Panyu Zhou

Selective laser sintering fabrication of nano-hydroxyapatite/poly-ε-caprolactone scaffolds for bone tissue engineering applications.

The regeneration of functional tissue in osseous defects is a formidable challenge in orthopedic surgery. In the present study, a novel biomimetic composite scaffold, here called nano-hydroxyapatite (HA)/poly-ε-caprolactone (PCL) was fabricated using a selective laser sintering technique. The macrostructure, morphology, and mechanical strength of the scaffolds were characterized. Scanning electronic microscopy (SEM) showed that the nano-HA/PCL scaffolds exhibited predesigned, well-ordered macropores and interconnected micropores. The scaffolds have a range of porosity from 78.54% to 70.31%, and a corresponding compressive strength of 1.38 MPa to 3.17 MPa. Human bone marrow stromal cells were seeded onto the nano-HA/PCL or PCL scaffolds and cultured for 28 days in vitro. As indicated by the level of cell attachment and proliferation, the nano-HA/PCL showed excellent biocompatibility, comparable to that of PCL scaffolds. The hydrophilicity, mineralization, alkaline phosphatase activity, and Alizarin Red S staining indicated that the nano-HA/PCL scaffolds are more bioactive than the PCL scaffolds in vitro. Measurements of recombinant human bone morphogenetic protein-2 (rhBMP-2) release kinetics showed that after nano-HA was added, the material increased the rate of rhBMP-2 release. To investigate the in vivo biocompatibility and osteogenesis of the composite scaffolds, both nano-HA/PCL scaffolds and PCL scaffolds were implanted in rabbit femur defects for 3, 6, and 9 weeks. The wounds were studied radiographically and histologically. The in vivo results showed that both nano-HA/PCL composite scaffolds and PCL scaffolds exhibited good biocompatibility. However, the nano-HA/PCL scaffolds enhanced the efficiency of new bone formation more than PCL scaffolds and fulfilled all the basic requirements of bone tissue engineering scaffolds. Thus, they show large potential for use in orthopedic and reconstructive surgery.

Enhanced bone tissue regeneration by antibacterial and osteoinductive silica-HACC-zein composite scaffolds loaded with rhBMP-2

Next-generation orthopedic implants with both osteoinductivity and antibacterial ability are greatly needed. In the present study, biodegradable rhBMP-2 loaded zein-based scaffolds with a macroporous structure were synthesized, and SBA-15 nanoparticles and hydroxypropyltrimethyl ammonium chloride chitosan (HACC) were incorporated into the scaffolds to produce an anti-infective composite scaffold for delivery of osteogenic factors that facilitate the functional repair of bone defects. The silica/HACC/zein scaffolds developed here showed bioactivity, biocompatibility, and effective antibacterial activity. Confocal laser scanning microscopy (CLSM) was used to quantitatively measure the bactericidal efficacy with respect to bacterial adhesion. Results showed that the sample zein-HACC-S20 exhibited long-lasting antibacterial activity against Escherichia coli and Staphylococcus aureus up to 5 d. At a low dosage of rhBMP-2 (ca. 80 μg), the scaffolds released rhBMP-2 protein efficiently at a relatively slow rate, even after 27 d. An ALP activity and ECM mineralization assay showed that the zein-HACC-S20 scaffolds exhibited significant early osteogenic differentiation by generating enhanced ALP product on day 14 and ECM mineralization on day 21. In a mouse model of thigh muscle pouches, zein-S20 and zein-HACC-S20 groups resulted in obvious bone formation and gave more extensive mineralization to the implants than silica free groups, indicating effective bone induction in vivo. In a rabbit model of critical-sized radius bone defects (20 mm in length and 5 mm in diameter), the bone defects were almost fully repaired and bone marrow cavity recanalization was detectable by 3D micro-CT technique and histological analysis after 12 weeks. In this way, the zein-HACC-S20 scaffolds were proven to significantly promote the bone repair. They also demonstrated considerable promise for tissue engineering. Silica/HACC/zein scaffolds with both antibacterial activity and the ability to induce osteogenesis have immense potential in orthopedics and other biomedical applications.

Organic/inorganic composite membranes based on poly(L-lactic-co-glycolic acid) and mesoporous silica for effective bone tissue engineering.

