Search

AimDendrimers dendritic structural design holds vast promises, predominantly for drug delivery, owing to their unique properties. Dendritic architecture is widespread topology found in nature and offers development of specific properties of chemical substances. Dendrimers are an ideal delivery vehicle candidate for open study of the effects of polymer size, charge, and composition on biologically relevant properties such as lipid bilayer interactions, cytotoxicity, bio-distribution, internalization, blood plasma retention time, and filtration. This article reviews role of dendrimers in advanced drug delivery and biomedical applications.

Periodontitis is a prevalent chronic, destructive inflammatory disease affecting tooth-supporting tissues in humans. Guided tissue regeneration strategies are widely utilized for periodontal tissue regeneration generally by using a periodontal membrane. The main role of these membranes is to establish a mechanical barrier that prevents the apical migration of the gingival epithelium and hence allowing the growth of periodontal ligament and bone tissue to selectively repopulate the root surface. Currently available membranes have limited bioactivity and regeneration potential. To address such challenges, an osteoconductive, antibacterial, and flexible poly(caprolactone) (PCL) composite membrane containing zinc oxide (ZnO) nanoparticles is developed. The membranes are fabricated through electrospinning of PCL and ZnO particles. The physical properties, mechanical characteristics, and in vitro degradation of the engineered membrane are studied in detail. Also, the osteoconductivity and antibacterial properties of the developed membrane are analyzed in vitro. Moreover, the functionality of the membrane is evaluated with a rat periodontal defect model. The results confirmed that the engineered membrane exerts both osteoconductive and antibacterial properties, demonstrating its great potential for periodontal tissue engineering.

More than 90% of cancer-related deaths can be attributed to the occurrence of metastatic diseases. Recent studies have highlighted the importance of the multicellular, biochemical and biophysical stimuli from the tumor microenvironment during carcinogenesis, treatment failure, and metastasis. Therefore, there is a need for experimental platforms that are able to recapitulate the complex pathophysiological features of the metastatic microenvironment. Recent advancements in biomaterials, microfluidics, and tissue engineering have led to the development of living multicellular microculture systems, which are maintained in controllable microenvironments and function with organ level complexity. The applications of these "on-chip" technologies for detection, separation, characterization and three dimensional (3D) propagation of cancer cells have been extensively reviewed in previous works. In this contribution, we focus on integrative microengineered platforms that allow the study of multiple aspects of the metastatic microenvironment, including the physicochemical cues from the tumor associated stroma, the heterocellular interactions that drive trans-endothelial migration and angiogenesis, the environmental stresses that metastatic cancer cells encounter during migration, and the physicochemical gradients that direct cell motility and invasion. We discuss the application of these systems as in vitro assays to elucidate fundamental mechanisms of cancer metastasis, as well as their use as human relevant platforms for drug screening in biomimetic microenvironments. We then conclude with our commentaries on current progress and future perspectives of microengineered systems for fundamental and translational cancer research.

We demonstrate ultrastrong and flexible hydrogels by self-assembling chitin nanofiber in the presence of gelatin methacryloyl. We tune the mechanical properties of the hydrogel with chitin nanofiber content and show proof-of-concept applications in engineering vascular tissue.

Hydrogels have been extensively used for tissue engineering applications due to their versatility in structure and physical properties, which can mimic native tissues. Although significant progress has been made towards designing hydrogels for soft tissue repair, engineering hydrogels that resemble load-bearing tissues is still considered a great challenge due to their specific mechano-physical demands. Here, we report microporous, tough, yet highly compressible poly(vinyl alcohol) (PVA)-based hydrogels for potential applications in repairing or replacing different load-bearing tissues. The synergy of freeze-thawing and the Hofmeister effect, which controlled the spatial arrangement and aggregation of polymer chains, facilitated the formation of micro-structured frameworks with tunable porosity. While the maximum mechanical strength, toughness, and stretchability of the engineered hydrogel were ~390 kPa, ~388 kJ/m3, and ~170%, respectively, the Young's modulus based on compression testing was found to be in the range of ~0.02 - 0.30 MPa, highlighting the all-in-one mechanically enriched nature of the hydrogel system. Furthermore, the minimal swelling and degradation rate of the engineered hydrogel met the specific requirements of load-bearing tissues. Finally, excellent antibacterial resistance as well as in vitro biocompatibility of the hydrogel demonstrated its potential for the replacement of load-bearing tissues.

