A Biomimetic Fibrous Composite Scaffold with Nanotopography-Regulated Mineralization for Bone Defect Repair.

The effective regeneration of large bone defects via bone tissue engineering is challenging due to the difficulty in creating an osteogenic microenvironment. Inspired by the fibrillar architecture of the natural extracellular matrix, we developed a nanoscale bioengineering strategy to produce bone fibril-like composite scaffolds with enhanced osteogenic capability. To activate the surface for biofunctionalization, self-adaptive ridge-like nanolamellae were constructed on poly(ε-caprolactone) (PCL) electrospinning scaffolds via surface-directed epitaxial crystallization. This unique nanotopography with a markedly increased specific surface area offered abundant nucleation sites for Ca2+ recruitment, leading to a 5-fold greater deposition weight of hydroxyapatite than that of the pristine PCL scaffold under stimulated physiological conditions. Bone marrow mesenchymal stem cells (BMSCs) cultured on bone fibril-like scaffolds exhibited enhanced adhesion, proliferation, and osteogenic differentiation in vitro. In a rat calvarial defect model, the bone fibril-like scaffold significantly accelerated bone regeneration, as evidenced by micro-CT, histological histological and immunofluorescence staining. This work provides the way for recapitulating the osteogenic microenvironment in tissue-engineered scaffolds for bone repair.

Biomimetic Mineralized 3D-Printed Polycaprolactone Scaffold Induced by Self-Adaptive Nanotopology to Accelerate Bone Regeneration.

Three-dimensional (3D)-printed biodegradable polymer scaffolds are at the forefront of personalized constructs for bone tissue engineering. However, it remains challenging to create a biological microenvironment for bone growth. Herein, we developed a novel yet feasible approach to facilitate biomimetic mineralization via self-adaptive nanotopography, which overcomes difficulties in the surface biofunctionalization of 3D-printed polycaprolactone (PCL) scaffolds. The building blocks of self-adaptive nanotopography were PCL lamellae that formed on the 3D-printed PCL scaffold via surface-directed epitaxial crystallization and acted as a linker to nucleate and generate hydroxyapatite crystals. Accordingly, a uniform and robust mineralized layer was immobilized throughout the scaffolds, which strongly bound to the strands and had no effect on the mechanical properties of the scaffolds. In vitro cell culture experiments revealed that the resulting scaffold was biocompatible and enhanced the proliferation and osteogenic differentiation of mouse embryolous osteoblast cells. Furthermore, we demonstrated that the resulting scaffold showed a strong capability to accelerate in vivo bone regeneration using a rabbit bone defect model. This study provides valuable opportunities to enhance the application of 3D-printed scaffolds in bone repair, paving the way for translation to other orthopedic implants.

Antibacterial, Fatigue-Resistant, and Self-Healing Dressing from Natural-Based Composite Hydrogels for Infected Wound Healing.

The treatment of infected wounds faces substantial challenges due to the high incidence and serious infection-related complications. Natural-based hydrogel dressings with favorable antibacterial properties and strong applicability are urgently needed. Herein, we developed a composite hydrogel by constructing multiple networks and loading ciprofloxacin for infected wound healing. The hydrogel was synthesized via a Schiff base reaction between carboxymethyl chitosan and oxidized sodium alginate, followed by the polymerization of the acrylamide monomer. The resultant hydrogel dressing possessed a good self-healing ability, considerable compression strength, and reliable compression fatigue resistance. In vitro assessment showed that the composite hydrogel effectively eliminated bacteria and exhibited an excellent biocompatibility. In a model of Staphylococcus aureus-infected full-thickness wounds, wound healing was significantly accelerated without scars through the composite hydrogel by reducing wound inflammation. Overall, this study opens up a new way for developing multifunctional hydrogel wound dressings to treat wound infections.

Hierarchically Biomimetic Scaffolds with Anisotropic Micropores and Nanotopological Patterns to Promote Bone Regeneration via Geometric Modulation.

