Modular and Photoreversible Polymer-Nanoparticle Hydrogels via Host-Guest Interactions.

Polymer-nanoparticle (PNP) hydrogels are a class of nanocomposite materials showing potential as injectable platforms for biomedical applications. Their design is limited by incomplete knowledge of how the binding motif impacts the viscoelastic properties of the material and is generally constrained to non-responsive supramolecular interactions. Expanding the scope of available interactions and advancing the understanding of how defined interactions influence network formation would accelerate PNP hydrogel design. To address this gap in the design of PNP hydrogels, the study designs and investigates a tunable platform based on beta-cyclodextrin (ßCD) host-guest cross-links between functionalized polymers and nanoparticles. A host-functionalized polymer (ßCD hyaluronic acid) and guest harboring block co-polymer (poly(ethylene glycol)-b-poly(lactic acid)) NPs are synthesized. The presence and accessibility for binding of the host and guest moieties are characterized via isothermal titration calorimetry. PNP hydrogels with varying concentrations of functionalized polymer and NPs reveal a limited window of concentrations for gelation. It is hypothesized that network formation is governed by the capacity of polymer chains to effectively bridge NPs, which is related to the host-guest ratios present in the system. Further, photo-responsive guests are incorporated to engineer photoreversible gelation of PNP hydrogels via exposure to specific wavelengths of light.

Hydrogels as a Potential Biomaterial for Multimodal Therapeutic Applications.

Hydrogels, composed of hydrophilic polymer networks, have emerged as versatile materials in biomedical applications due to their high water content, biocompatibility, and tunable properties. They mimic natural tissue environments, enhancing cell viability and function. Hydrogels' tunable physical properties allow for tailored antibacterial biomaterial, wound dressings, cancer treatment, and tissue engineering scaffolds. Their ability to respond to physiological stimuli enables the controlled release of therapeutics, while their porous structure supports nutrient diffusion and waste removal, fostering tissue regeneration and repair. In wound healing, hydrogels provide a moist environment, promote cell migration, and deliver bioactive agents and antibiotics, enhancing the healing process. For cancer therapy, they offer localized drug delivery systems that target tumors, minimizing systemic toxicity and improving therapeutic efficacy. Ocular therapy benefits from hydrogels' capacity to form contact lenses and drug delivery systems that maintain prolonged contact with the eye surface, improving treatment outcomes for various eye diseases. In mucosal delivery, hydrogels facilitate the administration of therapeutics across mucosal barriers, ensuring sustained release and the improved bioavailability of drugs. Tissue regeneration sees hydrogels as scaffolds that mimic the extracellular matrix, supporting cell growth and differentiation for repairing damaged tissues. Similarly, in bone regeneration, hydrogels loaded with growth factors and stem cells promote osteogenesis and accelerate bone healing. This article highlights some of the recent advances in the use of hydrogels for various biomedical applications, driven by their ability to be engineered for specific therapeutic needs and their interactive properties with biological tissues.

Nanomaterial-integrated injectable hydrogels for craniofacial bone reconstruction.

The complex anatomy and biology of craniofacial bones pose difficulties in their effective and precise reconstruction. Injectable hydrogels (IHs) with water-swollen networks are emerging as a shape-adaptive alternative for noninvasively rebuilding craniofacial bones. The advent of versatile nanomaterials (NMs) customizes IHs with strengthened mechanical properties and therapeutically favorable performance, presenting excellent contenders over traditional substitutes. Structurally, NM-reinforced IHs are energy dissipative and covalently crosslinked, providing the mechanics necessary to support craniofacial structures and physiological functions. Biofunctionally, incorporating unique NMs into IH expands a plethora of biological activities, including immunomodulatory, osteogenic, angiogenic, and antibacterial effects, further favoring controllable dynamic tissue regeneration. Mechanistically, NM-engineered IHs optimize the physical traits to direct cell responses, regulate intracellular signaling pathways, and control the release of biomolecules, collectively bestowing structure-induced features and multifunctionality. By encompassing state-of-the-art advances in NM-integrated IHs, this review offers a foundation for future clinical translation of craniofacial bone reconstruction.

Injectable hybrid hydrogels enable enhanced combination chemotherapy and roused anti-tumor immunity in the synergistic treatment of pancreatic ductal adenocarcinoma.

