The complex interaction between extracellular matrix and cells makes the design of materials for dental regeneration challenging. Chemical composition is an important characteristic of biomaterial surfaces, which plays an essential role in modulating the adhesion and function of cells. The effect of different chemical groups on directing the fate of human dental pulp stem cells (hDPSCs) was thus explored in our study. A range of self-assembled monolayers (SAMs) with amino (−NH2), hydroxyl (−OH), carboxyl (−COOH), and methyl (−CH3) modifications were prepared. Proliferation, morphology, adhesion, and differentiation of hDPSCs were then analyzed to demonstrate the effects of surface chemical groups. The results showed that hDPSCs attached to the −NH2 surface displayed a highly branched osteocyte-like morphology with improved cell adhesion and proliferation abilities. Moreover, hDPSCs cultured on the −NH2 surface also tended to obtain an increased osteo/odontogenesis differentiation potential. However, the hDPSCs on the −COOH, −OH, and −CH3 surfaces preferred to maintain the mesenchymal stem cell-like phenotype. In summary, this study indicated the influence of chemical groups on hDPSCs in vitro and demonstrated that −NH2 might be a promising surface modification strategy to achieve improved biocompatibility, osteoconductivity/osteoinductivity, and osseointegration of dental implants, potentially facilitating dental tissue regeneration.Keywords: adhesion; cell fate; dental pulp stem cells; self-assembled monolayer; surface chemistry;

Implant-associated infections in orthopaedic surgeries are very critical as they may hinder bone healing, cause implant failure and even progress to osteomyelitis. Drug-eluting implants for local delivery of antibiotics at surgical sites are thought to be promising in preventing infections. Herein, the antibiotic vancomycin was encapsulated in a poly(ethylene glycol) (PEG)-based hydrogel film that was covalently bound to Ti implants and subsequently covered by a PEG-poly(lactic-co-caprolactone) (PEG-PLC) membrane. Additionally, crosslinked starch (CSt) was mixed with the hydrogel because its porous microstructure is able to inhibit hydrogel swelling and thus slow down drug release. The release behavior could be regulated by the drug loading and the coating thickness. The vancomycin-loaded Ti implants showed no initial burst release, offering a sustained drug release for nearly 3 weeks in vitro and more than 4 weeks in vivo. In a rabbit model of S. aureus infection, the implants with a 4 mg vancomycin loading significantly reduced the inflammatory reaction and exhibited a good antimicrobial capability. The immobilization of the antibiotic-loaded polymeric coatings on orthopaedic implants can offer a sustainable drug release with no initial burst release and maintain an effective concentration for a longer time, so it is expected to be an effective strategy to treat and prevent local bone infections.

Currently, the major issues in the treatment of osteoarticular tuberculosis (TB) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. The application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. Herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (INH)-loaded alginate microparticles was fixed to Ti implants via adhesive polydopamine, subsequently capped by poly(lactic-co-glycolic acid) membranes for the sustained and localized delivery of the anti-TB drug. The antibacterial efficacy of the released INH was confirmed by a 4.5 ± 0.8 cm inhibition zone formed in the fourth week after inoculation of Mycobacterium tuberculosis. The INH-loaded Ti implants showed no toxicity to the osteoblast cell and provided a consistent drug release for nearly one week in vitro. The release profile in vivo showed a high local concentration and low systemic exposure. The local INH concentration could be kept higher than its minimum inhibitory concentration over a period of 8 weeks, which proves that it is a promising strategy to improve the severe osteoarticular TB treatment.

In recent years, hydroxyapatite (HAp) and β-tricalcium phosphate (TCP) were extensively used to prepare composite scaffolds for bone repair. However, due to a lack of systematical evaluation of HAp and TCP composite scaffolds for bone repair, their distinctions on bone regeneration in vivo have not been clearly clarified to date. In this study, we constructed HAp and TCP composite poly(lactic-co-glycolic acid) (PLGA) scaffolds with the same contents of HAp and TCP and similar structures and porosities, and systematically investigated their performance in the repair of rabbits’ calvarial bone defects. The HAp/PLGA scaffold possessed stronger mechanical property and higher cell proliferation than the TCP/PLGA scaffold, endowing it with better performance of bone regeneration at an early stage. Since TCP could greatly neutralize degraded acidic products and be slowly absorbed in vivo to release occupied room for new bone growth compared to HAp, the TCP/PLGA scaffold yielded more intact new bone for long-term repair of the defects. Our results clearly demonstrate that TCP is a superior bioceramic for bone tissue engineering, showing promise for the perfect repair of bone defects via tissue engineering.

