Cross-linked Collagen Matrix Research Articles

Reconstructive surgical therapy of peri-implant defects with ribose cross-linked collagen matrix and crosslinked hyaluronic acid – a prospective case series

ObjectiveTo investigate the efficacy of ribose-crosslinked collagen (RCLC) matrices functionalized by crosslinked hyaluronic acid (xHya) for reconstructive treatment of class I and III (b-c) peri-implantitis lesions in a transmucosal healing mode.Materials and methodsThirteen patients presenting with 15 implants were included in this prospective case series. Upon flap reflection, the implants were thoroughly decontaminated employing glycine powder air polishing and adjunctive sodium hypochlorite. For defect augmentation, xHyA was administered to the bony defect walls, exposed implant surfaces, and the RCLC matrix before defect grafting. The full-thickness flap was readapted and sutured around the implant neck for transmucosal healing. Baseline and respective values at the 12 months post-op evaluation were recorded for the clinical parameters peri-implant probing depth (PPD), buccal soft tissue dehiscence (BSTD) and bleeding on probing (BoP). Furthermore, two independent investigators analyzed radiographic changes in the defect area. The mean changes for all variables were analyzed with a paired t-test.ResultsThe initial mean PPD was 7.2 ± 1.9 mm, and BoP was present in 63% of sites. After 12 months, PPD at the latest visit was 3.2 ± 0.66 mm, which amounted to a respective 3.9 ± 1.85 mm reduction, while the BoP frequency dropped to 10% at all sites. Radiographic bone fill was accomplished for 62.8% of the former defect area, accompanied by a mean MBL gain of 1.02 mm around the treated implants (all p < 0.001).ConclusionsWithin the limits of this case series, we conclude that the proposed treatment sequence substantially improved peri-implant defects and offered a simplified but predictive technique.Clinical relevanceReconstructive treatment approaches for peri-implantitis are effective but remain non-superior to open flap debridement. Further research on novel biomaterial combinations that may improve reconstructive treatment outcomes are warranted. Ribose-crosslinked collagen matrices biofunctionalized by hyaluronic acid used in this study yield improved clinical and radiographic peri-implant conditions after 12 months.Graphical

Porcine Cross-Linked Collagen Matrix for Peri-Implant Vertical Soft Tissue Augmentation: A Randomized Prospective Observational Study.

The mucosa height has always been of interest in modern implant dentistry to obtain biomimetic results. Papilla height, mucosa scalloping, and free mucosal margin level are crucial to achieve "pink aesthetics". The aim of this study was to investigate the vertical increase in the peri-implant soft tissues with a porcine cross-linked collagen matrix (Geistlich Fibro-Gide®). Methods: A total of 60 patients were divided into the following three groups: Group 1-patients who received porcine cross-linked collagen matrix for vertical soft tissue augmentation and a cover screw combined with a coronally advanced flap (CAF); Group 2-patients who received the collagen matrix combined with a healing abutment and CAF; Group 3 (control group)-patients who received a traditional surgical approach based on crestal incision and no collagen matrix as well as no CAF. Results: The average horizontal tissue thickness growth after 3 months was more effective for Group 1 (1.35 ± 1.23 mm) compared to Group 2 (0.85 ± 0.67 mm) and the control group (0.20 ± 0.41 mm). The average tissue height growth was 1.05 ± 1.39 mm for Group 1, 0.32 ± 1.28 mm for Group 2, and -0.05 ± 0.39 mm for the control group. Finally, the average increase in the band of keratinized mucosa was 0.60 ± 1.23 mm for Group 1, -0.60 ± 0.94 mm for Group 2, and 0.45 ± 0.60 mm for the control group. Conclusions: The combination of the CAF, porcine cross-linked collagen matrix, and cover screw resulted in better clinical results compared to Group 2 and 3.

Controlled Release of Ceria and Ferric Oxide Nanoparticles via Collagen Hydrogel for Enhanced Osteoarthritis Therapy.

