Enhancing BMP-2-mediated osteogenesis with a synthetic heparan sulfate mimetic.

Bone morphogenetic protein 2 (BMP-2) is an osteoinductive protein and a potent inducers of bone formation, playing an essential role during bone fracture repair. Heparan sulfate (HS), a highly charged and linear polysaccharide, is known to interact with and enhance BMP-2 bioactivity. Despite showing potential as a potent adjuvant of the endogenous bone healing response, commercially available HS is derived from animal sources which are less desirable when considering translation into the clinic.

Rational synthesis of a heparan sulfate saccharide that promotes the activity of BMP2.

Heparan sulfate (HS) is a glycosaminoglycan (GAG) found throughout nature and is involved in a wide range of functions including modulation of cell signalling via sequestration of growth factors. Current consensus is that the specificity of HS motifs for protein binding are individual for each protein. Given the structural complexity of HS the synthesis of libraries of these compounds to probe this is not trivial.

Affinity-selected heparan sulfate collagen device promotes periodontal regeneration in an intrabony defect model in Macaca fascicularis.

It is challenging to regenerate periodontal tissues fully. We have previously reported a heparan sulfate variant with enhanced affinity for bone morphogenetic protein-2, termed HS3, that enhanced periodontal tissue regeneration in a rodent model. Here we seek to transition this work closer to the clinic and investigate the efficacy of the combination HS3 collagen device in a non-human primate (NHP) periodontitis model.

Biphasic calcium phosphate with submicron surface topography in an model of instrumented posterolateral spinal fusion.

As spinal fusions require large volumes of bone graft, different bone graft substitutes are being investigated as alternatives. A subclass of calcium phosphate materials with submicron surface topography has been shown to be a highly effective bone graft substitute. In this work, a commercially available biphasic calcium phosphate (BCP) with submicron surface topography (MagnetOs; Kuros Biosciences BV) was evaluated in an model of instrumented posterolateral fusion.

A Heparan Sulfate Device for the Regeneration of Osteochondral Defects.

Repairing damaged joint cartilage remains a significant challenge. Treatment involving microfracture, tissue grafting, or cell therapy provides some benefit, but seldom regenerates lost articular cartilage. Providing a point-of-care solution that is cell and tissue free has the potential to transform orthopedic treatment for such cases.

Variation of the bone forming ability with the physicochemical properties of calcium phosphate bone substitutes.

Because of their bioactive properties and chemical similarity to the inorganic component of bone, calcium phosphate (CaP) materials are widely used for bone regeneration. Six commercially available CaP bone substitutes (Bio-Oss, Actifuse, Bi-Ostetic, MBCP, Vitoss and chronOs) as well as two tricalcium phosphate (TCP) ceramics with either a micron-scale (TCP-B) or submicron-scale (TCP-S) surface structure are characterized and their bone forming potential is evaluated in a canine ectopic implantation model. After 12 weeks of implantation in the paraspinal muscle of four beagles, sporadic bone (0.

Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis.

Unlabelled: The surface topography of synthetic biomaterials is known to play a role in material-driven osteogenesis. Recent studies show that TGFβ signalling also initiates osteogenic differentiation. TGFβ signalling requires the recruitment of TGFβ receptors (TGFβR) to the primary cilia.

Cells responding to surface structure of calcium phosphate ceramics for bone regeneration.

Surface structure largely affects the inductive bone-forming potential of calcium phosphate (CaP) ceramics in ectopic sites and bone regeneration in critical-sized bone defects. Surface-dependent osteogenic differentiation of bone marrow stromal cells (BMSCs) partially explained the improved bone-forming ability of submicron surface structured CaP ceramics. In this study, we investigated the possible influence of surface structure on different bone-related cells, which may potentially participate in the process of improved bone formation in CaP ceramics.

Biocompatibility evaluation of dicalcium phosphate/calcium sulfate/poly (amino acid) composite for orthopedic tissue engineering in vitro and in vivo.

In vitro cytocompatibility of ternary biocomposite of dicalcium phosphate (DCP) and calcium sulfate (CS) containing 40 wt% poly (amino acid) (PAA) was evaluated using L929 fibroblasts and MG-63 osteoblast-like cells. Thereafter, the biocompatibility of biocomposite in vivo was investigated using an implantation in muscle and bone model. In vitro L929 and MG-63 cell culture experiments showed that the composite and PAA polymer were noncytotoxic and allowed cells to adhere and proliferate.

Submicron-surface structured tricalcium phosphate ceramic enhances the bone regeneration in canine spine environment.

Calcium phosphate ceramics with submicron-scaled surface structure can trigger bone formation in non-osseous sites and are expected to enhance bone formation in spine environment. In this study, two tricalcium phosphate ceramics having either a submicron-scaled surface structure (TCP-S) or a micron-scaled one (TCP-B) were prepared and characterized regarding their physicochemical properties. Granules (size 1-2 mm) of both materials were implanted on either left or right side of spinous process, between the two lumbar vertebrae (L3-L4), and in paraspinal muscle of eight beagles.

