Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids.

Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in spinal cord injury (SCI) models. This suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.

Construction of functional neural network tissue combining CBD-NT3-modified linear-ordered collagen scaffold and TrkC-modified iPSC-derived neural stem cells for spinal cord injury repair.

Induced pluripotent stem cells (iPSCs) can be personalized and differentiated into neural stem cells (NSCs), thereby effectively providing a source of transplanted cells for spinal cord injury (SCI). To further improve the repair efficiency of SCI, we designed a functional neural network tissue based on TrkC-modified iPSC-derived NSCs and a CBD-NT3-modified linear-ordered collagen scaffold (LOCS). We confirmed that transplantation of this tissue regenerated neurons and synapses, improved the microenvironment of the injured area, enhanced remodeling of the extracellular matrix, and promoted functional recovery of the hind limbs in a rat SCI model with complete transection. RNA sequencing and metabolomic analyses also confirmed the repair effect of this tissue from multiple perspectives and revealed its potential mechanism for treating SCI. Together, we constructed a functional neural network tissue using human iPSCs-derived NSCs as seed cells based on the interaction of receptors and ligands for the first time. This tissue can effectively improve the therapeutic effect of SCI, thus confirming the feasibility of human iPSCs-derived NSCs and LOCS for SCI repair and providing a valuable direction for SCI research.

Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1.

Introduction: Acute kidney injury (AKI) was a disease with a high mortality mainly caused by renal ischemia/reperfusion injury (I/R). Although the current non-targeted administration of vascular endothelial growth factor (VEGF) for AKI had been revealed to facilitate the recovery of renal I/R, how to targeted deliver VEGF and to retain it efficiently in the ischemic kidney was critical for its clinical application. Methods: In present study, bi-functional KIT-PR1P peptides were constructed which bond VEGF through PR1P domain, and targeted ischemic kidney through KIT domain to interact with biomarker of AKI-kidney injury molecule-1 (Kim-1). Then the targeted and therapeutic effects of KIT-PR1P/VEGF in AKI was explored in vitro and in vivo. Results: The results showed KIT-PR1P exhibited better angiogenic capacity and targeting ability to hypoxia HK-2 cells with up-regulated Kim-1 in vitro. When KIT-PR1P/VEGF was used for the treatment of renal I/R through intravenous administration in vivo, KIT-PR1P could guide VEGF and retain its effective concentration in ischemic kidney. In addition, KIT-PR1P/VEGF promoted angiogenesis, alleviated renal tubular injury and fibrosis, and finally promoted functional recovery of renal I/R. Conclusion: These results indicated that the bi-functional KIT-PR1P peptides combined with VEGF would be a promising strategy for the treatment of AKI by targeting to Kim-1.

Switchable product selectivity in dehydration of N-acetyl-d-glucosamine promoted by choline chloride-based deep eutectic solvents.

Herein, we report choline chloride-based deep eutectic solvents (DESs) promoted conversion of N-acetyl-d-glucosamine (GlcNAc) into nitrogen-containing compounds, i.e., 3-acetamido-5-(1',2'-dihydroxyethyl) furan (Chromogen III) and 3-acetamido-5-acetylfuran (3A5AF). The binary deep eutectic solvent choline chloride-glycerin (ChCl-Gly), was found to promote the dehydration of GlcNAc to form Chromogen III, which reaches a maximum yield of 31.1%. On the other hand, the ternary deep eutectic solvent, choline chloride-glycerol-B(OH)3 (ChCl-Gly-B(OH)3), promoted the further dehydration of GlcNAc into 3A5AF with a maximum yield of 39.2%. In addition, the reaction intermediate, 2-acetamido-2,3-dideoxy-d-erythro-hex-2-enofuranose (Chromogen I), was detected by in situ nuclear magnetic resonance (NMR) techniques when promoted by ChCl-Gly-B(OH)3. The experimental results of the 1H NMR chemical shift titration showed ChCl-Gly interactions with α-OH-3 and α-OH-4 of GlcNAc, which is responsible for promoting the dehydration reaction. Meanwhile, the strong interaction between Cl- and GlcNAc was demonstrated by 35Cl NMR.