Structural engineering is an appealing means to modulate osteogenesis without the intervention of exogenous cells or therapeutic agents. In this work, a novel 3D scaffold with anisotropic micropores and nanotopographical patterns is developed. Scaffolds with oriented pores are fabricated via the selective extraction of water-soluble polyethylene oxide from its poly(ε-caprolactone) co-continuous mixture and uniaxial stretching. The plate apatite-like lamellae are subsequently hatched on the pore walls through surface-induced epitaxial crystallization. Such a unique geometric architecture yields a synergistic effect on the osteogenic capability. The prepared scaffold leads to a 19.2% and 128.0% increase in the alkaline phosphatase activity of rat bone mesenchymal stem cells compared to that of the scaffolds with only oriented pores and only nanotopographical patterns, respectively. It also induces the greatest upregulation of osteogenic-related gene expression in vitro. The cranial defect repair results demonstrate that the prepared scaffold effectively promotes new bone regeneration, as indicated by a 350% increase in collagen I expression in vivo compared to the isotropic porous scaffold without surface nanotopology after implantation for 14 weeks. Overall, this work provides geometric motifs for the transduction of biophysical cues in 3D porous scaffolds, which is a promising option for tissue engineering applications.

ECM-inspired calcium/zinc laden cellulose scaffold for enhanced bone regeneration.

Cellulose-based polymer scaffolds are highly diverse for designing and fabricating artificial bone substitutes. However, realizing the multi-biological functions of cellulose-based scaffolds has long been challenging. In this work, inspired by the structure and function of the extracellular matrix (ECM) of bone, we developed a novel yet feasible strategy to prepare ECM-like scaffolds with hybrid calcium/zinc mineralization. The 3D porous structure was formed via selective oxidation and freeze drying of bacterial cellulose. Following the principle of electrostatic interaction, calcium/zinc hybrid hydroxyapatite nucleated, crystallized, and precipitated on the 3D scaffold in simulated physiological conditions, which was well confirmed by morphology and composition analysis. Compared with alternative scaffold cohorts, this hybrid ion-loaded cellulose scaffold exhibited a pronounced elevation in alkaline phosphatase (ALP) activity, osteogenic gene expression, and cranial defect regeneration. Notably, the hybrid ion-loaded cellulose scaffold effectively fostered an M2 macrophage milieu and had a strong immune effect in vivo. In summary, this study developed a hybrid multifunctional cellulose-based scaffold that appropriately simulates the ECM to regulate immunomodulatory and osteogenic differentiation, setting a measure for artificial bone substitutes.

Periodic Lamellae-Based Nanofibers for Precise Immunomodulation to Treat Inflammatory Bone Loss in Periodontitis.

Periodontitis is a common oral disease accompanied by inflammatory bone loss. The pathological characteristics of periodontitis usually accompany an imbalance in the periodontal immune microenvironment, leading to difficulty in bone regeneration. Therefore, effective treatment strategies are needed to modulate the immune environment in order to treat periodontitis. Here, highly-oriented periodic lamellae poly(ε-caprolactone) electrospun nanofibers (PLN) are developed by surface-directed epitaxial crystallization. The in vitro result shows that the PLN can precisely modulate macrophage polarization toward the M2 phenotype. Macrophages polarized by PLN significantly enhance the migration and osteogenic differentiation of Bone marrow stromal cells, Scanning electron microscopy. Notably, results suggest that the topographical cues presented by PLN can modulate macrophage polarization by activating YAP, which reciprocally inhibits the NF-κB signaling pathway. The in vivo results indicate that PLN can inhibit inflammatory bone loss and facilitate bone regeneration in periodontitis. The authors' findings suggest that topographical nanofibers with periodic lamellae is a promising strategy for modulating immune environment to treat inflammatory bone loss in periodontitis.

Nano-Topographically Guided, Biomineralized, 3D-Printed Polycaprolactone Scaffolds with Urine-Derived Stem Cells for Promoting Bone Regeneration.

Currently, biomineralization is widely used as a surface modification approach to obtain ideal material surfaces with complex hierarchical nanostructures, morphologies, unique biological functions, and categorized organizations. The fabrication of biomineralized coating for the surfaces of scaffolds, especially synthetic polymer scaffolds, can alter surface characteristics, provide a favorable microenvironment, release various bioactive substances, regulate the cellular behaviors of osteoblasts, and promote bone regeneration after implantation. However, the biomineralized coating fabricated by immersion in a simulated body fluid has the disadvantages of non-uniformity, instability, and limited capacity to act as an effective reservoir of bioactive ions for bone regeneration. In this study, in order to promote the osteoinductivity of 3D-printed PCL scaffolds, we optimized the surface biomineralization procedure by nano-topographical guidance. Compared with biomineralized coating constructed by the conventional method, the nano-topographically guided biomineralized coating possessed more mineral substances and firmly existed on the surface of scaffolds. Additionally, nano-topographically guided biomineralized coating possessed better protein adsorption and ion release capacities. To this end, the present work also demonstrated that nano-topographically guided biomineralized coating on the surface of 3D-printed PCL scaffolds can regulate the cellular behaviors of USCs, guide the osteogenic differentiation of USCs, and provide a biomimetic microenvironment for bone regeneration.