Mechanics, degradability, bioactivity, in vitro, and in vivo biocompatibility evaluation of poly(amino acid)/hydroxyapatite/calcium sulfate composite for potential load-bearing bone repair.

A ternary composite of poly(amino acid), hydroxyapatite, and calcium sulfate (PAA/HA/CS) was prepared using in situ melting polycondensation method and evaluated in terms of mechanical strengths, in vitro degradability, bioactivity, as well as in vitro and in vivo biocompatibility. The results showed that the ternary composite exhibited a compressive strength of 147 MPa, a bending strength of 121 MPa, a tensile strength of 122 MPa, and a tensile modulus of 4.6 GPa.

Strontium-containing apatite/polylactide composites enhance bone formation in osteopenic rabbits.

Unlabelled: Strontium (Sr) has been shown to favor bone formation and is used clinically to treat osteoporosis. We have previously reported that Sr addition in apatite/polylactide composites could enhance the BMP-induced bone formation around implants at ectopic site in healthy animals. In this study we aimed to investigate the effectiveness of Sr addition on the local bone formation in osteoporosis.

Osteoclast resorption of beta-tricalcium phosphate controlled by surface architecture.

A resorbable bone graft substitute should mimic native bone in its capacity to support bone formation and be remodeled by osteoclasts (OCl) or other multinucleated cells such as foreign body giant cells (FBGC). We hypothesize that by changing the scale of surface architecture of beta-tricalcium phosphate (TCP), cellular resorption can be influenced. CD14(+) monocyte precursors were isolated from human peripheral blood (n = 4 independent donors) and differentiated into OCl or FBGC on the surface of TCP discs comprising either submicron- or micron-scale surface topographical features (TCPs and TCPb, respectively).

Degradability and cytocompatibility of tricalcium phosphate/poly(amino acid) composite as bone tissue implants in orthopaedic surgery.

In this study, a tricalcium phosphate (TCP) and poly (amino acid) copolymer (PAA) biocomposite were fabricated for bone repair and characterized. The results show that the compressive strength of the TCP/PAA composites increased with an increase in the TCP content at TCP contents less than 40 w%. The weight loss of the composite after soaking in phosphate buffered saline for 12 weeks significantly increased with an increase in the TCP content, revealing its good degradability.

The size of surface microstructures as an osteogenic factor in calcium phosphate ceramics.

The microporosity of calcium phosphate (CaP) ceramics has been shown to have an essential role in osteoinduction by CaP ceramics after ectopic implantation. Here we show that it is not the microporosity but the size of surface microstructural features that is the most likely osteogenic factor. Two tricalcium phosphate (TCP) ceramics, namely TCP-S and TCP-B, were fabricated with equivalent chemistry and similar microporosity but different sizes of surface microstructural features.

Zinc in calcium phosphate mediates bone induction: in vitro and in vivo model.

Zinc-containing tricalcium phosphate (Zn-TCP) was synthesized to investigate the role of zinc in osteoblastogenesis, osteoclastogenesis and in vivo bone induction in an ectopic implantation model. Zinc ions were readily released in the culture medium. Zn-TCP with the highest zinc content enhanced the alkaline phosphatase activity of human bone marrow stromal cells and tartrate-resistant acid phosphatase activity, as well as multinuclear giant cell formation of RAW264.

Influence of polymer molecular weight in osteoinductive composites for bone tissue regeneration.

In bone tissue regeneration, certain polymer and calcium-phosphate-based composites have been reported to enhance some biological surface phenomena, facilitating osteoinduction. Although the crucial role of inorganic fillers in heterotopic bone formation by such materials has been shown, no reports have been published on the potential effects the polymer phase may have. The present work starts from the assumption that the polymer molecular weight regulates the fluid uptake, which determines the hydrolysis rate and the occurrence of biological surface processes.

Controlling dynamic mechanical properties and degradation of composites for bone regeneration by means of filler content.

Bone tissue is a dynamic composite system that adapts itself, in response to the surrounding daily (cyclic) mechanical stimuli, through an equilibrium between growth and resorption processes. When there is need of synthetic bone grafts, the biggest issue is to support bone regeneration without causing mechanically-induced bone resorption. Apart from biological properties, such degradable materials should initially support and later leave room to bone formation.

Bone substitute biomedical material of multi-(amino acid) copolymer: in vitro degradation and biocompatibility.

Degradable polymers with good mechanical strength as bone repair biomaterials have been paid more attention in biomedical application. In this study, a multi-(amino acid) copolymer consisting of 6-aminocaproic acid and five natural amino acids was prepared by a reaction of acid-catalyzed condensation. The results revealed that the copolymer could be slowly degradable in Tris-HCl solution, and lost its initial weight of 31.