Jiamin Zhang

Zwitterionic hydrogels promote skin wound healing

Skin traumas are among the most common health problems in the world, and are routinely treated with wound dressings such as bandages and gauze. Traditional dressings are typically made of dry cotton, which tends to adhere to the wound, causing scab formation and bacterial infections. Ideally, a dressing should accelerate wound healing while avoiding any side effects or complications. Recent studies have found that wet dressings, especially hydrogels, can provide a moist environment for wounds that mimics the in vivo environment, thus facilitating debridement of necrotic tissue, enhancing tissue regeneration, and avoiding scab formation. Zwitterionic hydrogels exhibit strong hydration, are biomimetic in nature, and show excellent anti-fouling properties; their resulting high water content, excellent biocompatibility, and negligible interactions with proteins and cells make them ideal wet wound dressings. In this work, we demonstrated that zwitterionic hydrogels, especially poly-carboxybetaine (PCB) hydrogels, can efficiently promote skin wound healing. Skin wounds treated with zwitterionic hydrogels healed significantly better than those treated with PHEMA hydrogels and the commercial product DuoDerm. Moreover, these zwitterionic hydrogels can be easily coated on cotton gauze or bandage pads for easy handling and application. The findings in this work hold great promise for the development of next-generation wound dressings to improve healthcare.

Antifouling zwitterionic hydrogel coating improves hemocompatibility of activated carbon hemoadsorbent

Activated carbon has been widely used in hemoperfusion treatments. However, its performance has been significantly compromised by their poor hemocompatibility. In this work, we developed a novel antifouling adsorbent based on zwitterionic poly-carboxybetaine (PCB) hydrogel and powdered activated carbon (PAC) to improve hemocompatibility. We found this new adsorbent (PCB-PAC) was highly stable with negligible leakage of activated carbon debris. It could efficiently resist protein adsorption and avoid any hemolysis effect. The adsorption performance of PCB-PAC for methylene blue was not influenced in a single protein solution or even in 100% fetal bovine serum (FBS), in which pristine PAC lost 50% of its adsorption ability. The isotherms results showed that the adsorption process of PCB-PAC fitted the Langmuir isotherm well, indicating that the PAC particles were homogenously distributed in the PCB hydrogel matrix. Moreover, PCB-PAC could also adsorb bilirubin molecules bound to albumin in solution, while pristine PAC showed no discernible adsorption effect. Findings in this work hold great potential to significantly improve the performance and efficiency of current extracorporeal devices for removing toxins from blood directly.

Natural zwitterionic betaine enables cells to survive ultrarapid cryopreservation

Cryoprotectants (CPAs) play a critical role in cryopreservation because they can resist the cell damage caused by the freezing process. Current state-of-the-art CPAs are mainly based on an organic solvent dimethyl sulfoxide (DMSO), and several DMSO-cryopreserved cell products have been brought to market. However, the intrinsic toxicity and complex freezing protocol of DMSO still remain as the bottleneck of the wide use for clinical applications. Herein, we reported that betaine, a natural zwitterionic molecule, could serve as a nontoxic and high efficient CPA. At optimum concentration of betaine, different cell types exhibited exceptional post-thaw survival efficiency with ultrarapid freezing protocol, which was straightforward, cost efficient but difficult to succeed using DMSO. Moreover, betaine showed negligible cytotoxicity even after long-term exposure of cells. Mechanistically, we hypothesized that betaine could be ultra-rapidly taken up by cells for intracellular protection during the freezing process. This technology unlocks the possibility of alternating the traditional toxic CPAs and is applicable to a variety of clinical applications.