The early and late intervention effects of collagen-binding FGF2 on elastase-induced lung injury.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) has high morbidity and mortality, with no effective treatment at present. Emphysema, a major component of COPD, is a leading cause of human death worldwide. Fibroblast growth factor 2 (FGF2) is implicated in the pathogenesis of pulmonary emphysema and may play an important role in the lung repair process after injury, but concerns remain with respect to its effectiveness. OBJECTIVE: In the present work, we sought to determine how the timing (early and late intervention) of sustained-release FGF2 system administration impacted its effectiveness on a porcine pancreatic elastase (PPE)-induced lung injury mouse model. METHODS: To examine the early intervention efficiency of collagen-binding FGF2 (CBD-FGF2), mice received intratracheally nebulized CBD-FGF2 with concurrent intratracheal injection of PPE. To explore the late intervention effect, CBD-FGF2 was intratracheally aerosolized after PPE administration, and lungs were collected after CBD-FGF2 treatment for subsequent analysis. RESULT: In response to PPE, mice had significantly increased alveolar diameter, collagen deposition and expression of inflammatory factors and decreased lung function indices and expression of alveolar epithelium markers. Our results indicate that CBD-FGF2 administration was able to prevent and repair elastase-induced lung injury partly through the suppression of the inflammatory response and recovery of the alveolar epithelium. The early use of CBD-FGF2 for the prevention of PPE-induced emphysema showed better results than late therapeutic administration against established emphysema. CONCLUSION: These data provide insight regarding the prospective role of a drug-based option (CBD-FGF2) for preventing and curing emphysema.

Modified CFBP-bFGF targeting to ischemic brain promoted the functional recovery of cerebral ischemia.

The cerebral ischemia was one of the most common causes of disability and death worldwide. Basic fibroblast growth factor (bFGF) was reported to have neuroprotective function as well as promoting angiogenesis in the ischemic brain, but the targeting delivery of bFGF to ischemic brain was still difficult. In present study, a specific peptide was used to modify bFGF to construct recombinant CFBP-bFGF, and CFBP-bFGF could specifically deliver to ischemic brain through binding with the upregulated protein-connective tissue growth factor (CTGF). When CFBP-bFGF was used in rats with cerebral ischemia by intravenous injection, local concentration of the bFGF in ischemic brain was significantly increased. In addition, enhanced neurons survival, increased angiogenesis, decreased neuroinflammation were observed, that improved the motor functional recovery of cerebral ischemic injury. These results demonstrated that the targeting delivery of CFBP-bFGF would be a potential therapeutic approach for cerebral ischemia.

Degradation of vinyl ester resin and its composites via cleavage of ester bonds to recycle valuable chemicals and produce polyurethane.

Vinyl ester resins (VER) and its composites are widely used in chemical industry and municipal engineering. However, its dense three-dimensional network structure makes its degradation and recycling a great challenge. Herein, a novel, efficient and green degradation system gamma-valerolactone (GVL)-H2O/p-toluene sulfonic (PTSA) was developed to degrade VER and its composites. VER was completely degraded in the GVL-H2O/PTSA at 210 °C and 0.6 MPa. By combing SEM-EDS, IR, NMR, GPC and MALDI-TOF-MS analysis, it was clarified that VER swelled well in GVL, allowing the transfer of PTSA and H2O through the resin matrix. The ester bonds in VER were cleaved via hydrolysis with H2O catalyzed by the sulfonic acid of PTSA, and high value-added polymer products, i.e., copolymer of styrene and methacrylic acid (SMAA) and bisphenol-A diglycidyl ether (DGEBA), were recycled, which accounted for ca. 87.0 wt% of raw VER. DGEBA can be recycled to prepare a new PU material. The GVL-H2O/PTSA system was also effective for degrading UPR and VER-containing composites. This work provides a practical strategy for chemical degradation and recovery of thermoset VER resins.

Specific bFGF targeting of KIM-1 in ischemic kidneys protects against renal ischemia-reperfusion injury in rats.

