[Silver Ion Decreases Foreign Body Reaction and Venous Neointimal Hyperplasia through the Inhibition of Interleukin-33 Expression].

INTRODUCTION: Vascular prosthetic grafts are widely used in vascular surgery; however, graft infection remains a major concern. Silver-coated vascular grafts have demonstrated anti-infection properties in clinical settings; however, whether the silver irons influence foreign body reaction or neointimal hyperplasia remains unclear. METHODS: Sodium alginate and hyaluronic acid (SA/HA) hydrogel patches loaded with rhodamine, with or without silver, were fabricated. Patches were implanted in the subcutaneous or abdominal cavity and inferior vena cava of rats. Samples were harvested on day 14 and examined via immunohistochemical and immunofluorescence analyses. RESULTS: Silver hydrogel was found to decrease the foreign body reaction; after subcutaneous and abdominal cavity implantation in rats, the capsule was found to be thinner in the silver hydrogel group than in the control hydrogel group. The silver hydrogel group had fewer CD68-positive cells and proliferating cell nuclear antigen and interleukin-33 (IL-33) dual-positive cells than the control hydrogel group. Additionally, the silver hydrogel patch reduced the neointimal thickness after patch venoplasty in rats, and the number of IL-33- and IL-1ß-positive cells was lower than that in the control patch. CONCLUSION: Silver-loaded SA/HA hydrogel patches decreased the foreign body reaction and venous neointimal hyperplasia in rats by the inhibition of IL-33 expression.

Preparation of Fluorescent Carbon Dots Composites and Their Potential Applications in Biomedicine and Drug Delivery-A Review.

Carbon dots (CDs), a new member of carbon nanostructures, rely on surface modification and functionalization for their good fluorescence phosphorescence and excellent physical and chemical properties, including small size (<10 nm), high chemical stability, biocompatibility, non-toxicity, low cost, and easy synthesis. In the field of medical research on cancer (IARC), CDs, a new material with unique optical properties as a photosensitizer, are being applied to heating local apoptosis induction of cancer cells. In addition, imaging tools can also be combined with a drug to form the nanometer complex compound, the imaging guidance for multi-function dosage, so as to improve the efficiency of drug delivery, which also plays a big role in genetic diagnosis. This paper mainly includes three parts: The first part briefly introduces the synthesis and preparation of carbon dots, and summarizes the advantages and disadvantages of different preparation methods; The second part introduces the preparation methods of carbon dot composites. Finally, the application status of carbon dot composites in biomedicine, cancer theranostics, drug delivery, electrochemistry, and photocatalysis is summarized.

Wood-Derived Vascular Patches Loaded With Rapamycin Inhibit Neointimal Hyperplasia.

Background: Patches are commonly used to close blood vessels after vascular surgery. Most currently used materials are either prosthetics or animal-derived; although natural materials, such as a leaf, can be used as a patch, healing of these natural materials is not optimal; rhodamine and rapamycin have been used to show that coating patches with drugs allow drug delivery to inhibit neointimal hyperplasia that may improve patch healing. Wood is abundant, and its stiffness can be reduced with processing; however, whether wood can be used as a vascular patch is not established. We hypothesized that wood can be used as a vascular patch and thus may serve as a novel plant-based biocompatible material. Method: Male Sprague-Dawley rats (aged 6-8 weeks) were used as an inferior vena cava (IVC) patch venoplasty model. After softening, wood patches coated with rhodamine and rapamycin were implanted into the rat subcutaneous tissue, the abdominal cavity, or the IVC. Samples were explanted on day 14 for analysis. Result: Wood patches became soft after processing. Patches showed biocompatibility after implantation into the subcutaneous tissue or the abdominal cavity. After implantation into the IVC, the patches retained mechanical strength. There was a significantly thinner neointima in wood patches coated with rapamycin than control patches (146.7 ± 15.32 µm vs. 524.7 ± 26.81 µm; p = 0.0001). There were CD34 and nestin-positive cells throughout the patch, and neointimal endothelial cells were Eph-B4 and COUP-TFII-positive. There was a significantly smaller number of PCNA and α-actin dual-positive cells in the neointima (p = 0.0003), peri-patch area (p = 0.0198), and adventitia (p = 0.0004) in wood patches coated with rapamycin than control patches. Piezo1 was expressed in the neointima and peri-patch area, and there were decreased CD68 and piezo1 dual-positive cells in wood patches coated with rapamycin compared to control patches. Conclusion: Wood can be used as a novel biomaterial that can be implanted as a vascular patch and also serve as a scaffold for drug delivery. Plant-derived materials may be an alternative to prosthetics or animal-based materials in vascular applications.