Osteoarthritis (OA), characterized by chronic inflammation and cartilage degeneration, significantly affects over 500 million people globally. Nanoparticles have emerged as promising treatments for OA; however, current strategies often employ a single type of nanoparticle targeting specific disease stages, limiting sustained therapeutic efficacy. In this study, a novel collagen hydrogel is introduced, thiol crosslinked collagen-cerium oxide-poly(D,L-lactic-co-glycolic acid) microspheres encapsulating nanoparticles (CSH-CeO2-pFe2O3), designed for the controlled release of cerium oxide (CeO2) and ferric oxide (Fe2O3) nanoparticles for comprehensive OA management. The sulfhydryl cross-linked collagen matrix embeds CeO2 nanoparticles and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres encapsulating Fe2O3 nanoparticles. The CSH-CeO2-pFe2O3 hydrogel exhibits enhanced mechanical strength and remarkable injectability, along with a significant promotion of cell adhesion, proliferation, and chondrogenic differentiation. Notably, the hydrogel demonstrates intelligent responsiveness to high levels of reactive oxygen species, initiating the rapid release of CeO2 nanoparticles to address the intense inflammatory responses of early-stage OA, followed by the sustained release of Fe2O3 nanoparticles to facilitate cartilage regeneration during the proliferative phase. In a rat model with cartilage defects, the hydrogel significantly alleviates inflammation and enhances cartilage regeneration, holding substantial potential for effectively managing the pathologically complex OA.

Lysyl Oxidase Production by Murine C3H10T1/2 Mesenchymal Stem Cells Is Increased by TGFβs and Differentially Modulated by Mechanical Stimuli.

Tendons are frequently injured and have limited regenerative capacity. This motivates tissue engineering efforts aimed at restoring tendon function through strategies to direct functional tendon formation. Generation of a crosslinked collagen matrix is paramount to forming mechanically functional tendon. However, it is unknown how lysyl oxidase (LOX), the primary mediator of enzymatic collagen crosslinking, is regulated by stem cells. This study investigates how multiple factors previously identified to promote tendon formation and healing (transforming growth factor [TGF]β1 and TGFβ2, mechanical stimuli, and hypoxia-inducible factor [HIF]-1α) regulate LOX production in the murine C3H10T1/2 mesenchymal stem cell (MSC) line. We hypothesized that TGFβ signaling promotes LOX activity in C3H10T1/2 MSCs, which is regulated by both mechanical stimuli and HIF-1α activation. TGFβ1 and TGFβ2 increased LOX levels as a function of concentration and time. Inhibiting the TGFβ type I receptor (TGFβRI) decreased TGFβ2-induced LOX production by C3H10T1/2 MSCs. Low (5 mPa) and high (150 mPa) magnitudes of fluid shear stress were applied to test impacts of mechanical stimuli, but without TGFβ2, loading alone did not alter LOX levels. Low loading (5 mPa) with TGFβ2 increased LOX at 7 days greater than TGFβ2 treatment alone. Neither HIF-1α knockdown (siRNA) nor activation (CoCl2) affected LOX levels. Ultimately, results suggest that TGFβ2 and appropriate loading magnitudes contribute to LOX production by C3H10T1/2 MSCs. Potential application of these findings includes treatment with TGFβ2 and appropriate mechanical stimuli to modulate LOX production by stem cells to ultimately control collagen matrix stiffening and support functional tendon formation.

Profilometric analysis of cross-linked collagen matrix for soft tissue thickness augmentation in dental implants: A randomized controlled clinical trial

BACKGROUND: Dental implantation is an effective method for rehabilitating patients without teeth. The long-term survival of implants is influenced by various factors, one of which is the condition of the soft tissue surrounding the implant.&#x0D; AIM: To evaluate the effectiveness of cross-linked collagen matrix for soft tissue augmentation in the implant area.&#x0D; MATERIALS AND METHODS: Thirty-two patients with soft tissue thickness deficiency were examined. The patients were divided into two groups depending on the method of surgery. Group 1 received a cross-linked collagen matrix, whereas group 2 underwent the transplantation of a free connective tissue graft. The increase in soft tissue thickness was assessed 3 and 6 months after surgery.&#x0D; RESULTS: Soft tissue thickness 3 months after surgery increased by 1.77±0.61 and 1.26±0.41 mm in groups 1 and 2, respectively (p 0.001). Moreover, 6 months after surgery, soft tissue thickness increased by 1.11±0.44 and 1.43±0.81 mm compared with the initial value (p=0.012).&#x0D; CONCLUSION: The use of the collagen matrix increases the soft tissue thickness in the implant area; however, the effect size is lower than that obtained by autograft transplantation.

