Many factors contribute to the poor axonal regrowth and ineffective functional recovery after spinal cord injury (SCI). Biomaterials have been used for SCI repair by promoting bridge formation and reconnecting the neural tissue at the lesion site. The mechanical properties of biomaterials are critical for successful design to ensure the stable support as soon as possible when compressed by the surrounding spine and musculature. Poly(propylene fumarate) (PPF) scaffolds with high mechanical strength have been shown to provide firm spatial maintenance and to promote repair of tissue defects. A multichannel PPF scaffold is combined with collagen biomaterial to build a novel biocompatible delivery system coated with neurotrophin-3 containing an engineered collagen-binding domain (CBD-NT3). The parallel-aligned multichannel structure of PPF scaffolds guide the direction of neural tissue regeneration across the lesion site and promote reestablishment of bridge connectivity. The combinatorial treatment consisting of PPF and collagen loaded with CBD-NT3 improves the inhibitory microenvironment, facilitates axonal and neuronal regeneration, survival of various types of functional neurons and remyelination and synapse formation of regenerated axons following SCI. This novel treatment strategy for SCI repair effectively promotes neural tissue regeneration after transected spinal injury by providing a regrowth-supportive microenvironment and eventually induces functional improvement.

Cartilage damage is one of the main causes of disability, and 3D bioprinting technology can produce complex structures that are particularly suitable for constructing a customized and irregular tissue engineering scaffold for cartilage repair. Alginate is an attractive biomaterial for bioinks because of its good biological safety profile and fast ionic gelation. However, ionically crosslinked alginate hydrogels are recognized as lacking enough mechanical property and long-term stability due to ion exchange. Here, we developed a double crosslinked alginate (DC-Alg) hydrogel for 3D bioprinting, and human umbilical cord mesenchymal stem cells (huMSCs) could differentiate into chondrocytes on its printed 3D scaffold after 4 weeks’ culture. We performed sequential modification of alginate with L-cysteine and 5-norbornene-2-methylamine, and the DC-Alg hydrogels were obtained in the presence of CaCl2 and ultraviolet light with stronger mechanical properties than those of the single ionic crosslinked alginate hydrogels, which was similar to natural cartilage. They also had better stability and could be maintained in DMEM medium for over 1 month, as well good viability for huMSCs. Moreover, the DC-Alg as 3D printing inks demonstrated a better printing accuracy (∼200 µm). After 4 weeks culture of huMSCs in the 3D printed DC-Alg scaffolds, the expressions of chondrogenic genes such as aggrecan (agg), collagen II (col II), and SRY-box transcription factor 9 (sox-9) were obviously observed, indicating the differentiation of huMSCs into cartilage. Immumohistochemical staining analysis further exhibited cartilage tissue developed well in the 3D printed scaffolds. Our study is the first demonstration of DC-Alg in 3D printing for MSC differentiation into cartilage, which shows a potential application in cartilage defect repair.

Basic fibroblast growth factor (bFGF) is an important protein for wound healing and angiogenesis in tissue engineering, but the lack of a viable delivery system hampers its clinical application. This study aims to maintain the long-term controlled release of bFGF by utilizing a collagen/heparin bi-affinity multilayer delivery system (CHBMDS), which is fabricated by the alternate deposition of negatively charged heparin, positively charged collagen, and CBD-bFGF (a collagen-binding domain [CBD] was fused into the native bFGF) via specific or electrostatic interaction. The results show that CHBMDS not only support localized and prolonged release of CBD-bFGF(over 35 days) but also lead to enhanced angiogenesis (higher density and larger diameter (≈70 µm) of newly formed blood vessels in subcutaneous tissue of SD rat after 5 weeks). This system could act as a versatile approach for bFGF delivery and further improve therapeutic efficacy for injured tissues.