Renal ischemia-reperfusion (I/R) injury is one of the major causes of acute kidney injury. However, there is still no effective treatment for this disease. Basic fibroblast growth factor (bFGF) has been reported to be beneficial for recovery from ischemic diseases. It is vital to increase the local concentration and reduce the diffusion of bFGF in vivo for renal I/R injury therapy. A targeted growth factor delivery system that responds to specific biological signals in the regenerative environment to guide release has been highlighted in tissue repair. In the present study, a specific peptide was fused with bFGF and called bFGF-kidney injury targeting (KIT-bFGF), and this compound specifically targeted kidney injury molecule-1 both in hypoxic renal HK-2 cells in vitro and ischemic kidneys in vivo after intravenous injection. When administered to rat models of renal I/R injury, KIT-bFGF attenuated renal tubule damage and fibrosis, and promoted functional recovery compared to the effects of native bFGF and the control. We also investigated the mechanism by which KIT-bFGF activated the ERK1/2 and Akt signaling pathways to significantly reduce apoptosis and protect against ischemic injury in the kidney. These results demonstrated that targeted delivery of KIT-bFGF could be an effective strategy for the treatment of renal I/R injury.

Application of biomaterials and tissue engineering in bladder regeneration.

The primary functions of the bladder are storing urine under low and stable pressure and micturition. Various forms of trauma, tumors, and iatrogenic injuries can cause the loss of or reduce bladder function or capacity. If such damage is not treated in time, it will eventually lead to kidney damage and can even be life-threatening in severe cases. The emergence of tissue engineering technology has led to the development of more possibilities for bladder repair and reconstruction, in which the selection of scaffolds is crucial. In recent years, a growing number of tissue-engineered bladder scaffolds have been constructed. Therefore, this paper will discuss the development of tissue-engineered bladder scaffolds and will further analyze the limitations of and challenges encountered in bladder reconstruction.

Chemical recycling of waste poly-p-phenylene terephthamide via selective cleavage of amide bonds catalyzed by strong Brönsted base in alcohols.

Poly-p-phenylene terephthamide (PPTA) is widely applied in bulletproof products and composite materials because of its high strength, high modulus, high temperature resistance and creep resistance. The PPTA molecule with highly symmetrical and regular structure is linear structure formed by the alternating connection of benzene ring and amide bond, and the amide bonds between the molecular chains form strong hydrogen bonds. Therefore, the dissolution and depolymerization of PPTA is very challenging. In this work, an efficient catalytic system was developed for the controllable degradation of waste PPTA, and the high-value added monomers terephthalic acid (TPA) and p-phenylenediamine (PPD) were recovered. The results show that the amide bonds of PPTA can be selectively cleaved by the strong Brönsted base catalysts in alcohols, especially in the NaOH/n-butanol system. Under the optimal degradation conditions (5 wt% NaOH in n-butanol, 180 °C, 6 h), the percentage degradation of PPTA is 100%, and the yields of TPA and PPD are 92.0% and 91.5%, respectively. In addition, it is found that the wettability of n-alcohols on PPTA monofilament and the addition of a small amount of water have important influences on the degradation of PPTA. The work elucidates the degradation mechanism of PPTA, and reveals the important factors affecting the depolymerization of PPTA.

Urethral Tissue Reconstruction Using the Acellular Dermal Matrix Patch Modified with Collagen-Binding VEGF in Beagle Urethral Injury Models.

OBJECTIVES: Urethral tissue reconstruction for hypospadias is challenging for urologists. In this study, bovine acellular dermal matrix (ADM) patch loading with collagen-binding vascular endothelial growth factor (CBD-VEGF) was used to repair the urethral injury in beagles. METHODS: The safety and effectiveness of the scaffold implantation were carefully evaluated by comparing among the urethral injury control group, ADM implantation group, and ADM modified with CBD-VEGF implantation group during 6 months. Urodynamic examination, urethral angiography, and pathological examination were performed to evaluate the recovery of urethral tissue. RESULTS: Stricture, urethral diverticulum, and increased urethral closure pressure were observed in the control group. Fistula was observed in one animal in the ADM group. By contrast, no related complications or other adverse situations were observed in animals treated with ADM patch modified with CBD-VEGF. The average urethra diameter was significantly smaller in the control animals than in scaffold implantation groups. Pathological examination revealed more distribution of proliferative blood vessels in the animals treated with ADM modified with CBD-VEGF. CONCLUSIONS: Overall, ADM patches modified with CBD-VEGF demonstrated an optimized tissue repair performance in a way to increase tissue angiogenesis and maintain urethral function without inducing severe inflammation and scar formation.

Effect of Coordination Environment Surrounding a Single Pt Site on the Liquid-Phase Aerobic Oxidation of 5-Hydroxymethylfurfural.