[Preparation and Performance Evaluation of Polyacrylamide Hydrogel Coating on the Surface of Silicone Rubber Nasogastric Tube].

Objective: To prepare the hydrogel coating on the surfaces of nasogastric tubes and to evaluate its effect on the insertion of nasogastric tubes in a rabbit model. Methods: The polyacrylamide (PAAm) hydrogel coating was prepared by UV-induced free radical polymerization. The morphology of the PAAm coating and its interfacial bonding with the silicone rubber substrates of nasogastric tubes were observed with scanning electron microscope. The composition of the coating was analyzed by Fourier transform infrared (FTIR) spectrometer and X-ray photoelectron spectrometer (XPS). The water absorption power and stability of the coating were measured by the weighing method. Water contact angle meter was used to measure the wettability of the coating and tribometer was used to determine the friction coefficient of the silicone rubber substrates before and after the modification. The cytotoxicity of the coating on L929 murine fibroblast cell line was explored with CCK-8 assay after 24-h coculturing of the L929 cell line with silicone rubber substrates before and after modification. An animal model of nasogastric tube insertion in New Zealand rabbits was used to evaluate the effect of the lubrication coating by assessing the insertion time and nasal damage. Results: In this study, PAAm hydrogel coating was prepared and constructed on the surface of silicone rubber nasogastric tubes. The coating, with a three-dimensional network structure, showed strong interfacial bonding with silicone rubber substrates. The appearance of amino and carbonyl groups indicated that the PAAm hydrogel coating was grafted on the surfaces of nasogastric tubes. Before the modification, the silicone rubber substrate essentially did not absorb much water, whereas, after the modification, the silicone rubber substrate showed significant improvement of as much as 2.9% in water absorption. After sonication for 90 min, the weight loss rate was only 0.15%. Compared with pristine nasogastric tubes, the water contact angle of the modified nasogastric tubes was reduced from 111.9°±2.2° to 58.9°±1.5° ( t=22.59, P<0.05). In addition, the friction coefficient of silicone rubber nasogastric tubes decreased by 69.3% from 0.378±0.05 to 0.116±0.004 ( t=42.80, P<0.05) after modification. Moreover, there was no significant difference in the cytocompatibility between L929 cells cocultured with pristine nasogastric tube and those cocultured with modified nasogastric tube. The animal experiment of nasogastric tube insertion showed that the insertion time of the modified nasogastric tubes was reduced from (41.6±7.8) s to (12.4±2.9) s ( t=8.509, P<0.05). Laryngoscopy revealed that the PAAm hydrogel coating significantly reduced the mucosal damage caused by the insertion of nasogastric tubes. Conclusion: In this study, PAAm hydrogel coating with strong interfacial bonding was prepared on the surface of silicone rubber nasogastric tubes. The coating has excellent hydrophilic lubrication property and cytocompatibility, effectively shortens the insertion time, and reduces the damage caused by nasogastric tube insertion.

Scalable Fabrication of Polymeric Composite Microspheres to Inhibit Oral Pathogens and Promote Osteogenic Differentiation of Periodontal Membrane Stem Cells.

Periodontitis is a worldwide bacterial infectious disease, resulting in the resorption of tooth-supporting structures. Biodegradable polymeric microspheres are emerging as an appealing local therapy candidate for periodontal defect regeneration but suffer from tedious procedures and low yields. Herein, we developed a facile yet scalable approach to prepare polylactide composite microspheres with outstanding drug-loading capability. It was realized by blending equimolar polylactide enantiomers at the temperature between the melting point of homocrystallites and stereocomplex (sc) crystallites, enabling the precipitation of sc crystallites in the form of microspheres. Meanwhile, epigallocatechin gallate (EGCG) and nano-hydroxyapatite were encapsulated in the microspheres in the designated amount. Such an assembly allowed the fast and sustained release of EGCG and Ca2+ ions. The resultant hybrid composite microspheres not only exhibited strong antimicrobial activity against typical oral pathogens (Porphyromonas gingivalis and Enterococcus faecalis), but also directly promoted osteogenic differentiation of periodontal ligament stem cells with good cytocompatibility. These dual-functional composite microspheres offer a desired drug delivery platform to address the practical needs for periodontitis treatment.

