Chitosan (CS) hydrogels are widely used in wound hemostatic agents due to their superior biocompatibility, biodegradability, and hemostatic effect. However, most of them fail to achieve great hemostatic effect because of poor adhesion to bleeding tissues. Also, the conventional implantation surgery of hemostatic hydrogels to internal bleeding wounds may cause secondary trauma to the human body. In this work, catechol-hydroxybutyl chitosan (HBCS-C) has been designed and prepared by grafting hydroxybutyl groups and catechol groups to the CS backbones. The multifunctional HBCS-C hydrogels are fabricated with the properties of thermosensitivity, injectability, tissue-adhesion, biodegradation, biocompatibility, and wound hemostasis. They exhibit excellent liquid-gel transition at different temperatures, through the changes of hydrophilic−hydrophobic interaction and hydrogen bonds generating from hydroxybutyl groups. By the multiple interactions between catechol groups/amino groups and tissues, the biocompatible hydrogels can strongly adhere on the surface of tissue. To further study, the bleeding rat-liver models are made to evaluate the hemostatic effects. After injecting the hydrogel precursor solution into the rat body, the hydrogels are not only formed in situ within 30 s but are also firmly adhered to the bleeding tissues which shows effective hemostasis. The injectability and tissue-adhesion improvement in this study gives a new insight into hemostatic agents, and the multifunctional hydrogels have a great potential in the biomedical application.

Porous microcarriers have aroused increasing attention recently, which can create a protected environment for sufficient cell seeding density, facilitate oxygen and nutrient transfer, and well support the cell attachment and growth. In this study, porous microcarriers fabricated from the strontium-substituted hydroxyapatite- graft-poly(γ-benzyl-l-glutamate) (Sr10-HA- g-PBLG) hybrid nanocomposite were developed. The surface grating of PBLG, the micromorphology and element distribution, mechanical strength, in vitro degradation, and Sr ion release of the obtained Sr10-HA- g-PBLG porous microcarriers were investigated, respectively. The grafting ratio and the molecular weight of the grafted PBLG of Sr10-HA- g-PBLG could be effectively controlled by varying the initial ratio of BLG-NCA to Sr10-HA-NH. The microcarriers exhibited a highly porous and interconnected microstructure with the porosity of about 90% and overall density of 1.03-1.06 g/cm. Also, the degradation rate of Sr10-HA-PBLG microcarriers could be effectively controlled and long-term Sr release was obtained. The Sr10-HA-PBLG microcarriers allowed cells adhesion, infiltration, and proliferation and promoted the osteogenic differentiation of rabbit adipose-derived stem cells (ADSCs). Successful healing of femoral bone defect was proved by injection of the ADSCs-seeded Sr10-HA-PBLG microcarriers in a rabbit model.

Microgels, with large surface area per volume, show great advantages in adipose tissue engineering due to their injectability and similarity with natural extracellular matrix. However, to date, no studies have tried applying microgels to adipose tissue regeneration. Herein, based on double-bonded poly(l-glutamic acid)-g-2-hydroxyethyl methacrylate (PLGA-g-HEMA) and maleic anhydride-modified chitosan (MCS), an open porous microgel with high hydrophilicity and great injectability is successfully prepared (microgels diameters of 200-300 μm, pore diameter of 38 μm, and porosity of 88.3%). The storage modulus of 30 mg/mL of the microgel dispersions is 2000 Pa, which is similar to that of the native adipose tissue. The spheroidal stem cell shape and extensive cell-cell connections can be formed in the present microgels to promote adipogenic differentiation and realize adipose tissue regeneration. After injection in vitro, the microgels can maintain high stem cell viability up to 14 days. The extensive Oil red O staining is observed after adipogenic induction for 14 days. After 12 weeks postimplantation, adipose tissues can be regenerated well. Blood vessels are formed in the neogenerated tissues. The degradation rate of microgels roughly matches with the adipose tissue formation rate. The study offers an applicable microgel system to boost the adipose tissue regeneration.

Bone tissue engineering scaffold based on microcarriers provides an effective approach for the repair of irregular bone defects. The implantation of microcarriers by injection can reduce surgical trauma and fill various irregular shaped bone defects. Microcarriers with porous structure and osteogenic properties have shown great potential in promoting the repair of bone defects. In this study, two kinds of hydroxyapatite/poly-(γbenzyl-L-glutamate) (HA/PBLG) microcarriers were constructed by emulsion/in situ precipitation method and their structures and properties were studied. First, PBLG porous microcarriers were prepared by an emulsion method. Surface carboxylation of PBLG microcarriers was performed to promote the deposition of HA on PBLG microcarriers. Next, the modified porous PBLG microcarriers were used as the matrix, combined with the in situ precipitation method; the cluster HA and acicular HA were precipitated onto the surface of porous microcarriers in the presence of ammonia water and tri(hydroxymethyl)aminomethane (Tris) solution, respectively. The micromorphology, composition, and element distribution of the two kinds of microcarriers were characterized by TEM, SEM, and AFM. Adipose stem cells (ADSCs) were cultured on the cluster HA/PBLG and acicular HA/PBLG microcarriers, respectively. ADSCs could grow and proliferate normally on both kinds of microcarriers wherein the acicular HA/PBLG microcarriers were more favorable for early cell adhesion and showed a beneficial effect on mineralization and osteogenic differentiation of ADSCs. Successful healing of a rabbit femur defect verified the bone regeneration ability of acicular HA/PBLG microcarriers.

Supramolecular hydrogels formed by noncovalent bonds are attractive “smart” materials, which can rapidly respond to external stimuli. However, only a handful of supramolecular hydrogels is applicable in tissue engineering, due to the instability and poor mechanical strength of noncovalent cross-linking hydrogels. Thus, a rigid and stable supramolecular hydrogel has been developed based on poly­(l-glutamic acid) and 2-ureido-4­[1H]­pyrimidinones (UPy), and the UPy stacks are noncovalent cross-linking interactions. The hydrogels show excellent mechanical strength and stability, in sharp contrast to noncovalent hydrogels cross-linked by UPy dimers and covalent hydrogels cross-linked by esterification. The hydrogels also exhibit remoldability, self-healing, and thermoplastic printing characteristics, which are caused by the reversible supramolecular property of UPy stacks. Also, the formation of hydrogels dependent on UPy stacks is further investigated by atomic force microscope, small-angle X-ray scattering, in situ X-ray diffraction, circular dichroism, and UV–vis spectroscopies. Finally, the hydrogels show commendable biocompatibility and degradability, which have high potential applications in regenerative medicine.