Chemotherapy and immunotherapy have shown no significant outcome for unresectable pancreatic ductal adenocarcinoma (PDAC). Multi-drug combination therapy has become a consensus in clinical trials to explore how to arouse anti-tumor immunity and meanwhile overcome the poorly tumoricidal effect and the stroma barrier that greatly hinders drug penetration. To address this challenge, a comprehensive strategy is proposed to fully utilize both the ferroptotic vulnerability of PDAC to potently irritate anti-tumor immunity and the desmoplasia-associated focal adhesion kinase (FAK) to wholly improve the immunosuppressive microenvironment via sustained release of drugs in an injectable hydrogel for increasing drug penetration in tumor location and averting systematic toxicity. The injectable hydrogel ED-M@CS/MC is hybridized with micelles loaded with erastin that exclusively induces ferroptosis and a FAK inhibitor defactinib for inhibiting stroma formation, and achieves sustained release of the drugs for up to 12 days. With only a single intratumoral injection, the combination treatment with erastin and defactinib produces further anti-tumor performance both in xenograft and KrasG12D-engineered primary PDAC mice and synergistically promotes the infiltration of CD8+ cytotoxic T cells and the reduction of type II macrophages. The findings may provide a novel promising strategy for the clinical treatment of PDAC.

Mussel-Inspired Injectable Adhesive Hydrogels for Biomedical Applications.

The impressive adhesive capacity of marine mussels has inspired various fascinating designs in biomedical fields. Mussel-inspired injectable adhesive hydrogels, as a type of promising mussel-inspired material, have attracted much attention due to their minimally invasive property and desirable functions provided by mussel-inspired components. In recent decades, various mussel-inspired injectable adhesive hydrogels have been designed and widely applied in numerous biomedical fields. The rational incorporation of mussel-inspired catechol groups endows the injectable hydrogels with the potential to exhibit many properties, including tissue adhesiveness and self-healing, antimicrobial, and antioxidant capabilities, broadening the applications of injectable hydrogels in biomedical fields. In this review, we first give a brief introduction to the adhesion mechanism of mussels and the characteristics of injectable hydrogels. Further, the typical design strategies of mussel-inspired injectable adhesive hydrogels are summarized. The methodologies for integrating catechol groups into polymers and the crosslinking methods of mussel-inspired hydrogels are discussed in this section. In addition, we systematically overview recent mussel-inspired injectable adhesive hydrogels for biomedical applications, with a focus on how the unique properties of these hydrogels benefit their applications in these fields. The challenges and perspectives of mussel-inspired injectable hydrogels are discussed in the last section. This review may provide new inspiration for the design of novel bioinspired injectable hydrogels and facilitate their application in various biomedical fields.

Injectable Hydrogels Based on Hyaluronic Acid and Gelatin Combined with Salvianolic Acid B and Vascular Endothelial Growth Factor for Treatment of Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI) leads to structural damage in the brain, and is one of the major causes of disability and death in the world. Herein, we developed a composite injectable hydrogel (HA/Gel) composed of hyaluronic acid (HA) and gelatin (Gel), loaded with vascular endothelial growth factor (VEGF) and salvianolic acid B (SAB) for treatment of TBI. The HA/Gel hydrogels were formed by the coupling of phenol-rich tyramine-modified HA (HA-TA) and tyramine-modified Gel (Gel-TA) catalyzed by horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2). SEM results showed that HA/Gel hydrogel had a porous structure. Rheological test results showed that the hydrogel possessed appropriate rheological properties, and UV spectrophotometry results showed that the hydrogel exhibited excellent SAB release performance. The results of LIVE/DEAD staining, CCK-8 and Phalloidin/DAPI fluorescence staining showed that the HA/Gel hydrogel possessed good cell biocompatibility. Moreover, the hydrogels loaded with SAB and VEGF (HA/Gel/SAB/VEGF) could effectively promote the proliferation of bone marrow mesenchymal stem cells (BMSCs). In addition, the results of H&E staining, CD31 and α-SMA immunofluorescence staining showed that the HA/Gel/SAB/VEGF hydrogel possessed good in vivo biocompatibility and pro-angiogenic ability. Furthermore, immunohistochemical results showed that the injection of HA/Gel/SAB/VEGF hydrogel to the injury site could effectively reduce the volume of defective tissues in traumatic brain injured mice. Our results suggest that the injection of HA/Gel hydrogel loaded with SAB and VEGF might provide a new approach for therapeutic brain tissue repair after traumatic brain injury.

Pomegranate Polyphenol-Derived Injectable Therapeutic Hydrogels to Enhance Neuronal Regeneration.