As the frontier in heterogeneous catalyst, a monomer and positively charged active sites in the single-atom catalyst (SAC), anchored by high electronegative N, O, S, P, etc., atoms, may not be active for the multispecies (O2, substrates, intermediates, solvent etc.) involved liquid-phase aerobic oxidation. Here, with catalytic, aerobic oxidation of 5-hydroxymethylfurfural as an example, Pt SAC (Pt1-N4) was synthesized and tested first. With commercial Pt/C (Pt loading of 5 wt %) as a benchmark, 2,5-furandicarboxylic acid (FDCA) yield of 97.6% was obtained. Pt SAC (0.56 wt %) gave a much lower FDCA yield (28.8%). By changing the coordination atoms from highly electronegative N to low electronegative Co atoms, the prepared Pt single-atom alloy (SAA, Pt1-Co3) catalyst with ultralow Pt loading (0.06 wt %) gave a much high FDCA yield (99.6%). Density functional theory (DFT) calculations indicated that positively charged Pt sites (+0.712e) in Pt1-N4 almost lost the capability for oxygen adsorption and activation, as well as the adsorption for the key intermediate. In Pt1-Co3 SAA, the central negatively charged Pt atom (-0.446e) facilitated the adsorption of the key intermediate; meanwhile, the nearby Co atoms around the Pt atom constituted the O2-preferred adsorption/activation sites. This work shows the difference between the SAC with NPs and the SAA during liquid-phase oxidation of HMF and gives a useful guide in the future single-atom catalyst design in other related reactions.

Probing the interactions of GlcNH2 with boric acid via NMR spectroscopy.

The essential role of boronic esters in controlling both the direction and selectivity of chemical reactions as well as their significant function in catalytic activity have been demonstrated for industrially important processes. The specific interaction analyses of the monosaccharide GlcNH2 with boric acid are of interest since monosaccharides serve as model systems for the more sophisticated carbohydrate molecules. The interaction of GlcNH2 with boric acid was systematically investigated by numerous NMR techniques. A 1 : 1 chelate boron complex coordinated at the cis-1,2 position of GlcNH2 was identified as the major species in DMSO-d6 solution via1H and 13C INEPT DOSY NMR spectroscopy. This specific boron nitrogen coordination mechanism was further supported by the 1H-15N HSQC spectra. Variations in the spin-lattice relaxation times (T1) of the 13C1 nucleus also provided quantitative data regarding this non-covalent interactions. This is an application of 1H, 13C INEPT DOSY, 1H-15N HSQC, and relaxation methods to study such aggregations in solutions. These methods have potential applications in the characterization of reactive intermediates in biomass conversions.

Amino Acid Ionic Liquids Catalyzed d-Glucosamine into Pyrazine Derivatives: Insight from NMR Spectroscopy.

Using environment-friendly catalysts to convert biomass into compounds with high values is one of the central topics of green chemistry. In this work, [Ch][Pro] (cholinium as the cation and l-proline as the anion) ionic liquid was synthesized and applied as a model catalyst in the production of deoxyfructosazine (DOF) and fructosazine (FZ) from d-glucosamine (GlcNH2). The 13C NMR chemical shift titration experiments and the diffusion-ordered NMR spectroscopy (DOSY) measurements showed that, when the [Ch][Pro] interacted with GlcNH2, the l-proline anion ([Pro]-) played a major catalytic role instead of cholinium cation ([Ch]+). The effects of the reaction temperature and the amount of [Ch][Pro] on the product yields were surveyed. The experimental results showed that the highest DOF yield (33.78%) was obtained after 30 min at 100 °C when the molar ratio of [Ch][Pro]/GlcNH2 was 1. Moreover, in situ 1H NMR and in situ 13C NMR experiments were applied to monitor the reaction process with [Ch][Pro] as the catalyst. The reactive intermediate, dihydrofructosazine, was clearly detected by these in situ techniques. Accordingly, a possible reaction pathway was proposed. By applying other amino acids as the anions, we also prepared five other [Ch][AA] ionic liquids, and they showed different catalytic activities and selectivity in the GlcNH2 self-condensation reaction.

Binary scaffold facilitates in situ regeneration of axons and neurons for complete spinal cord injury repair.