Tetrahedral Framework Nucleic Acids Promote Senile Osteoporotic Fracture Repair by Enhancing Osteogenesis and Angiogenesis of Callus.

Senile osteoporotic fracture has aroused increasing attention due to high morbidity and mortality. However, to date, there is no effective therapeutic approach available. Senile osteoporosis is characterized by impaired osteogenesis and angiogenesis, osteoporotic fracture repair could also be promoted by enhancing osteogenesis and angiogenesis. Tetrahedral framework nucleic acids (tFNAs) are a multifunctional nanomaterial that have recently been extensively used in biomedical fields, which could enhance osteogenesis and angiogenesis in vitro. Therefore, we applied tFNAs to intact and femoral fractural senile osteoporotic mice, respectively, to evaluate the effects of tFNAs on senile osteoporosis and osteoporotic fracture repair regarding the osteogenesis and angiogenesis of the callus at the early healing stages and to initially explore the potential mechanism. The outcomes showed that tFNAs had no significant effects on the osteogenesis and angiogenesis of the femur and mandible in intact senile osteoporotic mice within 3 weeks after tFNA treatment, while tFNAs could promote osteogenesis and angiogenesis of callus in osteoporotic fracture repair, which may be regulated by a FoxO1-related SIRT1 pathway. In conclusion, tFNAs could promote senile osteoporotic fracture repair by enhancing osteogenesis and angiogenesis, offering a new strategy for the treatment of senile osteoporotic fracture.

Adiponectin overexpression promotes fracture healing through regulating the osteogenesis and adipogenesis balance in osteoporotic mice.

INTRODUCTION: Osteoporosis invariably manifests as loss of bone, which is replaced by adipose tissue; this can easily lead to fractures, accompanied by delayed and poor healing. Adiponectin (APN) balances osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs). Therefore, this study explored whether adiponectin promotes bone fracture healing by regulating the balance between osteogenesis and adipogenesis. MATERIALS AND METHODS: We used adenovirus overexpression vectors carrying APN (Ad-APN-GFP) to treat ovariectomized (OVX) mouse BMSCs and osteoporotic bone fractures to investigate the role of APN in bone microenvironment metabolism in osteoporotic fractures. We subsequently established an OVX mice and bone fracture model using Ad-APN-GFP treatment to investigate whether APN could promote bone fracture healing in osteoporotic mice. RESULTS: The experimental results showed that APN is a critical molecule in diverse differentiation directions in OVX mouse BMSCs, with pro-osteogenesis and anti-adipogenesis properties. Importantly, our study revealed that Ad-APN-GFP treatment facilitates bone generation and healing around the osteoporotic fracture ends. Moreover, we identified that Sirt1 and Wnt signaling were closely related to the pro-osteogenesis and anti-adipogenesis commitment of APN in OVX mouse BMSCs and femoral tissues. CONCLUSION: We demonstrated that APN overexpression facilitates bone fracture healing in osteoporosis. Furthermore, APN overexpression promoted bone formation in OVX mouse BMSCs and bone fracture ends by regulating the balance between osteogenesis and adipogenesis both in vitro and in vivo.

Improved oxidation stability and crosslink density of chemically crosslinked ultrahigh molecular weight polyethylene using the antioxidant synergy for artificial joints.

Vitamin E (VE) is currently an approved antioxidant to improve the oxidation stability of highly crosslinked ultrahigh molecular weight polyethylene (UHMWPE) insert used commercially in total joint arthroplasty. However, the decrease in crosslink density caused by VE reduces wear resistance of UHMWPE, showing an uncoordinated challenge. In this work, we hypothesized that D-sorbitol (DS) as a secondary antioxidant can improve the antioxidant efficacy of VE on chemically crosslinked UHMWPE. The combined effect of VE and DS on oxidation stability of UHMWPE was investigated at a set of controlled hybrid antioxidant content. The hybrid antioxidant strategy showed significantly synergistic enhancement on the oxidation stability of chemically crosslinked UHMWPE compared with the single VE strategy. More strikingly, the crosslink density of the blends with hybrid antioxidants stayed at a high level since DS is not sensitive to crosslinking. The relationships between oxidation stability, mechanical properties, crosslink density, and crystallinity were investigated, by which the clinically relevant overall performance of UHMWPE was optimized. This work provides a leading-edge design mean for the development of joint bearings.

