Clinical efficacy of mineralized collagen (MC) versus anorganic bovine bone (Bio-Oss) for immediate implant placement in esthetic area: a single-center retrospective study.

BACKGROUND: The purpose of this retrospective study was to evaluate the clinical efficacy of mineralized collagen (MC) versus anorganic bovine bone (Bio-Oss) for immediate implant placement in esthetic area. METHODS: Medical records of Department of Oral and Maxillofacial Surgery of Shandong Provincial Hospital were screened for patients who had been treated with immediate implant implantation in the esthetic area using either MC (Allgens®, Beijing Allgens Medical Science and Technology Co., Ltd., China) or Bio-Oss (Bio-Oss®, Geistlich Biomaterials, Wolhusen, Switzerland), between January 2018 and December 2019. All patients fulfilling the in-/exclusion criteria and following followed for a minimum period of 1 year after surgery were enrolled into the presented study. Implant survival rate, radiographic, esthetic and patient satisfactory evaluations were performed. RESULTS: Altogether, 70 patients were included in the study; a total of 80 implants were inserted. All implants had good initial stability. The survival rate of implants was 100% at 1-year follow-up. The differences in horizontal and vertical bone loss between the MC group (0.72 ± 0.26 mm, 1.62 ± 0.84 mm) and the Bio-Oss group (0.70 ± 0.52 mm, 1.57 ± 0.88 mm) were no significant difference statistically no significant 6 months after permanent restoration. Similar results occurred at 12 months after permanent restoration functional loaded. Clinical acceptability defined by pink esthetic score (PES) ≥ 6 (6.07 ± 1.62 vs. 6.13 ± 1.41) was not significantly different between groups. Patient satisfaction estimated by visual analog scale (VAS) was similar (8.56 ± 1.12 vs. 8.27 ± 1.44), and the difference was no significant difference between the two groups. CONCLUSIONS: The biomimetic MC showed a similar behaviour as Bio-Oss not only in its dimensional tissues changes but also in clinical acceptability and patient satisfaction. Within the limitations of this study, these cases show that MC could be considered as an alternative bone graft in IIP.

Poly(methyl methacrylate) bone cement composited with mineralized collagen for osteoporotic vertebral compression fractures in extremely old patients.

To examine the clinical effects of a new bone cement composed of poly(methyl methacrylate) (PMMA) and mineralized collagen (MC) compared with pure PMMA bone cement in treating osteoporotic vertebral compression fractures (OVCFs) in patients aged over 80. In all, 32 cases using pure PMMA bone cement and 31 cases using MC-modified PMMA (MC-PMMA) bone cement for OVCFs between June 2014 and March 2016 were screened as PMMA group and MC-PMMA group, respectively, with an average age of over 80. The operation duration, intraoperative blood loss, hospital stay, oswestry disability index (ODI), visual analogue scale (VAS), anterior vertebral height (AVH), intermediate vertebral height (IVH) and posterior vertebral height (PVH) of injured vertebrae, vertebral computed tomography value, re-fracture rate of adjacent vertebrae, correction rate of spinal kyphotic angle and wedge-shaped vertebra angle and surgical complications were compared between the two groups. In the early post-operative period, the VAS, ODI, AVH and IVH in MC-PMMA group were comparable to those in the traditional PMMA group. Moreover, the MC-PMMA group showed better effects compared with the PMMA group 12 months after surgery. Thus, this new bone cement has superior clinic effects in the long term.

The observed difference of RAW264.7 macrophage phenotype on mineralized collagen and hydroxyapatite.

Understanding the interaction between biomaterials and the immune system has become increasingly important. Mineralized collagen (MC) has the same chemical components and microstructures to natural bone tissue, and is considered as a better biomaterial for bone prostheses compared to hydroxyapatite (HA). However, there is little information about how MC affects inflammatory responses. In this study, we investigate the inflammatory responses to MC and HA by culturing RAW264.7 cells on their surfaces. We observed that MC increases CD206+ staining and IL-10 (M2 macrophages), whereas HA shows cells expressing more CD86 and secreting more TNF-α. This result indicates that MC may attenuate inflammatory responses to implanted bone prostheses.

Effects of the bilayer nano-hydroxyapatite/mineralized collagen-guided bone regeneration membrane on site preservation in dogs.

