Two Techniques for the Preparation of Cell-Scaffold Constructs Suitable for Sinus Augmentation: Steps into Clinical Application

Abstract

The objective of this clinical trial was the analysis of 2 methods for engineering of autologous bone grafts for maxillary sinus augmentation with secondary implant placement. Group 1 (8 patients, 12 sinuses): cells of mandibular periosteum were cultured in a good manufacturing practice laboratory (2 weeks) with autologous serum and then transferred onto a collagen matrix. After another week, these composites were transplanted into the sinuses. In group 2A (2 patients, 3 sinuses), cells of maxillary bone were cultivated with autologous serum for 2 weeks, seeded onto natural bone mineral (NBM, diameter [Ø] = 8 mm) blocks, and cultivated for another 1.5 months. These composites were transplanted into the sinuses. Group 2B (control, 3 patients, 5 sinuses) received NBM blocks alone. In the course of implant placement 6 (group 1) and 8 (group 2) months later, core biopsy were taken. Clinical follow-up period was 1 to 2.5 years in group 1 and approximately 7 years in groups 2A and 2B. New vital bone was found in all cases at median densities of 38% (n = 12) in group 1, 32% in group 2A (n = 3), and 25% in group 2B (n = 5). Differences between group 1 and 2B as well as 2A and 2B were statistically significant ( p = 0.025). No adverse effects were seen. All methods described were capable of creating new bone tissue with sufficient stability for successful implant placement.

Primary Human Alveolar Bone Cells Isolated from Tissue Samples Acquired at Periodontal Surgeries Exhibit Sustained Proliferation and Retain Osteogenic Phenotype during In Vitro Expansion

“…With clinical application in mind, we limited the cell characterization studies to <8 culture passages, when the cultures reached sufficient cell numbers for the preparation of TE-bone substitutes [41]. Currently, most clinical study protocols involve the use of early (<5) passage cells, to minimize the changes associated with in vitro cultivation [29], [30], [31], [47], [48], [49]. However, to fully utilize the primary alveolar bone cells as an in vitro model, the phenotype and proliferation of cells in later passages should be evaluated in future studies.…”

“…In contrast to several clinical reports where periosteal cells were harvested specifically for the purpose of TE-bone substitutes preparation [31], [47], [48], [49], our approach involves the use of bone tissue remnants, obtained during routine periodontal surgical procedures, as a source of osteogenic cells, thus avoiding additional injury to patient due to tissue harvesting. A few prior studies reported clinical application of TE-bone substitutes derived from alveolar bone cells [29], [30], [31], [50].…”

“…A few prior studies reported clinical application of TE-bone substitutes derived from alveolar bone cells [29], [30], [31], [50]. Pradel and colleagues used second passage mandibular and maxillary osteoblasts, isolated by establishing explant cultures and cultured on collagen scaffolds 3–4 days, to regenerate bone after mandibular cyst enucleation and for osteoplasty in patients with cleft alveolus [29], [30].…”

“…After 6 months, bone regeneration was comparable between the tissue engineering group and the control autologous iliac bone transplant group. Springer and colleagues used first passage maxillary osteoblasts, isolated by establishing explant cultures and cultured on deproteinized bovine bone scaffolds in vitro for 1.5 months, as one of the groups in sinus augmentation procedures [31]. New vital bone formation with sufficient stability for implant placement was found with osteoblast-derived TE-substitutes, similarly to periosteal cells-derived TE-substitutes.…”

“…Previous studies indicate that alveolar bone can be used to isolate cells expressing characteristic mesenchymal surface markers, which have the potential to undergo osteogenic differentiation in appropriate culture conditions [12], [24], [25], [26], [27]. Furthermore, TE-constructs prepared from alveolar bone cells were shown to enhance de novo bone formation in critical-size skull defects in immunodeficient mice [26], [28], and were more recently used to treat jaw bone defects in several clinical case studies [29], [30], [31]. Importantly, prior work also suggests that osteogenic cells originating from the jaw bone exhibit distinct differentiation properties in vitro and in vivo [32], as well as distinct drug responses compared to osteogenic cells originating from the long/iliac bones [10], [11].…”