Polycaprolactone Electrospun Nanofiber Membrane with Sustained Chlorohexidine Release Capability against Oral Pathogens.

Multiple-pathogen periodontal disease necessitates a local release and concentration of antibacterial medication to control inflammation in a particular location of the mouth cavity. Therefore, it is necessary to effectively load and deliver medicine/antibiotics to treat numerous complex bacterial infections. This study developed chlorhexidine (CHX)/polycaprolactone (PCL) nanofiber membranes with controlled release properties as periodontal dressings to prevent or treat oral disorders. Electrostatic spinning was adopted to endow the nanofiber membranes with a high porosity, hydrophilicity, and CHX loading capability. The release of CHX occurred in a concentration-dependent manner. The CHX/PCL nanofiber membranes exhibited good biocompatibility with human periodontal ligament stem cells, with cell viability over 85% in each group via CCK-8 assay and LIVE/DEAD staining; moreover, the good attachment of the membrane was illustrated by scanning electron microscopy imaging. Through the agar diffusion assay, the nanofiber membranes with only 0.075 wt% CHX exhibited high antibacterial activity against three typical oral infection-causing bacteria: Porphyromonas gingivalis, Enterococcus faecalis, and Prevotella intermedia. The results indicated that the CHX/PCL nanofiber holds great potential as a periodontal dressing for the prevention and treatment periodontal disorders associated with bacteria.

Coaxial TP/APR electrospun nanofibers for programmed controlling inflammation and promoting bone regeneration in periodontitis-related alveolar bone defect models.

Periodontitis is a pathological dental condition that damages the periodontal tissue and leads to tooth loss. Bone regeneration in periodontitis-related alveolar bone defects remains a challenge for periodontists and tissue engineers because of the complex periodontal microenvironment. The inflammatory microenvironment is associated with poor osteogenesis; therefore, the reduction of inflammation is essential for bone regeneration in periodontitis-related alveolar bone defects. Here, we developed a programmed core-shell nanofibers that allows the sequential and controlled release of tea polyphenols (TP) and AdipoRon (APR) to control inflammation and promote bone regeneration to repair periodontitis-related alveolar bone defects. Core-shell nanofibers with a sequentially controlled release function were synthesized using electrospinning. We investigated the therapeutic effects of the nanofibers in vitro and in a mouse periodontitis model. The results of the release profiles demonstrated that TP was released rapidly in the early stages and APR was continuously released thereafter. In vitro experiments showed that the programmed core-shell nanofibers reduced the levels of proinflammatory cytokines and increased osteogenic differentiation in an inflammatory microenvironment. In vivo experiments, the programmed core-shell nanofibers ameliorated periodontal tissue inflammation and improved alveolar bone regeneration. Our results indicated that the programmed core-shell nanofibers with a sequential-release function provides an ideal strategy for repairing periodontitis-related alveolar bone defects, and its application in the treatment of diseases with spatiotemporal specificity is promising.

Nanotopographical 3D-Printed Poly(ε-caprolactone) Scaffolds Enhance Proliferation and Osteogenic Differentiation of Urine-Derived Stem Cells for Bone Regeneration.

3D-printing technology can be used to construct personalized bone substitutes with customized shapes, but it cannot regulate the topological morphology of the scaffold surface, which plays a vital role in regulating the biological behaviors of stem cells. In addition, stem cells are able to sense the topographical and mechanical cues of surface of scaffolds by mechanosensing and mechanotransduction. In our study, we fabricated a 3D-printed poly(ε-caprolactone) (PCL) scaffold with a nanotopographical surface and loaded it with urine-derived stem cells (USCs) for application of bone regeneration. The topological 3D-printed PCL scaffolds (TPS) fabricated by surface epiphytic crystallization, possessed uniformly patterned nanoridges, of which the element composition and functional groups of nanoridges were the same as PCL. Compared with bare 3D-printed PCL scaffolds (BPS), TPS have a higher ability for protein adsorption and mineralization in vitro. The proliferation, cell length, and osteogenic gene expression of USCs on the surface of TPS were significantly higher than that of BPS. In addition, the TPS loaded with USCs exhibited a good ability for bone regeneration in cranial bone defects. Our study demonstrated that nanotopographical 3D-printed scaffolds loaded with USCs are a safe and effective therapeutic strategy for bone regeneration.

