensional cultured cells. We also fabricated gelatin-based tissue adhesive biosealants via a thiol-ene reaction and disulfide bond formation. This biosealant showed stronger tissue adhesiveness than commercial fibrin glue. Furthermore, we successfully applied S_3DP using a biosealant in a rat MI model without suturing in vivo, thereby improving cardiac function and reducing heart fibrosis. In summary, S_3DP and biosealant have excellent potential as advanced stem cell therapies with a sutureless approach to MI treatment.
... CoSt shows repeatable strong wet tissue adhesiveness (62 ± 4.8 KPa), high sealing performance (153.2 ± 35.1 mmHg), and high haemostatic efficiency compared with fibrin glue . Previous studies have confirmed that adhesiveness is determined by the balance and synergy of interfacial adhesion and cohesion qualities inside the sticky matrix Bu and Pandit, 2022). The introduction of enzymes [e.g., horseradish peroxidase (HRP)] into the material system not only increases the crosslinking strength of the material and thus the cohesion but also aids in the conversion of catechol to catechol aldehyde, which further increases the adhesive properties of the material. ...
Article
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Uncontrollable haemorrhage from deep, noncompressible wounds remains a persistent and intractable challenge, accounting for a very high proportion of deaths in both war and disaster situations. Recently, injectable hydrogels have been increasingly studied as potential haemostatic materials, highlighting their enormous potential for the management of noncompressible haemorrhages. In this review, we summarize haemostatic mechanisms, commonly used clinical haemostatic methods, and the research progress on injectable haemostatic hydrogels. We emphasize the current status of injectable hydrogels as haemostatic materials, including their physical and chemical properties, design strategy, haemostatic mechanisms, and application in various types of wounds. We discuss the advantages and disadvantages of injectable hydrogels as haemostatic materials, as well as the opportunities and challenges involved. Finally, we propose cutting-edge research avenues to address these challenges and opportunities, including the combination of injectable hydrogels with advanced materials and innovative strategies to increase their biocompatibility and tune their degradation profile. Surface modifications for promoting cell adhesion and proliferation, as well as the delivery of growth factors or other biologics for optimal wound healing, are also suggested. We believe that this paper will inform researchers about the current status of the use of injectable haemostatic hydrogels for noncompressible haemorrhage and spark new ideas for those striving to propel this field forward.
... Figure 6 displays In this sense, a cross-link complex might be formed by metallic oxides which chelate with the functional sites in the blend matrix throughout certain intermolecular interactions, resulting in a highly compact polymer matrix, therefore inhibiting water absorption. 57 Additional information based on the total soluble matter (TSM) percentage for nanocomposite biofilms supported the WCA results, as summarized in Table 1. It was found that an acute decrease in TSM values with increasing the MgO NPs ratio in the matrix was observed. ...
... We speculated that this was due to excessive PDA chains competing with acrylamide (AM) for the free radicals generated by ammonium persulfate (APS), resulting in the excessive polymerization of PDA. Consequently, the number of phenolic hydroxyl groups available for tissue adhesion decreased, ultimately leading to a deterioration in the adhesive performance [34,35]. Because of the presence of microvillous structures and adhesive proteins on the uterine mucosa, we speculate that these will contribute to the formation of a stronger adhesion between the hydrogel and the mucosal surface. ...
Article
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Intrauterine adhesions (IUA) has become one of the main causes of female infertility. How to effectively prevent postoperative re-adhesion has become a clinical challenge. In this study, a mussel-inspired dual-network hydrogel was proposed for the postoperative anti-adhesion of IUA. First, a calcium alginate/polyacrylamide (CA-PAM) hydrogel was prepared via covalent and Ca2+ cross-linking. Benefiting from abundant phenolic hydroxyl groups, polydopamine (PDA) was introduced to further enhance the adhesion ability and biocompatibility. This CA-PAM hydrogel immersed in 10 mg/mL dopamine solution possessed remarkable mechanical strength (elastic modulus > 5 kPa) and super stretchability (with a breaking elongation of 720%). At the same time, it showed excellent adhesion (more than 6 kPa). Surprisingly, the coagulation index of the hydrogel was 27.27 ± 4.91, demonstrating attractive coagulation performance in vitro and the potential for rapid hemostasis after surgery.