Inspired by the highly ordered nanostructure of bone, nanodopant composite biomaterials are gaining special attention for their ability to guide bone tissue regeneration through structural and biological cues. However, bone malformation in orthopedic surgery is a lingering issue, partly due to the high surface energy of traditional nanoparticles contributing to aggregation and inhomogeneity. Recently, carboxyl-functionalized synthetic polymers have been shown to mimic the carboxyl-rich surface motifs of non-collagenous proteins in stabilizing hydroxyapatite and directing intrafibrillar mineralization in-vitro. Based on this biomimetic approach, it is herein demonstrated that carboxyl functionalization of poly(lactic-co-glycolic acid) can achieve great material homogeneity in nanocomposites. This ionic colloidal molding method stabilizes hydroxyapatite precursors to confer even nanodopant packing, improving therapeutic outcomes in bone repair by remarkably improving mechanical properties of nanocomposites and optimizing controlled drug release, resulting in better cell in-growth and osteogenic differentiation. Lastly, better controlled biomaterial degradation significantly improved osteointegration, translating to highly regular bone formation with minimal fibrous tissue and increased bone density in rabbit radial defect models. Ionic colloidal molding is a simple yet effective approach of achieving materials homogeneity and modulating crystal nucleation, serving as an excellent biomimetic scaffolding strategy to rebuild natural bone integrity.

Immediate hemorrhage control and infection prevention are pivotal for saving lives in critical situations such as battlefields, natural disasters, traffic accidents, and so on. In situ hydrogels are promising candidates, but their mechanical strength is often not strong enough for use in critical situations. In this study, we constructed three hydrogels with different amounts of Schiff-base moieties from 4-arm-PEG-NH2, 4-arm-PEG-NHS, and 4-arm-PEG-CHO in which vancomycin was incorporated as an antimicrobial agent. The hydrogels possess porous structures, excellent mechanical strength, and high swelling ratio. The cytotoxicity studies indicated that the composite hydrogel systems possess good biocompatibility. The Schiff bases incorporated improve the adhesiveness and endow the hydrogels with bacteria-sensitivity. The in vivo hemostatic and antimicrobial experiments on rabbits and pigs demonstrated that the hydrogels are able to aid in rapid hemorrhage control and infection prevention. In summary, vancomycin-loaded hydrogels may be excellent candidates as hemostatic and antibacterial materials for first aid treatment of the wounded in critical situations.

•Starch microcapsules were used as low-cost carriers for the release of pesticides.•Starch microcapsules were mass produced and favorable for practical application.•The size of microcapsules were uniform and easily adjustable.•The release behavior could be tuned by particle size and drug content.In recent years, starch microparticles have gained interest in many fields. However, low production, uncontrollable size, and varying size distribution hinder their practical application. Here, we adopt a premix membrane emulsification (PME) method to prepare starch microcapsules at high production rates. The process conditions were optimized to fabricate uniform microcapsules with controllable sizes and narrow size distribution (PDI < 0.1). Through encapsulating avermectin (Av), a kind of water-insoluble pesticide, into the shell of the microcapsules in situ during the process, we developed a pesticide delivery system that enabled a controlled and consistent release of Av over a period of 2 weeks. Kinetic analysis indicated that the mechanisms of Av release involved non-Fickian and Case-II transport. The diameters (0.70–4.8 μm) of the microcapsules and Av contents (16–47%) were adjusted to achieve suitable release profiles. The results will lay the foundation for further field experiments.

To cure serious bone tuberculosis, a novel long-term drug delivery system was designed and prepared to satisfy the needs of both bone regeneration and antituberculous drug therapy. An antituberculous drug (rifampicin, RFP) was loaded into a porous scaffold, which composed of a newly designed polylactone, poly(ε-caprolactone)-block-poly(lactic-co-glycolic acid) (b-PLGC) copolymer, and β-tricalcium phosphate (β-TCP). The releasing results demonstrated that RFP could be steadily released for as long as 12 weeks both in vitro and in vivo. During the in vivo experimental period, the drug concentration in tissues surrounding implants was much higher than that in blood which was still superior to the effective value to kill mycobacterium tuberculosis. MC3T3-E1 osteoblasts proliferated well in extracts and co-cultures on composite scaffolds, indicating good cytocompatibility and cell affinity of the scaffolds. The results of a rabbit radius repair experiment displayed that scaffolds have good bone regeneration capacity. The RFP-loaded b-PLGC/TCP composite scaffold thus could be envisioned to be a potential and promising substrate in clinical treatment of bone tuberculosis.