Successful nerve repair using bioadhesive hydrogels demands minimizing tissue-material interfacial mechanical mismatch to reduce immune responses and scar tissue formation. Furthermore, it is crucial to maintain the bioelectrical stimulation-mediated cell-signaling mechanism to overcome communication barriers within injured nerve tissues. Therefore, engineering bioadhesives for neural tissue regeneration necessitates the integration of electroconductive properties with tissue-like biomechanics. In this study, we propose a stretchable bioadhesive based on a custom-designed chemically modified elastin-like polypeptides (ELPs) and a choline-based bioionic liquid (Bio-IL), providing an electroconductive microenvironment to reconnect damaged nerve tissue. The stretchability akin to native neural tissue was achieved by incorporating hydrophobic ELP pockets, and a robust tissue adhesion was obtained due to multi-mode tissue-material interactions through covalent and noncovalent bonding at the tissue interface. Adhesion tests revealed adhesive strength ~10 times higher than commercially available tissue adhesive, Evicel®. Furthermore, the engineered hydrogel supported in vitro viability and proliferation of human glial cells. We also evaluated the biodegradability and biocompatibility of the engineered bioadhesive in vivo using a rat subcutaneous implantation model, which demonstrated facile tissue infiltration and minimal immune response. The outlined functionalities empower the engineered elastic and electroconductive adhesive hydrogel to effectively enable sutureless surgical sealing of neural injuries and promote tissue regeneration., Competing Interests: Dr. Nasim Annabi holds equity in GelMEDIX Inc. The remaining authors declare no competing financial interest., (© 2024 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Controlling traumatic bleeding from damaged internal organs while effectively sealing the wound is critical for saving the lives of patients. Existing bioadhesives suffer from blood incompatibility, insufficient adhesion to wet surfaces, weak mechanical properties, and complex application procedures. Here, we engineered a ready-to-use hemostatic bioadhesive with ultra-strengthened mechanical properties and fatigue resistance, robust adhesion to wet tissues within a few seconds of gentle pressing, deformability to accommodate physiological function and action, and the ability to stop bleeding efficiently. The engineered hydrogel, which demonstrated high elasticity (>900%) and toughness (>4600 kJ/m 3 ), was formed by fine-tuning a series of molecular interactions and crosslinking mechanisms involving N-hydroxysuccinimide (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe 3+ ions. Dual adhesive moieties including mussel-inspired pyrogallol/catechol and NHS synergistically enhanced wet tissue adhesion (>400 kPa in a wound closure test). In conjunction with physical sealing, the high affinity of TA/Fe 3+ for blood could further augment hemostasis. The engineered bioadhesive demonstrated excellent in vitro and in vivo biocompatibility as well as improved hemostatic efficacy as compared to commercial Surgicel®. Overall, the hydrogel design strategy described herein holds great promise for overcoming existing obstacles impeding clinical translation of engineered hemostatic bioadhesives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Designing adhesive hydrogels with optimal properties for the treatment of injured tissues is challenging due to the tradeoff between material stiffness and toughness while maintaining adherence to wet tissue surfaces. In most cases, bioadhesives with improved mechanical strength often lack an appropriate elastic compliance, hindering their application for sealing soft, elastic, and dynamic tissues. Here, we present a novel strategy for engineering tissue adhesives in which molecular building blocks are manipulated to allow for precise control and optimization of the various aforementioned properties without any tradeoffs. To introduce tunable mechanical properties and robust tissue adhesion, the hydrogel network presents different modes of covalent and noncovalent interactions using N -hydroxysuccinimide ester (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe 3+ ions. Through combining and tuning different molecular interactions and a variety of crosslinking mechanisms, we were able to design an extremely elastic (924%) and tough (4697 kJ/m 3 ) multifunctional hydrogel that could quickly adhere to wet tissue surfaces within 5 s of gentle pressing and deform to support physiological tissue function over time under wet conditions. While Alg-NHS provides covalent bonding with the tissue surfaces, the catechol moieties of TA molecules synergistically adopt a mussel-inspired adhesive mechanism to establish robust adherence to the wet tissue. The strong adhesion of the engineered bioadhesive patch is showcased by its application to rabbit conjunctiva and porcine cornea. Meanwhile, the engineered bioadhesive demonstrated painless detachable characteristics and in vitro biocompatibility. Additionally, due to the molecular interactions between TA and Fe 3+ , antioxidant and antibacterial properties required to support the wound healing pathways were also highlighted. Overall, by tuning various molecular interactions, we were able to develop a single-hydrogel platform with an "all-in-one" multifunctionality that can address current challenges of engineering hydrogel-based bioadhesives for tissue repair and sealing., (© 2023 The Authors.)

