Aims. A large number of surgical operations are available to treat osteochondral defects of the knee. However, the knee joint arthroplasty materials cannot completely mimic the articular cartilage and subchondral bone, which may bring some obvious side effects. Thus, this study proposed a biocompatible osteochondral repair material prepared from a double-layer scaffold of collagen and nanohydroxyapatite (CHA), consisting of collagen hydrogel as the upper layer of the scaffold, and the composite of CHA as the lower layer of the scaffold. Methods. The CHA scaffold was prepared, and properties including morphology, internal structure, and mechanical strength of the CHA scaffold were measured by scanning electron microscopy (SEM) and a MTS electronic universal testing machine. Then, biocompatibility and repair capability of the CHA scaffold were further evaluated using a rabbit knee cartilage defect model. Results. The CHA scaffold was well suited for the repair of articular cartilage and subchondral bone; the in vitro results showed that the CHA scaffold had good cytocompatibility. In vivo experiments demonstrated that the material had high biocompatibility and effectively induced cartilage and subchondral bone regeneration. Conclusion. The CHA scaffold has a high potential for commercialization and could be used as an effective knee repair material in clinical applications. Cite this article: Bone Joint Res 2025;14(2):155–165

Sustained release of BMP-2 is reported to be able to reduce the required dose of BMP-2 for bone induction. Nanohydroxyapatite (nHAp) has an osteoinduction capability which is lack in conventional hydroxyapatite. In this study, we combined PLA-PEG with nHAp and investigated the bone regenerative capacity of the newly established composite material of rhBMP-2/PLA-PEG/nHAp in a rat model of spinal fusion. The PLA-PEG was liquidized in acetone and mixed with nHAp and rhBMP-2. The sheet-shaped BMP-2/PLA-PEG (5mg)/nHAp (12.5mg) composites were prepared while evaporating the acetone. The release kinetics of rhBMP-2 from the composite was investigated by ELISA. In vivo bone formation was investigated by posterolateral spinal fusion in rats (the dosage of rhBMP-2; 0µg/ 0.5µg / 3µg). Bone formation was assessed by µCT and histology at post-op. 8 weeks. The composite showed the burst-release in the initial 24 hours (69% of total release) and the subsequent sustained-release for 25 days. According to µCT and histology of the spinal fusion experiment for all groups the bone formation was observed. While no bony bridging was observed in 0 µg and 0.5 µg BMP groups; in 3 µg group bony bridging and fusion were achieved. We developed a new technology for bone regeneration with rhBMP-2/PLA-PEG/nHAp composite. The reduction in the required dose of BMP-2 for bone induction was achieved. This result can be explained by the high bone induction ability of nHAp and sustainable release of BMP from PLA-PEG in the composite

To prevent the reported side effects of rhBMP-2, an important cytokine with bone forming capacity, the sustained release of rhBMP-2 is highly important. Synthetic copolymer polylactic acid-polyethylene glycol (PLA-PEG) is already shown to be a good carrier for rhBMP-2. The nano-sized hydroxyapatite (nHAp) is mentioned to be superior to conventional hydroxyapatite due to its decreased particle size which increases the surface area, so protein-cell adhesion and mechanical properties concomitantly. In the literature no study is reported with PLA-PEG / rhBMP-2/ nHAp for bone regeneration. In this study, we assessed the controlled release profile of rhBMP-2 from the novel biomaterial of PLA-PEG / rhBMP-2 / nHAp in vitro and evaluated the bone forming capacity of the composite in rat posterolateral spinal fusion (PSF) model in vivo.

Composites were prepared via addition of rhBMP-2 (0µg, 3µg or 10µg) and nHAp (12.5mg) into PLA-PEG (5mg) + acetone solution and shaping. The release kinetics of the cytokine from the composites with 5µg BMP-2 was investigated by ELISA. The effect of nHAp and nHAp with rhBMP-2 on cell differentiation (rat BMSC cells, passage 3) was tested with ALP staining. In vivo bone formation was investigated by PSF on L4-L5 in a total of 36 male SD rats and weekly µCT results and histology at 8^th weeks post operation were used for assessment of the bone formation. All animal experiments was approved by the institutional review board confirming to the laws and regulations of Japan.

The composite showed an initial burst release in the first 24 hours (51.7% of the total released rhBMP-2), but the release was continued for the following 21 days. Thus, the sustained release of rhBMP-2 from the composite was verified. ALP staining results showed nHAp with rhBMP-2 contributed better on differentiation than nHAp itself. µCT and histology demonstrated that spinal fusion was achieved either one or both transverse processes in almost all BMP 3µg and BMP 10µg treated animals. On the contrary, only small or no bone formation was observed in the BMP0µg group (bilateral non-union / unilateral fusion/ bilateral fusion, BMP0µg group; 9/0/0, BMP3µg group; 1/0/11, BMP10µg group; 0/1/11).

We developed a new technology for bone regeneration with BMP-2/PLA-PEG/nHAp composite. With this composite, the required dose of BMP-2 for spinal fusion in rats (10µg) was decreased to 1/3 (3µg) which can be explained by the superior properties of nano-sized hydroxyapatite and by the achievement of sustainable release of rhBMP-2 from the composite.

This study is supported by Japanese Society of the Promotion of Science (JSPS) and Scientific and Technological Research Council of Turkey (TUBITAK). [Project No: 215S834]

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.

Cite this article: Bone Joint Res 2024;13(12):725–740.

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.