Advances in Hyaluronic Acid for Biomedical Applications.

Hyaluronic acid (HA) is a large non-sulfated glycosaminoglycan that is the main component of the extracellular matrix (ECM). Because of its strong and diversified functions applied in broad fields, HA has been widely studied and reported previously. The molecular properties of HA and its derivatives, including a wide range of molecular weights but distinct effects on cells, moisture retention and anti-aging, and CD44 targeting, promised its role as a popular participant in tissue engineering, wound healing, cancer treatment, ophthalmology, and cosmetics. In recent years, HA and its derivatives have played an increasingly important role in the aforementioned biomedical fields in the formulation of coatings, nanoparticles, and hydrogels. This article highlights recent efforts in converting HA to smart formulation, such as multifunctional coatings, targeted nanoparticles, or injectable hydrogels, which are used in advanced biomedical application.

ADAM17: A novel treatment target for aneurysms.

PURPOSE: The mechanisms underlying abdominal aortic aneurysms (AAAs) are still not fully understood, previous researches showed ADAM17 is increased in aneurysm. We hypothesized that inhibiting ADAM17 can decrease AAA formation and progression. MATERIALS AND METHODS: Aneurysm models were established in mouses and rats by aortic adventitial CaCl2 incubation and aortic pericardial patch angioplasty respectively. In mouse, control (no treatment) or SA/HA hydrogel loaded with TAPI-1 (ADAM17 inhibitor) were adventitial applied; in rat, control and TAPI-1 coated pericardial patch were used in rat aortic pericardial patch angioplasty. Samples were harvested on day 14 or 30 and analyzed by immunofluorescence. Bioinformatics analysis and immunostaining analysis were carried out to confirm the therapeutic potential of ADAM17 in the human AAA. RESULTS: ADAM17 was highly expressed in mouses, rats and human aneurysms. Adventitial application of SA/HA hydrogel loaded TAPI-1 or TAPI-1 conjugated pericardial patch can decrease AAA formation and progression in mouses and rats, respectively. Bioinformatic analysis showed ADAM17 promotes transformation of M1 macrophages and synthetic vascular smooth muscle cells, together with immunostaining analysis and results from animal models, the therapeutic potential of ADAM17 in the human AAA were confirmed. CONCLUSION: We showed that local delivery of ADAM17 inhibitor can inhibit aneurysm formation and progression in mouse and rat, these results showed ADAM17 plays an important role in the aneurysm formation and may be a potential treatment target.

Investigation of Mg-xLi-Zn alloys for potential application of biodegradable bone implant materials.

Implant therapy after osteosarcoma surgery is a major clinical challenge currently, especially the requirements for mechanical properties, degradability of the implants, and their inhibition of residual tumor cells. Biodegradable magnesium (Mg) alloy as medical bone implant material has full advantages and huge potential development space. Wherein, Mg-lithium (Li) based alloy, as an ultra-light alloy, has good properties for implants under certain conditions, and both Mg and Li have inhibitory effects on tumor cells. Therefore, Mg-Li alloy is expected to be applied in bone implant materials for mechanical supporting and inhibiting tumor cells simultaneously. In this contribution, the Mg-xLi-Zinc (Zn) series alloys (x = 3 wt%, 6 wt%, 9 wt%) were prepared to study the influence of different elements and contents on the structure and properties of the alloy, and the biosafety of the alloy was also evaluated. Our data showed that the yield strength, tensile strength, and elongation of as-cast Mg-xLi-Zn alloy were higher than those of as-cast Mg-Zn alloy; Mg-xLi-Zn alloy can kill osteosarcoma cells (MG-63) in a concentration-dependent manner, wherein Mg-3Li-Zn alloy (x = 3 wt%) and Mg-6Li-Zn alloy (x = 6 wt%) promoted the proliferation of osteoblasts (MC3T3) at a certain concentration of Li. In summary, our study demonstrated that the Mg-6Li-Zn alloy could be potentially applied as a material of orthopedic implant for its excellent multi-functions.

Hyaluronic acid/polyethyleneimine nanoparticles loaded with copper ion and disulfiram for esophageal cancer.