The extracellular matrix (ECM), an integral component of all organs, is inherently tissue adhesive and plays a pivotal role in tissue regeneration and remodeling. However, man-made three-dimensional (3D) biomaterials that are designed to mimic ECMs do not intrinsically adhere to moisture-rich environments and often lack an open macroporous architecture required for facilitating cellularization and integration with the host tissue post-implantation. Furthermore, most of these constructs usually entail invasive surgeries and potentially a risk of infection. To address these challenges, we recently engineered biomimetic and macroporous cryogel scaffolds that are syringe injectable while exhibiting unique physical properties, including strong bioadhesive properties to tissues and organs. These biomimetic catechol-containing cryogels were prepared from naturally-derived polymers such as gelatin and hyaluronic acid and were functionalized with mussel-inspired dopamine (DOPA) to impart bioadhesive properties. We found that using glutathione as an antioxidant and incorporating DOPA into cryogels via a PEG spacer arm led to the highest tissue adhesion and improved physical properties overall, whereas DOPA-free cryogels were weakly tissue adhesive. As shown by qualitative and quantitative adhesion tests, DOPA-containing cryogels were able to adhere strongly to several animal tissues and organs such as the heart, small intestine, lung, kidney, and skin. Furthermore, these unoxidized (i.e., browning-free) and bioadhesive cryogels showed negligible cytotoxicity toward murine fibroblasts and prevented the ex vivo activation of primary bone marrow-derived dendritic cells. Finally, in vivo data suggested good tissue integration and a minimal host inflammatory response when subcutaneously injected in rats. Collectively, these minimally invasive, browning-free, and strongly bioadhesive mussel-inspired cryogels show great promise for various biomedical applications, potentially in wound healing, tissue engineering, and regenerative medicine., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: Fragile soft clots and stiff clots remain challenging in the treatment of acute ischemic stroke. This study aims to investigate the impact of clot stiffness on the efficacy of thrombectomy devices and a new aspiration catheter with a hydro-separator., Methods: The Neurostar aspiration catheter has a novel hydro-separator technology that macerates clots by a stream of saline inside the catheter. The Neurostar catheter and two commercially available devices, the SOFIA aspiration catheter and Solitaire stent retriever, were tested in this study. We evaluated the efficacy of each device on clots with various stiffness in a simple in vitro model. We also assessed single-pass recanalization performance in challenging situations with large erythrocyte-rich clots and fibrin-rich clots in a realistic vascular model., Results: We observed an inverse association between the clot stiffness and recanalization rates. The aspiration catheter, SOFIA ingested soft clots but not moderately stiff clots. When removing soft clots with the stent retriever, fragmentation was observed, although relatively stiff clots were well-integrated and removed. The Neurostar ingested soft clots similar to the aspiration catheter, and also aspirated stiff clots by continuous suction with hydro-separator. In the experiments with challenging clots, the Neurostar led to significantly higher recanalization rates than the stent retriever and aspiration catheter., Conclusions: The stiffness of the clots affected the efficacy of endovascular thrombectomy based on the type of device. The Neurostar catheter with hydro-separator resulted in better success rates than a commercially available aspiration catheter and stent retriever in this experimental model.