An ultrasound contrast agent (UCA) plays a key role in ultrasound imaging to precisely diagnose coronary heart disease. Microcapsules composed of inner gas and shell materials are most commonly employed as ultrasound contrast agents. The ultrasonic properties of the microcapsules are significantly dependent on their size and size distribution. Herein, we prepared several uniform sized biodegradable polylactone microcapsules by combining a premix membrane emulsification technique and W/O/W method. We investigated various size-dependent factors to optimize the size and size distribution of the microcapsules. After evaluation for ultrasound imaging, ∼4 μm PLLA (poly(L-lactide)) microcapsules generated more intense ultrasound signals than PLGA7030 or PLGA5050 (poly(lactic-co-glycolic acid), the molar ratio of lactic acid and glycolic acid being 70:30 or 50:50), PEG-b-PLGA7030 (poly(ethylene glycol)-block-poly(lactic-co-glycolic acid)), PLC5050 (poly(L-lactide-co-caprolactone), the molar ratio of lactide and caprolactone being 50:50) and PEG-b-PLLA microcapsules. The signal duration of the PLLA and PEG-PLLA microcapsules could reach ca. 3 and 3.5 min continuously. The ultrasound signal intensity and duration of the signals of PLLA microcapsules were considerably stronger and longer than those of commercially available UCAs, showing that the PLLA microcapsules have a great potential as more efficient UCAs for biomedical imaging.

To cure serious bone tuberculosis, a novel long-term drug delivery system was designed and prepared to satisfy the needs of both bone regeneration and antituberculous drug therapy. An antituberculous drug (rifampicin, RFP) was loaded into a porous scaffold, which composed of a newly designed polylactone, poly(ε-caprolactone)-block-poly(lactic-co-glycolic acid) (b-PLGC) copolymer, and β-tricalcium phosphate (β-TCP). The releasing results demonstrated that RFP could be steadily released for as long as 12 weeks both in vitro and in vivo. During the in vivo experimental period, the drug concentration in tissues surrounding implants was much higher than that in blood which was still superior to the effective value to kill mycobacterium tuberculosis. MC3T3-E1 osteoblasts proliferated well in extracts and co-cultures on composite scaffolds, indicating good cytocompatibility and cell affinity of the scaffolds. The results of a rabbit radius repair experiment displayed that scaffolds have good bone regeneration capacity. The RFP-loaded b-PLGC/TCP composite scaffold thus could be envisioned to be a potential and promising substrate in clinical treatment of bone tuberculosis.

Currently, the major issues in the treatment of osteoarticular tuberculosis (TB) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. The application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. Herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (INH)-loaded alginate microparticles was fixed to Ti implants via adhesive polydopamine, subsequently capped by poly(lactic-co-glycolic acid) membranes for the sustained and localized delivery of the anti-TB drug. The antibacterial efficacy of the released INH was confirmed by a 4.5 ± 0.8 cm inhibition zone formed in the fourth week after inoculation of Mycobacterium tuberculosis. The INH-loaded Ti implants showed no toxicity to the osteoblast cell and provided a consistent drug release for nearly one week in vitro. The release profile in vivo showed a high local concentration and low systemic exposure. The local INH concentration could be kept higher than its minimum inhibitory concentration over a period of 8 weeks, which proves that it is a promising strategy to improve the severe osteoarticular TB treatment.

In recent years, hydroxyapatite (HAp) and β-tricalcium phosphate (TCP) were extensively used to prepare composite scaffolds for bone repair. However, due to a lack of systematical evaluation of HAp and TCP composite scaffolds for bone repair, their distinctions on bone regeneration in vivo have not been clearly clarified to date. In this study, we constructed HAp and TCP composite poly(lactic-co-glycolic acid) (PLGA) scaffolds with the same contents of HAp and TCP and similar structures and porosities, and systematically investigated their performance in the repair of rabbits’ calvarial bone defects. The HAp/PLGA scaffold possessed stronger mechanical property and higher cell proliferation than the TCP/PLGA scaffold, endowing it with better performance of bone regeneration at an early stage. Since TCP could greatly neutralize degraded acidic products and be slowly absorbed in vivo to release occupied room for new bone growth compared to HAp, the TCP/PLGA scaffold yielded more intact new bone for long-term repair of the defects. Our results clearly demonstrate that TCP is a superior bioceramic for bone tissue engineering, showing promise for the perfect repair of bone defects via tissue engineering.