We have explored the applicability of printed scaffold by comparing osteogenic ability and biodegradation property of three resorbable biomaterials. A polylactic acid/hydroxyapatite (PLA/HA) composite with a pore size of 500 μm and 60% porosity was fabricated by three-dimensional printing. Three-dimensional printed PLA/HA, β-tricalcium phosphate (β-TCP) and partially demineralized bone matrix (DBM) seeded with bone marrow stromal cells (BMSCs) were evaluated by cell adhesion, proliferation, alkaline phosphatase activity and osteogenic gene expression of osteopontin (OPN) and collagen type I (COL-1). Moreover, the biocompatibility, bone repairing capacity and degradation in three different bone substitute materials were estimated using a critical-size rat calvarial defect model in vivo. The defects were evaluated by micro-computed tomography and histological analysis at four and eight weeks after surgery, respectively. The results showed that each of the studied scaffolds had its own specific merits and drawbacks. Three-dimensional printed PLA/HA scaffolds possessed good biocompatibility and stimulated BMSC cell proliferation and differentiation to osteogenic cells. The outcomes in vivo revealed that 3D printed PLA/HA scaffolds had good osteogenic capability and biodegradation activity with no difference in inflammation reaction. Therefore, 3D printed PLA/HA scaffolds have potential applications in bone tissue engineering and may be used as graft substitutes in reconstructive surgery.

The fabrication of highly biocompatible hydrogels with multiple unique healing abilities for the whole healing process, for example, multifunctional hydrogels with injectable, degradation, antibacterial, antihypoxic, and wound healing–promoting properties that match the dynamic healing process of skin flap regeneration, is currently a research challenge. Here, a multifunctional and dynamic coordinative polyethylene glycol (PEG) hydrogel with mangiferin liposomes (MF‐Lip@PEG) is developed for clinical applications through Ag–S coordination of four‐arm‐PEG‐SH and Ag+. Compared to MF‐PEG, MF‐Lip@PEG exhibits self‐healing properties, lower swelling percentages, and a longer endurance period. Moreover, the hydrogel exhibits excellent drug dispersibility and release characteristics for slow and persistent drug delivery. In vitro studies show that the hydrogel is biocompatible and nontoxic to cells, and exerts an outstanding neovascularization‐promoting effect. The MF‐Lip@PEG also exhibits a strong cytoprotective effect against hypoxia‐induced apoptosis through regulation of the Bax/Bcl‐2/caspase‐3 pathway. In a random skin flap animal model, the MF‐Lip@PEG is injectable and convenient to deliver into the skin flap, providing excellent anti‐inflammation, anti‐infection, and proneovascularization effects and significantly reducing the skin flap necrosis rate. In general, the MF‐Lip@PEG possesses outstanding multifunctionality for the dynamic healing process of skin flap regeneration.

The repair of large bone defects with complex geometries remains a major clinical challenge. Here, we explored the feasibility of fabricating polylactic acid-hydroxyapatite (PLA-HA) composite scaffolds. These scaffolds were constructed from vascularized tissue engineered bone using an in vivo bioreactor (IVB) strategy with three-dimensional printing technology. Specifically, a rabbit model was established to prefabricate vascularized tissue engineered bone in two groups. An experimental group (EG) was designed using a tibial periosteum capsule filled with 3D printed (3DP) PLA-HA composite scaffolds seeded with bone marrow stromal cells (BMSCs) and crossed with a vascular bundle. 3DP PLA-HA scaffolds were also combined with autologous BMSCs and transplanted to tibial periosteum without blood vessel as a control group (CG). After four and eight weeks, neovascularisation and bone tissues were analysed by studying related genes, micro-computed tomography (Micro-CT) and histological examinations between groups. The results showed that our method capably generated vascularized tissue engineered bone in vivo. Furthermore, we observed significant differences in neovascular and new viable bone formation in the two groups. In this study, we demonstrated the feasibility of generating large vascularized bone tissues in vivo with 3DP PLA-HA composite scaffolds.