This study was aimed at assessing the effects of the porous mineralized collagen plug with or without the bilayer mineralized collagen-guided bone regeneration membrane on alveolar ridge preservation in dogs. The third premolars in the bilateral maxilla of mongrel dogs ( N = 12) were extracted. Twenty-four alveolar sockets were thus randomly divided into three groups: membrane + collagen plug (MP, n = 8), nonmembrane + collagen plug (NP, n = 8) and blank group without any implantation (BG, n = 8). Radiographic assessment was carried out immediately and in the 2nd, 6th, and 12th week after surgery. The bone-repairing effects of the two grafts were respectively evaluated by clinical observation, X-ray micro-computed tomography examination, and histological analysis in the 8th and 12th week after surgery. Three groups presented excellent osseointegration without any inflammation or dehiscence. X-ray micro-computed tomography and histological assessment indicated that the ratios of new bone formation of MP group were significantly higher than those of NP group and BG group in the 8th and 12th week after surgery ( P < 0.05). As a result, the porous mineralized collagen plug with or without the bilayer mineralized collagen-guided bone regeneration membrane could reduce the absorption of alveolar ridge compared to BG group, and the combined use of porous mineralized collagen plug and bilayer mineralized collagen-guided bone regeneration could further improve the activity of bone regeneration.

Comparison of rabbit rib defect regeneration with and without graft.

Rib segment, as one of the most widely used autologous boneresources for bone repair, is commonly isolated with an empty left in the defect. Although defective rib repair is thought to be unnecessary traditionally, it's of vital importance actually to promote rib regeneration for patients with better postoperative recovery and higher life quality. Comparative investigations on rabbit rib bone regeneration with and without graft were reported in this article. A segmental defect was performed on the 8th rib of 4-month-old male New Zealand rabbits. The mineralized collagen bone graft (MC) was implanted into the defect and evaluated for up to 12 weeks. The rib bone repair was investigated by using X-ray at 4, 8 and 12 weeks and histological examinations at 12 weeks after surgery, which showed a higher bone remodeling activity in the groups with MC implantation in comparison with blank control group, especially at the early stage of remodeling.

Rib Composite Flap With Intercostal Nerve and Internal Thoracic Vessels for Mandibular Reconstruction.

PURPOSE: The purpose of this study was to present the outcome and discuss the feasibility of rib composite flap with intercostal nerve and internal thoracic vessels for reconstructing mandibular defect. METHODS: Rib composite flaps have been used in 82 patients for reconstructing benign tumor-caused large mandibular defects: 66 of the 82 patients were reconstructed using rib composite flap with intercostal nerve and internal thoracic vessels, whereas the other 16 patients were reconstructed using rib composite flap with internal thoracic vessels, without intercostal nerve. After operation, clinical observation, imageological examination, and sensory detection were used to evaluate the effect of reconstruction. RESULTS: All rib composite flaps with intercostal nerve and internal thoracic vessels were successfully harvested and transplanted. Both immediate and long-term examination showed good appearance reconstruction. All followed-up patients conveyed good satisfaction degree with function and appearance reconstruction. Postoperative panoramic x-ray examination showed new bone formation between the transplanted rib and mandibular stump. Good recoveries of mandibular nerve sensory were observed when followed up after reconstruction surgery. CONCLUSIONS: Rib composite flap with intercostal nerve and internal thoracic vessels could be a promising method for reconstruction of mandibular defects.

A novel method to in vitro evaluate biocompatibility of nanoscaled scaffolds.

This study provided a new method to in vitro evaluate the biocompatibility of nanoscaled scaffolds for tissue engineering with neutrophils other than ordinary cell culture. The neutrophils were separated from human peripheral blood of healthy subjects. In vitro degradation product of nanohydroxyapatite/collagen (nHAC), nanohydroxyapatite/collagen/poly (L-lactic acid) (nHACP), and nHACP reinforced by chitin fibers (nHACP/CF) in the D-Hank's Balanced Salt Solution (D-HBSS) was used as the testing solution, which was thereafter mixed with the neutrophils. It was shown that the cell survival rate in the testing solutions had no significant difference from that in the D-HBSS (control). However, from both gene and protein expression levels, the lactate dehydrogenase and tumor necrosis factor-alpha of the neutrophils in the nHACP/CF testing solution were found lowest during the whole testing period; the main reasons of which might be that the calcium release rate of the scaffold was slowest and that the pH value of its degradation solution was nearest to that of human body. Moreover, in vivo experiments showed that most inflammation reactions happened for nHAC and poly (L-lactic acid) groups, while the least inflammation reactions happened for nHACP/CF group in the subcutaneous dorsum of mice at 2 weeks after the surgery, which confirmed the in vitro findings. These results indicated that the pH value and the certain metal iron concentration of the nanoscaled scaffold degradation solution should be two important factors that significantly affect its biocompatibility. This study provides a simple and effective biocompatibility test method for biodegradable nanoscaled tissue engineering scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2117-2125, 2016.