Drug delivery for the treatment of neurological disorders has long been considered complex due to difficulties in ensuring the drug targeting on a specific site of the damaged neural tissues and its prolonged release. A syringe-injectable polymeric hydrogel with mechanical moduli matching those of brain tissues can provide a solution to deliver the drugs to the specific region through intracranial injections in a minimally invasive manner. In this study, an injectable therapeutic hydrogel with antioxidant pomegranate polyphenols, punicalagin, is reported for efficient neuronal repair. The hydrogels composed of tyramine-functionalized hyaluronic acid and collagen crosslinked by enzymatic reactions have great injectability with high shape fidelity and effectively encapsulate the polyphenol therapeutics. Furthermore, the punicalagin continuously released from the hydrogels over several days could enhance the growth and differentiation of the neurons. Our findings for efficacy of the polyphenol therapeutic-encapsulated injectable hydrogels on neuronal regeneration would be promising for designing a new type of antioxidative biomaterials in brain disorder therapy.

MnO2 Decorated Metal-Organic Framework-Based Hydrogel Relieving Tumor Hypoxia for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) has emerged as a promising cancer treatment modality; however, its therapeutic efficacy is greatly limited by tumor hypoxia. In this study, a metal-organic framework (MOF)-based hydrogel (MOF Gel) system that synergistically combines PDT with the supply of oxygen is designed. Porphyrin-based Zr-MOF nanoparticles are synthesized as the photosensitizer. MnO2 is decorated onto the surface of the MOF, which can effectively convert H2O2 into oxygen. Simultaneously, the incorporation of MnO2 -decorated MOF (MnP NPs) into a chitosan hydrogel (MnP Gel) serves to enhance its stability and retention at the tumor site. The results show that this integrated approach significantly improves tumor inhibition efficiency by relieving tumor hypoxia and enhancing PDT. Overall, the findings underscore the potential for employing nano-MOF-based hydrogel systems as promising agents for cancer therapy, thus advancing the application of multifunctional MOFs in cancer treatment.

Injectable, Self-Healing and Multiple Responsive Histamine Modified Hyaluronic Acid Hydrogels with Potentialities in Drug Delivery, Antibacterial and Tissue Engineering.

Hydrogels are 3D network structures composed of physically or chemically crosslinked, hydrophilic molecules. Compared with conventional hydrogels with static and permanent network structures, injectable and responsive hydrogels generated from dynamic networks, have attracted increasing attention from various disciplines due to their wide-ranging applications in tissue engineering, drug delivery, soft robotics, etc. Herein, an injectable self-healing and multiple-responsive hyaluronic acid (HA)- histamine (His)/metal hydrogel is developed by modifying His onto HA and the subsequent, dynamic coordination between imidazole and metal ions. The pH-responsive and mechanical behaviors exhibited by the HA-His/metal hydrogels are tunable with the kinds and the concentrations of metal ions. The HA-His/Zr4+ hydrogels demonstrate a moldable capability at a neutral pH and a multi-stimulus-responsive capability when exposed to a weak alkaline environment and hyaluronidase, which inhibits bacterial growth and biofilm formation. Biocompatibilities and accelerated wound healing are demonstrated in vitro and in vivo and are thoroughly investigated and well characterized. The HA-His/Zr4+ hydrogel has great potential in various biomedical applications, such as pH- and hyaluronidase-responsive sustained release, antibacterial, and implantable materials for tissue engineering.

Nanoengineered injectable hydrogels derived from layered double hydroxides and alginate for sustained release of protein therapeutics in tissue engineering applications.

Chronic Kidney Disease (CKD) which involves gradual loss of kidney function is characterized by low levels of a glycoprotein called Erythropoietin (EPO) that leads to red blood cell  deficiency and anemia. Recombinant human EPO (rhEPO) injections that are administered intravenously or subcutaneously is the current gold standard for treating CKD. The rhEPO injections have very short half-lives and thus demands frequent administration with a risk of high endogenous EPO levels leading to severe side effects that could prove fatal. To this effect, this work provides a novel approach of using lamellar inorganic solids with a brucite-like structure for controlling the release of protein therapeutics such as rhEPO in injectable hydrogels. The nanoengineered injectable system was formulated by incorporating two-dimensional layered double hydroxide (LDH) clay materials with a high surface area into alginate hydrogels for sustained delivery. The inclusion of LDH in the hydrogel network not only improved the mechanical properties of the hydrogels (5-30 times that of alginate hydrogel) but also exhibited a high binding affinity to proteins without altering their bioactivity and conformation. Furthermore, the nanoengineered injectable hydrogels (INHs) demonstrated quick gelation, injectability, and excellent adhesion properties on human skin. The in vitro release test of EPO from conventional alginate hydrogels (Alg-Gel) showed 86% EPO release within 108 h while INHs showed greater control over the initial burst and released only 24% of EPO in the same incubation time. INH-based ink was successfully used for 3D printing, resulting in scaffolds with good shape fidelity and stability in cell culture media. Controlled release of EPO from INHs facilitated superior angiogenic potential in ovo (chick chorioallantoic membrane) compared to Alg-Gel. When subcutaneously implanted in albino mice, the INHs formed a stable gel in vivo without inducing any adverse effects. The results suggest that the proposed INHs in this study can be utilized as a minimally invasive injectable platform or as 3D printed patches for the delivery of protein therapeutics to facilitate tissue regeneration.

