Bioinspired polydopamine and polyphenol tannic acid functionalized titanium suppress osteoclast differentiation: a facile and efficient strategy to regulate osteoclast activity at bone-implant interface.

Osseointegration of metallic implants in porous osteoporotic bone remains a challenge. Surface modification of implants to reduce peri-implant osteoclastic bone resorption was explored in the study. Bioinspired polydopamine (pDOP) and polyphenol tannic acid (pTAN) are nature-derived universal coating systems that have emerged either as a sole coating or ad-layer for biomolecular conjugation on different biomaterials. The effects pDOP and pTAN on osteoclast development have not been reported before. In this study, osteoclast development was investigated on titanium (Ti) substrates coated with pDOP (Ti-pDOP) and pTAN (Ti-pTAN). The results showed that Ti-pDOP and Ti-pTAN coating reduced tartrate-resistant acid phosphatase activity and osteoclast cell number as compared with pristine Ti. Intriguingly, the reduction was higher on Ti-pTAN than on Ti-pDOP. Economical and biocompatible tannic acid serves as a superior coating in decreasing osteoclast activity when compared with that of pDOP coating and could be used to modulate osteoclast activity at bone-implant interfaces.

Use of Polyphenol Tannic Acid to Functionalize Titanium with Strontium for Enhancement of Osteoblast Differentiation and Reduction of Osteoclast Activity.

Implant anchorage remains a challenge, especially in porous osteoporotic bone with high osteoclast activity. The implant surface is modified with osteogenic molecules to stimulate osseointegration. Strontium (Sr) is known for its osteogenic and anti-osteoclastogenic effects. In this study, Sr was immobilized on a titanium (Ti) surface using bioinspired polyphenol tannic acid (pTAN) coating as an ad-layer (Ti-pTAN). Two separate coating techniques were employed for comparative analysis. In the first technique, Ti was coated with a tannic acid solution containing Sr (Ti-pTAN-1Stp). In the second method, Ti was first coated with pTAN, before being immersed in a SrCl2 solution to immobilize Sr on Ti-pTAN (Ti-pTAN-2Stp). Ti-pTAN-1Stp and Ti-pTAN-2Stp augmented the alkaline phosphatase activity, collagen secretion, osteocalcin production and calcium deposition of MC3T3-E1 cells as compared to those of Ti and Ti-pTAN. However, osteoclast differentiation of RAW 264.7, as studied by TRAP activity, total DNA, and multinucleated cell formation, were decreased on Ti-pTAN, Ti-pTAN-1Stp and Ti-pTAN-2Stp as compared to Ti. Of all the substrates, osteoclast activity on Ti-pTAN-2Stp was the lowest. Hence, an economical and simple coating technique using pTAN as an adlayer preserved the dual biological effects of Sr. These results indicate a promising new approach to tailoring the cellular responses of implant surfaces.

Superior capsular reconstruction for irreparable supraspinatus tendon tears using the long head of biceps: A biomechanical study on cadavers.

INTRODUCTION: The superior articular capsule complements the rotator cuff's function in shoulder stability. With irreparable rotator cuff tears, superior capsular reconstruction (SCR) improves dynamic glenohumeral (GH) joint kinematics. We present a novel method of SCR in cadaveric shoulders using the long head of bicep (LHB) tendon instead of previously explored fascia lata autograft, thereby reducing harvest site and suture anchor associated complications. HYPOTHESIS: This novel method of SCR using the LHB is feasible biomechanically in restoring shoulder stability in irreparable supraspinatus tendon tear. MATERIALS AND METHODS: Seven cadaveric shoulders were tested in a custom shoulder testing system. Superior translation of the humerus, subacromial contact pressure and area, and glenohumeral range of motion were tested at 0°, 30°, and 60° of glenohumeral abduction in the following conditions: (1) intact shoulder, (2) simulated complete supraspinatus tendon tear, (3) modified SCR using LHB, (4) and modified SCR using LHB and side-to-side repair augmentation. RESULTS: The complete cuff tear shifted the humeral head superiorly as compared to the intact shoulder. Subacromial peak contact pressure was also increased at 30° and 60° while contact area was increased at 0° and 30°. The modified SCR both with and without side-to-side repair shifted the humeral head inferiorly at 30° and 60°, with contact area further reduced at 60°. Both techniques had comparable results for contact pressure and total rotational range of motion. CONCLUSION: The LHB with appropriate distal insertion on the greater tuberosity restores shoulder stability in irreparable rotator cuff tears by re-centering the humeral head on the glenoid. LEVEL OF EVIDENCE: Basic science study, biomechanical testing.

