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Long bone defects still represent a major clinical challenge in orthopedics, with the inherent loss of function considerably impairing the quality of life of the affected patients. Thus, the purpose of this study was to assess the safety and potential of bone regeneration offered by a load-bearing scaffold characterized by unique hierarchical architecture and high strength, with active surface facilitating new bone penetration and osseointegration in critical size bone defects. The results of this study showed the potential of bio-ceramization processes applied to vegetable hierarchical structures for the production of new wood-derived bone scaffolds, further improved by surface functionalization, with good biological and mechanical properties leading to successful treatment of critical size bone defects in the sheep model. Future studies are needed to evaluate if these scaffolds prototypes, as either biomaterial alone or in combination with augmentation strategies, may represent an optimal solution to enhance bone regeneration in humans., (© 2019 Wiley Periodicals, Inc.)

Several biomaterials have recently been developed to address the challenge of osteochondral regeneration. Among these, chitosan holds promises both for cartilage and bone healing. The aim of this in vivo study was to evaluate the regeneration potential of a novel hybrid magnesium-doped hydroxyapatite (MgHA), collagen, chitosan-based scaffold, which was tested in a sheep model to ascertain its osteochondral regenerative potential, and in a rabbit model to further evaluate its ability to regenerate bone tissue. Macroscopic, microtomography, histology, histomorphometry, and immunohistochemical analysis were performed. In the sheep model, all analyses did not show significant differences compared to untreated defects ( p > 0.05), with no evidence of cartilage and subchondral bone regeneration. In the rabbit model, this bone scaffold provided less ability to enhance tissue healing compared with a commercial bone scaffold. Moreover, persistence of scaffold material and absence of integration with connective tissue around the scaffolds were observed. These results raised some concerns about the osteochondral use of this chitosan composite scaffold, especially for the bone layer. Further studies are needed to explore the best formulation of chitosan-reinforced composites for osteochondral treatment.

The present work investigates heterogeneous gas-solid reactions involved in the biomorphic transformation of natural wood into large 3-D hydroxyapatite (HA) scaffolds recapitulating physico-chemical, morphological and mechanical features typical of natural bone. In particular, we found that the use of a reactive CO2/H2O gas mixture, under supercritical conditions at high pressure, permits to control heterogeneous CaO-CO2 reactions throughout the whole bulk and to direct the nucleation-growth of CaCO3 at a relatively low temperature, thus obtaining a highly reactive 3-D precursor enabling the formation of a large biomorphic HA scaffold preserving fine nanostructure by a hydrothermal process. To the best of our knowledge, the application of heterogeneous chemical reactions in the 3-D state is an original way to generate large HA scaffolds maintaining bio-relevant ionic substitutions, with specific regard to Mg2+, Sr2+ and CO32- ions, conferring a superior ability to guide cell fate. We hypothesize that the original nanostructure of the final 3-D HA scaffold, not achievable by the classic sintering procedure, and the multi-scale hierarchical organization inherited by the original template, account for its high compression strength with damage-tolerant mechanical behaviour. The ability of the new scaffold to induce bone regeneration is attested by the overexpression of genes, early and late markers of the osteogenic differentiation pathway, and by the in vivo osteoinductivity. We hypothesize that the unique association of bioactive chemical composition, nanostructure and multi-scale hierarchy can synergistically act as instructing signals for cells to generate new bone tissue with organized 3-D architecture. These results point to its great applicative potential for the regeneration of large bone defects, which is a still unmet clinical need.

Current therapeutic strategies for osteochondral restoration showed a limited regenerative potential. In fact, to promote the growth of articular cartilage and subchondral bone is a real challenge, due to the different functional and anatomical properties. To this purpose, alginate is a promising biomaterial for a scaffold-based approach, claiming optimal biocompatibility and good chondrogenic potential. A previously developed mineralized alginate scaffold was investigated in terms of the ability to support osteochondral regeneration both in a large and medium size animal model. The results were evaluated macroscopically and by microtomography, histology, histomorphometry, and immunohistochemical analysis. No evidence of adverse or inflammatory reactions was observed in both models, but limited subchondral bone formation was present, together with a slow scaffold resorption time.The implantation of this biphasic alginate scaffold provided partial osteochondral regeneration in the animal model. Further studies are needed to evaluate possible improvement in terms of osteochondral tissue regeneration for this biomaterial.