The hypothermic preservation of mammalian cells with assembling extracellular-matrix-mimetic microparticles

Hypothermic preservation at a refrigerated temperature allows feasible and flexible storage of living cells, and is of great importance for the widespread use of cell-based applications, such as cell diagnostics and cell therapy. The University of Wisconsin (UW) cold storage solution is one of the current state-of-the-art protectants for hypothermic cell preservation. However, even by using the UW solution, the current effective preservation time under refrigerated conditions is still no more than 1 or 2 days, which restraints larger geographic cell-sharing regions. Herein, we presented a facile technology based on the assembly of extracellular-matrix-mimetic microparticles, which can significantly enhance cell survival in hypothermic preservation under refrigerated conditions for at least 4 days. Moreover, compared with UW solution-based preservation, this strategy significantly inhibited cell nucleus deformation, indicating its ability to inhibit cell apoptosis. Furthermore, after being preserved, both the morphology and proliferation of the recovered cells were similar to normal cells. In addition, microparticle-based preservation could allow the free diffusion of nutrients and metabolic waste, and it was possible to easily and physically retrieve the cells using a permanent magnet. This new technology could significantly extend the preservation duration of cells and hold great promise to improve the outcome of cell therapy and diagnostic accuracy, which will benefit patients in various cell-based applications.

Facile modification of electrospun fibrous structures with antifouling zwitterionic hydrogels

Electrospinning technology can easily produce different shaped fibrous structures, making them highly valuable to various biomedical applications. However, surface contamination of biomolecules, cells, or blood has emerged as a significant challenge to the success of electrospun devices, especially artificial blood vessels, catheters and wound dressings etc. Many efforts have been made to resist the surface non-specific biomolecules or cells adsorption, but most of them require complex pre-treatment processes, hard-to-remove metal catalysts or rigorous reaction conditions. In addition, the stability of antifouling coatings, especially in complex conditions, is still a major concern. In this work, inspired by the interpenetrating polymer network and reinforced concrete structure, an efficient and facile strategy for modifying hydrophobic electrospun meshes and tubes with antifouling zwitterionic hydrogels has been introduced. The resulting products could efficiently resist the adhesion of proteins, cells, or even fresh whole blood. Meanwhile, they could maintain the shapes and mechanical strength of the original electrospun structures. Furthermore, the hydrogel structures could retain stable in a physiological condition for at least 3 months. This paper provided a general antifouling and hydrophilicity surface modification strategy for various fibrous structures, and could be of great value for many biomedical applications where antifouling properties are critical.

A poly(hydroxyethyl methacrylate)–Ag nanoparticle porous hydrogel for simultaneous in vivo prevention of the foreign-body reaction and bacterial infection

The use of implants or indwelling medical devices has greatly enhanced the quality and efficacy of health care. However, foreign-body reactions (FBRs) and infections can lead to potential failure or removal of the devices, or increased morbidity and mortality of patients. Herein, we develop a silver nanoparticle (AgNP) loaded poly(hydroxyethyl methacrylate) hydrogel with spherical, interconnected 40 μm pores. The resulting hydrogels displayed good antibacterial properties regarding both gram positive bacteria (Staphylococcus aureus) and gram negative bacteria (Escherichia coli (E. coli)) in vitro and were highly efficient at inhibiting bacterial cell growth. Moreover, they exhibited an in vivo resistance to FBRs by reducing the immune responses, and completely prevented the formation of collagen capsules. Finally, in vivo studies of the E. coli infected mouse model demonstrated that the AgNP loaded porous hydrogels were highly efficient at resisting the bacterial FBRs and infections, while they promoted cell mitigation and infiltration. Findings from this work suggest that AgNP loaded porous hydrogels hold promise in various biomedical applications including in the new generation of implantable biomedical devices and tissue engineering scaffolds.

A comprehensive study and comparison of four types of zwitterionic hydrogels

Zwitterionic materials have been attracting significant attentions due to their excellent non-fouling and biocompatible properties and thus have been widely used in many biomedical applications. However, differences among different types of zwitterionic materials have rarely been investigated and compared. In this work, four types of zwitterionic monomers were systematically studied and compared by testing the properties of the hydrogels. Their hydration, diffusion coefficient of water and mechanical properties were evaluated and analyzed. It was found that poly(carboxybetaine methacrylate) (PCBMA) hydrogel possessed the strongest compressive modulus, while poly(carboxybetaine acrylamide) (PCBAA) hydrogel showed the highest diffusion coefficient of water and highest hydration of water. Compared with other hydrogels, the mesh size of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) hydrogel was the largest. Furthermore, poly(sulfobetaine methacrylate) (PSBMA) hydrogel with disulfide crosslinker degraded faster than the others. Findings in this work provided insights and guidance for the selection of different zwitterionic polymers to suit different applications.