Modulation of Osteoclast Interactions with Orthopaedic Biomaterials.

Biomaterial integration in bone depends on bone remodelling at the bone-implant interface. Optimal balance of bone resorption by osteoclasts and bone deposition by osteoblasts is crucial for successful implantation, especially in orthopaedic surgery. Most studies examined osteoblast differentiation on biomaterials, yet few research has been conducted to explore the effect of different orthopaedic implants on osteoclast development. This review covers, in detail, the biology of osteoclasts, in vitro models of osteoclasts, and modulation of osteoclast activity by different implant surfaces, bio-ceramics, and polymers. Studies show that surface topography influence osteoclastogenesis. For instance, metal implants with rough surfaces enhanced osteoclast activity, while smooth surfaces resulted in poor osteoclast differentiation. In addition, surface modification of implants with anti-osteoporotic drug further decreased osteoclast activity. In bioceramics, osteoclast development depended on different chemical compositions. Strontium-incorporated bioceramics decreased osteoclast development, whereas higher concentrations of silica enhanced osteoclast activity. Differences between natural and synthetic polymers also modulated osteoclastogenesis. Physiochemical properties of implants affect osteoclast activity. Hence, understanding osteoclast biology and its response to the natural microarchitecture of bone are indispensable to design suitable implant interfaces and scaffolds, which will stimulate osteoclasts in ways similar to that of native bone.

Development of mesoporous bioactive glass nanoparticles and its use in bone tissue engineering.

The incidence of bone disorders, from trauma, tissue degeneration due to ageing, pathological conditions to cancer, has been increasing. The pursuit for bone graft substitutes to assist in regenerating large bone defects is ever growing as a result of the shortage in conventional autografts and allografts, in addition to the associated risks of disease transmission. However, the use of alloplastic biomaterials is limited in clinical settings, as further investigations are required to address the properties of synthetic grafts to mimic the native bone tissue and deliver desirable biomolecules to facilitate bone regeneration. This review discusses the fundamental structure and properties of bone with the emphasis on organic and inorganic components that are important for the biomaterial design. The main focus will be on the advancement and usage of bioactive glass (BG) for bone tissue engineering due to its similarity to the natural inorganic constituent of bone. The various BG synthetic processes, modifications of composition, as well as the biomolecule delivery will be discussed in great detail. As the properties of BG are tuneable according to clinical needs, it creates a new paradigm in addition to displaying its superior potential for bone tissue engineering and translational medicine in the field of orthopedic surgery. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2878-2887, 2018.

Beta-cyclodextrin modified mesoporous bioactive glass nanoparticles/silk fibroin hybrid nanofibers as an implantable estradiol delivery system for the potential treatment of osteoporosis.