In situ graphene oxide-gelatin hydrogels with enhanced mechanical property for tissue adhesive and regeneration.

Extracellular matrix (ECM) is playing a critical role which is component of mammalian tissue that provide structural support to cells. In addition, ECM act as a local depot for growth factors that control cell phenotype and differentiation. In this regard, scaffold that mimicking the ECM structure is important to growth or wound healing process. Gelatin is natural polymer and derived from collagen which is a major component of ECM. Using gelatin as an ECM mimicking structure has advantage of providing three-dimensional growth or supporting to regulate the cell behavior, proliferation, migration, cell survival, and differentiation. In this study, we developed enzyme-mediated crosslinking gelatin-based hydrogels with robust mechanical property to mimicking ECM and effectively attach to the surrounding tissue with high adhesive property. The effect of different concentration of graphene oxide (GO) on the physico-chemical properties of gelatin hydrogels were investigated, particularly tissue adhesion strength. In vitro proteolytic degradation behavior and human dermal fibroblast proliferation study confirmed the hydrogels were biodegradable and promote cell proliferation. Overall, we suggest that GO incorporated gelatin hydrogels with additional interfacial interactions, showing a promising potential as an injectable tissue adhesive.

All-in-One: Multifunctional Hydrogel Accelerates Oxidative Diabetic Wound Healing through Timed-Release of Exosome and Fibroblast Growth Factor.

The treatment of diabetic wounds remains a major challenge in clinical practice, with chronic wounds characterized by multiple drug-resistant bacterial infections, angiopathy, and oxidative damage to the microenvironment. Herein, a novel in situ injectable HA@MnO2 /FGF-2/Exos hydrogel is introduced for improving diabetic wound healing. Through a simple local injection, this hydrogel is able to form a protective barrier covering the wound, providing rapid hemostasis and long-term antibacterial protection. The MnO2 /ε-PL nanosheet is able to catalyze the excess H2 O2 produced in the wound, converting it to O2 , thus not only eliminating the harmful effects of H2 O2 but also providing O2 for wound healing. Moreover, the release of M2-derived Exosomes (M2 Exos) and FGF-2 growth factor stimulates angiogenesis and epithelization, respectively. These in vivo and in vitro results demonstrate accelerated healing of diabetic wounds with the use of the HA@MnO2 /FGF-2/Exos hydrogel, presenting a viable strategy for chronic diabetic wound repair.

Sticking Together: Injectable Granular Hydrogels with Increased Functionality via Dynamic Covalent Inter-Particle Crosslinking.

Granular hydrogels are an exciting class of microporous and injectable biomaterials that are being explored for many biomedical applications, including regenerative medicine, 3D printing, and drug delivery. Granular hydrogels often possess low mechanical moduli and lack structural integrity due to weak physical interactions between microgels. This has been addressed through covalent inter-particle crosslinking; however, covalent crosslinking often occurs through temporal enzymatic methods or photoinitiated reactions, which may limit injectability and material processing. To address this, a hyaluronic acid (HA) granular hydrogel is developed with dynamic covalent (hydrazone) inter-particle crosslinks. Extrusion fragmentation is used to fabricate microgels from photocrosslinkable norbornene-modified HA, additionally modified with either aldehyde or hydrazide groups. Aldehyde and hydrazide-containing microgels are mixed and jammed to form adhesive granular hydrogels. These granular hydrogels possess enhanced mechanical integrity and shape stability over controls due to the covalent inter-particle bonds, while maintaining injectability due to the dynamic hydrazone bonds. The adhesive granular hydrogels are applied to 3D printing, which allows the printing of structures that are stable without any further post-processing. Additionally, the authors demonstrate that adhesive granular hydrogels allow for cell invasion in vitro. Overall, this work demonstrates the use of dynamic covalent inter-particle crosslinking to enhance injectable granular hydrogels.