... The addition of 8 wt.% PCL showed the highest wet adhesion strength. The adhesion performance of these tissue adhesives is determined by their own cohesion and covalent bonding strength with the tissue surface, besides the wet adhesion strength is affected by the hydrophobicity of the adhesive [55]. The PCL/HCPU-NHS (with 8 wt.% PCL) had the larger tensile strength and the largest water contact angle, showing higher cohesion and hydrophobicity in the study group. ...
Article
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As a superior alternative to sutures, tissue adhesives have been developed significantly in recent years. However, existing tissue adhesives struggle to form fast and stable adhesion between tissue interfaces, bond weakly in wet environments and lack bioactivity. In this study, a degradable and bioactive citrate-based polyurethane adhesive is constructed to achieve rapid and strong tissue adhesion. The hydrophobic layer was created with polycaprolactone to overcome the bonding failure between tissue and adhesion layer in wet environments, which can effectively improve the wet bonding strength. This citrate-based polyurethane adhesive provides rapid, non-invasive, liquid-tight and seamless closure of skin incisions, overcoming the limitations of sutures and commercial tissue adhesives. In addition, it exhibits biocompatibility, biodegradability and hemostatic properties. The degradation product citrate could promote the process of angiogenesis and accelerate wound healing. This study provides a novel approach to the development of a fast-adhering wet tissue adhesive and provides a valuable contribution to the development of polyurethane-based tissue adhesives.
... Figure 6 displays In this sense, a cross-link complex might be formed by metallic oxides which chelate with the functional sites in the blend matrix throughout certain intermolecular interactions, resulting in a highly compact polymer matrix, therefore inhibiting water absorption. 57 Additional information based on the total soluble matter (TSM) percentage for nanocomposite biofilms supported the WCA results, as summarized in Table 1. It was found that an acute decrease in TSM values with increasing the MgO NPs ratio in the matrix was observed. ...
Article
Fabricating active and intelligent packaging materials has become the highest demand for catering to market needs, especially after the COVID-19 pandemic, for ensuring food safety. Thus, the wider objective of this article was to promote active and smart packaging biofilms possessing antibacterial and humidity-sensing properties for sustainable poly(vinyl alcohol) (PVA)/gelatin (Ge) reinforced with biosynthesized magnesium nanoparticles (MgO NPs) by a solvent-casting route. The UV−visible spectrum has been utilized to determine the optimized biosynthesized MgO NPs and then the nanostructure of optimized MgO NPs investigated by varying techniques such as XRD, SEM−EDX, TEM, FT-IR, and thermogravi-metric analysis. Four MgO NPs proportions (i.e., 1, 3, 5, and 10 wt %) were used to fabricate PVA/Ge biofilms. In the biofilms system, the tensile results showcased that the nanocomposite film containing 5 wt % of MgO NPs had the highest tensile strength value (i.e., 22.10 MPs) compared to the other biofilms or the unfilled blank (i.e., 6.30 MPs). Correspondingly, the humidity-sensing data revealed that the PVA/Ge-1% MgO NPs sensor had higher sensitivity over a broad range of relative humidity from (7−97% RH) and at 100 Hz. Additionally, the hydrophobicity of biofilms, measured by water contact angle, UV-stability, and antioxidant and antibacterial properties was also analyzed to possibly use these biofilms in active food packaging with extended shelf life of foodstuffs. However, the PVA/Ge-1% MgO NPs biofilm was predominately found to possess attractive sensing properties and could be considered as a sensor for intelligent food packaging.
... When these two forces are properly combined, they contribute to a mechanically and chemically stable, and highly adhesive material [38]. Yazhong et al. [39] categorized the combination of these two types of mechanisms into three major strategies (Fig. 2). It can be achieved by using: i) the same functional groups, ii) additional groups specifically to enhance cohesion, or iii) a cohesion mechanism completely different from the adhesion mechanism. ...
... However, since both adhesion and cohesion rely on the same functional groups, competition to establish stable bonds will take place [16]. Therefore, a fine balance between adhesion and cohesion is needed, and this can be accomplished by adjusting the ratio of crosslinkers and polymer composition [39]. There are cases where incorporating additional groups becomes necessary to enhance cohesion forces, for instance, dopamine-based adhesives often exhibit inadequate cohesive forces in wet environments, resulting in adhesive failure [40]. ...
