Coupled benefits of nanotopography and titania surface chemistry in fostering endothelialization and reducing in-stent restenosis in coronary stents.

Recent advances in coronary stents have all been distinctively focused towards directing re-endothelialization with minimal in-stent restenosis, potentially via alterations in surface topographical cues, for augmenting the efficacy of vascular implants. This perspective was proven by our group utilizing a simple and easily scalable nanosurface modification strategy on metallic stents devoid of any drugs or polymers. In the present work, we explore the impact of surface characteristics in modulating this cell response in-vitro and in-vivo, using titania coated cobalt-chromium (CC) stents, with and without nanotopography, in comparison to commercial controls. Interestingly, titania nanotopography facilitated a preferential cell response in-vitro as against the titania coated and bare CC surfaces, which can be attributed to surface topography, hydrophilicity, and roughness. This in turn altered the cellular adhesion, proliferation and focal contact formations of endothelial and smooth muscle cells. We also demonstrate that titania nanotexturing plays a pivotal role in fostering rapid re-endothelialization with minimal neointimal hyperplasia, leading to excellent in-vivo patency of CC stents post 8 weeks implantation in rabbit iliac arteries, in comparison to bare CC, nano-less titania coated CC, and commercial drug-eluting stents (CC DES), without administering antiplatelet agents. This exciting result for the drug and polymer-free titania nanotextured stents, in the absence of platelet therapy, reveals the possibility of proposing an alternative to clinical DES for coronary stenting.

Superhydrophilic multifunctional nanotextured titanium dental implants: in vivo short and long-term response in a porcine model.

Current clinical demand in dental implantology is for a multifunctional device with optimum mechanical properties, improved biocompatibility and bioactivity, and having differential interactions with cells and pathogenic agents. This would minimise bacterial infection, biofilm formation and modulate inflammation, leading to a fast and durable osseointegration. The present study intends to establish the multifunctional behaviour of surface modified titanium dental implants that are superhydrophilic, with unique micro-nano or nanoscale topographies, developed by a facile hydrothermal technique. Here, the short and long-term performances of these textured implants are tested in a split mouth design using a porcine model, in pre- and post-loaded states. Quantitative and qualitative analyses of the bone implant interphase are performed through µ-CT and histology. Parameters that evaluate bone mineral density, bone contact volume and bone implant contact reveal enhanced bone apposition with better long-term response for the nano and micro-nano textured surfaces, compared to the commercial microtextured implant. Concurrently, the nanoscale surface features on implants reduced bacterial attachment by nearly 90% in vivo, outperforming the commercial variant. This preclinical evaluation data thus reveal the superiority of nano/micro-nano textured designs for clinical application and substantiate their improved osseointegration and reduced bacterial adhesion, thus proposing a novel dental implant with multifunctional characteristics.

Effect of wheat gluten on improved thermal cross-linking and osteogenesis of hydroxyapatite-gelatin composite scaffolds.

Promising strategies to stabilize gelatin or collagen include glutaraldehyde-based chemical cross-linking or dehydrothermal treatment at different temperatures (120-180 °C). However, these procedures require 24-48 h for complete cross-linking to occur. The present study aims to evaluate the role of wheat gluten on enhancing thermal cross-linking of silica-nanohydroxyapatite (nanoHA)-gelatin composite scaffolds within a shorter period (2 h). Changes in properties were evaluated by varying the ratio of gelatin and gluten in silica-nanoHA matrix (60 wt% ceramic: 40 wt% polymer). The results showed that the scaffolds cross-linked at 170 °C were stable in phosphate-buffered saline for 21 days. It was crystalline and porous in nature. However, the scaffolds with high weight percentage of wheat gluten were brittle, while those with low gluten degraded fast in vitro. The mesenchymal stem cells could adhere, proliferate and differentiate into osteogenic lineage on wheat gluten-containing scaffolds for 21 days (mainly medium concentration). The scaffold also supported new bone formation in critical-sized rat calvarial defect, showing its osteoconductive and osteointegrative nature. In short, this study showed the potential of wheat gluten on improving thermal cross-linking within a shorter period and its suitability to use as a biomimetic bone graft for bone tissue engineering.

Decellularization and oxidation process of bamboo stem enhance biodegradation and osteogenic differentiation.