Current investigations into magnetic nanoparticles for biomedical applications.

It is generally recognized that nanoparticles possess unique physicochemical properties that are largely different from those of conventional materials, specifically the electromagnetic properties of magnetic nanoparticles (MNPs). These properties have attracted many researchers to launch investigations into their potential biomedical applications, which have been reviewed in this article. First, common types of MNPs were briefly introduced. Then, the biomedical applications of MNPs were reviewed in seven parts: magnetic resonance imaging (MRI), cancer therapy, the delivery of drugs and genes, bone and dental repair, tissue engineering, biosensors, and in other aspects, which indicated that MNPs possess great potentials for many kinds of biomedical applications due to their unique properties. Although lots of achievements have been obtained, there is still a lot of work to do. New synthesis techniques and methods are still needed to develop the MNPs with satisfactory biocompatibility. More effective methods need to be exploited to prepare MNPs-based composites with fine microstructures and high biomedical performances. Other promising research points include the development of more appropriate techniques of experiments both in vitro and in vivo to detect and analyze the biocompatibility and cytotoxicity of MNPs and understand the possible influencing mechanism of the two properties. More comprehensive investigations into the diagnostic and therapeutic applications of composites containing MNPs with "core-shell" structure and deeper understanding and further study into the properties of MNPs to reveal their new biomedical applications, are also described in the conclusion and perspectives part.

Osteogenic Differentiation Gene Expression Profiling of hMSCs on Hydroxyapatite and Mineralized Collagen.

In this study, human mesenchymal stem cells (hMSCs) were cultured on the hydroxyapatite (HA) and mineralized collagen (MC), and their proliferation, adhesion, and differentiation, especially the molecular mechanisms on gene level, were investigated. Proliferation and morphological responses of hMSCs and their osteogenic differentiation were detected by quantitative detection of alkaline phosphatase. Gene expression profilings were examined by microarrays, and the gene expression data were studied through gene ontology terms and pathway analyses. The results showed that MC promoted cell proliferation and osteogenic differentiation of hMSCs. Microarray analysis showed that MC was conducive to express osteogenesis-related genes, such as BMP-2, COL1A1, and CTSK, and stimulate osteogenic differentiation, such as osteoblast differentiation pathway and skeletal system development pathway.

Comparison of human mesenchymal stem cells proliferation and differentiation on poly(methyl methacrylate) bone cements with and without mineralized collagen incorporation.

Poly(methyl methacrylate) bone cement is widely used in vertebroplasty, joint replacement surgery, and other orthopaedic surgeries, while it also exposed many problems on mechanical property and biocompatibility. Better performance in mechanical match and bone integration is highly desirable. Recently, there reported that incorporation of mineralized collagen into poly(methyl methacrylate) showed positive results in mechanical property and osteointegration ability in vivo. In the present study, we focused on the comparison of osteogenic behavior between mineralized collagen incorporated in poly(methyl methacrylate) and poly(methyl methacrylate). Human marrow mesenchymal stem cells are used in this experiment. Adhesion and proliferation were used to characterize biocompatibility. Activity of alkaline phosphatase was used to assess the differentiation of human marrow mesenchymal stem cells into osteoblasts. Real-time PCR was performed to detect the expression of osteoblast-related markers at messenger RNA level. The results show that osteogenic differentiation on mineralized collagen incorporated in poly(methyl methacrylate) bone cement is more than two times higher than that of poly(methyl methacrylate) after culturing for 21 days. Thus, important mechanism on mineralized collagen incorporation increasing the osteogenetic ability of poly(methyl methacrylate) bone cement may be understood in this concern.

In vitro and in vivo enhancement of osteogenic capacity in a synthetic BMP-2 derived peptide-coated mineralized collagen composite.