... By providing other interactions, the additional cohesion mechanism will result in more robust cohesion forces without interfering with the adhesion capacity. Lastly, by individually selecting the adhesion and the cohesion forces, a higher level of control over the material adhesion can be achieved [39], this can be done by the combination of covalent or non-covalent crosslinkings or both. For example, Lu et al. [41], developed a doublenetwork adhesive that combines methacrylated cellulose with a copolymer containing both dopamine and cationic quaternary ammonium groups. ...
Article
Full-text available
Conventional surgical closure techniques, such as sutures, clips, or skin closure strips, may not always provide optimal wound closure and may require invasive procedures, which can result in potential post-surgical complications. As result, there is a growing demand for innovative solutions to achieve superior wound closure and improve patient outcomes. To overcome the abovementioned issues, in situ generated hemostatic adhesives/sealants have emerged as a promising alternative, offering a targeted, controllable, and minimally invasive procedure for a wide variety of medical applications. The aim of this review is to provide a comprehensive overview of the mechanisms of action and recent advances of in situ generated hemostatic adhesives, particularly protein-based, thermoresponsive, bioinspired, and photocrosslinkable formulations, as well as the design challenges that must be addressed. Overall, this review aims to enhance a comprehensive understanding of the latest advancements of in situ generated hemostatic adhesives and their mechanisms of action, with the objective of promoting further research in this field.
... Furthermore, the adherent HA layer might act as a mechanical and biochemical protective shield, offering further cartilage tissue protection and potentially decelerating OA progression [49,[60][61][62][63][64]. Such fundamental elements are especially important for viscosupplementation applications, as cartilage surfaces are never perfectly smooth and often present a certain degree of roughness, especially in patients suffering from OA [65,66]. Therein, the artificial presence of an exogeneous adhesive hydrogel could aid in filling such structural irregularities or in promoting aggregation. ...
... Therein, the artificial presence of an exogeneous adhesive hydrogel could aid in filling such structural irregularities or in promoting aggregation. Consequently, this could enable the hydrogel to establish a boundary layer on the treated cartilage surface, potentially enhancing the therapeutic effects of the treatment [62,63,65]. Overall, advanced knowledge of the adhesive properties of HA-based systems is deemed to be essential not only for applications in drug delivery, but also for optimization of their therapeutic role in joint lubrication and protection/repair [55,[58][59][60][61]. ...
... The results of the in vitro oxidative challenge assays revealed that the four considered hydrogel systems behave quite differently in the presence of a strong and standardized oxidant source (i.e., 30% H 2 O 2 , Figure 4). cartilage surfaces are never perfectly smooth and often present a certain degree of roughness, especially in patients suffering from OA [65,66]. Therein, the artificial presence of an exogeneous adhesive hydrogel could aid in filling such structural irregularities or in promoting aggregation. ...
Article
Full-text available
While many injectable viscosupplementation products are available for osteoarthritis (OA) management, multiple hydrogel functional attributes may be further optimized for efficacy enhancement. The objective of this study was to functionally benchmark four commercially available hyaluronan-based viscosupplements (Ostenil, Ostenil Plus, Synvisc, and Innoryos), focusing on critical (rheological, lubricative, adhesive, and stability) attributes. Therefore, in vitro and ex vivo quantitative characterization panels (oscillatory rheology, rotational tribology, and texture analysis with bovine cartilage) were used for hydrogel product functional benchmarking, using equine synovial fluid as a biological control. Specifically, the retained experimental methodology enabled the authors to robustly assess and discuss various functional enhancement options for hyaluronan-based hydrogels (chemical cross-linking and addition of antioxidant stabilizing agents). The results showed that the Innoryos product, a niacinamide-augmented linear hyaluronan-based hydrogel, presented the best overall functional behavior in the retained experimental settings (high adhesivity and lubricity and substantial resistance to oxidative degradation). The Ostenil product was conversely shown to present less desirable functional properties for viscosupplementation compared to the other investigated products. Generally, this study confirmed the high importance of formulation development and control methodology optimization, aiming for the enhancement of novel OA-targeting product critical functional attributes and the probability of their clinical success. Overall, this work confirmed the tangible need for a comprehensive approach to hyaluronan-based viscosupplementation product functional benchmarking (product development and product selection by orthopedists) to maximize the chances of effective clinical OA management.