Many features that are appropriate for an ideal tissue engineered biomaterial are found in plant tissues. Hierarchically organized Bambusa vulgaris exhibits structural similarities to native bone, but the degradation of cellulose that is the main component of the plant cell wall is a challenge. In this study, Bamboo stem was subjected to decellularization followed by a chemical oxidation process (treated with sodium periodate) to enhance biocompatibility and biodegradation. The crystallinity of oxidised plant scaffolds was reduced, resulting in lower mechanical strength. In contrast, hydrophilicity was enhanced in those scaffolds. In vitro studies demonstrated better mesenchymal stem cell adhesion, viability, and osteogenic differentiation on oxidized scaffolds. Those scaffolds also induced angiogenesis, biocompatibility, and biodegradation when implanted subcutaneously in vivo. Hence, the present study demonstrated the usefulness of "oxidized decellularized plant" as bone scaffold for non-load-bearing applications.

Successful Reduction of Neointimal Hyperplasia on Stainless Steel Coronary Stents by Titania Nanotexturing.

Bare metal stents (BMSs) of stainless steel (SS) were surface engineered to develop nanoscale titania topography using a combination of physical vapor deposition and thermochemical processing. The nanoleafy architecture formed on the stent surface remained stable and adherent upon repeated crimping and expansion, as well as under flow. This titania nanoengineered stent showed a preferential proliferation of endothelial cells over smooth muscle cells in vitro, which is an essential requirement for improving the in vivo endothelialization, with concurrent reduction of intimal hyperplasia. The efficacy of this surface-modified stent was assessed after implantation in rabbit iliac arteries for 8 weeks. Significant reduction in neointimal thickening and thereby in-stent restenosis with complete endothelial coverage was observed for the nanotextured stents, compared to BMSs, even without the use of any antiproliferative agents or polymers as in drug-eluting stents. Nanotexturing of stents did not induce any inflammatory response, akin to BMSs. This study thus indicates the effectiveness of a facile titania nanotopography on SS stents for coronary applications and the possibility of bringing this low-priced material back to clinics.

Biodegradable nanocomposite fibrous scaffold mediated local delivery of vancomycin for the treatment of MRSA infected experimental osteomyelitis.

There is an increased demand for an ideal biodegradable biomaterial that eradicates infection, while concurrently promoting tissue regeneration in osteomyelitic bone, which eliminates the need for revision surgery. In this study, our objective was to evaluate the efficacy of a nanocomposite fibrous scaffold (silica coated nanohydroxyapatite-gelatin reinforced with poly-l-lactic acid yarns) containing vancomycin for treating methicillin-resistant Staphylococcus aureus (MRSA) induced osteomyelitis in rat models. The antibiotic was either incorporated during scaffold synthesis (SE-V) or loaded directly after the development of the scaffold (SA-V) at 5 wt% and 15 wt%. There was a sustained release of vancomycin from both the groups of scaffolds for 30 days and the released drug demonstrated antibacterial activity against MRSA. Furthermore, implantation of the composite scaffold into osteomyelitic rat femur resulted in significant bacterial reduction, mainly with 15 wt% drug and its efficacy was comparable to that of commercial graft Stimulan. Both drug entrapped and absorbed composite scaffolds promoted bone regeneration in 3 months, with no distinguishable difference between them. However, Stimulan resorbed fast and there were bone voids at the defect site after 3 months. Hence, the nanocomposite fibrous scaffold containing vancomycin can be proposed as a bi-functional graft that can reduce bacterial infection, while subsequently engineer new bone in osteomyelitis.

Bioinspired nanocomposite fibrous scaffold mediated delivery of ONO-1301 and BMP2 enhance bone regeneration in critical sized defect.

Treatment aiming to enhance bone tissue regeneration can benefit from multiple growth factor or small molecule delivery. In the present study, the objective was to evaluate the feasibility of using nanocomposite fibrous scaffold to deliver prostacyclin I2 agonist ONO-1301 in combination with BMP2 for treating critical sized bone defect. For this, ONO-1301 at three different concentrations (1.67 µg, 5 µg, 15 µg) and a fixed dose of BMP2 (5 µg) was loaded on the scaffold via physical adsorption. The results showed fast release of ONO-1301 for two weeks, whereas BMP2 exhibited slow and sustained release for four weeks. The scaffold with dual factors promoted the migration and osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro when compared to the scaffold with BMP2 alone. It also augmented bone tissue regeneration in critical sized rat calvarial defect at 12 weeks; mainly with lower dose of ONO-1301. However, synergistic effect on osteogenic differentiation and bone regeneration were not obtained through the concurrent release of BMP-2 and ONO-1301.