Enhancement of osteogenic capacity was achieved in a mineralized collagen composite, nano-hydroxyapatite/collagen (nHAC), by loading with synthetic peptides derived from BMP-2 residues 32-48 (P17-BMP-2). Rabbit marrow stromal cells (MSCs) were used in vitro to study cell biocompatibility, attachment and differentiation on the mineralized collagen composite by a cell counting kit, scanning electron microscopy (SEM) and real-time reversed transcriptase-polymerase chain reaction analysis (RT-PCR). Optimal peptide dosage (1.0 µg/mL) was obtained by RT-PCR analysis in vitro. In addition, the relative expression level of OPN and OCN was significantly upregulated on P17-BMP-2/nHAC compared with nHAC. In vitro results of P17-BMP-2 release kinetics demonstrated that nHAC released P17-BMP-2 in a controlled and sustained manner. In the rabbit mandibular box-shaped bone defect model, osteogenic capacity of three groups (nHAC, P17-BMP-2/nHAC, rhBMP-2/nHAC) was evaluated. Compared to the nHAC group, bone repair responses in both P17-BMP-2/nHAC and rhBMP-2/nHAC group implants were significantly improved based on histological analysis. The osteogenic response of the P17-BMP-2/nHAC group was similar to that of the rhBMP-2/nHAC group.

Self­assembled monolayers of alkanethiolates on surface chemistry groups in osteosarcoma cells.

Cell biomedical behavior is influenced by a number of factors, and the extracellular matrix (ECM) of the cellular microenvironment affects certain cancer cells. In the current study, U­2OS cells were cultured on gold surfaces modified with different terminal chemical groups [methyl (­CH3), amino (­NH2), hydroxyl (­OH) and carboxyl (­COOH)]. The results revealed that different chemical surfaces convey different behaviors. The density of the different functional surfaces was confirmed by atomic force microscopy. Cell morphology, proliferation rate and cell cycle were investigated using scanning electron microscopy, cell counting and flow cytometry. In conclusion, the type of chemical group on a biomaterial is an important property for the growth of osteosarcoma cells; ­NH2 and ­COOH surfaces sustained visible cell adhesion and promoted cell growth.

Peripheral nerve regeneration inside collagen-based artificial nerve guides in humans.

PURPOSE: Nerve gap injuries may be associated with lesions in other structures, like tendons or bones; in these cases, it is common to plan a second surgery to improve functional recovery. Since macroscopic observations of nerve regeneration in humans are rare, we exploited these second surgeries for the purpose of studying nerve regeneration in humans. METHODS: We assessed the clinical outcomes of 50 implants of collagen-based nerve guides in the upper limb. We performed a second look at 20, assessing macroscopically both nerve regeneration and collagen degradation. RESULTS AND CONCLUSIONS: Pain was never recorded in these patients. An adequate sensory recovery took place whenever nerve regeneration was found inside the guide. Motor recovery seemed to occur only when the gap lesion was shorter than 10 mm. The degree of degradation appeared to be variable and was not directly correlated with time; we hypothesize that it could be associated with the site of implantation. Such a large number of second looks in humans has never been previously reported in the literature.

In vitro and in vivo angiogenic capacity of BM-MSCs/HUVECs and AT-MSCs/HUVECs cocultures.

The aim of this study was to comparatively evaluate the angiogenic capacity of cocultures using either human bone marrow- or human adipose tissue-derived mesenchymal stem cells (MSCs) (BM- or AT-MSCs) with human umbilical vein endothelial cells (HUVECs) both in vitro and in vivo at early time points (i.e. days 3 and 7). In vitro, cells were either monocultured (i.e. BM-MSCs, AT-MSCs or HUVECs) or cocultured (i.e. BM-MSCs/HUVECs and AT-MSCs/HUVECs) on Thermanox® (2-dimensional, 2D) or in collagen gels (3-dimensional, 3D). For the in vivo experiment, cells (cocultures) were embedded in collagen gels and implanted subcutaneously in nude mice. For both in vitro and in vivo experiments, samples were collected on days 3 and 7 and histologically processed for hematoxylin-eosin and platelet endothelial cell adhesion molecule (PECAM-1; CD31) staining. For in vivo samples, quantitative parameters for evaluating angiogenesis included CD31-positive staining percentage, total vessel-like structure (VLS) area percentage, VLS density, and average VLS area (i.e. the size of per VLS). In vitro results showed the formation of VLS in both cocultures, while none of the monocultures showed VLS formation, irrespective of 2D or 3D culture condition. Although VLS formation occurred after in vivo implantation, no significant difference in angiogenic capacity was observed between the two cocultures, either on day 3 or on day 7. Further, VLS density decreased and anastomosis of the new human vessels with the murine host vasculature occurred over time. In conclusion, this study demonstrated that AT-MSCs/HUVECs and BM-MSCs/HUVECs have equal angiogenic capacity both in vitro and in vivo, and that vessels from donor origin can anastomose with the host vasculature within seven days of implantation.