Full-thickness wounds to the eye can lead to serious vision impairment. Current standards of care (from suturing to tissue transplantation) usually require highly skilled surgeons and use of an operating theater. In this study, we report the synthesis, optimization, and in vitro and ex vivo testing of photocrosslinkable hydrogel-based adhesive patches that can easily be applied to globe injuries or corneal incisions. According to the type and concentration of polymers used in the adhesive formulations, we were able to finely tune the physical properties of the bioadhesive including viscosity, elastic modulus, extensibility, ultimate tensile strength, adhesion, transparency, water content, degradation time, and swellability. Our in vitro studies showed no sign of cytotoxicity of the hydrogels. Moreover, the hydrogel patches showed higher adhesion on freshly explanted pig eyeballs compared to a marketed ocular sealant. Finally, ex vivo feasibility studies showed that the hydrogel patches could seal complex open-globe injuries such as large incision, cruciform injury, and injury associated with tissue loss. These results suggest that our photocrosslinkable hydrogel patch could represent a promising solution for the sealing of open-globe injuries or surgical incisions. STATEMENT OF SIGNIFICANCE: Current management of severe ocular injuries require advanced surgical skills and access to an operating theater. To address the need for emergent management of wounds that cannot be handled in the operating room, surgical adhesives have gained popularity, but none of the currently available adhesives have optimal bioavailability, adhesive or mechanical properties. This study describes the development, optimization and testing of a light-sensitive adhesive patch that can easily be applied to the eye. After solidification using visible light, the patch shows no toxicity and is more adherent to the tissue than a marketed sealant. Thus this technology could represent a promising solution to stabilize ocular injuries in emergency settings before definitive surgical repair., Competing Interests: Declaration of Competing Interest Dr. Dana and Dr. Annabi have equity interest in Gelmedix Inc., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Controlling bleeding from a raptured tissue, especially during the surgeries, is essentially important. Particularly for soft and dynamic internal organs where use of sutures, staples, or wires is limited, treatments with hemostatic adhesives have proven to be beneficial. However, major drawbacks with clinically used hemostats include lack of adhesion to wet tissue and poor mechanics. In view of these, herein, we engineered a double-crosslinked sealant which showed excellent hemostasis (comparable to existing commercial hemostat) without compromising its wet tissue adhesion. Mechanistically, the engineered hydrogel controlled the bleeding through its wound-sealing capability and inherent chemical activity. This mussel-inspired hemostatic adhesive hydrogel, named gelatin methacryloyl-catechol (GelMAC), contained covalently functionalized catechol and methacrylate moieties and showed excellent biocompatibility both in vitro and in vivo . Hemostatic property of GelMAC hydrogel was initially demonstrated with an in vitro blood clotting assay, which showed significantly reduced clotting time compared to the clinically used hemostat, Surgicel®. This was further assessed with an in vivo liver bleeding test in rats where GelMAC hydrogel closed the incision rapidly and initiated blood coagulation even faster than Surgicel®. The engineered GelMAC hydrogel-based seaalant with excellent hemostatic property and tissue adhesion can be utilized for controlling bleeding and sealing of soft internal organs., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: N. A. hold equity in GelMEDIX Inc., (© 2021 Published by Elsevier Ltd.)

More than 90% of surgical patients develop postoperative adhesions, and the incidence of hospital re-admissions can be as high as 20%. Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions. To solve this clinical limitation, we developed an injectable and sprayable shear-thinning hydrogel barrier (STHB) composed of silicate nanoplatelets and poly(ethylene oxide). We optimized this technology to recover mechanical integrity after stress, enabling its delivery though injectable and sprayable methods. We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro. The STHB was then tested in a rodent model of peritoneal injury to determine its efficacy preventing the formation of postoperative adhesions. After two weeks, the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions, and STHB formulations presented superior efficacy compared to a commercially available adhesion barrier. Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations. Our technology demonstrated increased efficacy, ease of use in complex anatomies, and compatibility with different delivery methods, providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions., (© 2021. The Author(s).)