The "Tunneled Sandwich" Technique for Preserving the Buccal Tissue Volume After Immediate Implantation: A Retrospective Report of 10 Cases.

The tooth loss or extraction is associated with significant diminishing the volume of alveolar ridge extensively expressed in the anterior zone. The immediate implant placement itself is considered inappropriate to overcome this problem. The proposed approach combined the technique of immediate implant placement with the enhancement of the buccal tissue by applying a cross-linked collagen matrix hydrated with a cross-linked hyaluronic acid. In a series of ten cases, all presenting with a retained but narrow buccal socket wall, an immediate implant placement along with the "tunneled sandwich" technique was performed following tooth extraction. The tunneled sandwich technique helped to create a subperiosteal pouch for insertion of the collagen matrix buccal to the alveolar bone crest. The implants healed transmucosally by receiving either a gingiva former or an immediate temporary restoration. Ten sites in ten patients demonstrated stable non-inflamed peri-implant conditions and suitable ridge volume at the implant's neck and achieved high pink esthetic scores estimated 6 months after implant loading. The "tunneled sandwich" technique appears a suitable method to preserve the buccal volume, which contributes as biologically as esthetically to favorable long-term results. Int J Periodontics Restorative Dent. 10.11607/prd.6205.

Echo intensity and gray-level co-occurrence matrix analysis of soft tissue grafting biomaterials and dental implants: an in vitro ultrasonographic pilot study.

To characterize different allogeneic and xenogeneic soft tissue graft substitutes and to assess their echo intensity and grayscale texture-related outcomes by using high-frequency ultrasonography (HFUS). Ten samples from each of the following biomaterials were scanned using HFUS: bilayered collagen matrix (CM), cross-linked collagen matrix (CCM), multilayered cross-linked collagen matrix (MCCM), human-derived acellular dermal matrix (HADM), porcine-derived acellular dermal matrix (PADM), collagen tape dressing (C) and dental implants (IMPs). The obtained images were then imported in a commercially available software for grayscale analysis. First-order grayscale outcomes included mean echo intensity (EI), standard deviation, skewness, and kurtosis, while second-order grayscale outcomes comprised entropy, contrast, correlation, energy and homogeneity derive from the gray-level co-occurrence matrix analysis. Descriptive statistics were performed for visualization of results, and one-way analysis of variance with Bonferroni post-hoc tests were performed to relative assessments of the biomaterials. The statistical analysis revealed a statistically significant difference among the groups for EI (p < .001), with the group C showing the lowest EI, and the IMP group presenting with the greatest EI values. All groups showed significantly higher EI when compared with C (p < .001). No significant differences were observed for energy, and correlation, while a statistically significant difference among the groups was found in terms of entropy (p < 0.01), contrast (p < .001) and homogeneity (p < .001). IMP exhibited the highest contrast, that was significantly higher than C, HADM, PADM, CCM and CM. HFUS grayscale analysis can be applied to characterize the structure of different biomaterials and holds potential for translation to in-vivo assessment following soft tissue grafting-related procedures.

A prospective case series on the efficacy of a cross-linked collagen matrix to increase buccal soft tissue thickness at large edentulous gaps: One-year results.