Adipose tissue-derived mesenchymal stem cells as monocultures or cocultures with human umbilical vein endothelial cells: performance in vitro and in rat cranial defects.

The aim of this study was to compare the osteogenic capacity between human adipose tissue-derived mesenchymal stem cells (AT-MSCs) and their cocultures with human umbilical vein endothelial cells (HUVECs) in vitro and their biological performance in vivo. First, the optimal cell ratio in cocultures for osteogenic differentiation was determined by seeding AT-MSCs and HUVECs in ratios varying from 100:0 to 0:100 on tissue culture plates. Afterward, AT-MSCs and AT-MSCs/HUVECs (50:50) were seeded on porous titanium fiber mesh scaffolds (Ti) for both in vitro and in vivo osteogenic evaluation. For in vitro evaluation, cell osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity and calcium assay. For in vivo evaluation, the scaffolds were implanted bilaterally into rat cranial defects (5 mm diameter) and bone formation was assessed histologically and histomorphometrically after 8 weeks. The ratio of 50:50 was chosen in the cocultures because this coculture condition retained similar amount of calcium deposition while using the least amount of AT-MSCs. Moreover, AT-MSCs showed higher osteogenic differentiation in comparison to AT-MSCs/HUVECs on Ti in vitro. Furthermore, superior bone formation was observed in AT-MSCs compared to AT-MSCs/HUVECs in rat cranial defects. In conclusion, AT-MSCs showed significantly higher osteogenic potential compared to AT-MSCs/HUVECs both in vitro and in vivo.

Comparison of cell-loading methods in hydrogel systems.

Bone regenerative medicine, based on the combined use of cells and scaffolds, represents a promising strategy in bone regeneration. Hydrogels have attracted huge interests for application as a scaffold for minimally invasive surgery. Collagen and oligo(poly(ethylene glycol)fumarate) (OPF) hydrogels are the representatives of two main categories of hydrogels, that is, natural- and synthetic-based hydrogels. With these the optimal cell-loading (i.e., cell distribution inside the hydrogels) method was assessed. The cell behavior of both bone marrow- and adipose tissue-derived mesenchymal stem cells (BM- and AT-MSCs) in three loading methods, which are dispersed (i.e., homogeneous cell encapsulation, D), sandwich (i.e., cells located in between two hydrogel layers, S), and spheroid (i.e., cell pellets encapsulation, Sp) loading in two hydrogel systems (i.e., collagen and OPF), was compared. The results suggested that the cell behavior was influenced by the hydrogel type, meaning cells cultured in collagen hydrogels had higher proliferation and osteogenic differentiation capacity than in OPF hydrogels. In addition, AT-MSCs exhibited higher proliferation and osteogenic properties compared to BM-MSCs. However, no difference was observed for mineralization among the three loading methods, which did not approve the hypothesis that S and Sp loading would increase osteogenic capacity compared to D loading. In conclusion, D and Sp loading represents two promising cell loading methods for injectable bone substitute materials that allow application of minimally invasive surgery for cell-based regenerative treatment.

Concise review: cell-based strategies in bone tissue engineering and regenerative medicine.

Cellular strategies play an important role in bone tissue engineering and regenerative medicine (BTE/RM). Variability in cell culture procedures (e.g., cell types, cell isolation and expansion, cell seeding methods, and preculture conditions before in vivo implantation) may influence experimental outcome. Meanwhile, outcomes from initial clinical trials are far behind those of animal studies, which is suggested to be related to insufficient nutrient and oxygen supply inside the BTE/RM constructs as some complex clinical implementations require bone regeneration in too large a quantity. Coculture strategies, in which angiogenic cells are introduced into osteogenic cell cultures, might provide a solution for improving vascularization and hence increasing bone formation for cell-based constructs. So far, preclinical studies have demonstrated that cell-based tissue-engineered constructs generally induce more bone formation compared with acellular constructs. Further, cocultures have been shown to enhance vascularization and bone formation compared with monocultures. However, translational efficacy from animal studies to clinical use requires improvement, and the role implanted cells play in clinical bone regeneration needs to be further elucidated. In view of this, the present review provides an overview of the critical procedures during in vitro and in vivo phases for cell-based strategies (both monoculture and coculture) in BTE/RM to achieve more standardized culture conditions for future studies, and hence enhance bone formation.