In the clinical treatment of cancer, improving the effectiveness and targeting of drugs has always been a bottleneck problem that needs to be solved. In this contribution, inspired by the targeted inhibition on cancer from combination application of disulfiram and divalent copper ion (Cu2+), we optimized the concentration of disulfiram and Cu2+ ion for inhibiting esophageal cancer cells, and loaded them in hyaluronic acid (HA)/polyethyleneimine (PEI) nanoparticles with specific scales, in order to improve the effectiveness and targeting of drugs. The in vitro cell experiments demonstrated that more drug loaded HA/PEI nanoparticles accumulated to the esophageal squamous cell carcinoma (Eca109) and promoted higher apoptosis ratio of Eca109. Both in vitro and in vivo biological assessment verified that the disulfiram/Cu2+ loaded HA/PEI nanoparticles promoted the apoptosis of cancer cells and inhibited the tumor proliferation, but had no toxicity on other normal organs.

Environmentally responsive hydrogels for repair of cardiovascular tissue.

Cardiovascular diseases (CVDs) pose a serious threat to human health, which are characterized by high disability and mortality rate globally such as myocardial infarction (MI), atherosclerosis, and heart failure. Although stem cells transplantation and growth factors therapy are promising, their low survival rate and loss at the site of injury are major obstacles to this therapy. Recently, the development of hydrogel scaffold materials provides a new way to solve this problem, which have shown the potential to treat CVD. Among these scaffold materials, environmentally responsive hydrogels have great prospects in repairing the microenvironment of cardiovascular tissues and vascular regeneration. They provide a new method for the treatment of cardiovascular tissue repair and space-time control for the release of various therapeutic drugs, including small-molecule drugs, growth factors, and stem cells. Herein, this article reviews the occurrence and current treatment of CVD, as well as the repair of cardiovascular injury by several environmental responsive hydrogels systems currently used, mainly focusing on the delivery of growth factors or the application of cell therapy to revascularization. In addition, we will also discuss the enormous potential and personal perspectives of environmentally responsive hydrogels in cardiovascular repair.

Inhibition of programmed death-1 decreases neointimal hyperplasia after patch angioplasty.

Neointimal hyperplasia remains an obstacle after vascular interventions. Programmed death-1 (PD-1) antibody treatment decreases tumor cell proliferation and secretion of inflammatory factors, and several antineoplastic drugs show efficacy against neointimal hyperplasia. We hypothesized that inhibition of PD-1 inhibits neointimal hyperplasia in a rat patch angioplasty model. In a rat aorta patch angioplasty model, four groups were compared: the control group without treatment, a single dose of humanized PD-1 antibody (4 mg/kg) injected immediately after patch angioplasty, PD-1 antibody-coated patches, and BMS-1 (PD-1 inhibitor)-coated patches. Patches were harvested (Day 14) and analyzed. After patch angioplasty, PD-1-positive cells were present. Inhibition of PD-1 using both intraperitoneal injection of humanized PD1 antibody as well as using patches coated with humanized PD1 antibody significantly decreased neointimal thickness (p = 0.0199). There were significantly fewer PD-1 (p = 0.0148), CD3 (p = 0.0072), CD68 (p = 0.0001), CD45 (p = 0.001), and PCNA (p < 0.0001)-positive cells, and PCNA/α-actin dual positive cells (p = 0.0005), in the treated groups. Patches coated with BMS-1 showed similarly decreased neointimal thickness and accumulation of inflammatory cells. Inhibition of PD-1 using PD-1 antibody or its inhibitor BMS-1 can significantly decrease neointimal thickness in vascular patches. Inhibition of the PD-1 pathway may be a promising therapeutic strategy to inhibit neointimal hyperplasia.

Sulfur Contents in Sulfonated Hyaluronic Acid Direct the Cardiovascular Cells Fate.

Hyaluronic acid (HA) is recognized as a functional carbohydrate polymer applied for the surface modification of cardiovascular implanted materials due to its molecular weight (MW) dependent cellular regulation. However, due to the enzyme digestion of hyaluronidase on HA in vivo, the stability of HA MW needs to be further improved. It has been reported that the stability of HA MW can be improved by sulfonation. In this study, sulfonated hyaluronic acids (S-HA) with sulfur content of 2.06, 3.69, 7.10, 8.98, and 9.71 were prepared through different sulfuric acid treatment procedures. Cell tests showed that S-HA with higher sulfur content played a significant role in promoting the proliferation and migration of endothelial cells and regulating smooth muscle cells to the physiological phenotype. In addition, it was also proved to inhibit the inflammatory macrophages adhesion/activation. Our data indicates that S-HA may be a better carbohydrate polymer for potential application of cardiovascular biomaterials.

