Bone defects requiring grafts to promote healing are frequently occurring and costly problems in health care. Chitosan, a biodegradable, naturally occurring polymer, has drawn considerable attention in recent years as a scaffolding material in tissue engineering and regenerative medicine. Chitosan is especially attractive as a bone scaffold material because it supports the attachment and proliferation of osteoblast cells as well as formation of mineralized bone matrix. In this review, we discuss the fundamentals of bone tissue engineering and the unique properties of chitosan as a scaffolding material to treat bone defects for hard tissue regeneration. We present common methods for fabrication and characterization of chitosan scaffolds, and discuss the influence of material preparation and addition of polymeric or ceramic components or biomolecules on chitosan scaffold properties such as mechanical strength, structural integrity, and functional bone regeneration. Finally, we highlight recent advances in the development of chitosan-based scaffolds with enhanced bone regeneration capability.

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Chitosan-based scaffolds for bone tissue engineering

In recent years, significant development has been achieved in the construction of artificial bone with ceramics, polymers and metals. Nano-hydroxyapatite (nHA) is widely used bioceramic material for bone graft substitute owing to its biocompatibility and osteoconductive properties. nHA with chitin, chitosan, collagen, gelatin, fibrin, polylactic acid, polycaprolactone, poly(lactic-co-glycolic) acid, polyamide, polyvinyl alcohol, polyurethane and polyhydroxybutyrate based composite scaffolds have been explored in the present review for bone graft substitute. This article further reviews the preparative methods, chemical interaction, biocompatibiity, biodegradation, alkaline phosphatase activity, mineralization effect, mechanical properties and delivery of nHA-based nanocomposites for bone tissue regeneration. The nHA based composite biomaterials proved to be promising biomaterials for bone tissue engineering.

Nano-hydroxyapatite composite biomaterials for bone tissue engineering--a review.

Chitosan based biocomposite scaffolds for bone tissue engineering.

Chitosan is a deacetylated polysaccharide from chitin, the natural biopolymer primarily found in shells of marine crustaceans and fungi cell walls. Upon deacetylation, the protonation of free amino groups of the d-glucosamine residues of chitosan turns it into a polycation, which can easily interact with DNA, proteins, lipids, or negatively charged synthetic polymers. This positive-charged characteristic of chitosan not only increases its solubility, biodegradability, and biocompatibility, but also directly contributes to the muco-adhesion, hemostasis, and antimicrobial properties of chitosan. Combined with its low-cost and economic nature, chitosan has been extensively studied and widely used in biopharmaceutical and biomedical applications for several decades. In this review, we summarize the current chitosan-based applications for bone and dental engineering. Combining chitosan-based scaffolds with other nature or synthetic polymers and biomaterials induces their mechanical properties and bioactivities, as well as promoting osteogenesis. Incorporating the bioactive molecules into these biocomposite scaffolds accelerates new bone regeneration and enhances neovascularization in vivo.

https://www.mdpi.com/1420-3049/24/16/3009/pdf

Application of Chitosan in Bone and Dental Engineering

Dietary supplements and foods for special medical purposes are special medical products classified according to the legal basis. They are regulated, for example, by the European Food Safety Authority and the U.S. Food and Drug Administration, as well as by various national regulations issued most frequently by the Ministry of Health and/or the Ministry of Agriculture of particular countries around the world. They constitute a concentrated source of vitamins, minerals, polyunsaturated fatty acids and antioxidants or other compounds with a nutritional or physiological effect contained in the food/feed, alone or in combination, intended for direct consumption in small measured amounts. As nanotechnology provides “a new dimension” accompanied with new or modified properties conferred to many current materials, it is widely used for the production of a new generation of drug formulations, and it is also used in the food industry and even in various types of nutritional supplements. These nanoformulations of supplements are being prepared especially with the purpose to improve bioavailability, protect active ingredients against degradation, or reduce side effects. This contribution comprehensively summarizes the current state of the research focused on nanoformulated human and veterinary dietary supplements, nutraceuticals, and functional foods for special medical purposes, their particular applications in various food products and drinks as well as the most important related guidelines, regulations and directives.