... Therefore, they have been used to prevent gas/liquid leakage and bleeding and immobilize implantable medical devices on target tissues [54]. Currently, various tissue adhesive biosealants, such as Tisseel®, Coseal®, Duraseal®, Progel™, and others, have been successfully approved by Food and Drug Administration (FDA) and are widely used in clinics [54]. ...
... Therefore, they have been used to prevent gas/liquid leakage and bleeding and immobilize implantable medical devices on target tissues [54]. Currently, various tissue adhesive biosealants, such as Tisseel®, Coseal®, Duraseal®, Progel™, and others, have been successfully approved by Food and Drug Administration (FDA) and are widely used in clinics [54]. However, these commercialized biosealants have relatively lower tissue adhesiveness when applied to myocardial tissue owing to the presence of the body or pericardial uid and the dynamic pulsation of the heart [36, [55][56][57][58]. ...
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Full-text available
Background Myocardial infarction (MI) is treated with stem cell transplantation using various methods. However, current methods, such as stem cell/spheroids injection, cell sheets, and cardiac patches have some limitations, such as low stem cell engraftment and poor therapeutic effects. Furthermore, these methods cause secondary damage due to injection and suturing to immobilize them in the heart, inducing side effects. Methods We fabricated human adipose-derived stem cell spheroids-laden three-dimensional (3D)-printed patches. The morphology, viability, and paracrine angiogenic effect of spheroids formed within 3D patches were analyzed in in vitro experiments. We synthesized thiolated gelatin and maleimide-conjugated gelatin as the polymers and fabricated a tissue adhesive biosealant using the polymers. The biocompatibility and biodegradability of the biosealant were evaluated using human dermal fibroblasts in vitro and the mouse subcutaneous models in vivo. In addition, the therapeutic effects of stem cell spheroid-laden 3D patches (S_3DP) with biosealant were evaluated using a rat MI model in vivo. Results The spheroids showed increased viability and expression of angiogenic factors compared to two-dimensional cultured cells. Our gelatin-based tissue adhesive biosealants were rapidly formed via a thiol-ene reaction and disulfide bond formation and revealed stronger tissue adhesiveness than commercial fibrin glue. Furthermore, we successfully applied S_3DP using a biosealant in a rat MI model without suturing in vivo, thereby improving cardiac function and reducing fibrosis of the heart. Conclusion We developed S_3DP with gelatin-based tissue adhesive biosealant to treat MI. This 3D patch has dual modules, such as open pockets to directly deliver the spheroids with their paracrine effects and closed pockets to improve the engraft rate by protecting the spheroid from harsh microenvironments. In summary, S_3DP and biosealant have excellent potential as advanced stem cell therapies with a sutureless approach to MI treatment.
... HA can also be used as a transporter in the treatment of intrauterine adhesions (Liu et al., 2019). However the advantage of gelatin over hyaluronic acid is that gelatin can offer tissue adhesiveness through ionic bonding with tissue (Duan et al., 2023;Bu and Pandit, 2022). Here, the commercially available HA hydrogel of IUA prevention was used as control. ...
Article
Full-text available
Introduction: Uterine adhesion (IUA) is a severe complication that results from uterine operations or uterine infections. Hysteroscopy is considered the gold standard for the diagnosis and treatment of uterine adhesions. Yet, this invasive procedure leads to re-adhesions after hysteroscopic treatment. Hydrogels loading functional additives (e.g., placental mesenchymal stem cells (PC-MSCs)) that can act as physical barriers and promote endometrium regeneration are a good solution. However, traditional hydrogels lack tissue adhesion which makes them unstable under a rapid turnover of the uterus, and PC-MSCs have biosafety risks when used as functional additives. Methods: In this study, we coupled an adhesive hydrogel with a PC-MSCs conditioned medium (CM) to form a hybrid of gel and functional additives (CM/Gel-MA). Results and Discussion: Our experiments show that CM/Gel-MA enhances the activity of endometrial stromal cells (ESCs), promotes cell proliferation, and reduces the expression of α-SMA, collagen I, CTGF, E-cadherin, and IL-6, which helps to reduce the inflammatory response and inhibit fibrosis. We conclude that CM/Gel-MA can more potentially prevent IUA by combining the physical barriers from adhesive hydrogel and functional promotion from CM.