The objective of this study is to assess profilometric changes following soft tissue augmentation with a cross-linked porcine-derived collagen matrix (CMX) at large edentulous gaps of at least two units. Systemically healthy, nonsmoking patients with a large edentulous gap of at least two units demonstrating a horizontal soft tissue defect, were enrolled in a prospective case series. Soft tissue augmentation was performed in a one-stage approach with a 6 mm thick CMX at the time of implant placement. The primary outcome was the change in buccal soft tissue profile (BSP) at a mesial, central, and distal area of interest (AOI) up to 1 year when compared to the preoperative situation based on superimposed digital surface models. Secondary outcomes included the horizontal dimension of the soft tissue defect, complications, and marginal bone loss (MBL). Fifteen patients (eight females; mean age 58.73 years) were enrolled and 13 could be re-assessed at 1-year follow-up. The mean linear increase in BSP at 1 year was 0.66 mm (98.3% CI: 0.37-0.94), 0.80 mm (98.3% CI: 0.39-1.22), and 0.69 mm (98.3% CI: 0.32-1.06) at the mesial, central, and distal AOI, respectively. Substantial shrinkage of about 75% was observed in all areas between augmentation and 1-year follow-up. Even though 11 of 13 sites were fully augmented immediately postoperative, a soft tissue defect recurred in all sites at 1-year follow-up with a mean deficit of 2.30 mm. Altogether, 25% of the original soft tissue defect was eliminated by soft tissue augmentation. CMX was safe since no postoperative complications occurred and MBL was limited (0.70 mm). CMX is efficacious for horizontal soft tissue augmentation at large edentulous gaps. However, considerable graft resorption may be expected, and the clinical relevance of the augmentation may be questionable since all patients demonstrated a recurring and considerable soft tissue defect 1 year after surgery.

A Multi-Centre Randomized Controlled Trial Comparing Connective Tissue Graft with Collagen Matrix to Increase Buccal Soft Tissue Thickness: A Cone-Beam CT Analysis.

(1) Aim: a cross-linked porcine-derived collagen matrix (CMX) has been developed for soft tissue augmentation. Although this grafting material does not require a second surgical site, recent findings have indicated deeper pockets, more marginal bone loss and more midfacial recession in the short term when compared to connective tissue graft (CTG). Hence, the aim of the present study was to evaluate the safety of CMX based on buccal bone loss over a one-year period. (2) Methods: Patients who were missing a single tooth in the anterior maxilla were included, in whom the failing tooth had been removed at least 3 months prior and who presented a horizontal mucosa defect. All sites had a bucco-palatal bone dimension of at least 6 mm as assessed on Cone-Beam Computed Tomography (CBCT) to ensure complete embedding of an implant by bone. All patients received a single implant and an immediate implant restoration using a full digital workflow. Sites were randomly allocated to the control (CTG) or test group (CMX) to increase buccal soft tissue thickness. All surgeries were performed by means of full thickness mucoperiosteal flap elevation, placing CTG and CMX in contact with the buccal bone wall. Safety was assessed by evaluating the impact of CTG and CMX on buccal bone loss over a one-year period using superimposed CBCT scans. (3) Results: thirty patients were included per group (control: 50% females, mean age 50; test: 53% females, mean age 48) and 51 (control: 25; test: 26) could be analyzed for buccal bone loss. At 1 mm apical to the implant-abutment interface (IAI), most horizontal resorption was found pointing to 0.44 mm in the control group and 0.59 mm in the test group. The difference of 0.14 mm (95% CI: -0.17-0.46) was not statistically significant (p = 0.366). At 3 mm and 5 mm apical to the IAI, the difference between the groups was 0.18 mm (95% CI: -0.05-0.40; p = 0.128) and 0.02 mm (95% CI: -0.24-0.28; p = 0.899), respectively. Vertical buccal bone loss amounted to 1.12 mm in the control group and 1.14 mm in the test group. The difference of 0.02 mm (95% CI: -0.53-0.49) was not statistically significant (p = 0.926). (4) Conclusions: In the short term, soft tissue augmentation with CTG or CMX results in limited buccal bone loss. CMX is a safe alternative to CTG. Longer follow-up is needed to assess the impact of soft tissue augmentation on buccal bone.