ONO-1301 loaded nanocomposite scaffolds modulate cAMP mediated signaling and induce new bone formation in critical sized bone defect.

Recent studies on bone regeneration demonstrate the use of low cost and stable small molecules, which avoid the adverse effect and high cost of growth factors. Herein, we investigate the chemotactic, angiogenic and osteoinductive potential of a prostacyclin analogue, ONO-1301, when delivered through a biomimetic nanocomposite scaffold (nanohydroxyapatite-gelatin matrix reinforced with fibers) for bone tissue regeneration. The small molecule was loaded onto the scaffold in three different concentrations. There was burst release from all the groups of scaffolds within 24 h followed by a sustained release up to 14 days, but the concentration was dependent on loading percentage. ONO-1301 loaded scaffolds augmented the migration, proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs), but increasing the concentration beyond a certain dose did not show any effect. The osteoinduction was mediated through the prostaglandin I2 receptor and cyclic AMP (cAMP) signaling pathway. They also promoted new bone formation in large sized calvarial defects in rats compared to the scaffold alone, but did not show any impact on angiogenesis. Hence, this study suggests the chemotactic and osteoinductive capability of ONO-1301 for the repair and regeneration of critical sized bone defects.

Evaluation of osseointegration of staged or simultaneously placed dental implants with nanocomposite fibrous scaffolds in rabbit mandibular defect.

Implant-supported dental prosthesis in patients with edentulism or those with reconstructed bone have long survival rate, but the success depends largely on the quality and quantity of the available bone at the recipient site. The usage of autograft is the gold standard treatment for vertical bone augmentation, but it has many limitations. In this study, we have developed a nanocomposite fibrous scaffold [silica coated nanoHA-gelatin reinforced with electrospun poly(L-lactic acid) (PLLA) nanoyarns] and evaluated its efficacy to promote osseointegration in rabbit mandibular defect in comparison to the scaffold without fibers and commercial nanoHA-collagen graft. For this, critical sized bilateral defect (10 mm length, 3 mm depth and 3 mm width) was created in rabbit mandible and dental implantation was done in two manners. In strategy 1, Ti dental implant was placed along with the scaffold and in strategy 2, the scaffold was implanted for 3 months to facilitate new bone formation followed by Ti dental implantation. In strategy 2, the fibrous scaffold could promote new bone formation and osseointegration in rabbit mandibular defect when compared to the scaffolds without fibers and commercial graft, but strategy 1 was not successful. These findings demonstrated that nanocomposite fibrous scaffold is a promising biomaterial to promote new bone formation and osseointegration in mandibular defect.

Nanofibrous yarn reinforced HA-gelatin composite scaffolds promote bone formation in critical sized alveolar defects in rabbit model.

Alveolar ridge resorption and crestal bone loss necessitate the use of bone graft substitutes for dental rehabilitation. The aim of this study was to compare the bone regenerative property of nanofibre incorporated two composite matrices (nanofibrous sheet layered matrix (CS-S) and nanofibrous yarn reinforced matrix (CS-Y)) in critical sized mandibular defect in a rabbit model (under load bearing scenario). Histological evaluation revealed continuous bone formation in the defect implanted with fibre reinforced scaffolds than those without fibres as well as commercial nanoHA-collagen graft. Interestingly, the mineralisation and the mineral density were significantly higher with nanoyarn reinforced scaffolds. Moreover, the compressive strength of new bone formed from CS-Y scaffolds was almost similar to that of native rabbit mandible. It can be concluded that the mechanical strength provided by three-dimensionally reinforced nanoyarns in the matrix could promote bone formation in load bearing mandibular region, and these can be proposed as a scaffold of choice for alveolar bone augmentation and dental rehabilitation.

Dual release of growth factor from nanocomposite fibrous scaffold promotes vascularisation and bone regeneration in rat critical sized calvarial defect.