Cerebrovascular ischemia from intracranial atherosclerosis remains difficult to treat. Although current revascularization procedures, including intraluminal stents and extracranial to intracranial bypass, have shown some benefit, they suffer from perioperative and postoperative morbidity. To address these limitations, here we developed a novel approach that involves gluing of arteries and subsequent transmural anastomosis from the healthy donor into the ischemic recipient. This approach required an elastic vascular sealant with distinct mechanical properties and adhesion to facilitate anastomosis. We engineered two hydrogel-based glues: an elastic composite hydrogel based on methacryloyl elastin-like polypeptide (mELP) combined with gelatin methacryloyl (GelMA) and a stiff glue based on pure GelMA. Two formulations with distinct mechanical characteristics were necessary to achieve stable anastomosis. The elastic GelMA/mELP composite glue attained desirable mechanical properties (elastic modulus: 288 ± 19 kPa, extensibility: 34.5 ± 13.4%) and adhesion (shear strength: 26.7 ± 5.4 kPa) to the blood vessel, while the pure GelMA glue exhibited superior adhesion (shear strength: 49.4 ± 7.0 kPa) at the cost of increased stiffness (elastic modulus: 581 ± 51 kPa) and reduced extensibility (13.6 ± 2.5%). The in vitro biocompatibility tests confirmed that the glues were not cytotoxic and were biodegradable. In addition, an ex vivo porcine anastomosis model showed high arterial burst pressure resistance of 34.0 ± 7.5 kPa, which is well over normal (16 kPa), elevated (17.3 kPa), and hypertensive crisis (24 kPa) systolic blood pressures in humans. Finally, an in vivo swine model was used to assess the feasibility of using the newly developed two-glue system for an endovascular anastomosis. X-ray imaging confirmed that the anastomosis was made successfully without postoperative bleeding complications and the procedure was well tolerated. In the future, more studies are required to evaluate the performance of the developed sealants under various temperature and humidity ranges., (© 2021 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Wound healing is a complex process based on the coordinated signaling molecules and dynamic interactions between the engineered scaffold and newly formed tissue. So far, most of the engineered scaffolds used for the healing of full-thickness skin wounds do not mimic the natural extracellular matrix (ECM) complexity and therefore are not able to provide an appropriate niche for endogenous tissue regeneration [1]. To address this gap and to accelerate the wound healing process, we present biomimetic bilayer scaffolds compositing of gelatin nanofibers (GFS) and photocrosslinkable composite hydrogels loaded with epidermal growth factors (EGF). The nanofibers operate as the dermis layer, and EGF-loaded composite hydrogels acted as the epidermis matrix for the full-thickness wound healing application. The hydrogels are composed of gelatin metacryloyl (GelMA) modified with silicate nanoplatelets (Laponite). To overcome the challenges of transdermal delivery of EGF, including short half-life and lack of efficient formulation precise, controlled delivery was attained by immobilization of EGF on Laponite. It is shown that the addition of 1wt% silicate nanoplatelet increases the compressive modulus of the hydrogels by 170%. In vitro wound closure analysis also demonstrated improved adhesion of the scaffolds to the native tissue by 3.5 folds. Moreover, the tunable hemostatic ability of the scaffolds due to the negatively charged nanoplatelets is shown. In an established excisional full-thickness wound model, an enhanced wound closure (up to 93.1 ± 1.5%) after 14 days relative to controls (GFS and saline-treated groups) is demonstrated. The engineered adhesive and hemostatic scaffolds with sustained release of the growth factors have the potential to stimulate complete skin regeneration for full-thickness wound healing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The development of bioinks based on shear-thinning and self-healing hydrogels has recently attracted significant attention for constructing complex three-dimensional physiological microenvironments. For extrusion-based bioprinting, it is challenging to provide high structural reliability and resolution of printed structures while protecting cells from shear forces during printing. Herein, we present shear-thinning and printable hydrogels based on silicate nanomaterials, laponite (LA), and glycosaminoglycan nanoparticles (GAGNPs) for bioprinting applications. Nanocomposite hydrogels (GLgels) were rapidly formed within seconds due to the interactions between the negatively charged groups of GAGNPs and the edges of LA. The shear-thinning behavior of the hydrogel protected encapsulated cells from aggressive shear stresses during bioprinting. The bioinks could be printed straightforwardly into shape-persistent and free-standing structures with high aspect ratios. Rheological studies demonstrated fast recovery of GLgels over multiple strain cycles. In vitro studies confirmed the ability of GLgels to support cell growth, proliferation, and spreading. In vitro osteogenic differentiation of pre-osteoblasts murine bone marrow stromal cells encapsulated inside the GLgels was also demonstrated through evaluation of ALP activity and calcium deposition. The subcutaneous implantation of the GLgel in rats confirmed its in vivo biocompatibility and biodegradability. The engineered shear-thinning hydrogel with osteoinductive characteristics can be used as a new bioink for 3D printing of constructs for bone tissue engineering applications., (Published by Elsevier Ltd.)

