Developing biomaterials for bone regeneration that are highly bioactive, resorbable and mechanically strong remains a challenge. Zreiqat's lab recently developed novel scaffolds through the controlled substitution of strontium (Sr) and zinc (Zn) into calcium silicate, to form Sr-Hardystonite and Hardystonite, respectively and investigated their in vivo biocompatibility and osteoconductivity

We synthesized 3D scaffolds of Sr-Hardystonite, Hardystonite and compared them to the clinically used tricalcium phosphate (micro-TCP) (6 × 6 × 6 mm) using a polyurethane foam template to produce a porous scaffold. The scaffolds were surgically implanted in the proximal tibial metaphysis of each tibia of Female Wistar rats. Animals were sacrificed at three weeks and six weeks post-implantation and bone formation and scaffold resorption were assessed by microcomputed tomography (micro-CT) histomorphometry and histology. Histological staining on undecalcified sections included Toluidine blue, tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP).

The bone formation rate and mineral apposition rate will be determined by analysing the extent and separation of fluorescent markers by fluorescent microscopy micro-CT results revealed higher resorbability of the developed scaffolds (Sr-Hardystonite and Hardystonite) which was more pronounced with the Sr-Hardystonite. Toluidine blue staining revealed that the developed ceramics were well tolerated with no signs of rejection, necrosis, or infection. At three weeks post implantation, apparent bone formation was evident both at the periphery and within the pores of the all the scaffolds tested. Bone filled in the pores of the Sr- Hardystonite and Hardystonite scaffolds and was in close contact with the ceramic. In contrast, the control scaffolds showed more limited bone ingrowth and a cellular layer separating the ceramic scaffolds from the bone. By six weeks the Hardystonite and Sr Hardystonite scaffolds were integrated with the bone with most pores filled with new bone. The control scaffold showed new bone formation in the plane of the cortical bone but little new bone where the scaffold entered the marrow space. Sr Hardystonite showed the greatest resorbability with replacement of the ceramic material by bone.

We have developed novel engineered scaffolds (Sr-Hardystonite) for bone tissue regeneration. The developed scaffolds resorbed faster than the clinically used micro- TCP with greater amount of bone formation replacing the resorbed scaffold.

Scaffolds and Biomaterials used for skeletal tissue regeneration need to be biocompatible, osteo-inductive, osteo-conductive and mechanically compatible with bone to meet the requirements for bone tissue engineering. The aim of our research is to deliver

a new generation of stable, life-long orthopedic/dental implants that offer strong bone–implant anchorage.

Currently available modalities for treating large bone defects, are limited in their success. Developing synthetic scaffolds that promote bone growth and adequate vascularization is vital in orthopaedic and maxillofacial surgeries. The current generation of synthetic scaffolds, does not combine the required posorsity, mechanical properties and bioactivity. This presentation will highlight some of our newly developed novel highly porous and mechanically strong scaffolds that promote the migration, proliferation and differentiation of bone and endothelial cells for effective skeletal tissue integration and vascularization. Despite major advances in prosthetic technologies, implants have a finite life of 1015 years, due to their premature failure. Novel micro-engineered surfaces are required to anchor prosthetic implants to the surrounding bony skeleton. Various surface chemical modifications have been applied to prosthetic devices to enhance osseointegration. To-date none have resulted in a stable interface strong enough to support functional loading for the lifetime of the implant. Our group demonstrated that surface chemisrty modification of biomaterials with bioactive molecules have the potential to provide a surface on a prosthesis that is conducive to normal bone metabolism

Currently available calcium silicate based ceramics pseudowollostonite (CaSiO3) ceramics are regarded as a potential bioactive material for bone tissue regeneration due to their osseointegration properties. A drawback of CaSiO3 ceramics is that they possess high dissolution rate, leading to a high pH value in the surrounding environment thereby affecting the biological activity of bone cells. We hypothesize that chemical modification of CaSiO3 ceramics will improve their physical and biological properties. The coordinated activities of osteoblasts (OB) and osteoclasts (OC) are critical for proper bone remodelling. Moreover, growing evidence indicate that vascular endothelial cells are involved in bone development and remodelling.

Present study aims at Chemically modifying CaSiO3 by incorporating zinc (Zn) and titanium (Ti) into their structure to develop novel materials Hardystonite (HT, Ca2ZnSi2O7) and Sphene (CaTiSiO5), respectively and to determine their effect on bone cells OB & OC and on endothelial cells.

It is well known that cell behaviour in a culture system is influenced by the physiochemical characteristics of the substrate. Human bone derived cells (HBDC) cultured on HT and Sphene supported the HBDC attachment (cells exhibited well defined cytoskeletal structure) showed characteristic features of cellular proliferation and differentiation. In addition, Zn and Ti incorporation into CaSiO3 supported the formation of mature, active and functional OC. Moreover, the modified bio-materials were found to be conducive to Human micro-vascular dermal endothelial cell growth. Our results suggest that HT and Sphene possessed an improved physical characteristics and enhanced biological activities of bone cells (OB & OC) and endothelial cells thus rendering it a potential material for bone tissue regeneration and coatings onto commonly used orthopaedic and dental implants.

CaSiO3 has been used a potential bioactive material for bone regeneration. A drawback of the CaSiO3 ceramics is that they possess high dissolution rate of Ca ions leading to a high pH value environment [1], which can disadvantage cell growth. Zn can enhance osteoconductivity of CaP ceramics and stimulate bone formation [2]. The aims of this study are:

In situ preparation and optimization of Zn-CaSiO3 ceramics by the evaluating of physical and chemical properties, osteoblast and osteoclast behavior;

Zn-CaSiO3 ceramics containing zero, ten, 20 and 50-mol% of Zn were sintered at 1260 °C. The dissolution and apatite formation ability were evaluated by soaking in simulated body fluids. Attachment, proliferation and differentiation of human primary bone-derived cells (HBDC) on ceramic disks were evaluated. Human monocytes isolated from buffy coats were differentiated into mature and functional osteoclast (OC) by culturing them for 21 days on ceramic disks. Then, the optimized HT (50%Zn-CaSiO3) coating on Ti-6Al-4V was prepared by sol-gel spinning method.

The incorporation of Zn in CaSiO3 resulted in part of new phase formation (HT) formation in Zn-Ca-Si ceramics. When adding 50 mol% of Zn, only pure HT phase existed.

The incorporation of Zn in CaSiO3 decreased the dissolution and pure 50 mol% of Zn (HT ceramics) resulted in the lowest dissolution.

Zn-CaSiO3 ceramics with different Zn contents supported HBDC attachment. With the increase of Zn contents, HBDC proliferation and differentiation improved. The surface roughness of Sol-gel HT coating is about 0.49 μm. The thickness of coating is about 1 μm. HT coating has a similar dissolution kinetics and stability with hydroxyapatite coating.

Zn decreases the dissolution in Zn-Ca-Si ceramics and enhances HBDC proliferation and differentiation. The optimized HT ceramics (50mol% Zn) support OC resorption and can be used for a stable biomedical coating application.