Atelocollagen (AC) is a low-immunogenic collagen derivative with longer degradation time, which can be a suitable material for alveolar ridge preservation (ARP). However, there are few human studies on AC using for ARP. This research aims to radiographically evaluate the efficacy of AC in comparison to deproteinized bovine bone minerals covered with a collagen membrane (DBBM/CM) in ARP.
Medical records in the Implantology Department of the Hospital of Stomatology of Wuhan University were screened for patients who received flapless ARP using either AC or DBBM/CM. A total of 58 patients were included in this retrospective study. 28 patients were treated with AC, while 30 patients were used DBBM/CM. Cone-beam computed tomography (CBCT) scans were taken before extraction and after 6 months of healing. To assess the dimensional change of the extraction sockets, the scanning data were output and transferred to the digital software to measure horizontal bone width change, vertical bone height change and bone volume change in region of interest. To evaluate the bone quality of healed sockets, the bone density of virtual implants was evaluated.
The horizontal bone width changes at all five different levels showed no significant difference between the two groups. The largest horizontal bone width decrement in both groups occurred at the crest of ridge, which decreased 3.71 ± 1.67 mm in AC group and 3.53 ± 1.51 mm in DBBM/CM group (p = 0.68). At the central buccal aspect, the ridge height reduced 0.10 ± 1.30 mm in AC group, while increased 0.77 ± 2.43 mm in DBBM/CM group (p = 0.10). The vertical bone height differences between two groups showed no statistical significance. The percentages of volume absorption in AC group and DBBM/CM group were 12.37%±6.09% and 14.54%±11.21%, respectively. No significant difference in volume absorption was found (p = 0.36). The average bone density around virtual implants in AC group (649.41 ± 184.71 HU) was significantly lower than that in DBBM/CM group (985.23 ± 207.85 HU) (p < 0.001).
ARP with AC had a similar effect on limiting the dimensional alteration of alveolar ridge, when radiographically compared with DBBM/CM.

The development of biomimetic scaffolds containing cartilage, calcified cartilage, and bone regeneration for precise osteochondral repair remains a challenge. Herein, a novel tri-layered scaffold-with a top layer containing type II atelocollagen and chondroitin sulphate for cartilage regeneration, an intermediate layer with type II atelocollagen and hydroxyapatite for calcified cartilage formation, and a bottom layer with type I atelocollagen and hydroxyapatite for bone growth-that can be built using liquid-phase cosynthesis, is described. The tri-layered scaffolds are mechanically demonstrably superior and have a lower risk of delamination than monolayer scaffolds. This is due to higher cohesion arising from the interfaces between each layer. In vitro results show that although monolayer scaffolds can stimulate bone marrow stem cells to differentiate and form cartilage, calcified cartilage, and bone separately (detected using quantitative polymerase chain reaction analysis and staining with safranin-O and Alizarin Red S), the tri-layered scaffolds support the regeneration of cartilage, calcified cartilage, and bone simultaneously after 2 and 4 months of implantation (detected using gross and micro-computed tomography images, histological staining, and Avizo, a software used to detect microlevel defects in metals). This work presents data on a promising approach in devising strategies for the precise repair of osteochondral defects.

The fabrication of biomimetic tracheas with cartilaginous rings alternately interspersed between vascularized fibrous tissue (CRVFT) architecture has the potential to perfectly recapitulate normal tracheal structure and function. Herein, we describe the development of a customized chondroitin sulfate-incorporated type II atelocollagen (COL II/CS) scaffold with excellent chondrogenic capacity and a type I atelocollagen (COL I) scaffold to facilitate the formation of vascularized fibrous tissue. An efficient modular ring strategy was then adopted to develop a CRVFT-based biomimetic trachea. The in vitro engineering of cartilaginous rings was achieved via the recellularization of ring-shaped COL II/CS scaffolds using bone marrow stem cells as a mimetic for native cartilaginous ring tissue. A CRVFT-based trachea with biomimetic mechanical properties composed of bionic biochemical components was additionally successfully generated in vivo via the alternating stacking of cartilaginous rings and ring-shaped COL I scaffolds on a silicone pipe. The resultant biomimetic trachea with pedicled muscular flaps was used for extensive tracheal reconstruction and exhibited satisfactory therapeutic outcomes with structural and functional properties similar to those of native trachea. This is the first study to utilize stem cells for long-segmental tracheal cartilaginous regeneration and this represents a promising method for extensive tracheal reconstruction. This article is protected by copyright. All rights reserved.