Background: Organ transplantation is a standard therapeutic strategy for irreversible organ damage, but the utility of nerve transplantation remains generally unexplored, despite its potential benefit to a large patient population. Here, we aimed to establish a feasible preclinical mouse model for understanding the cellular mechanisms behind the rejection of peripheral and optic nerves., Methods: We performed syngenic and allogenic transplantation of optic and sciatic nerves in mice by inserting the nerve grafts inside the kidney capsule, and we assessed the allografts for signs of rejection through 14 d following transplantation. Then, we assessed the efficacy of CTLA4 Ig, Rapamycin, and anti-CD3 antibody in suppressing immune cell infiltration of the nerve allografts., Results: By 3 d posttransplantation, both sciatic and optic nerves transplanted from BALB/c mice into C57BL/6J recipients contained immune cell infiltrates, which included more CD11b + macrophages than CD3 + T cells or B220 + B cells. Ex vivo immunogenicity assays demonstrated that sciatic nerves demonstrated higher alloreactivity in comparison with optic nerves. Interestingly, optic nerves contained higher populations of anti-inflammatory PD-L1 + cells than sciatic nerves. Treatment with anti-CD3 antibody reduced immune cell infiltrates in the optic nerve allograft, but exerted no significant effect in the sciatic nerve allograft., Conclusions: These findings establish the feasibility of a preclinical allogenic nerve transplantation model and provide the basis for future testing of directed, high-intensity immunosuppression in these mice., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background Delivery of hydrogels to the heart is a promising strategy for mitigating the detrimental impact of myocardial infarction (MI). Challenges associated with the in vivo delivery of currently available hydrogels have limited clinical translation of this technology. Gelatin methacryloyl (GelMA) bioadhesive hydrogel could address many of the limitations of available hydrogels. The goal of this proof-of-concept study was to evaluate the cardioprotective potential of GelMA in a mouse model of MI. Methods and Results The physical properties of GelMA bioadhesive hydrogel were optimized in vitro. Impact of GelMA bioadhesive hydrogel on post-MI recovery was then assessed in vivo. In 20 mice, GelMA bioadhesive hydrogel was applied to the epicardial surface of the heart at the time of experimental MI. An additional 20 mice underwent MI but received no GelMA bioadhesive hydrogel. Survival rates were compared for GelMA-treated and untreated mice. Left ventricular function was assessed 3 weeks after experimental MI with transthoracic echocardiography. Left ventricular scar burden was measured with postmortem morphometric analysis. Survival rates at 3 weeks post-MI were 89% for GelMA-treated mice and 50% for untreated mice ( P =0.011). Left ventricular contractile function was better in GelMA-treated than untreated mice (fractional shortening 37% versus 26%, P <0.001). Average scar burden in GelMA-treated mice was lower than in untreated mice (6% versus 22%, P =0.017). Conclusions Epicardial GelMA bioadhesive application at the time of experimental MI was performed safely and was associated with significantly improved post-MI survival compared with control animals. In addition, GelMA treatment was associated with significantly better preservation of left ventricular function and reduced scar burden.

Dental implants constitute the standard of care to replace the missing teeth, which has led to an increase in the number of patients affected by peri-implant diseases (PIDs). Here, we report the development of an antimicrobial bioadhesive, GelAMP, for the treatment of PIDs. The hydrogel is based on a visible light-activated naturally-derived polymer (gelatin) and an antimicrobial peptide (AMP). The optimized formulation of GelAMP could be rapidly crosslinked using commercial dental curing systems. When compared to commercial adhesives, the bioadhesives exhibited significantly higher adhesive strength to physiological tissues and titanium. Moreover, the bioadhesive showed high cytocompatibility and could efficiently promote cell proliferation and migration in vitro . GelAMP also showed remarkable antimicrobial activity against Porphyromonas gingivalis . Furthermore, it could support the growth of autologous bone after sealing calvarial bone defects in mice. Overall, GelAMP could be used as a platform for the development of more effective therapeutics against PIDs.