A promising strategy for augmenting bone formation involves the local delivery of multiple osteoinductive and vasculogenic growth factors. However, success depends on sustained growth factor release and its appropriate combination to induce stem cells and osteogenic cells at the bony site. Herein, we have developed a nanocomposite fibrous scaffold loaded with fibroblast growth factor 2 (FGF2), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) and its ability to promote vascularisation and bone regeneration in critical sized calvarial defect was compared to the scaffold with VEGF + BMP2 and FGF2 + BMP2. Simple loading of growth factors on the scaffold could provide a differential release pattern, both in vitro and in vivo (VEGF release for 1 week where as BMP2 and FGF2 release for 3 weeks). Among all the groups, dual growth factor loaded scaffold (VEGF + BMP2 & FGF2 + BMP2) enhanced vascularisation and new bone formation, but there was no difference between FGF2 and VEGF loaded scaffolds although its release pattern was different. FGF2 mainly promoted stem cell migration, whereas VEGF augmented new blood vessel formation at the defect site. This study suggests that biomimetic nanocomposite scaffold is a promising growth factor delivery vehicle to improve bone regeneration in critical sized bone defects. STATEMENT OF SIGNIFICANCE: Many studies have shown the effect of growth factors like VEGF-BMP2 or FGF2-BMP2 in enhancing bone formation in critical sized defects, but there are no reports that demonstrate the direct comparison of VEGF-BMP2 and FGF2-BMP2. In this study, we have developed a nanocomposite fibrous scaffold that could differentially release growth factors like VEGF, BMP2 and FGF2 (VEGF release for 1 week where as BMP2 and FGF2 release for 3 weeks), which in turn promoted neovascularisation and new bone formation in critical sized defects. There was no difference in vascularisation and bone formation induced by VEGF + BMP2 or FGF2 + BMP2. The growth factor was loaded in a simple manner, which would ensure ease of use for the end-user, especially for the surgeons treating a patient in an operating room.

BMP2 expressing genetically engineered mesenchymal stem cells on composite fibrous scaffolds for enhanced bone regeneration in segmental defects.

The treatment of critical sized bone defect remains a significant challenge in orthopedics. The objective of the study is to evaluate the effect of the combination of bone morphogenetic protein 2 (BMP2) expressing genetically engineered mesenchymal stem cells (MSCs) [MSCs engineered using a multimam vector, pAceMam1, an emerging gene delivery vector] and an osteoconductive scaffold [silica coated nanohydroxyapatite-gelatin reinforced with fibers] in enhancing bone regeneration in critical sized segmental defects. The scaffold with transfected MSCs showed significantly higher viability, proliferation and osteogenic differentiation in vitro. Further, this group augmented union and new bone formation in critical sized rat femoral segmental defect at 12 weeks when compared to control groups (scaffold with MSCs and scaffold alone). These data demonstrated that the MSCs engineered for transient expression of BMP2 can improve the repair of segmental defects, which paves an avenue for using pAceMam1 as a vector for bone tissue regeneration.

Poly(L-lactic acid) nanofibers containing Cissus quadrangularis induced osteogenic differentiation in vitro.

Cissus quadrangularis (CQ) is known as "bone setter" in Ayurvedic Medicine because of its ability to promote fracture healing. Polymers incorporated with CQ at lower concentration have shown to enhance osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. However, for the healing of clinically relevant critical sized bone defects, large amount of CQ would be required. Based on this perception, a herbal fibrous sheet containing high weight percentage of CQ [20,40 and 60wt/wt% in poly (L-lactic acid) (PLLA)] was fabricated through electrospinning. The solution concentration, flow rate, voltage and tip-target distance was optimized to obtain nanofibers. The hydrophobicity of PLLA fibers was reduced through CQ incorporation. There was considerable increase in the adhesion, proliferation and osteogenic differentiation of MSCs on herbal fibers than normal fibers, mainly on P-Q20 and P-CQ40. MSCs were differentiated into osteoblasts without providing any osteogenic supplements in the medium, indicating its osteoinductive capability. The herbal sheet also could promote mineralization when immersed in simulated body fluid for 14days. These studies specify that PLLA nanofibers loaded with 20 and 40wt% of CQ could serve as a potential candidate for bone tissue engineering applications.

Bioinspired Composite Matrix Containing Hydroxyapatite-Silica Core-Shell Nanorods for Bone Tissue Engineering.