An Injectable Nanocomposite Hydrogel for Potential Application of Vascularization and Tissue Repair.

In this contribution, an injectable hydrogel was developed with chitosan, gelatin, ß-glycerphosphate and Arg-Gly-Asp (RGD) peptide: this hydrogel is liquid in room temperature and rapidly gels at 37 °C; RGD peptide promises better growth microenvironment for various cells, especially endothelial cells (EC), smooth muscle cells (SMC) and mesenchymal stem cells (MSC). Both stromal cell-derived factor-1 (SDF-1) nanoparticle and vascular endothelial growth factor (VEGF) nanoparticles were loaded in the injectable hydrogel to simulate the natural nanoparticles in the extracellular matrix (ECM) to promote angiogenesis. In vitro EC/SMC and MSC/SMC co-culture experiment indicated that the nanocomposite hydrogel accelerated constructing embryonic form of blood vessels, and chick embryo chorioallantoic membrane model demonstrated its ability of improving cells migration and blood vessel regeneration. We injected this nanocomposite hydrogel into rat myocardial infarction (MI) model and the results indicated that the rats heart function recovered better compared control group. We hope this injectable nanocomposite hydrogel may possess wider application in tissue engineering.

Investigation of Mg-Zn-Y-Nd alloy for potential application of biodegradable esophageal stent material.

In recent years, due to unhealthy dietary habits and other reasons, advanced esophageal cancer patients are on the rise, threatening human health and life safety at all times. Stents implantation as an important complementary or alternative method for chemotherapy has been widely applied in clinics. However, the adhesion and proliferation of pathological cells, such as tumor cells, fibroblasts and epithelial cells, may interfere the efficacy of stents. Further multiple implantation due to restenosis may also bring pain to patients. In this contribution, we preferred a biodegradable material Mg-Zn-Y-Nd alloy for potential application of esophageal stent. The hardness testing showed that Mg-Zn-Y-Nd alloy owned less mechanical properties compared with the commercial esophageal stents material, 317L stainless steel (317L SS), while Mg-Zn-Y-Nd displayed significantly better biodegradation than 317L SS. Cell apoptosis assay indicated Mg-Zn-Y-Nd inhibited adhesion and proliferation of tumor cells, fibroblasts and epithelial cells. Our research suggested potential application of Mg-Zn-Y-Nd alloy as a novel material for biodegradable esophageal stent.

The mechanism of PDA/PEI/5-Fu coated esophageal stent material on inhibiting cancer associated pathological cells.

Metal stent implantation is usually applied to alleviate nonoperative palliative esophageal obstruction for esophageal cancer in the later period. However, in-stent restenosis after stent implantation limits the esophageal stents' performance due to lack of effective suppression of pathological cells from cancer microenvironment. In previous work, we modified the esophageal stent material 317L stainless steel (317LSS) surface with a poly-dopamine/poly-ethylenimine/5-fluorouracil layer (PDA/PEI/5-Fu), which had strong anti-tumor and anti-restenosis functions. Nevertheless, the mechanism of PDA/PEI/5-Fu layer against tumor and inflammation remains unclear. In this work, we revealed the mechanism of PDA/PEI/5-Fu suppressing the esophageal cancer related pathological cells (esophageal tumor cells, epithelial cells, and fibroblast) and inflammatory cells (macrophages) via series of experiments. Our data suggested that the PEI inhibited viability and E-cadherin expression of the pathological cells, and blocked the NF-κB signal pathway (reducing levels of p-NF-κB proteins). The loaded 5-Fu inhibited the inflammatory factors (TNF-α and IL-1ß) release and promoted the anti-inflammation/anti-tumor factors (IL-10 and IL-4) release from macrophages, and also suppressed pathological cells migration; both the PEI and 5-Fu contributed to the upregulation of Bax and Caspase-3 (pro-tumor-apoptosis factor), as well as the downregulation of Bcl-2 (anti-tumor-apoptosis factor) in esophageal tumor cells. All the results showed that PDA/PEI/5-Fu coating had potential multipath anti-cancer and anti-inflammatory effects in the surface modification of esophageal stents.