Fabrication of membranes with excellent biocompatibility and bioactivity remains an important technical challenge in bone tissue engineering. In this paper, poly(l-lactic-co-glycolic acid) (PLGA)-SBA15 (Santa Barbara Amorphous 15) composite membranes were prepared by using an electrospinning technique; PLGA was used as a biocompatible and biodegradable polymer and SBA15 was used as a mesoporous silica. The PLGA-SBA15 composite membrane facilitates the cell attachment and the cell proliferation versus pure PLGA membrane where human bone marrow-derived mesenchymal stem cells (hMSCs) were seeded. Furthermore, the analysis of alkaline phosphatase (ALP) activity indicated that this PLGA-SBA15 composite membrane has better osteogenic induction compared with the pure PLGA membrane. Moreover, the presence of SBA15 increased the loading efficiency of the recombinant human bone morphogenetic protein-2 (rhBMP-2) to the membranes. Furthermore, the composite membrane had optimized sustained release of rhBMP-2. Overall, this PLGA-SBA15 composite is an excellent material for bone tissue engineering.

New minimally invasive option for the treatment of gluteal muscle contracture.

Gluteal muscle contracture is a clinical syndrome that involves contracture and distortion of the gluteal muscles and fascia fibers due to multiple causes. Physical examination demonstrates a characteristic gait due to hip adduction and internal thigh rotation. This study introduces a new minimally invasive method for surgical release of gluteal muscle contracture. Patients with gluteal muscle contracture were assigned to 4 categories: type A, contracture occurred mainly in the iliotibial tract; type B, contracture occurred in the Iliotibial tract and gluteus maximus; type C1, movement of the contraction band was palpable and a snapping sound was audible during squatting; and type C2, movement of the contraction band was not palpable or almost absent and a snapping sound was audible during squatting. This classification method allowed prediction of the anatomic location of these pathological contractures and determination of the type of surgery required. Four critical points were used to define the operative field and served as points to mark a surgical incision smaller than 4 mm. The contracture was easily released in this carefully marked operative field without causing significant neurovascular damage. Over a period of 5 years, between March 2003 and June 2008, the authors treated 1059 patients with this method and achieved excellent outcomes. Most patients were fully active within 12 weeks, with the assistance of an early postoperative rehabilitation program. The most significant complication was a postoperative periarticular hematoma, which occurred in 3 patients within 10 days postoperatively and required surgical ligation of the bleeding vessel.

Deletion of mammalian sterile 20-like kinase 1 attenuates neuronal loss and improves locomotor function in a mouse model of spinal cord trauma

Neuronal cell death following spinal cord injury (SCI) is an important contributor to neurological deficits. The purpose of our work was to delineate the function of mammalian sterile 20-like kinase 1 (Mst1), a pro-apoptotic kinase and key mediator of apoptotic signaling, in the pathogenesis of an experimental mouse model of SCI. Male mice received a mid-thoracic spinal contusion injury, and it was found that phosphorylation of Mst1 at the injured site was enhanced significantly following SCI. Furthermore, when compared to the wild-type controls, Mst1-deficient mice displayed improved locomotor function by increased Basso mouse scale score. Deletion of Mst1 in mice attenuated loss of motor neurons and suppressed microglial and glial activation following SCI. Deletion of Mst1 in mice reduced apoptosis via suppressing cytochrome c release and caspase-3 activation following SCI. Deletion of Mst1 attenuated mitochondrial dysfunction and increased ATP formation following SCI. Deletion of Mst1 in mice inhibited local inflammation following SCI, evidenced by reduced activities of myeloperoxidase and protein levels of TNF-α, IL-1β, and IL-6. In conclusion, the present study demonstrated that deletion of Mst1 attenuated neuronal loss and improved locomotor function in a mouse model of SCI, via preserving mitochondrial function, attenuating mitochondria-mediated apoptotic pathway, and suppressing inflammation, at least in part.

Highly Effective Antibacterial Vesicles Based on Peptide-Mimetic Alternating Copolymers for Bone Repair

It is an important challenge for bone repair to effectively deliver growth factors and at the same time to prevent and cure inflammation without obvious pathogen resistance. We designed a kind of antibacterial peptide-mimetic alternating copolymers (PMACs) to effectively inhibit and kill both Gram-positive and Gram-negative bacteria. The minimum inhibition concentrations (MICs) of the PMACs against E. coli and S. aureus are 8.0 μg/mL, which are much lower than that of antibacterial peptides synthesized by other methods such as widely used ring-opening polymerization of N-carboxyanhydride. Furthermore, the PMACs can self-assemble into polymer vesicles (polymersomes) in pure water with low cytotoxicity (IC50 > 1000 μg/mL), which can encapsulate growth factors in aqueous solution and release them during long-term antibacterial process for facilitating bone repair. We also find that the alternating structure is essential for the excellent antibacterial activity. The in vivo tests in rabbits confirmed that the growth-factor-encapsulated antibacterial vesicles have better bone repair ability compared with control groups without antibacterial vesicles. Overall, we have provided a novel method for designing PMAC-based highly effective intrinsically antibacterial vesicles that may have promising biomedical applications in the future.

