Comparison of bone formation mediated by bone morphogenetic protein delivered by nanoclay gels with clinical techniques (autograft and InductOs^®) in an ovine bone model

Abstract

Development of a growth factor delivery vehicle providing appropriate temporal-spatial release together with an appropriate preclinical large animal model to evaluate bone formation is critical in the development of delivery strategies for bone tissue regeneration. Smectite nanoclays such as LAPONITE™ possess unique thixotropic and protein retention properties offering promise for use in growth factor delivery in bone repair and regeneration. This study has examined bone formation mediated by a clinically approved growth factor delivery system (InductOs®) in combination with Laponite gel in an aged female ovine femoral condyle defect preclinical model (10 weeks). Two different designs, one containing a low volume of Laponite gel (LLG) in combination with the InductOs® absorbable collagen sponge (ACS), the other in which Laponite gel formed the implant (HLG), were compared against InductOs® alone and an autograft positive control. Thus, five groups: (i) empty defect, (ii) autograft, (iii) BMP2 + ACS, (iv) BMP2 + ACS + LLG and (v) BMP2 + HLG + ACS were examined in 9 mm × 12 mm defects performed bilaterally in the medial femoral condyles of 24 aged (>5 years) sheep. Bone formation within the defect was assessed using micro-computed tomography (micro-CT), digital volume correlation (DVC) for biomechanical characterisation as well as histology. The autograft and InductOs® mediated enhanced bone formation ( p < 0001) compared to blank controls, while no significant differences were observed between the Laponite/Collagen/BMP delivery vehicles. However, the current study illustrated the excellent biocompatibility of Laponite and its ability to deliver localised active BMP-2, with the opportunity for improved efficacy with further optimisation. Interestingly, DVC-computed strain distributions indicated that the regenerated bone structure is mechanically adapted to bear external loads from the early remodelling stages of the bone reparation cascade. The current studies of selected nanoclay delivery platforms for BMP, assessed in a clinically relevant large animal model auger well for the development of bone fracture therapeutics for an ageing population.

Physicochemical and biological analysis of composite biomaterials containing hydroxyapatite for biological applications

“…12 Also important in the development of materials to promote bone tissue regeneration are the possibility of using fibrous biomaterials 13 and growth factor carriers. 14 Scaffolds designed for tissue engineering and containing hydroxyap- investigations were promisingit was concluded that the tested materials showed biocompatibility which make them promising in terms of their application potential for biomedical purposes. 15 On the other hand, Olam and Tosun proved that the 3D-printing technique was an effective method for fabrication of polymer composites based on poly(lactic acid) and containing both titanium dioxide and hydroxyapatite of natural and synthetic origin.…”

“…Yu et al demonstrated that such hydrogels promote the proliferation, migration and in vitro osteogenic differentiation of bone marrow‐derived stem cells 12 . Also important in the development of materials to promote bone tissue regeneration are the possibility of using fibrous biomaterials 13 and growth factor carriers 14 …”

Photocrosslinked Gelatin Methacryloyl (GelMA)/Hyaluronic Acid Methacryloyl (HAMA) Composite Scaffold Using Anthocyanidin as a Photoinitiator for Bone Tissue Regeneration

“…Hence, hydrogels’ mechanical strength and degradability can be controlled by combining natural hydrogels with synthetic biopolymers or dual crosslinking methods. , In previous studies, gelatin has been modified with methacrylic anhydride to form gelatin methacryloyl (GelMA). GelMA has been used in tissue engineering (including nerve engineering, skeletal muscle, liver, kidney, and bones), alternate 3D culture systems for cancer cells, controlled drug release, and nonviral gene or growth factor delivery applications. , Similar to gelatin, HA is a biopolymer with repeated units of β-1,4- d -glucuronic acid and β-1,3- N -acetyl- d -glucosamine connected by a glycosidic linkage; it is widely reported in various biomedical applications. , HA is a glycosaminoglycan present in the human body; moreover, it is a significant component of the ECM that plays a vital role in wound healing and regulating tissue formation. HA is an anionic polysaccharide biopolymer with poor cell adhesiveness and rapid degradation. , Recent reports have shown that photocrosslinked hyaluronic acid methacryloyl (HAMA) provides a better method for tissue engineering applications than unmodified HA.…”

“…GelMA has been used in tissue engineering (including nerve engineering, skeletal muscle, liver, kidney, and bones), alternate 3D culture systems for cancer cells, controlled drug release, and nonviral gene or growth factor delivery applications. 17,18 Similar to gelatin, HA is a biopolymer with repeated units of β-1,4-D-glucuronic acid and β-1,3-N-acetyl-D-glucosamine connected by a glycosidic linkage; it is widely reported in various biomedical applications. 19,20 HA is a glycosaminoglycan present in the human body; moreover, it is a significant component of the ECM that plays a vital role in wound healing and regulating tissue formation.…”

Nanocore–Shell Bone Filler Contained Mesoporous Silica Modified with Hydroxyapatite Precursors; Wrapped in a Natural Metal–Phenolic Network

“…Bone defects caused by bone disease, tumors, bone infections, congenital deformity, and societal aging lead to significant demand for bone substitutes, traditionally treated using the patient’s bone (autograft) . However, disadvantages associated with autografts, such as limited availability and risk of infection, have increased the need to develop artificial bone substitutes. , In this regard, natural bone ash, porous bioactive glass, polymeric microspheres for delivering growth factors, polymeric scaffolds including hydroxyapatite (HA), , surface-modified implants, nanoclay gels, and mesoporous calcium phosphates nanoparticles were investigated for the treatment of bone disease in vitro and in vivo.…”