The development of science and technology often drew lessons from natural phenomena. Herein, inspired by drying‐driven curling of apple peels, hydrogel‐based micro‐scaled hollow tubules (MHTs) are proposed for biomimicking microvessels, which promote microcirculation and improve the survival of random skin flaps. MHTs with various pipeline structures are fabricated using hydrogel in corresponding shapes, such as Y‐branches, anastomosis rings, and triangle loops. Adjustable diameters can be achieved by altering the concentration and cross‐linking time of the hydrogel. Based on this rationale, biomimetic microvessels with diameters of 50–500 µm are cultivated in vitro by coculture of MHTs and human umbilical vein endothelial cells. In vivo studies show their excellent performance to promote microcirculation and improve the survival of random skin flaps. In conclusion, the present work proposes and validifies a biomimetic 3D self‐forming method for the fabrication of biomimetic vessels and microvascular scaffolds with high biocompatibility and stability based on hydrogel materials, such as gelatin and hyaluronic acid.

Conditioned medium (CM) contains variety of factors secreted by cells, which directly regulate cellular processes, showing tremendous potential in regenerative medicine. Here, for the first time, we proposed a novel regenerative therapy mediated by biodegradable micro-nano electrospun fibers loaded with highly active conditioned medium of adipose-derived stem cells (ADSC-CM). ADSC-CM was successfully loaded into the nanofibers with biological protection and controllable sustained-release properties by emulsion electrospinning and protein freeze-drying technologies. In vitro , ADSC-CM released by the fibers accelerated the migration rate of fibroblasts; inhibited the over proliferation of fibroblasts by inducing apoptosis and damaging cell membrane; in addition, ADSC-CM inhibited the transformation of fibroblasts into myofibroblasts and suppressed excessive production of extracellular matrix (ECM). In vivo , the application of CM-biomaterials significantly accelerated wound closure and improved regeneration outcome, showing superior pro-regenerative performance. This study pioneered the application of CM-biomaterials in regenerative medicine, and confirmed the practicability and significant biological effects of this innovative biomaterials.

Inspired by drying‐driven curling of apple peels, hydrogel‐based micro‐scaled hollow tubules are proposed in article number 1903553 by Yuguang Zhang, Xiaoming Sun, Hélder A. Santos, Wenguo Cui, and co‐workers for biomimicking microvessels with diameters of 50–500 μm, which promote microcirculation and improve the survival of random skin flaps. The 3D‐shape‐morphing technique is of great flexibility and potential to lay the foundation for the construction of complex vascular networks, such as Y‐branches, anastomosis rings, and triangle loops.

Exudate management is critical to improve chronic wound healing. Herein, inspired by a Janus‐structured lotus leaf with asymmetric wettability, a Janus electrospun short fiber scaffold is fabricated via electrospinning technologies and short fiber modeling. This scaffold is composed of hydrophilic 2D curcumin‐loaded electrospun fiber and hydrophobic 3D short fiber via layer‐by‐layer assembly and electrostatic interactions which can aggregate the wound exudate by pumping from the hydrophobic layer to the hydrophilic via multiple contact points between hydrophilic and hydrophobic fibers, and simultaneously trigger the cascade release of curcumin in the upper 2D electrospun fiber. The 3D short fiber with high porosity and hydrophobicity can quickly aggregate exudate within 30 s after compounding with hydrophilic 2D electrospun fiber via a spontaneous pump. In vitro experiments show that Janus electrospun short fiber has good biocompatibility, and the cascade release of curcumin can significantly promote the proliferation and migration of fibroblasts. In vivo experiments show that it can trigger cascade release of curcumin by aggregating wound exudate, so as to accelerate wound healing process and promote collagen deposition and vascularization. Hence, this unique biometric Janus scaffold provides an alternative for chronic wound healing.

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