The discovery of new strategies to repair large segmental bone defects is currently an open challenge for worldwide clinicians. In the treatment of critical-sized bone defects, an alternative strategy to traditional bone grafting is always more frequently the use of tailor-made scaffolds modelled on the final size and shape of the implant site. Here, poly-ε-caprolactone-based composite scaffolds including poly-L-lactic acid continuous fibres and hyaluronan derivates (i.e. HYAFF11®) have been investigated for the peculiar 3D architecture characterized by interconnected macroporous networks and tunable mechanical properties. Composite scaffolds were immersed in simulated body fluid solution in order to support in vivo tissue in-growth. Scaffolds loaded with autologous cells (bone marrow stromal cells) plus platelet-rich plasma and osteoconductive protein such bone morphogenetic protein-7 were also tested to evaluate eventual enhancement in bone regeneration. The morphological and mechanical properties of poly-L-lactic acid-reinforced composite scaffolds have been studied to identify the optimal scaffold design to match the implant-site requirements of sheep metatarsal defects. Dynamic mechanical tests allowed to underline the viscoelastic response of the scaffold - resulting in elastic moduli from 2.5 to 1.3 MPa, suitable to temporarily support the structural function of damaged bone tissue. In vivo preliminary investigations in a sheep model of metatarsus shaft defect also showed the attitude of the scaffold to promote osteogenesis, preferentially in association with bone marrow stromal cell and platelet-rich plasma, even if the highest amount of mature bone was reached in the case of scaffold loaded with human bone morphogenetic protein-7 released via hydrolytic degradation of HYAFF11® phases in the implant site., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Current research aims to develop innovative approaches to improve chondral and osteochondral regeneration. The objective of this study was to investigate the regenerative potential of platelet-rich plasma (PRP) to enhance the repair process of a collagen-hydroxyapatite scaffold in osteochondral defects in a sheep model., Methods: PRP was added to a new, multi-layer gradient, nanocomposite scaffold that was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. Twenty-four osteochondral lesions were created in sheep femoral condyles. The animals were randomised to three treatment groups: scaffold, scaffold loaded with autologous PRP, and empty defect (control). The animals were sacrificed and evaluated six months after surgery., Results: Gross evaluation and histology of the specimens showed good integration of the chondral surface in both treatment groups. Significantly better bone regeneration and cartilage surface reconstruction were observed in the group treated with the scaffold alone. Incomplete bone regeneration and irregular cartilage surface integration were observed in the group treated with the scaffold where PRP was added. In the control group, no bone and cartilage defect healing occurred; defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed., Conclusions: The hydroxyapatite-collagen scaffold enhanced osteochondral lesion repair, but the combination with platelet growth factors did not have an additive effect; on the contrary, PRP administration had a negative effect on the results obtained by disturbing the regenerative process. In the scaffold + PRP group, highly amorphous cartilaginous repair tissue and poorly spatially organised underlying bone tissue were found.

The use of spinal fusion procedures has rapidly augmented over the last decades and although autogenous bone graft is the “gold standard” for these procedures, alternatives to its use have been investigated over many years. A number of emerging strategies as well as tissue engineering with mesenchymal stem cells (MSCs) have been planned to enhance spinal fusion rate. This descriptive systematic literature review summarizes the in vivo studies, dealing with the use of MSCs in spinal arthrodesis surgery and the state of the art in clinical applications. The review has yielded promising evidence supporting the use of MSCs as a cell-based therapy in spinal fusion procedures, thus representing a suitable biological approach able to reduce the high cost of osteoinductive factors as well as the high dose needed to induce bone formation. Nevertheless, despite the fact that MSCs therapy is an interesting and important opportunity of research, in this review it was detected that there are still doubts about the optimal cell concentration and delivery method as well as the ideal implantation techniques and the type of scaffolds for cell delivery. Thus, further inquiry is necessary to carefully evaluate the clinical safety and efficacy of MSCs use in spine fusion. [ABSTRACT FROM AUTHOR]

The article presents a study that evaluates the behavior of the scaffold and the changes in porosity for pre-clinical studies using a micro-CT system. It reveals that the system offers the possibility to study the porosity of a biomaterial in two- or three-dimension (3D) and to evaluate the unconnected and connected internal pores. It also suggests that the system is helpful in characterizing devices in the pre-implant phase and evaluating possible deformations in the explant phase.