A Self-Assembled Matrix System for Cell-Bioengineering Applications in Different Dimensions, Scales, and Geometries.

Stem cell bioengineering and therapy require different model systems and materials in different stages of development. If a chemically defined biomatrix system can fulfill most tasks, it can minimize the discrepancy among various setups. By screening biomaterials synthesized through a coacervation-mediated self-assembling mechanism, a biomatrix system optimal for 2D human mesenchymal stromal cell (hMSC) culture and osteogenesis is identified. Its utility for hMSC bioengineering is further demonstrated in coating porous bioactive glass scaffolds and nanoparticle synthesis for esiRNA delivery to knock down the SOX-9 gene with high delivery efficiency. The self-assembled injectable system is further utilized for 3D cell culture, segregated co-culture of hMSC with human umbilical vein endothelial cells (HUVEC) as an angiogenesis model, and 3D bioprinting. Most interestingly, the coating of bioactive glass with the self-assembled biomatrix not only supports the proliferation and osteogenesis of hMSC in the 3D scaffold but also induces the amorphous bioactive glass (BG) scaffold surface to form new apatite crystals resembling bone-shaped plate structures. Thus, the self-assembled biomatrix system can be utilized in various dimensions, scales, and geometries for many different bioengineering applications.

Advances in the Stimuli-Responsive Injectable Hydrogel for Controlled Release of Drugs.

The stimuli-responsiveness of injectable hydrogel has been drastically developed for the controlled release of drugs and has achieved encouraging curative effects in a variety of diseases including wounds, cardiovascular diseases, and tumors. The gelation, swelling, and degradation of such hydrogels respond to endogenous biochemical factors (such as pH, reactive oxygen species, glutathione, enzymes, glucose) and/or to exogenous physical stimulations (like light, magnetism, electricity, and ultrasound), thereby accurately releasing loaded drugs in response to specifically pathological status and as desired for treatment plan, and thus improving therapeutic efficacy effectively. This paper gives a detailed introduction of recent progresses in responsive injectable hydrogels and focuses on the design strategy of various stimuli-sensitivities and their resultant alteration of gel dissociation and drug liberation behavior. Their application in disease treatment is also discussed.

An injectable hydroxypropyl-ß-cyclodextrin cross-linked gelatin-based hydrogel loaded bone mesenchymal stem cell for osteogenic and in vivo bone regeneration of femoral head necrosis.

An injectable hydroxypropyl-ß-cyclodextrin (HPßCD) cross-linking of gelatin (Gel) based hydrogel was embedded with BMSC in vivo bone regeneration of femoral head necrosis. This HPßCD-Gel hydrogel possesses quick gelation within 6 min; a high-water uptake resulted in faster biodegradation, high swelling, and a 3D porous network that strengthened its mechanical, surface, and morphological properties. The results indicated that BMSC showed high cell viability (>90%) during measurement; HPßCD-Gel hydrogels induced BMSC differentiation into osteocytes within 14 days more efficiently than the osteogenic medium. The HPßCD-Gel/BMSC hydrogels that were injected into the necrosis site of the femoral head in the vessels were measured for 2 weeks. In addition, the vessel density and mean vessel diameters increased in the next 2-8 weeks followed by increased new bone formation, according to the in vivo analysis. Overall, our findings show that this method is a promising strategy for improving femoral head necrosis bone regeneration.

Hydroxyapatite-Integrated, Heparin- and Glycerol-Functionalized Chitosan-Based Injectable Hydrogels with Improved Mechanical and Proangiogenic Performance.

The investigation of natural bioactive injectable composites to induce angiogenesis during bone regeneration has been a part of recent minimally invasive regenerative medicine strategies. Our previous study involved the development of in situ-forming injectable composite hydrogels (Chitosan/Hydroxyapatite/Heparin) for bone regeneration. These hydrogels offered facile rheology, injectability, and gelation at 37 °C, as well as promising pro-angiogenic abilities. In the current study, these hydrogels were modified using glycerol as an additive and a pre-sterile production strategy to enhance their mechanical strength. These modifications allowed a further pH increment during neutralisation with maintained solution homogeneity. The synergetic effect of the pH increment and further hydrogen bonding due to the added glycerol improved the strength of the hydrogels substantially. SEM analyses showed highly cross-linked hydrogels (from high-pH solutions) with a hierarchical interlocking pore morphology. Hydrogel solutions showed more elastic flow properties and incipient gelation times decreased to just 2 to 3 min at 37 °C. Toluidine blue assay and SEM analyses showed that heparin formed a coating at the top layer of the hydrogels which contributed anionic bioactive surface features. The chick chorioallantoic membrane (CAM) assay confirmed significant enhancement of angiogenesis with chitosan-matrixed hydrogels comprising hydroxyapatite and small quantities of heparin (33 µg/mL) compared to basic chitosan hydrogels.