Potential of Nanomaterial Applications in Dietary Supplements and Foods for Special Medical Purposes.

Repair of massive bone loss remains a challenge to the orthopaedic surgeons. Autologous and allogenic bone grafts are choice for bone reconstructive surgery, but limited availability, risks of transmittable diseases and inconsistent clinical performances have prompted the development of tissue engineering. In the present work, the bone regeneration potential of nanohydroxyapatite/chitosan composite scaffolds were compared with pure chitosan scaffolds when implanted into segmental bone defects in rabbits. Critical size bone defects (6 mm diameter, 10 mm length) were created in the left femoral condyles of 43 adult New Zealand white rabbits. The femoral condyle bone defects were repaired by nanohydroxyapatite/chitosan compositions, pure chitosan or left empty separately. Defect-bridging was detected by plain radiograph and quantitative computer tomography at eight and 12 weeks after surgery. Tissue samples were collected for gross view and histological examination to determine the extent of new bone formation. Eight weeks after surgery, more irregular osteon formation was observed in the group treated with nanohydroxyapatite/chitosan composites compared with those treated with pure chitosan. 12 weeks after surgery, complete healing of the segmental bone defect was observed in the nanohydroxyapatite/chitosan-group, while the defect was still visible in the chitosan-group, although the depth of the defect had diminished. These observations suggest that the injectable nanohydroxyapatite/chitosan scaffolds are potential candidate materials for regeneration of bone loss.

Repair of rabbit femoral condyle bone defects with injectable nanohydroxyapatite/chitosan composites

Osteosarcoma is a malignant bone cancer of which the survival rate is still low. One reason for this low survival rate is drug resistance. In the past, it has been shown that microRNAs may play critical roles in osteosarcoma development and drug resistance. The mechanisms by which osteosarcoma cells acquire this resistance have, however, remained largely unknown. Here, we aimed at assessing the role of microRNA-488 in the acquisition of drug resistance by osteosarcoma cells. Quantitative RT-PCR was used to measure the expression of microRNA-488 in primary osteosarcoma samples and in osteosarcoma-derived cells, whereas microRNA-488 mimics and inhibitors were used to modify its expression in these cells. Luciferase reporter, Western blotting, cell viability, apoptosis and ChIP assays were used to assess the various effects of modified microRNA-488 expression in osteosarcoma-derived cells. We found that microRNA-488 is over-expressed in primary osteosarcoma tissues and osteosarcoma-derived cells and that hypoxia can induce microRNA-488 expression via binding to the hypoxia response element (HRE) in its promoter. We also found that exogenous over-expression of microRNA-488 promotes the proliferation, reduces the apoptosis and decreases the sensitivity to chemotherapy (doxorubicin) of osteosarcoma cells via direct targeting of the tumor suppressor Bim, which is a mediator of apoptosis. In contrast, we found that transfection of a microRNA-488 inhibitor resulted in an increase in both apoptosis and drug sensitivity, and a decrease in proliferation. Our data suggest that miRNA-488 may serve as a predictor of response to chemotherapy and as a therapeutic target in human osteosarcomas.

Hypoxia-inducible microRNA-488 regulates apoptosis by targeting Bim in osteosarcoma.