Within the past years, BMP9 has been characterized as one of the most osteogenic bone-inducers among the BMP family, however up until recently, BMP9 has only been available through adenovirus transfection experiments (gene therapy) not approved for clinical use. The aim of this study was to investigate recombinant rhBMP9 versus rhBMP2 at 2 concentrations (10 and 100 ng/mL) in combination with 2 bone grafts: (1) a natural bone mineral (NBM) without collagen versus (2) a novel NBM integrated with atelo-collagen type I (NBM-Col). Scanning electron microscopy revealed that while NBM demonstrated a mineralized roughened surface morphology, NBM-Col particles contained many more visible collagen fibrils throughout the scaffold surface significantly increasing rhBMP adsorption from 8 h to 10 days (as quantified by ELISA). Thereafter, ST2 preosteoblasts were used to investigate cell attachment, proliferation, and differentiation. While little change was observed for cell attachment/proliferation, osteoblast differentiation demonstrated a significant increase in alkaline phosphatase (ALP) activity when scaffolds were loaded with rhBMP9 when compared to rhBMP2. Furthermore, a 2-3 fold increase in alizarin red staining, and in mRNA levels of osteoblast differentiation markers Runx2, Collagen1α2, ALP, and osteocalcin was observed when rhBMP9 was combined with NBM-Col when compared to NBM without collagen at equivalent doses and when compared to rhBMP2. The results from this study demonstrate that (1) the use of rhBMP9 significantly and markedly induced osteoblast differentiation when compared to rhBMP2 and (2) the incorporation of atelo-collagen type I into NBM bone grafts markedly improved these findings by serving as a scaffold capable of improving growth factor adsorption and osteoblast behavior. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 408-418, 2017.

Bone is the primary site of skeletal metastasis in prostate cancer (PCa). Atelocollagen (ATE)-mediated siRNA delivery system can be used to silence endogenous genes involved in PCa metastatic tumor cell growth. However, we hope that the delivery system can target PCa cells to reduce damage to the bone tissue and improve the therapeutic effect. RNA aptamer (APT) A10-3.2 has been used as a ligand to target PCa cells that express prostate-specific membrane antigen (PSMA). APT was investigated as a PSMA-targeting ligand in the design of an ATE-based microRNA (miRNA; miR-15a and miR-16-1) vector to PCa bone metastasis. To observe the targeted delivery and transfection efficiency of ATE-APT in PSMA-overexpressing cells, luciferase activity and biodistribution of nanoparticles in Balb/c mice was analyzed. The anticancer effect of nanoparticles in vivo was investigated using the survival times of human PCa bone metastasis mice model. Luciferase assays of pGL-3 expression against PC3 (PSMA(-)) and LNCaP (PSMA(+)) cells showed that the transfection efficiency of the synthesized DNA/ATE-APT complex was higher than that of the DNA/ATE complex. The anticancer efficacy of miRNA/ATE-APT was superior to those of other treatments in vivo. This PSMA-targeted system may prove useful in widening the therapeutic window and allow for selective killing of PCa cells in bone metastatic foci.

Hypertrophic scar (HS) originates from the over-expression of transforming growth factor β (TGF-β) and downstream SMAD2. With attempts to rectify HS by RNA interference (RNAi) against SMAD2, we report the design of plasmid DNA encoding SMAD2 siRNA (pSUPER-SMAD2), and identify the optimal siRNA sequence toward maximal RNAi efficiency. To realize effective and sustained RNAi, we developed gene activated matrix (GAM) based on porous atelocollagen scaffold and embedded trimethyl chitosan-cysteine (TMCC)/pSUPER-SMAD2 polyplexes for promoting cell growth and gene transfection. The GAM exhibited porosity higher than 80%, pore size of 200-250 μm, desired mechanical strength, and sustained pSUPER-SMAD2 release profiles. Normal skin fibroblasts (NSFs) and hypertrophic scar fibroblasts (HSFs) were allowed to infiltrate and proliferate in GAM; at the meantime they were transfected with TMCC/pSUPER-SMAD2 polyplexes to display remarkably reduced SMAD2 levels that lasted for up to 10 days, consequently inhibiting the over-production of type I and type III collagen. We further unraveled the notably higher transfection levels of GAM in three-dimensional (3D) than in 2D environment, which was attributed to the improved cell-matrix interactions that promote cell proliferation and polyplex internalization. This highly safe and effective GAM may serve as a promising candidate towards HS treatment.