Recent Advances in Extracellular Matrix for Engineering Stem Cell Responses.

Stem cell transplantation is an advanced medical technology, which brings hope for the treatment of some difficult diseases in the clinic. Attributed to its self-renewal and differential ability, stem cell research has been pushed to the forefront of regenerative medicine and has become a hot topic in tissue engineering. The surrounding extracellular matrix has physical functions and important biological significance in regulating the life activities of cells, which may play crucial roles for in situ inducing specific differentiation of stem cells. In this review, we discuss the stem cells and their engineering application, and highlight the control of the fate of stem cells, we offer our perspectives on the various challenges and opportunities facing the use of the components of extracellular matrix for stem cell attachment, growth, proliferation, migration and differentiation.

Preparing Sodium Alginate/Polyethyleneimine Spheres for Potential Application of Killing Tumor Cells by Reducing the Concentration of Copper Ions in the Lesions of Colon Cancer.

Inhibition of residual malignant tumors in patients with colon cancer after operation is one of the difficulties in rehabilitation treatment. At present, using biocompatible materials to remove the copper ion which is the growth dependence of malignant tumors in the lesion site is considered to be the frontier means to solve this problem. In this work, we developed a sodium alginate (SA)/polyethyleneimine (PEI) hydrogel sphere via cross-linking method (SA/SP/SA; SP = SA/PEI) as an oral biomaterial for adsorbing and removing copper ions from colon cancer lesions. The evaluated results showed that the SA/PEI/SA (SPS) hydrogel sphere obtained the largest swelling rate at pH 8.3 which was the acid-base value of colon microenvironment and absorbed more copper ions compared with the SA control. The cell experiment presented that the SPS hydrogel sphere owned better compatibility on normal fibroblasts and promoted higher death of colon cancer cells compared with SA/PEI (SP) and SA control. Our data suggested that the SA/PEI hydrogel sphere had the potentiality as an oral biomaterial for inhibiting colon cancer cells.

An injectable scaffold based on temperature-responsive hydrogel and factor-loaded nanoparticles for application in vascularization in tissue engineering.

Controlled release of functional factors contributes to target migration of therapeutic cells and plays a crucial role in the in situ vascularization of tissue repair and regeneration. A biomedical application requires the selective release of multiple factors which will guide the synergy of the cells. Here, we developed an injectable system based on a temperature-responsive hydrogel and stromal cell-derived factor-1 (SDF-1)/vascular endothelial growth factor (VEGF) loaded into two types of nanoparticles to induce migration and rapid proliferation of mesenchymal stem cells (MSCs) and endothelial cells (ECs) via selective SDF-1/VEGF release. Series of in vitro and in vivo experiments demonstrate that our composited system can accurately guide MSCs and ECs for vascularization. In addition, the properties of the nanoparticles and hydrogel, including micro/nanoscales, characteristic of charge, and biocompatibility, played crucial roles for the selective release and cells behavior (target migration and rapid proliferation).

Nature-inspired extracellular matrix coating produced by micro-patterned smooth muscle and endothelial cells endows cardiovascular materials with better biocompatibility.

Functionalizing cardiovascular biomaterials with an extracellular matrix (ECM) via in vitro decellularization has been applied as an effective method to improve the biocompatibility of implants. However, the current ECM modified materials used for surface engineering implants have functional restrictions compared with the natural blood vessel due to distinguished cell phenotypes in vitro. Herein, we are inspired by the natural vascular basement membrane which is composed of an ECM secreted by physiological endothelial cells (EC) and smooth muscle cells (SMC), preparing a novel ECM coating by successive cell culture and decellularization: appropriately scaled hyaluronic acid (HA) micro-patterns are used to regulate the SMC phenotype to contraction and simulate the blood flow shear stress (BFSS) effect to control the EC physiological phenotype. The nature-inspired ECM coating significantly improves the material's hemocompatibility, cytocompatibility and tissue compatibility, and may be promising to break the function limitation of a single ECM and address more clinical complications.

Preparation of a biomimetic ECM surface on cardiovascular biomaterials via a novel layer-by-layer decellularization for better biocompatibility.

