Dental-derived stem cells and biowaste biomaterials:What’s next in bone regenerative medicine applications

The human teeth and oral cavity harbor various populations of mesenchymal stem cells(MSCs),so called dental-derived stem cells(D-dSCs)with self-renewing and multilineage differentiation capabilities.D-dSCs properties involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment.Altogether,this viewpoint develops a general picture of current innovative strategies to employ D-dSCs combined with biomaterials and bioactive factors for regenerative medicine purposes,and offers information regarding the available scientific data and possible applications.

Mimicking the native bone regenerative microenvironment for in situ repair of large physiological and pathological bone defects

Bone is a complex biological tissue with a complicated hierarchical nanocomposite structure.The native microen-vironment of the bone tissue may be significantly disrupted by large physiological and pathological bone defects.Bone defects are often treated via complex surgical procedures that involve the application of autografts or al-lografts.While these grafting procedures often suffer from insufficient natural bone stock and immunorejection.Moreover,these traditional treatment methods fail to simulate a regenerative microenvironment,which plays a significant role in regeneration of bone tissue and repair of large bone defects.To this end,various biomimetic scaffolds have been devised to mimic the native microenvironment of bone and thereby to simultaneously re-pair bone defects and promote bone regeneration.We propose here a novel concept,in vivo bone regenerative microenvironment(BRM),which enables repair of large bone defects and enhances new bone tissue formation with external regulation.In this review,we mainly focus on materials and methods for fabrication of biomimetic scaffolds,as well as their therapeutic efficacy in modulating the BRM of large physiological and pathological bone defects.

Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?

Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohistological staining and reverse transcription-PCR detection showed that transplanted bone marrow cells and bone marrow regenerative cells could migrate and survive in the ischemic regions, such as the cortical and striatal infarction zone. These cells promote vascular endothelial cell growth factor mRNA expression in the ischemic marginal zone surrounding the ischemic penumbra of the cortical and striatal infarction zone, and have great advantages in promoting the recovery of neurological function, reducing infarct size and promoting angiogenesis. Bone marrow regenerative cells exhibited stronger neuroprotective effects than bone marrow cells. Our experimental findings indicate that bone marrow regenerative cells are preferable over bone marrow cells for cell therapy for neural regeneration after cerebral ischemia. Their neuroprotective effect is largely due to their ability to induce the secretion of factors that promote vascular regeneration, such as vascular endothelial growth factor.

Optimal regenerative repair of large segmental bone defect in a goat model with osteoinductive calcium phosphate bioceramic implants

So far,how to achieve the optimal regenerative repair of large load-bearing bone defects using artificial bone grafts is a huge challenge in clinic.In this study,a strategy of combining osteoinductive biphasic calcium phosphate(BCP)bioceramic scaffolds with intramedullary nail fixation for creating stable osteogenic microenvironment was applied to repair large segmental bone defects(3.0 cm in length)in goat femur model.The material characterization results showed that the BCP scaffold had the initial compressive strength of over 2.0 MPa,and total porosity of 84%.The cell culture experiments demonstrated that the scaffold had the excellent ability to promote the proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells(BMSCs).The in vivo results showed that the intramedullary nail fixation maintained the initial stability and structural integrity of the implants at early stage,promoting the osteogenic process both guided and induced by the BCP scaffolds.At 9 months postoperatively,good integration between the implants and host bone was observed,and a large amount of newborn bones formed,accompanying with the degradation of the material.At 18 months postoperatively,almost the complete new bone substitution in the defect area was achieved.The maximum bending strength of the repaired bone defects reached to the 100% of normal femur at 18 months post-surgery.Our results demonstrated the good potential of osteoinductive BCP bioceramics in the regenerative repair of large load-bearing bone defects.The current study could provide an effective method to treat the clinical large segmental bone defects.

Regeneration of critical-sized defects, in a goat model, using a dextrin-based hydrogel associated with granular synthetic bone substitute

The development of injectable bone substitutes(IBS)have obtained great importance in the bone re-generation field,as a strategy to reach hardly accessible defects using minimally invasive techniques and able to fit to irregular topographies.In this scenario,the association of injectable hydrogels and bone graft granules is emerging as a well-established trend.Particularly,in situ forming hydrogels have arisen as a new IBS generation.An in situ forming and injectable dextrin-based hydrogel(HG)was developed,aiming to act as a carrier of granular bone substitutes and bioactive agents.In this work,the HG was associated to a granular bone substitute(Bonelike)and implanted in goat critical-sized calvarial defects(14mm)for 3,6 and 12weeks.The results showed that HG improved the han-dling properties of the Bonelike granules and did not affect its osteoconductive features,neither impairing the bone regener ation process.Human multipotent mesenchymal stromal cells from the umbilical cord,extracellular matrix hydrolysates and the pro-angiogenic peptide LLKKK18 were also combined with the IBS.These bioactive agents did not enhance the new bone formation significantly under the conditions tested,according to micro-computed tomography and histological analysis.