Osteoporosis, a systemic skeletal disease prevalent in elderly women, is associated with post-menopausal estrogen deficiency. Although systemic administration of exogenous estradiol (E2) reduced fragility fractures, the treatment has adverse effects. Localized delivery technologies of E2 could be utilized to circumvent the systemic adverse effects of systemic administration. In this study, a localized E2 delivery system is developed. Mesoporous bioactive glass nanoparticles (MBGNPs) with inherent osteogenic properties are modified with ß-cyclodextrin (CD-MBGNPs) to enhance their affinity for E2. To ensure mechanical stability and integrity, E2 loaded CD-MBGNPs are further electrospun with silk fibroin (SF) to produce a nanofibrous mesh (E2@CD-MBGNPs/SF). The incorporation of MBGNPs in SF enhances in vitro apatite formation and sustains the constant release of E2. Moreover, osteoblast proliferation and differentiation markers such as alkaline phosphatase activity, collagen 1 and osteocalcin expression of MC3T3-E1 are augmented in CD-MBGNPs/SF and E2@CD-MBGNPs/SF as compared to SF nanofibers. On the other hand, osteoclast DNA, tartrate resistant acid phosphatase activity and multinucleated cell formation are reduced in E2@CD-MBGNPs/SF as compared to CD-MBGNPs/SF and SF. Hence the presence of CD-MBGNPs in SF stimulates osteoblast function whereas E2 incorporation in CD-MBGNPs/SF reduces osteoclast activity. This is the first report to develop CD-MBGNPs/SF as a localized delivery system for hydrophobic molecules such as estradiol to treat osteoporosis.

Estradiol-Loaded Poly(ε-caprolactone)/Silk Fibroin Electrospun Microfibers Decrease Osteoclast Activity and Retain Osteoblast Function.

Estrogen, a steroid hormone, plays an important role in modulating osteoclast proliferation and development. Estrogen deficiency boosts osteoclast activity, leading to osteoporosis in elderly women. In this study, 17-ß estradiol (E2)-loaded poly(ε-caprolactone) (PCL)/silk fibroin (SF) electrospun microfibers were developed as a proposed localized E2 delivery system to treat osteoporotic fractures. PCL is a synthetic polymer known for its biocompatibility and excellent mechanical properties. The bioactivity of PCL was enhanced by mixing it with a natural SF polymer that has low immunogenicity and inherent bioactivity. Different ratios of PCL/SF blends were electrospun and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and water contact angle measurement. PCL and SF at a ratio of 50:50 (PCL50/SF50) augmented cell proliferation of murine preosteoblast MC3T3-E1 cells and murine preosteoclast RAW 264.7 cells. Hence, PCL50/SF50 was selected and mixed with three concentrations of E2 to produce electrospun fiber mesh (0.1% E2@PCL/SF, 1% E2@PCL/SF, and 5% E2@PCL/SF). Sustained release of E2 was obtained for about 3 weeks at higher E2 concentration 5% E2@PCL/SF. An E2-loaded PCL50/SF50 elecrospun microfiber (1% E2@PCL/SF and 5% E2@PCL/SF) reduced tartrate-resistant acid phosphate activity, total DNA, and multinucleated cell formation of osteoclasts. On the other hand, the alkaline phosphatase activity and collagen I expression of osteoblasts were retained on all E2-loaded electrospun microfibers. The E2@PCL/SF system shows potential to be used for localized E2 delivery for the treatment of osteoporotic fractures.

In Vitro Findings of Titanium Functionalized with Estradiol via Polydopamine Adlayer.

To improve orthopedic implant fixation and reduce post-operative complications, osteogenic molecules are delivered locally by immobilizing them on the surface of implants, which will modulate the biology of cell attachment and differentiation on the implant surface. Estradiol, a natural steroid hormone, maintains bone metabolism by decreasing bone resorption. It either directly or indirectly affects osteoclasts. In this work, estradiol was immobilized on a titanium surface by polydopamine adlayer. Immobilization of estradiol was confirmed by X-ray electron spectroscopy (XPS), immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA). Estradiol-modified substrates enhanced alkaline phosphatases activity (ALP) and calcium deposition of osteoblasts. However, these substrates did not decrease tartrate-resistant acid phosphatase (TRAP) activity and actin ring formation of the osteoclast. The scanning electron microscopic (SEM) images of estradiol-modified substrates showed the formation of estradiol crystals, which decreased the potency of immobilized estradiol. Despite having a successful immobilization of estradiol via the polydopamine technique, the bioavailability and potency of coated estradiol is reduced due to crystallization, suggesting that this is not a suitable system for localized estradiol delivery as tested in vitro here. Consequently, other suitable platforms have to be explored for immobilizing estradiol that will prevent crystal formation while preserving the biological activity.

