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). 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. 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). 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.

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.

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 β-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.

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.

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.