Degradability, biocompatibility, and osteogenesis of biocomposite scaffolds containing nano magnesium phosphate and wheat protein both in vitro and in vivo for bone regeneration.

In this study, bioactive scaffold of nano magnesium phosphate (nMP)/wheat protein (WP) composite (MWC) was fabricated. The results revealed that the MWC scaffolds had interconnected not only macropores (sized 400–600 μm) but also micropores (sized 10–20 μm) on the walls of macropores. The MWC scaffolds containing 40 w% nMP had an appropriate degradability in phosphate-buffered saline and produced a weak alkaline microenvironment. In cell culture experiments, the results revealed that the MWC scaffolds significantly promoted the MC3T3-E1 cell proliferation, differentiation, and growth into the scaffolds. The results of synchrotron radiation microcomputed tomography and analysis of the histological sections of the in vivo implantation revealed that the MWC scaffolds evidently improved the new bone formation and bone defects repair as compared with WP scaffolds. Moreover, it was found that newly formed bone tissue continued to increase with the gradual reduction of materials residual in the MWC scaffolds. Furthermore, the immunohistochemical analysis further offered the evidence of the stimulatory effects of MWC scaffolds on osteogenic-related cell differentiation and new bone regeneration. The results indicated that MWC scaffolds with good biocompability and degradability could promote osteogenesis in vivo, which would have potential for bone tissue repair.

Absence of NF-κB subunit p50 ameliorates cold immobilization stress-induced gastric ulcers

Stress ulcers are a common complication in critically ill patients, but the underlying mechanism is little known. This study characterized the function of the p50 subunit of NF-κB in an experimental model of cold immobilization stress-induced gastric ulcers. Stress-induced gastric mucosal inflammation and gastric injury were examined in wild-type and NF-κB p50-deficient mice. When subjected to cold immobilization stress, NF-κB was rapidly activated in the gastric mucosa in WT mice whereas the majority of κB DNA-binding activity was abrogated from p50(-/-) mice. Deficiency of p50 ameliorated stress-induced expression of TNF-α, MIP-2, and ICAM-1, resulting in reduced mucosal accumulation of neutrophils and gastric injury. These data indicated a critical role for the p50 in the gastric mucosal inflammatory response to cold restraint stress.

A novel technique for minimally invasive removal of a foreign body in the rectal wall

A foreign body lodged in the rectum is not a common surgical emergency, and it is somewhat rare for a foreign body to penetrate the rectal wall [1], but if this does occur and the object is not removed in a timely manner, there can be a variety of serious consequences [2]. The removal of foreign bodies from the rectal wall poses a challenge to the surgeon. In this article, we introduce a new type of navigation device which can accurately identify the position of a foreign body in the rectal wall. By using this device, it was possible to remove the foreign body using a minimally invasive technique.

Loading BMP-2 on nanostructured hydroxyapatite microspheres for rapid bone regeneration

Introduction Tissue engineering is a promising strategy for bone regeneration in repairing massive bone defects. The surface morphology of implanted materials plays a key role in bone healing; these materials incorporate osteoinductive factors to improve the efficiency of bone regeneration. Materials and methods In the current study, nanostructured hydroxyapatite (nHAp) micro-spheres were prepared via a hydrothermal transformation method using calcium silicate (CS) microspheres as precursors; the CS microspheres were obtained by a spray-drying method. The nHAp microspheres constructed by the nano-whiskers significantly improved the ability of the microspheres to adsorb the bioactive protein (BMP-2) and reduce its initial burst release. To evaluate the in vivo bone regeneration of microspheres, both conventional hydroxyapatite (HAp) and nHAp microspheres were either loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) or not loaded with the protein; these microspheres were implanted in rat femoral bone defects for 4 and 8 weeks. Results and discussion The results of our three-dimensional (3D) micro-computed tomography (CT) and histomorphometric observations showed that the combination of the nano-structured surface and rhBMP-2 obviously improved osteogenesis compared to conventional HAp microspheres loaded with rhBMP-2. Our results suggest that the nHAp microspheres with a nanostructured surface adsorb rhBMP-2 for rapid bone formation; they therefore show the potential to act as carriers in bone tissue regeneration.