Male orthopaedic surgeons and anaesthetists: equally good at estimating fluid volumes (and changing light bulbs) but equally poor at estimating procedure duration.

INTRODUCTION: How many orthopods does it take to change a light bulb? One - to refer to the medics for 'Darkness ?Cause'. Additionally, anaesthetists and surgeons often disagree on the estimated blood loss during surgery and the estimated procedure duration. We designed this study to compare the ability of orthopaedic surgeons and anaesthetists in: (a) estimating fluid volumes; (b) estimating procedure durations; and (c) changing light bulbs. METHODS: Participants had to either be a specialist in anaesthesia or orthopaedic surgery, or a trainee in that specialty for at least two years. Three different fluid specimens were used for volume estimation (44 mL, 88 mL and 144 mL). Two videos of different lengths (140 seconds and 170 seconds), showing the suturing of a banana skin, were used for procedure duration estimation. To determine the ability at changing light bulbs, the participants had to match eight different light sockets to their respective bulbs. RESULTS: 30 male anaesthetists and trainees and 31 male orthopaedic surgeons and trainees participated in this study. Orthopaedic surgeons underestimated the three fluid volumes by 3.9% and anaesthetists overestimated by 5.1% (p = 0.925). Anaesthetists and orthopaedic surgeons overestimated the duration of the two procedures by 21.2% and 43.1%, respectively (p = 0.006). Anaesthetists had a faster mean time in changing light bulbs (70.1 seconds vs. 74.1 seconds, p = 0.319). CONCLUSION: In an experimental environment, male orthopaedic surgeons are as good as male anaesthetists in estimating fluid volumes (in commonly seen surgical specimens) and in changing light bulbs. Both groups are poor at estimating procedure durations.

Resolution of ascending aortic dissection in a Stanford type A patient.

We observed an unusual natural course of a Stanford type A aortic dissection. The patient presented to the emergency department with an acute aortic dissection involving an ascending aorta and left-sided hemiparesis. The patient declined surgery and was managed conservatively. A follow-up scan after 1 month revealed that the patient had a complete spontaneous resolution of the dissection in the ascending aorta. Such a development is very rare and unexpected in patients with Stanford type A aortic dissection.

Characteristics of aortic wall extracellular matrix in patients with acute myocardial infarction: tissue microarray detection of collagen I, collagen III and elastin levels.

OBJECTIVES: Extracellular matrix (ECM) remodelling of the vessel wall is hypothesized to be an important step in atherosclerosis. Changes of the ECM are associated with the gradual progression of an atherosclerotic lesion from a lipid streak to complicated unstable plaque, leading to a complete vessel occlusion and eventually myocardial infarction (MI). Understanding of this process is critical in the treatment and prevention of ischaemic heart disease (IHD). METHODS: We investigated the histopathological characteristics of aortic wall ECM in IHD patients. Collagen I, collagen III and elastin were assessed immunohistochemically in patients with acute MI and those with stable angina, using aortic punch tissues obtained from coronary artery bypass graft surgery. Fluorescence tissue images were analysed using the tissue microarray technique. RESULTS: The results showed that collagen III expression was found to be significantly lower in the acute MI group (P < 0.001). As a result of this change, the patients with MI also revealed a significant reduction in the collagen III/collagen I ratio. The elastin/collagen III ratio was significantly higher in the MI group (P < 0.001). CONCLUSIONS: Our study provided evidence of a decrease in collagen III content in patients with MI, which could possibly explain the mechanism of plaque vulnerability and weakening of the plaque cap. A reduction in collagen III content, particularly away from the atherosclerotic lesions, might be explained by the systemic vascular changes in patients with MI, and inflammation and immune responses could be potential causes of these systemic transformations. The biochemical mechanisms and factors regulating collagen III production might be potential markers to predict possible cardiovascular events.