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 situ might 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.

A dual functional collagen scaffold coordinates angiogenesis and inflammation for diabetic wound healing.

Chronic diabetic wounds, which are associated with persistent inflammation and impaired angiogenesis, occur frequently in diabetic patients. Some studies have shown that separate administration of vascular endothelial growth factor (VEGF) or stromal cell derived factor 1α (SDF-1α) exhibited a therapeutic effect in promoting angiogenesis in the wound healing process. In this study, a collagen membrane is prepared as a drug delivery scaffold to investigate whether combined administration of SDF-1α and VEGF has a synergistic therapeutic effect on diabetic wound healing. We specifically fused a collagen-binding domain (CBD) with SDF-1α and VEGF separately, and sustained release of the two recombinant proteins from the collagen scaffold is successfully observed. Meanwhile, when a CBD-VEGF and CBD-SDF-1α co-modified scaffold is implanted in a diabetic rat skin wound model, it not only shows a synergistic effect in facilitating angiogenesis but also reduces inflammation in the short-term. Moreover, long-term results reveal that the co-modified scaffold is also able to enhance rapid wound healing, promote blood vessel regeneration, and assist cell proliferation, re-epithelialization and extracellular matrix accumulation. Taken together, our study indicates that the CBD-VEGF and CBD-SDF-1α co-modified scaffold helps in quick recovery from diabetic wounds by coordinating angiogenesis and inflammation.

Allotransplantation of adult spinal cord tissues after complete transected spinal cord injury: Long-term survival and functional recovery in canines.

Spinal cord injury (SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues (aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of aSCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein 2-, 5-hydroxytryptamine-, choline acetyltransferase- and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in aSCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.

Specific angiogenic peptide binding with injectable cardiac ECM collagen gel promotes the recovery of myocardial infarction in rat.

Restoring blood supply is an effective way for the therapy of myocardial infarction (MI). It was reported a specific angiogenic peptide (VMP) derived from vascular endothelial growth factor (VEGF) could activate its receptor to mimic the biological activity of VEGF. In this study, in order to improve the local concentration in infarction region, a collagen-binding domain was synthesized with VMP to construct collagen binding domain (CBD)-VMP peptides. The fused CBD-VMP could bind specifically to collagen which was rich in cardiac extracellular matrix (c-ECM), without impacting the biological activity of VMP peptides. When the CBD-VMP peptides loaded on collagen scaffold and implanted into the rats subcutaneously, significant vascularization was observed. Then, CBD-VMP peptides binding with injectable c-ECM injected into the MI rat by intramuscular administration, significant blood vessels regeneration, and decrease of cell apoptosis were observed, that corelated with the recovery of cardiac function. It might be an alternative promising strategy for the clinical application of MI.

Combination of pure shift NMR and chemical shift selective filters for analysis of Fischer-Tropsch waste-water.

Fischer-Tropsch (F-T) process is an important synthesis route to acquire clean liquid fuels through modern coal chemical industry, which converts syngas (CO and H2) into hydrocarbon, and also generates oxygenates discharged as the F-T waste-water. These oxygen-containing compounds in F-T waste-water have the similar molecular weight and some are even isomers of each other. Hence, it is necessary to develop rapid and efficient analysis tools to obtain identification and quantitative information of the F-T waste-water. The pure shift NMR techniques provided only chemical shift information in one-dimension 1H NMR spectra, without homonuclear JH-H coupling. In this work, we tested and compared three pure shift NMR techniques (including Zangger-Sterk, PSYCHE and TSE-PSYCHE methods) in the analysis of two F-T waste-water model mixtures, genuine waste-water and two alcohol isomer mixtures. The results show that JH-H coupling multiplicities are collapsed into singlets corresponding to individual chemically distinct protons of the compound. For some severely overlapped signals in the pure shift NMR spectra, the chemical shift selective filters with TOCSY (CSSF-TOCSY) experiments were conducted to assist the signal assignment. Thus, pure shift NMR approaches can identify most signals of components, and CSSF-TOCSY can extract the signal of a specific compound. The combination of these two NMR techniques offers a powerful tool to analyze the F-T waste-water or other complex mixtures including isomer mixtures.

Heparan sulfate proteoglycan promotes fibroblast growth factor-2 function for ischemic heart 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.