Hydroxylapatite-collagen hybrid scaffold induces human adipose-derived mesenchymal stem cells to osteogenic differentiation in vitro and bone regrowth in patients.

Tissue engineering-based bone graft is an emerging viable treatment modality to repair and regenerate tissues damaged as a result of diseases or injuries. The structure and composition of scaffolds should modulate the classical osteogenic pathways in human stem cells. The osteoinductivity properties of the hydroxylapatite-collagen hybrid scaffold named Coll/Pro Osteon 200 were investigated in an in vitro model of human adipose mesenchymal stem cells (hASCs), whereas the clinical evaluation was carried out in maxillofacial patients. Differentially expressed genes (DEGs) induced by the scaffold were analyzed using the Osteogenesis RT2 PCR Array. The osteoinductivity potential of the scaffold was also investigated by studying the alkaline phosphatase (ALP) activity, matrix mineralization, osteocalcin (OCN), and CLEC3B expression protein. Fifty patients who underwent zygomatic augmentation and bimaxillary osteotomy were evaluated clinically, radiologically, and histologically during a 3-year follow-up. Among DEGs, osteogenesis-related genes, including BMP1/2, ALP, BGLAP, SP7, RUNX2, SPP1, and EGFR, which play important roles in osteogenesis, were found to be upregulated. The genes to cartilage condensation SOX9, BMPR1B, and osteoclast cells TNFSF11 were detected upregulated at every time point of the investigation. This scaffold has a high osteoinductivity revealed by the matrix mineralization, ALP activity, OCN, and CLEC3B expression proteins. Clinical evaluation evidences that the biomaterial promotes bone regrowth. Histological results of biopsy specimens from patients showed prominent ossification. Experimental data using the Coll/Pro Osteon 200 indicate that clinical evaluation of bone regrowth in patients, after scaffold implantation, was supported by DEGs implicated in skeletal development as shown in "in vitro" experiments with hASCs.

Hydroxyapatite/Collagen Composite Is a Reliable Material for Malar Augmentation.

PURPOSE: To evaluate the long-term results of cheekbone augmentation using porous hydroxyapatite granules mixed with microfibrillar collagen in a large group of patients. MATERIALS AND METHODS: Four hundred thirty patients who underwent zygomatic augmentation and intermaxillary osteotomy were evaluated clinically, radiologically, and histologically. RESULTS: Complications were found in 13 patients (1.56%). There were no relevant radiologic differences in prosthesis volume after 1 month (T1) or after 24 months (T2) in any patient; there were no clinically relevant differences in 110 patients after 36 months. At T1, the prosthesis had a granular structure and the granules had not migrated; at T2, the prosthesis was staunchly adhering to the underlying bone. Over time, the radiopacity of the material increased. Histologic results of 19 biopsy specimens obtained from 8 patients 2 years after the procedure showed prominent ossification with low inflammation, confirming new bone formation over time. According to the visual analog scale, the patients were generally satisfied with the aspects that were considered. CONCLUSION: Hydroxyapatite and collagen composite used during malarplasty produced a successful outcome. Its main drawback is a learning curve that is longer than for more frequently used implantable biomaterials.

Pathophysiology and pharmacologic control of osseous mandibular condylar resorption.

PURPOSE: When osseous mandibular condylar resorption occurs there can be many different diagnoses: inflammatory arthritis, TMJ compression, trauma, hormone imbalances, and others. While each diagnosis has its own original inciting event, the pathophysiological pathway for articular bone loss is the same. The aim of this article is to review the relevant literature on condylar resorption and the use of pharmacotherapy to control arthritic erosions and resorption. MATERIALS AND METHODS: The literature search was performed using PubMed database with various combinations of related keywords. Preference was given to clinical trials when reviewing articles. RESULTS: The literature reveals that common cellular level events associated with articular resorption include the activation of osteoblasts by cytokines, free radicals, hormone imbalances and/or potent phospholipid catabolites. The osteoblast then activates the recruitment of osteoclasts and promotes the release of matrix degrading enzymes from the osteoclast. Research into articular erosions has focused on elucidating the important steps in the bone destructive pathways and interfering with them by pharmacological means. The use of antioxidants, tetracyclines, omega-3 fatty acids, non-steroidal anti-inflammatories and inflammatory cytokine inhibitors to aid in preventing and controlling articular bone loss including osseous mandibular condylar resorption has been successful. CONCLUSION: By understanding the known pathways that lead to condylar resorption and the individual patient's susceptibilities, targeted pharmacotherapy might be able to disturb these pathways and prevent further condylar resorption. Basic clinical investigations and randomized clinical trials are still required, but the present science is encouraging.

Oral contraceptive pill use and abnormal menstrual cycles in women with severe condylar resorption: a case for low serum 17beta-estradiol as a major factor in progressive condylar resorption.

INTRODUCTION: Progressive condylar resorption has been described for many years. Because condylar resorption favors women over men, many have thought that a prominent systemic factor for the pathogenesis of this disease might be related to sex hormones. METHODS: Over a 3-year period, 27 women without autoimmune disease came to our office for orthognathic surgical correction of their skeletal deformity secondary to severe condylar resorption. They all showed radiographic evidence of severe condylar resorption. Sex hormone dysfunction was evaluated, and midcycle serum levels of 17beta-estradiol were measured. Use of exogenous hormones was also documented. RESULTS: Twenty-six of the 27 women with severe condylar resorption had either laboratory findings of low 17beta-estradiol or a history of extremely irregular menstrual cycles. Of the 27 women, 25 showed abnormally low levels of serum 17beta-estradiol at midcycle. Two subsets were identified in the group with low 17beta-estradiol. The first did not produce estrogen naturally (8 of 27), and the second had low 17beta-estradiol levels secondary to oral contraceptive pill (OCP) use (19 of 27). Of the 19 OCP users, all 19 reported that chin regression and open bite changes occurred after starting OCP use. Nine of the 19 reported these condylar resorption symptoms within the first 6 months of starting the OCP. CONCLUSIONS: Whether induced by ethinyl estradiol birth control or by premature ovarian failure, low circulating 17beta-estradiol makes it impossible for the natural reparative capacity of the condyle to take place in the face of local inflammatory factors. This leads to cortical and medullary condylar lysis.