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The limited regrowth of transected axons and insufficient regeneration of lost neurons in adult mammals collectively hinder complete spinal cord injury (SCI) repair. Hence, designing an ideal bio-scaffold which could coordinate the regeneration of axons and neurons in situmight be able to effectively facilitate the reconstruction of neural circuits and the recovery of nerve function after complete SCI. In this study, a sponge-like collagen scaffold with good drug release characteristics and good nerve cell compatibility was prepared and used as a drug delivery platform. When doubly modified with Taxol liposomes and collagen-binding neurotrophic factor 3, the scaffold dually alleviated myelin-derived inhibition on neurite outgrowth of neurons and neuronal differentiation of neural stem cells in vitro. Meanwhile, the binary-drug modified scaffold was also able to simultaneously promote both axonal and neuronal regeneration when implanted into a complete transected SCI model. Additionally, the regenerated axons and neurons throughout the lesion site formed extensive synaptic connections. Finally, complete SCI rats that received binary scaffold implantation exhibited optimal neuroelectrophysiological recovery and hindlimb locomotor improvement. Taken together, implantation of the binary scaffold can establish neural bridging networks for functional recovery, representing a clinically promising strategy for complete SCI repair.

It is well known that the basic fibroblast growth factor (bFGF) promotes angiogenesis after myocardial infarction (MI), but its biological functions decrease in the event of diffusion, enzymolysis, and weak binding with co-receptors in vivo. Heparan sulfate proteoglycans (HSPG) are a major component of extracellular matrices and have been shown to regulate a wide range of cellular functions and bioprocesses by acting as a co-receptor for bFGF and affecting its bioactivities. However, the influence of HSPG on the function of bFGF after myocardial infarction is unknown. Here, exogenous HSPG along with bFGF was injected into the hearts of rats to deliver the angiogenic growth factor for ischemic heart repair following induced MI. The specific binding of HSPG with bFGF protein was demonstrated, which was about 6-fold stronger than the binding of bFGF with heparin. The biological mechanisms of HSPG binding with bFGF were further studied by cell adhesion assay, and assays of bFGF and matrix metalloproteinase 2 (MMP2) activities demonstrated that HSPG enhances cell adhesion, promotes the bioactivity of bFGF in angiogenesis, and protects bFGF from enzymolysis. Our results indicate that HSPG has potential clinical utility as a delivery agent for heparin-binding growth factors. Additionally, HSPG shows high binding affinities with different ECM proteins which also help to anchor bFGF to heart tissue. Therefore, extracellular proteins that mimic the bio-scaffold of the extracellular matrix could promote the activities of bFGF to facilitate ischemic heart repair.

An effective therapy for chronic myocardial infarction (MI) has yet to be developed. Vascular endothelial growth factor (VEGF) promotes angiogenesis and improves cardiac function after MI. However, non-targeted delivery of VEGF decreases its therapeutic efficacy. In this study, for targeting the cardiac extracellular matrix, a collagen-binding domain (CBD) VEGF was used to bind specifically to the collagen-rich cardiac extracellular matrix. When intramyocardially injected into the peri-infarct region of a chronically infarcted porcine heart, CBD-VEGF attenuated the remodeling of the left ventricle with a decreased infarct size and promoted cardiomyocyte survival and angiogenesis 3 months after injection. In the 12-month trial, mature vessel networks and myocardium-like tissues were observed in the infarct region after CBD-VEGF injection. Also these beneficial effects might derive from CBD-VEGF significantly protecting cardiomyocytes from apoptosis and recruiting cardiac progenitor cells to the infarcted region. These results demonstrated that CBD-VEGF could be a promising therapeutic strategy for chronic MI.

Bladder reconstruction remains challenging for urological surgery due to lack of suitable regenerative scaffolds. In a previous study, we had used a collagen-binding basic fibroblast growth factor (CBD-bFGF) to bind bFGF to the collagen scaffold, which could promote bladder regeneration in rats. However, the limited graft size in rodent models cannot provide enough evidence to demonstrate the repair capabilities of this method for severely damaged bladders in humans or large animals. In this study, the CBD-bFGF was used to activate a bladder acellular matrix (BAM) scaffold, and the CBD-bFGF/BAM functional scaffold was assessed in a canine model with a large segment defect (half of the entire bladder was resected). The results demonstrated that the functional biomaterials could promote bladder smooth muscle, vascular, and nerve regeneration and improve the function of neobladders. Thus, the CBD-bFGF/BAM functional scaffold may be a promising biomaterial for bladder reconstruction.