Mucosa-Like Conformal Hydrogel Coating for Aqueous Lubrication.

Mucosa is a protective and lubricating barrier in biological tissue, which has a great clinical inspiration because of its slippery, soft, and hydrophilic surface. However, mimicking mucosal traits on complex surface remains an enormous challenge. Herein, a novel approach to create mucosa-like conformal hydrogel coating is developed. A thin conformal hydrogel layer mimicking the epithelial layer is obtained by first absorbing micelles, followed by forming covalent interlinks with the polymer substrate via interface-initiated hydrogel polymerization. The resulting coating exhibits uniform thickness (≈15 µm), mucosa-matched compliance (Young's modulus = 1.1 ± 0.1 kPa) and lubrication (coefficients of friction = 0.018 ± 0.003), robust interfacial bonding against peeling (peeling strength = 1218.0 ± 187.9 J m-2 ), as well as high water absorption capacity. It effectively resists adhesion of proteins and bacteria without compromising biocompatibility. As demonstrated by an in vivo cynomolgus monkey model and clinical trial, applications of the mucosa-like conformal hydrogel coating on the endotracheal tube significantly reduce intubation-related complications, such as invasive stimuli, mucosal lesions, laryngeal edema, inflammation, and postoperative pain. This work offers a promising prototype for surface decoration of biomedical devices and holds great prospects for clinical translation to enable interventional operations with minimally invasive impacts.

Topographic Cues Guiding Cell Polarization via Distinct Cellular Mechanosensing Pathways.

Cell polarization exists in a variety of tissues to regulate cell behaviors and functions. Space constraint (spatially limiting cell extension) and adhesion induction (guiding adhesome growth) are two main ways to induce cell polarization according to the microenvironment topographies. However, the mechanism of cell polarization induced by these two ways and the downstream effects on cell functions are yet to be understood. Here, space constraint and adhesion induction guiding cell polarization are achieved by substrate groove arrays in micro and nano size, respectively. Although the morphology of polarized cells is similar on both structures, the signaling pathways to induce the cell polarization and the downstream functions are distinctly different. The adhesion induction (nano-groove) leads to the formation of focal adhesions and activates the RhoA/ROCK pathway to enhance the myosin-based intracellular force, while the space constraint (micro-groove) only activates the formation of pseudopodia. The enhanced intracellular force caused by adhesion induction inhibits the chromatin condensation, which promotes the osteogenic differentiation of stem cells. This study presents an overview of cell polarization and mechanosensing at biointerface to aid in the design of novel biomaterials.

Programmed core-shell electrospun nanofibers to sequentially regulate osteogenesis-osteoclastogenesis balance for promoting immediate implant osseointegration.

The biology of immediate post-extraction implant osseointegration is mediated by a coordinated cascade of osteoblast-osteoclast interactions. The aim of this study was to develop a dual-delivery system that allowed sequential release of substance P (SP) to promote bone regeneration and alendronate (ALN) to reduce bone resorption, which will improve the implant osseointegration. We used coaxial electrospinning to fabricate the core-shell poly lactic-co-glycolic acid (PLGA)/gelatin nanofibers, which consists of SP in the shell and ALN in the core. This programmed delivery system was shown to release SP and ALN sequentially to match the spatio-temporal specificity of bone healing. The migration assay demonstrated that the SP-ALN dual-delivery system increased bone marrow mesenchymal stem cells (BMSCs) transmigration. Besides, the expression of osteogenic/osteoclastic markers, Alizarin Red staining, tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and bone resorption experiment showed that the dual-delivery system can render a microenvironment favorable for osteogenic differentiation and adverse to osteoclastogenesis. Using a rat immediate implant model, we validated the promoted osteogenic property and osseointegration around the implants of SP-ALN dual-delivery system by micro-computed tomography (micro-CT) and histological analysis. These findings suggest that the dual-delivery system with time-controlled release of SP and ALN by core-shell nanofibers provides a promising strategy to facilitate immediate implant osseointegration through favorable osteogenesis. STATEMENT OF SIGNIFICANCE: Immediate implant placement is potentially challenged by the difficulties in achieving primary implant stability and early osteogenesis. Initial period of osteointegration is regulated by osteoblastic/osteoclastic cells resulting in a coordinated healing process. To have an efficient bone regeneration, the coaxial electrospinning was used to fabricate a programmed dual-delivery system. The SP released rapidly and favored for BMSCs migration and osteogenic differentiation, while the sustained release of ALN can reduce the bone resorption. The rat immediate implant model indicated that the SP-ALN dual-delivery system could present the promoted peri­implant osteogenic property and osseointegration through modulating the osteogenesis-osteoclastogenesis balance. This work highlights the sequential dual delivery of SP and ALN has a promising potential of achieving enhanced osseointegration for immediate implant placement.

