Intrinsic Osteoinductivity of Porous Titanium Scaffold for Bone Tissue Engineering.

Large bone defects and nonunions are serious complications that are caused by extensive trauma or tumour. As traditional therapies fail to repair these critical-sized defects, tissue engineering scaffolds can be used to regenerate the damaged tissue. Highly porous titanium scaffolds, produced by selective laser sintering with mechanical properties in range of trabecular bone (compressive strength 35 MPa and modulus 73 MPa), can be used in these orthopaedic applications, if a stable mechanical fixation is provided. Hydroxyapatite coatings are generally considered essential and/or beneficial for bone formation; however, debonding of the coatings is one of the main concerns. We hypothesised that the titanium scaffolds have an intrinsic potential to induce bone formation without the need for a hydroxyapatite coating. In this paper, titanium scaffolds coated with hydroxyapatite using electrochemical method were fabricated and osteoinductivity of coated and noncoated scaffolds was compared in vitro. Alizarin Red quantification confirmed osteogenesis independent of coating. Bone formation and ingrowth into the titanium scaffolds were evaluated in sheep stifle joints. The examinations after 3 months revealed 70% bone ingrowth into the scaffold confirming its osteoinductive capacity. It is shown that the developed titanium scaffold has an intrinsic capacity for bone formation and is a suitable scaffold for bone tissue engineering.

The effect of an alginate carrier on bone formation in a hydroxyapatite scaffold.

This study investigated the osteoconductive properties of a porous hydroxyapatite (HA) scaffold manufactured using a novel technique similar to the bread-making process, alone and in combination with an alginate polysaccharide fiber gel (HA/APFG putty) and autologous bone marrow aspirate (BMA). The hypothesis was that the HA/APFG putty would be as osteoconductive as granular HA and that the presence of BMA would further enhance bone formation in an ovine femoral condyle critical defect model. Thirty-six defects were created and either (1) porous HA granules, (2) HA/APFG putty, or (3) HA/APFG putty + BMA were implanted. After retrieval at 6 and 12 weeks, image analysis techniques were used to quantify bone apposition rates, new bone area, bone-HA scaffold contact, and implant resorption. At 6 weeks postsurgery, significantly lower bone apposition rates were observed in the HA/APFG putty group when compared to the HA (p = 0.014) and HA/APFG putty + BMA (p = 0.014) groups. At 12 weeks, significantly increased amounts of new bone formation were measured within the HA scaffold (33.56 ± 3.53%) when compared to both the HA/APFG putty (16.69 ± 2.7%; p = 0.043) and the defects containing HA/APFG putty + BMA (19.31 ± 3.8%; p = 0.043). The use of an APFG gel as a carrier for injectable CaP bone substitute materials delayed bone formation in this model compared to HA granules alone which enhanced bone formation especially within the interconnected smaller pores. Our results also showed that the addition of autologous BMA did not further enhance its osteoconductive properties. Further study is required to optimize the degradation rate of this APFG binding agent before using as a directly injectable material for repair of bone defect. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1328-1335, 2016.

A novel multiparameter in vitro model of three-dimensional cell ingress into scaffolds for dermal reconstruction to predict in vivo outcome.

The clinical demand for effective dermal substitutes continues as current commercially available products present limitations. However, there are no definitive in vitro methods to predict in vivo outcomes such as integration, cellularization and contraction, which may help the development of new dermal scaffolds. This study aimed to develop a multiparameter in vitro model of three-dimensional (3D) cell ingress into dermal scaffolds to predict in vivo outcomes of new dermal scaffolds under development. A new dermal scaffold, Smart Matrix, was compared to the scar-forming contractile collagen gel model and to the clinically well-established Integra(®) and Matriderm(®). Parameters studied were cell viability and proliferation, apoptosis, matrix contraction, cell morphology, α-smooth muscle actin, and growth factor expression. Combinatorial evaluation of the results in a scoring matrix showed that Smart Matrix could offer an advantage over existing products. This method would be useful as an international golden scoring matrix to develop new dermal scaffolds that effectively improve the existing products, thus enabling better treatments for burns or chronic wounds.

Effect of increased strut porosity of calcium phosphate bone graft substitute biomaterials on osteoinduction.

The effect of increasing strut porosity on the osteoinductivity of porous calcium phosphate (CaP) and silicate-substituted calcium phosphate (SiCaP) bone substitute materials was investigated in an ovine ectopic model. One to two millimeter-sized granules or block implants with strut porosities of 10, 20, or 30% were inserted into the left and right paraspinalis muscle. At 12 weeks, histological sections were prepared through the center of each implant and bone contact, bone area and implant area quantified. Backscattered scanning electron microscopy (bSEM) was used to visualize bone within small pores in the struts of the scaffolds. Increased bone formation was measured in the SiCaP with 30% strut porosity (5.482% ± 1.546%) when compared with the nonsilicate CaP with the same morphology (1.160% ± 0.502%, p = 0.02), indicating that silicate substitution may increase osteoinduction. Greater bone formation was seen in scaffolds with increased strut porosity. No bone growth was found in any of the SiCaP scaffold with 10% porosity. There was no significant difference between block and granule specimens. Scanning electron microscopy and EDX in combination with histology demonstrated bone formation within pores <5 µm in size. The use of silicate-substituted CaP material with increased strut porosity may further augment repair and regeneration in bony sites.

The osteoinductivity of silicate-substituted calcium phosphate.

BACKGROUND: The osteoinductivity of silicate-substituted calcium phosphate and stoichiometric calcium phosphate was investigated with use of ectopic implantation. Implants with a macroporosity of 80% and a strut porosity of 30% were inserted into sites located in the left and right paraspinal muscles of six female sheep. METHODS: After twelve weeks in vivo, a longitudinal thin section was prepared through the center of each implant. Bone formation within the implant, bone formation in contact with the implant surface, and implant resorption were quantified with use of a line intersection method. The specimens were also analyzed with use of backscattered scanning electron microscopy and energy-dispersive x-ray analysis. RESULTS: Silicate substitution had a significant effect on the formation of bone both within the implant and on the implant surface during the twelve-week period. Bone area within the implant was greater in the silicate-substituted calcium phosphate group (mean, 7.65% ± 3.2%) than in the stoichiometric calcium phosphate group (0.99% ± 0.9%, p = 0.01). The amount of bone formed at the surface of the implant was also significantly greater in the silicate-substituted calcium phosphate group (mean, 26.00% ± 7.8%) than in the stoichiometric calcium phosphate group (2.2% ± 2.0%, p = 0.01). Scanning electron microscopy demonstrated bone formation within pores that were <5 µm in size, and energy-dispersive x-ray analysis confirmed the presence of silicon within the new bone in the silicate-substituted calcium phosphate group. CONCLUSIONS: The formation of bone within muscle during the twelve-week period showed both silicate-substituted calcium phosphate and stoichiometric calcium phosphate to be osteoinductive in an ovine model. Silicate substitution significantly increased the amount of bone that formed and the amount of bone attached to the implant surface. New bone formation occurred through an intramembranous process within the implant structure.