The objective was to investigate the effective and safe range of paramedian CDH by percutaneous posterior full-endoscopy cervical intervertebral disc nucleus pulposus resection (PPFECD) to provide a reference for indications and patient selection. Sixteen patients with CDH satisfied the inclusion criteria. Before surgery the patients underwent cervical spine MRI, and the distance between the dural sac and herniated disc was measured. An assessment was performed by MRI immediately after surgery, measuring the distance between dural sac and medial border of discectomy (DSMD). The preoperative average distance between the dural sac and peak of the herniated disc (DSPHD) was 3.87 ± 1.32 mm; preoperative average distance between dural sac and medial border of herniated disc (DSMHD) was 6.91 ± 1.21 mm and an average distance of postoperative DSMD was 5.41 ± 1.40 mm. Postoperative VAS of neck and shoulder pain was significantly decreased but JOA was significantly increased in each time point compared with preoperative ones. In summary, the effective range of PPFECD to treat paramedian CDH was 5.41 ± 1.40 mm, indicating that DSMHD and DSPHD were within 6.91 ± 1.21 mm and 3.87 ± 1.32 mm, respectively. PPFECD surgery is, therefore, a safe and effective treatment option for patients with partial paramedian cervical disc herniation.

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Effective Range of Percutaneous Posterior Full-Endoscopic Paramedian Cervical Disc Herniation Discectomy and Indications for Patient Selection

Background The extraforaminal ligaments between the L1-L5 lumbar spinal nerves and the tissues surrounding the intervertebral foramina (IVF) have been well studied. However, little research has been performed to describe the local anatomy of the entrance zones at the L1-L5 level. Detailed anatomic studies of the intraforaminal ligaments (IFLs) in the entrance zones at the L1-L5 levels have not been performed. Objectives The objective of this study is to identify and describe the IFLs in the entrance zones of the L1-L5 IVF and to determine their possible clinical significance. Study design A dissection-based study of 10 fresh-frozen human cadavers. Setting Guangdong Provincial Key Laboratory of Medical Biomechanics in Anatomy Department of Southern Medical University. Methods Eighty L1-L5 IVF from 10 fresh cadavers were studied, and the IFLs in the entrance zones were identified. The quantities, morphologies, origins, insertions, and spatial orientations of the IFLs in the entrance zones of the L1-L5 IVF were observed. The lengths, widths, diameters, and thicknesses of the ligaments were measured using a vernier caliper. Ten intraforaminal radiating ligaments were removed for histological examination. Results A total of 197 ligaments were identified in the entrance zones of the 80 L1-L5 IVF, including 191 (96.95%) radiating ligaments and 6 (3.05%) transforaminal ligaments. The thickest ligaments were observed at the L3-L4 IVF. The lengths of the ligaments varied from 0.59 to 11.92 mm. There were 66 (33.50%) ligaments in the superior aspect of the entrance zone of the IVF, 58 (29.44%) ligaments at the anterior aspect, 43 (21.83%) ligaments at the posterior aspect, and 30 (15.23%) ligaments at the inferior aspect. The morphologies of the IFLs were divided into 2 types: the strap type and the trabs type. Histological examination of the meningovertebral ligaments revealed fibrous connective tissue. Limitations The major limitation of this study is the lack of actual clinical data from live patients. In addition, future medical biomechanics experiments are expected to contribute more objective data on the strength of the IFLs. Conclusions In the lumbar spine, IFLs are common structures in the entrance zones of the L1-L5 IVF, and radiating ligaments are more likely to be present. Key words Clinical Anatomy, microdissection, intraforaminal ligament, the entrance zone, L1-L5 intervertebral foramen, endoscopic spinal adhesiolysis, sacral hiatus, cerebrospinal fluid leakage, dural laceration.

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Hai Lv

Papers

Repair of rabbit femoral condyle bone defects with injectable nanohydroxyapatite/chitosan composites

Hypoxia-inducible microRNA-488 regulates apoptosis by targeting Bim in osteosarcoma.

Effective Range of Percutaneous Posterior Full-Endoscopic Paramedian Cervical Disc Herniation Discectomy and Indications for Patient Selection

The Morphology and Possible Clinical Significance of the Intraforaminal Ligaments in the Entrance Zones of the L1-L5 Levels.

How the brain encodes morphological constraints during Chinese word reading: An EEG-fNIRS study