Surface Epitaxial Nano-Topography Facilitates Biomineralization to Promote Osteogenic Differentiation and Osteogenesis.

Biomimetic modification of hydroxyapatite on a polymer surface is a potent strategy for activating biological functions in bone tissue engineering applications. However, the polymer surface is bioinert, and it is difficult to introduce a uniform calcium phosphate (CaP) layer. To overcome this limitation, we constructed a specific nano-topographical structure onto a poly(ε-caprolactone) substrate via surface-directed epitaxial crystallization. Formation of the CaP layer on the nano-topological surface was enhanced by 2.34-fold compared to that on a smooth surface. This effect was attributed to the abundant crystallization sites for CaP deposition because of the increased surface area and roughness. Bone marrow mesenchymal stromal cells (BMSCs) were used to examine the biological effect of biomineralized surfaces. We clearly demonstrated that BMSCs responded to surface biomineralization. Osteogenic differentiation and proliferation of BMSCs were significantly promoted on the biomineralized nano-topological surface. The expression of alkaline phosphatase and osteogenic-related genes as well as extracellular matrix mineralization was significantly enhanced. The proposed strategy shows potential for designing bone repair scaffolds.

Synergy between vitamin E and D-sorbitol in enhancing oxidation stability of highly crosslinked ultrahigh molecular weight polyethylene.

Oxidative stability of radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) artificial joints is significantly improved by vitamin E (VE), but there is a dilemma that VE hinders crosslinking and thus jeopardizes the wear of UHMWPE. In this effort, we proposed an efficient strategy to stabilize UHMWPE under limited antioxidant contents, where VE and D-sorbitol (DS) were used as the primary antioxidant and the secondary antioxidant respectively. For non-irradiated blends with fixed antioxidant contents, oxidative stability accessed by oxidation induction time (OIT) of VE/DS/UHMWPE blends was superior to that of VE/UHMWPE blends, while DS/UHMWPE blends showed no increase in OIT. The cooperation between DS and VE exhibited a synergistic effect on enhancing the oxidative stability of UHMWPE. Interestingly, the irradiated VE/DS/UHMWPE blends showed comparable OIT but a significantly higher crosslink density than the irradiated VE/UHMWPE blends. The crystallinity, melting point, and in vitro biocompatibility of the blends were not affected by VE and DS. The quantitative relationships of mechanical properties, oxidation stability, crystallinity and crosslink density were established to unveil the correlation of these key factors. The overall properties of VE/UHMWPE and VE/DS/UHMWPE blends were compared to elucidate the superiority of the antioxidant compounding strategy. These findings provide a paradigm to break the trade-off between oxidative stability, crosslink density and mechanical properties, which is constructive to develop UHMWPE bearings with upgraded performance for total joint replacements. STATEMENT OF SIGNIFICANCE: VE-stabilized UHMWPE is the most commonly used material in total joint replacements at present. However, oxidation and wear resistance of VE/UHMWPE implants cannot be unified since VE reduces the efficiency of radiation crosslinking. It limits the use of VE. Herein, we proposed a compounding stabilization by the synergy between VE and DS. The antioxidation capability of VE was revived by DS, thus enhancing the oxidation stability of unirradiated UHMWPE. The irradiated VE/DS/UHMWPE exhibited similar oxidation stability but higher crosslink density than irradiated VE/UHMWPE, which is beneficial to combat wear of UHMWPE and to inhibit the occurrence of osteolysis. This synergistic antioxidation strategy endows the UHMWPE joint material with good overall performance, which is of clinical significance.