Influence of Injection Application on the Sol-Gel Phase Transition Conditions of Polysaccharide-Based Hydrogels.

Polysaccharide matrices formed via thermoinduced sol-gel phase transition are promising systems used as drug carriers and minimally invasiveness scaffolds in tissue engineering. The strong shear field generated during injection may lead to changes in the conformation of polymer molecules and, consequently, affect the gelation conditions that have not been studied so far. Chitosan (CS) and hydroxypropyl cellulose (HPC) sols were injected through injection needles (14 G-25 G) or sheared directly in the rheometer measuring system. Then the sol-gel phase transition conditions were determined at 37 °C using rheometric, turbidimetric, and rheo-optical techniques. It was found that the use of low, respecting injection, shear rates accelerate the gelation, its increase extends the gelation time; applying the highest shear rates may significantly slow down (HPC) or accelerate gelation (CS) depending on thixotropic properties. From a practical point of view, the conducted research indicates that the use of thin needles without preliminary tests may lead to an extension of the gelation time and consequently the spilling of the polymeric carrier before gelation. Finally, an interpretation of the influence of an intensive shear field on the conformation of the molecules on a molecular scale was proposed.

In-Situ Forming pH and Thermosensitive Injectable Hydrogels to Stimulate Angiogenesis: Potential Candidates for Fast Bone Regeneration Applications.

Biomaterials that promote angiogenesis are required for repair and regeneration of bone. In-situ formed injectable hydrogels functionalised with bioactive agents, facilitating angiogenesis have high demand for bone regeneration. In this study, pH and thermosensitive hydrogels based on chitosan (CS) and hydroxyapatite (HA) composite materials loaded with heparin (Hep) were investigated for their pro-angiogenic potential. Hydrogel formulations with varying Hep concentrations were prepared by sol-gel technique for these homogeneous solutions were neutralised with sodium bicarbonate (NaHCO3) at 4 °C. Solutions (CS/HA/Hep) constituted hydrogels setting at 37 °C which was initiated from surface in 5-10 minutes. Hydrogels were characterised by performing injectability, gelation, rheology, morphology, chemical and biological analyses. Hydrogel solutions facilitated manual dropwise injection from 21 Gauge which is highly used for orthopaedic and dental administrations, and the maximum injection force measured through 19 G needle (17.191 ± 2.296N) was convenient for manual injections. Angiogenesis tests were performed by an ex-ovo chick chorioallantoic membrane (CAM) assay by applying injectable solutions on CAM, which produced in situ hydrogels. Hydrogels induced microvascularity in CAM assay this was confirmed by histology analyses. Hydrogels with lower concentration of Hep showed more efficiency in pro-angiogenic response. Thereof, novel injectable hydrogels inducing angiogenesis (CS/HA/Hep) are potential candidates for bone regeneration and drug delivery applications.

Application of injectable hydrogels for cardiac stem cell therapy and tissue engineering.

Cardiovascular diseases are responsible for approximately one-third of deaths around the world. Among cardiovascular diseases, the largest single cause of death is ischemic heart disease. Ischemic heart disease typically manifests as progressive constriction of the coronary arteries, which obstructs blood flow to the heart and can ultimately lead to myocardial infarction. This adversely affects the structure and function of the heart. Conventional treatments lack the ability to treat the myocardium lost during an acute myocardial infarction. Stem cell therapy offers an excellent solution for myocardial regeneration. Stem cell sources such as adult stem cells, embryonic and induced pluripotent stem cells have been the focal point of research in cardiac tissue engineering. However, cell survival and engraftment post-transplantation are major limitations that must be addressed prior to widespread use of this technology. Recently, biomaterials have been introduced as 3D vehicles to facilitate stem cell transplantation into infarct sites. This has shown significant promise with improved cell survival after transplantation. In this review, we discuss the various injectable hydrogels that have been tried in cardiac tissue engineering. Exploring and optimizing these cell-material interactions will guide cardiac tissue engineering towards developing stem cell based functional 3D constructs for cardiac regeneration.