Development of multifunctional bioinspired scaffolds that can stimulate vascularization and regeneration is necessary for the application in bone tissue engineering. Herein, we report a composite matrix containing hydroxyapatite (HA)-silica core-shell nanorods with good biocompatibility, osteogenic differentiation, vascularization, and bone regeneration potential. The biomaterial consists of a crystalline, rod-shaped nanoHA core with uniform amorphous silica sheath (Si-nHA) that retains the characteristic phases of the individual components, confirmed by high-resolution transmission electron microscopy, X-ray diffractometer, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The nanorods were blended with gelatinous matrix to develop as a porous, composite scaffold. The viability and functionality of osteogenically induced mesenchymal stem cells as well as endothelial cells have been significantly improved through the incorporation of Si-nHA within the matrix. Studies in the chicken chorioallantoic membrane and rat models demonstrated that the silica-containing scaffolds not only exhibit good biocompatibility, but also enhance vascularization in comparison to the matrix devoid of silica. Finally, when tested in a critical-sized femoral segmental defect in rats, the nanocomposite scaffolds enhanced new bone formation in par with the biomaterial degradation. In conclusion, the newly developed composite biomimetic scaffold may perform as a promising candidate for bone tissue engineering applications.

Antibacterial and cytocompatible nanotextured Ti surface incorporating silver via single step hydrothermal processing.

Nanosurface modification of Titanium (Ti) implants and prosthesis is proved to enhance osseointegration at the tissue-implant interface. However, many of these products lack adequate antibacterial capability, which leads to implant loosening. As a curative strategy, in this study, nanotextured Ti substrates embedded with silver nanoparticles were developed through a single step hydrothermal processing in an alkaline medium containing silver nitrate at different concentrations (15, 30 and 75µM). Scanning electron micrographs revealed a non-periodically oriented nanoleafy structure on Ti (TNL) decorated with Ag nanoparticles (nanoAg), which was verified by XPS, XRD and EDS analysis. This TNLAg substrate proved to be mechanically stable upon nanoindentation and nanoscratch tests. Silver ions at detectable levels were released for a period of ~28days only from substrates incorporating higher nanoAg content. The samples demonstrated antibacterial activity towards both Escherichia coli and Staphylococcus aureus, with a more favorable response to the former. Simultaneously, Ti substrates incorporating nanoAg at all concentrations supported the viability, proliferation and osteogenic differentiation of mesenchymal stem cells. Overall, nanoAg incorporation into surface modified Ti via a simple one-step thermochemical method is a favorable strategy for producing implants with dual characteristics of antibacterial activity and cell compatibility.

Stable Titania Nanostructures on Stainless Steel Coronary Stent Surface for Enhanced Corrosion Resistance and Endothelialization.

Stainless steel (SS) coronary stents continue to present risk of in-stent restenosis that impact its long term safety and efficacy. The present work focuses on developing a drug-free and polymer-less surface on coronary stents by utilizing a titania (TiO2 ) nanotexturing approach through hydrothermal processing, that will offer improved stent performance in vivo. Mechanically stable and durable nanotextured coatings are obtained on SS stents that also offer good corrosion resistance. In vitro vascular cell (endothelial and smooth muscle cells) studies on surface modified SS show preferential rapid endothelialization with enhanced nitric oxide production and reduce smooth muscle cell proliferation, in comparison to unmodified SS. In vivo evaluation of the nanotextured stents after subcutaneous implantation in rabbits show reduced irritability and minimal localized inflammatory response. These beneficial effects suggest that the stable, easily scalable titania nanosurface modification strategy on coronary stent surfaces can be a much cheaper alternative to drug eluting stents in addressing in-stent restenosis.

Electrospun Yarn Reinforced NanoHA Composite Matrix as a Potential Bone Substitute for Enhanced Regeneration of Segmental Defects.