Endothelial extracellular matrix (EC-ECM) modification by decellularization is generally recognized as an effective method for cardiovascular biomaterials to enhance their biocompatibility. However, the now available EC-ECM was mainly secreted by the in vitro cultured endothelial cells which lacked a physiological growth environment in vivo, such as blood flow shear stress (BFSS) acting, thus had a serious defect of biocompatibility. Our previous work markedly improved the biocompatibility of the EC-ECM modified materials by simulating the BFSS acting to control the endothelial cells with hyaluronic acid (HA) micro-pattern. In this contribution, the EC-ECM was further enriched onto the HA micro-pattern via a novel layer-by-layer decellularizatio method. In vitro platelets adhesion/activation, macrophages attachment test and ex vivo blood experiment of New Zealand White Rabbits suggested better blood compatibility and anti-inflammation property of this novel biomimetic ECM surface. The endothelial cells culture tests and in vivo rat subcutaneous implantation also proved its good pro-endothelialization function and tissue compatibility. In summary, the present study demonstrated better biocompatibility of the novel biomimetic ECM surface and its potential application for cardiovascular biomaterials modification.

Surface modification of esophageal stent materials by a polyethylenimine layer aiming at anti-cancer function.

Esophageal cancer is difficult to cure globally and possesses high mortality rate, and it is generally accepted that palliative care such as stent implantation is the main therapy method for esophageal cancer in later period. However, the restenosis caused by tumor cells and inflammatory cells seriously interferes the stent clinical application and limits its long-term services. To solve this problem, series of drug delivery stents were developed and proven rather effective in the early stage of implantation, but more serious restenosis occurred after the drug delivery was over, which endangered the patients' life. Therefore, endowing the esophageal stent continuous anti-cancer function become an ideal strategy for inhibiting the restenosis. In this contribution, the functional layer composed of polydopamine (PDA) and Poly-ethylenimine (PEI) with series of molecular weights (MW, 1.8 × 103, 1 × 104, 2.5 × 104 and 7 × 104 Da) were fabricated onto the esophageal stent material 317L stainless steel (317L SS) surface. The surface characterization including amine quantitative, atomic force microscopy (AFM) and water contact angle measurement indicated successful preparation of the PDA/PEI layer. The Eca109 cells culture results proved that the PDA/PEI layers significantly improve Eca109 cells apoptosis and necrosis, suggesting excellent anti-cancer function. In addition, we also found that the anti-cancer function of the PDA/PEI layers was positively correlated to the immobilized PEIs' MW. All the results demonstrated the potential application of the PDA/PEI layers on the surface modification of esophageal stent for continuous anti-cancer function. It is generally accepted that the restenosis caused by tumor cells seriously interferes the esophageal stent clinical application. Thus, endowing the esophageal stent continuous anti-cancer function is the ideal strategy for inhibiting the restenosis. In this work, we fabricated functional layers composed of polydopamine (PDA) and Poly-ethylenimine (PEI) with series of molecular weights (MW, 1.8 × 103, 1 × 104, 2.5 × 104 and 7 × 104 Da) onto the esophageal stent material 317L stainless steel (317L SS) surface to inhibit the tumor cells growth, and this function was related to the PEIs' molecular weights. The functional PDA/PEI layers were expected potentially applied for surface modification of esophageal stent materials.

Investigation of enhanced hemocompatibility and tissue compatibility associated with multi-functional coating based on hyaluronic acid and Type IV collagen.

The biocompatibility of cardiovascular devices has always been considered crucial for their clinical efficacy. Therefore, a biofunctional coating composed of Type IV collagen (CoIV) and hyaluronan (HA) was previously fabricated onto the titanium (Ti) substrate for the application of promoting vascular smooth muscle cell contractile phenotype and improving surface endothelialization. However, the anti-inflammation property, blood compatibility and in vivo tissue compatibility of the HA/CoIV coating, as paramount consideration of cardiovascular materials surface coating, have not been investigated. Thus, in this study, the three crucial properties of the HA/CoIV coating were tested. The platelet adhesion/activation test and the dynamic whole blood experiment implied that the HA/CoIV coating had better blood compatibility compared with Ti substrate and pure CoIV coating. The macrophage adhesion/activation and inflammatory cytokine release (tumor necrosis factor-alpha and interleukin-1) results indicated that the HA/CoIV coating could significantly improve the anti-inflammation property of the Ti substrate. The in vivo implantation of SD rats for 3 weeks' results demonstrated that the HA/CoIV coating caused milder tissue response. All these results suggested that the multi-functional HA/CoIV coating possessed good biocompatibility. This research is anticipated to be potentially applied for the surface modification of cardiovascular stents.