Activation of the ERK1/2 signaling pathway during the osteogenic differentiation of mesenchymal stem cells cultured on substrates modified with various chemical groups.

The current study examined the influence of culture substrates modified with the functional groups -OH, -COOH, -NH2, and -CH3 using SAMs technology, in conjunction with TAAB control, on the osteogenic differentiation of rabbit BMSCs. The CCK-8 assay revealed that BMSCs exhibited substrate-dependent cell viability. The cells plated on -NH2- and -OH-modified substrates were well spread and homogeneous, but those on the -COOH- and -CH3-modified substrates showed more rounded phenotype. The mRNA expression of BMSCs revealed that -NH2-modified substrate promoted the mRNA expression and osteogenic differentiation of the BMSCs. The contribution of ERK1/2 signaling pathway to the osteogenic differentiation of BMSCs cultured on the -NH2-modified substrate was investigated in vitro. The -NH2-modified substrate promoted the expression of integrins; the activation of FAK and ERK1/2. Inhibition of ERK1/2 activation by PD98059, a specific inhibitor of the ERK signaling pathway, blocked ERK1/2 activation in a dose-dependent manner, as revealed for expression of Cbf α -1 and ALP. Blockade of ERK1/2 phosphorylation in BMSCs by PD98059 suppressed osteogenic differentiation on chemical surfaces. These findings indicate a potential role for ERK in the osteogenic differentiation of BMSCs on surfaces modified by specific chemical functional groups, indicating that the microenvironment affects the differentiation of BMSCs. This observation has important implications for bone tissue engineering.

Improved workability of injectable calcium sulfate bone cement by regulation of self-setting properties.

Calcium sulfate hemihydrate (CSH) powder as an injectable bone cement was prepared by hydrothermal synthesis of calcium sulfate dihydrate (CSD). The prepared materials showed X-ray diffraction peaks corresponding to the CSH structure without any secondary phases, implying complete conversion from CSD phase to CSH phase. Thermogravimetric (TG) analyses showed the crystal water content of CSH was about 6.0% (wt.), which is near to the theoretic crystal water value of CSH. From scanning electron microscopy (SEM) micrographs, sheet crystal structure of CSD was observed to transform into rod-like crystal structure of CSH. Most interesting and important of all, CSD as setting accelerator was also introduced into CSH powder to regulate self-setting properties of injectable CSH paste, and thus the self-setting time of CSH paste can be regulated from near 30 min to less than 5 min by adding various amounts of setting accelerator. Because CSD is not only the reactant of preparing CSH but also the final solidified product of CSH, the setting accelerator has no significant effect on the other properties of materials, such as mechanical properties. In vitro biocompatibility and in vivo histology studies have demonstrated that the materials have good biocompatibility and good efficacy in bone regeneration. All these will further improve the workability of CSH in clinic applications.

Functionalized self-assembling peptide nanofiber hydrogels mimic stem cell niche to control human adipose stem cell behavior in vitro.

A class of designer functionalized self-assembling peptide nanofiber scaffolds developed from self-assembling peptide RADA16-I (AcN-RADARADARADARADA-CONH2) has become increasingly attractive not only for studying spatial behaviors of cells, but also for developing approaches for a wide range of medical applications including regenerative medicine, rapid hemostasis and cell therapy. In this study, we report three functionalized self-assembling peptide hydrogels that serve as a three-dimensional (3-D) artificial microenvironment to control human adipose stem cell (hASC) behavior in vitro. Short peptide motifs SKPPGTSS (bone marrow homing motif), FHRRIKA (heparin-binding motif) and PRGDSGYRGDS (two-unit RGD cell adhesion motif) were used to extend the C-terminus of RADA16-I to obtain functionalized peptides. Atomic force microscopy confirmed the formation of self-assembling nanofibers in the mixture of RADA16-I peptide and functionalized peptides. The behaviors of hASCs cultured in 3-D peptide hydrogels, including migration, proliferation and growth factor-secretion ability, were studied. Our results showed that the functionalized peptide hydrogels were suitable 3-D scaffolds for hASC growth with higher cell proliferation, migration and the secretion of angiogenic growth factors compared with tissue culture plates and pure RADA16-I scaffolds. The present study suggests that these functionalized designer peptide hydrogels not only have promising applications for diverse tissue engineering and regenerative medicine applications as stem cell delivery vehicles, but also could be a biomimetic 3-D system to study nanobiomaterial-stem cell interactions and to direct stem cell behaviors.