Myocardial infarction (MI) leads to a multi-phase reparative process at the site of damaged heart that ultimately results in the formation of non-conductive fibrous scar tissue. Despite the widespread use of electroconductive biomaterials to increase the physiological relevance of bioengineered cardiac tissues in vitro, there are still several limitations associated with engineering biocompatible scaffolds with appropriate mechanical properties and electroconductivity for cardiac tissue regeneration. Here, we introduce highly adhesive fibrous scaffolds engineered by electrospinning of gelatin methacryloyl (GelMA) followed by the conjugation of a choline-based bio-ionic liquid (Bio-IL) to develop conductive and adhesive cardiopatches. These GelMA/Bio-IL adhesive patches were optimized to exhibit mechanical and conductive properties similar to the native myocardium. Furthermore, the engineered patches strongly adhered to murine myocardium due to the formation of ionic bonding between the Bio-IL and native tissue, eliminating the need for suturing. Co-cultures of primary cardiomyocytes and cardiac fibroblasts grown on GelMA/Bio-IL patches exhibited comparatively better contractile profiles compared to pristine GelMA controls, as demonstrated by over-expression of the gap junction protein connexin 43. These cardiopatches could be used to provide mechanical support and restore electromechanical coupling at the site of MI to minimize cardiac remodeling and preserve normal cardiac function., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A primary goal in the management of burn wounds is early wound closure. The use of skin allografts represents a lifesaving strategy for severe burn patients, but their ultimate rejection limits their potential efficacy and utility. IL-6 is a major pleiotropic cytokine which critically links innate and adaptive immune responses. Here, we devised anti-IL-6 receptor eluting gelatin methacryloyl (GelMA) biomaterials (GelMA/anti-IL-6), which were implanted at the interface between the wound beds and skin allografts. Our visible light crosslinked GelMA/anti-IL-6 immunomodulatory biomaterial (IMB) demonstrated a stable kinetic release profile of anti-IL-6. In addition, the incorporation of anti-IL-6 within the GelMA hydrogel had no effect on the mechanical properties of the hydrogels. Using a highly stringent skin transplant model, the GelMA/anti-IL-6 IMB almost doubled the survival of skin allografts. The use of GelMA/anti-IL-6 IMB was far superior to systemic anti-IL-6 receptor treatment in prolonging skin allograft survival. As compared to the untreated control group, skin from the GelMA/anti-IL-6 IMB group contained significantly fewer alloreactive T cells and macrophages. Interestingly, the environmental milieu of the draining lymph nodes (DLNs) of the mice implanted with the GelMA/anti-IL-6 IMB was also considerably less pro-inflammatory. The percentage of CD4 + IFNγ + cells was much lower in the DLNs of the GelMA/anti-IL-6 IMB group in comparison to the GelMA group. These data highlight the importance of localized immune delivery in prolonging skin allograft survival and its potential utility in treating patients with severe burns.

Bioengineered tissues have become increasingly more sophisticated owing to recent advancements in the fields of biomaterials, microfabrication, microfluidics, genetic engineering, and stem cell and developmental biology. In the coming years, the ability to engineer artificial constructs that accurately mimic the compositional, architectural, and functional properties of human tissues, will profoundly impact the therapeutic and diagnostic aspects of the healthcare industry. In this regard, bioengineered cardiac tissues are of particular importance due to the extremely limited ability of the myocardium to self-regenerate, as well as the remarkably high mortality associated with cardiovascular diseases worldwide. As novel microphysiological systems make the transition from bench to bedside, their implementation in high throughput drug screening, personalized diagnostics, disease modeling, and targeted therapy validation will bring forth a paradigm shift in the clinical management of cardiovascular diseases. Here, we will review the current state of the art in experimental in vitro platforms for next generation diagnostics and therapy validation. We will describe recent advancements in the development of smart biomaterials, biofabrication techniques, and stem cell engineering, aimed at recapitulating cardiovascular function at the tissue- and organ levels. In addition, integrative and multidisciplinary approaches to engineer biomimetic cardiovascular constructs with unprecedented human and clinical relevance will be discussed. We will comment on the implementation of these platforms in high throughput drug screening, in vitro disease modeling and therapy validation. Lastly, future perspectives will be provided on how these biomimetic platforms will aid in the transition towards patient centered diagnostics, and the development of personalized targeted therapeutics., (Copyright © 2018 Elsevier Ltd. All rights reserved.)