Nanohydroxyapatite (nanoHA) is a well-established synthetic bone substitute with excellent osteoconduction and osteointegration. However, brittleness coupled with slow degradation curtails its load-bearing and bone regeneration potential, respectively. To address these limitations, nanoHA composite matrix reinforced with electrospun fibrous yarns was fabricated and tested in vitro and in vivo. Different weight percentages (5, 10, 15 wt%) and varying lengths (short and continuous) of poly(l-lactic acid) yarns were randomly dispersed in a gelatinous matrix containing nanoHA. This significantly improved the compressive strength as well as work of fracture, especially for continuous yarns at high weight percentages (10 and 15 wt%). Incorporation of yarns did not adversely affect the pore size (50-350 µm) or porosity of the scaffolds as well as the in vitro cellular response. Finally, when tested in a critical-sized femoral segmental defect in rat, the nanocomposite scaffolds induced osteoblast cell infiltration at 2 months that subsequently underwent increased mature lamellar bone formation at 4 months, in both the mid and peripheral defect regions. Histomorphometric analysis demonstrated that new bone formation and biomaterial degradation were significantly enhanced in the composite scaffold when compared to commercially available HA. Overall, the composite matrix reinforced with electrospun yarns proved to be a potential bone substitute having an appropriate balance between mechanical strength, porosity, biodegradation, and bone regeneration ability.

Biomimetic composite scaffolds containing bioceramics and collagen/gelatin for bone tissue engineering - A mini review.

Bone is a natural composite material consisting of an organic phase (collagen) and a mineral phase (calcium phosphate, especially hydroxyapatite). The strength of bone is attributed to the apatite, while the collagen fibrils are responsible for the toughness and visco-elasticity. The challenge in bone tissue engineering is to develop such biomimetic composite scaffolds, having a balance between biological and biomechanical properties. This review summarizes the current state of the field by outlining composite scaffolds made of gelatin/collagen in combination with bioactive ceramics for bone tissue engineering application.

Evaluation of osteoinductive and endothelial differentiation potential of Platelet-Rich Plasma incorporated Gelatin-Nanohydroxyapatite Fibrous Matrix.

In this study, platelet-rich plasma (PRP) was incorporated into gelatin-nanohydroxyapatite fibrous scaffold in two forms (PRP gel as coating on the scaffold [PCSC] and PRP powder within the scaffold [PCSL] and investigated for (a) growth factor release; (b) stability of scaffold at different temperature; (c) stability of scaffold before and after ETO sterilization; and (d) osteogenic and endothelial differentiation potential using mesenchymal stem cells (MSCs). PCSC demonstrated a high and burst growth factor release initially followed by a gradual reduction in its concentration, while PCSL showed a steady state release pattern for 30 days. The stability of growth factors released from PCSL was not altered either through ETO sterilization or through its storage at different temperature. PRP-loaded scaffolds induced the differentiation of MSCs into osteogenic and endothelial lineage without providing any induction factors in the cell culture medium and the differentiation rate was significantly higher when compared to the scaffolds devoid of PRP. PCSC performed better than PCSL. In general, PRP in combination with composite fibrous scaffold could be a promising candidate for bone tissue engineering applications.

Composite hydrogel of chitosan-poly(hydroxybutyrate-co-valerate) with chondroitin sulfate nanoparticles for nucleus pulposus tissue engineering.

Intervertebral disc degeneration, occurring mainly in nucleus pulposus (NP), is a leading cause of low back pain. In seeking to mitigate this condition, investigators in the field of NP tissue engineering have increasingly studied the use of hydrogels. However, these hydrogels should possess appropriate mechanical strength and swelling pressure, and concurrently support the proliferation of chondrocyte-like cells. The objective of this study was to develop and validate a composite hydrogel for NP tissue engineering, made of chitosan-poly(hydroxybutyrate-co-valerate) (CP) with chondroitin sulfate (CS) nanoparticles, without using a cross linker. The water uptake ability, as well as the viscoelastic properties of this composite hydrogel, was similar to native tissue, as reflected in the complex shear modulus and stress relaxation values. The hydrogel could withstand varying stress corresponding to daily activities like lying down (0.01 MPa), sitting (0.5 MPa) and standing (1.0 MPa) under dynamic conditions. The hydrogels were stable in PBS for 2 weeks and its stiffness, elastic and viscous modulus did not alter significantly during this period. Both CP and CP-CS hydrogels could assist the viability and adhesion of adipose derived rat mesenchymal stem cells (ADMSCs). The viability and chondrogenic differentiation of MSCs was significantly enhanced in presence of CS nanoparticles. Thus, CS nanoparticles-incorporated chitosan-PHBV hydrogels offer great potential for NP tissue engineering.