Encapsulation of laccase within zwitterionic poly-carboxybetaine hydrogels for improved activity and stability

Laccase is an important oxidase for many applications such as bioremediation, chemical synthesis, and biosensors, due to its wide range of substrates and prominent capacity to degrade phenolic compounds. However, its unsatisfactory stability, activity, and reusability still remain a major challenge for practical applications. In this work, we found that when laccase was encapsulated in zwitterionic hydrogels, especially poly-carboxybetaine (PCB), its performance could be significantly enhanced. Compared with the free enzyme, PCB–laccase displayed a remarkably increased activity (∼20-fold higher Kcat/Km value). Meanwhile, its stability could also be effectively maintained even in an extensive range of temperatures, pH values and organic solvents. In addition, PCB–laccase demonstrated excellent storage stability, and retained 80% of its initial activity after an 8-week storage period. In a successive 6-cycle decoloration of acid orange 7, PCB–laccase could still retain 52% of its initial activity, demonstrating superior durability to the free laccase. Therefore, we have provided an efficient and stable support matrix for enzyme immobilization, which exhibits potential for practical applications even in harsh environments.

Novel Balanced Charged Alginate/PEI Polyelectrolyte Hydrogel that Resists Foreign-Body Reaction

Foreign-body reaction (FBR) has been a long-term obstacle for implantable biomedical devices and materials, especially to those that require mass/signal transport between the implants and the body. However, currently, very limited biomaterials can mitigate FBR. In this work, we develop a balanced charged polyelectrolyte hydrogel that can efficiently resist FBR and collagenous capsule formation in a mouse model. Using this new strategy, we can easily tune the antifouling properties of the polyelectrolyte hydrogels by changing the ratio of negatively charged alginate and positively charged poly(ethylene imine). We find that at the optimum ratio where the net charge of hydrogel is neutral, the adhesion of proteins, cells, bacteria, and fresh blood on its surface can be significantly inhibited, indicating its excellent antifouling properties. In vivo studies show that after being implanted subcutaneously, this balanced charged hydrogel can prevent the capsule formation for at least 3 months. Furthermore, immunofluorescent staining results indicate that this balanced charged hydrogel elicits negligible inflammation, significantly reducing macrophage migration to the tissue-implant interface. This flexible and versatile approach holds a great promise for designing a wide spread of new antifouling hydrogels and using as immunoisolation materials for biomedical applications.

Exploring the potential of biocompatible osmoprotectants as high efficient cryoprotectants

Cryoprotectants (CPAs) are critical to successful cryopreservation because they can protect cells from cryoinjuries. Because of the limitations of current CPAs, especially the toxicity, the search for new effective CPAs is attracting increasing attention. In this work, we reported that natural biocompatible osmoprotectants, which could protect cells from osmotic injury in various biological systems, might also be ideal candidates for CPAs. Three representative biocompatible osmoprotectants (proline, glycine, and taurine) were tested and compared. It was found that, aside from presenting a different ability to prevent osmotic injury, these biocompatible osmoprotectants also possessed a different ability to inhibit ice formation and thus mitigate intra-/extracellular ice injury. Because of the strongest ability to prevent the two types of injuries, we found that proline performed the best in cryopreserving five different types of cells. Moreover, the natural osmoprotectants are intrinsically biocompatible with the cells, superior to the current state-of-the-art CPA, dimethyl sulfoxide (DMSO), which is a toxic organic solvent. This work opens a new window of opportunity for DMSO-free cryopreservation, and sheds light on the applications of osmoprotectants in cryoprotection, which may revolutionize the current cryopreservation technologies.