Stromal Cells Associated with Soft Tissue Augmentation by a Volume-Stable Collagen Matrix (VCMX) Are Predominated by Anti-inflammatory/Reparative Macrophages.

This article defines immunophenotypes of stromal inflammatory and endothelial cells and fibroblasts 3 months after augmentation of the peri-implant soft tissue using a porcine cross-linked collagen matrix (VCMX). Peri-implant soft tissue samples were obtained from 12 patients at the lining mucosa (LM)-masticatory mucosa (MM) junction before (1) and 3 months after (2) augmentation. Immu- nohistochemical stains were performed to identify inflammatory cells (T [CD3] and B [CD20] lym- phocytes, plasma cells [CD138]), macrophages (CD68-proinflammatory, CD163-anti-inflammatory/ reparative), endothelial cells (CD31, CD34), and fibroblasts (CD90, TE-7). Differences in the mean positively stained cells pre- and postaugmentation were analyzed by Wilcoxon signed-rank test. CD31&#43; endothelial cells showed increased mean numbers in MM2 compared to MM1 (P &#61; .025) and in LM2 compared to LM1 (P &#61; .047). CD163&#43; anti-inflammatory macrophages showed higher mean numbers in MM2 than in MM1 (P &#61; .021) and in LM2 than in LM1 (P &#61; .012). All other cell phenotypes showed nonsignificant changes between pre- and postaugmentation. This molecular study provides novel insight on the frequency of stromal cell phenotypes in the wound healing process at 3 months postaugmentation with VCMX, with anti-inflammatory CD163&#43; macrophages being predominant. This should be further investigated to help find novel therapeutic approaches to modulate and promote the VCMX-related healing process.

Comparative morphological assessment of crosslinked and non-crosslinked xenograft biointegration quality

Relevance. Autografts are nowadays the gold standard for soft tissue augmentation and gingival recession coverage. However, as this method has a number of significant disadvantages, xenografts of various origins are more frequently used in dental practice. The study aimed to conduct a comparative morphological assessment of crosslinked and non-crosslinked xenogenous scaffold biointegration quality at different healing times.Materials and Methods. The study used 108 Wistar rats (54 males, six months old, fat mass 462 ± 20; 54 females, six months old, fat mass 414 ± 7) and randomly divided them into three groups. Group 1 had a xenogenous collagen matrix (Mucograft) placed in the subperiosteal tunnel in the mandibular vestibule area; Group 2 had an acellular dermal collagen matrix (Mucoderm) implanted in the subperiosteal tunnel, group 3 had D-ribose crosslinked xenogenous scaffold (Ossix Volumax) placed in the subperiosteal tunnel.Results. The studied xenogenous materials showed different integration and biodegradation extents. By postoperative day 7, Group 1 (Mucograft) showed a more pronounced inflammation. Non-crosslinked collagen materials had almost completely resorbed by the 30th day of observation, while a crosslinked collagen matrix was detected as homogenous masses. By the 90th day, all groups demonstrated the formation of new connective tissue with different functional characteristics; only Group 3 histologically revealed microfragments of the graft.Conclusion. The study shows that the xenogenous crosslinked and non-crosslinked collagen membranes may promote an increase in soft tissue thickness to a different extent. However, it is essential to improve the available materials to reach an outcome comparable to the autologous soft tissue graft treatment result.

Recombinant human platelet-derived growth factor improves root coverage of a collagen matrix for multiple adjacent gingival recessions: A triple-blinded, randomized, placebo-controlled trial.

To evaluate the efficacy of recombinant human platelet-derived growth factor (rhPDGF)-BB combined with a cross-linked collagen matrix (CCM) for the treatment of multiple adjacent gingival recession type 1 defects (MAGRs) in combination with the coronally advanced flap (CAF). Thirty patients were enrolled in this triple-blind, randomized, placebo-controlled trial and treated with either CAF + CCM + rhPDGF, or CAF + CCM + saline. The primary outcome was mean root coverage (mRC) at 6months. Complete root coverage, gain in gingival thickness (GT), keratinized tissue width, volumetric and ultrasonographic changes, and patient-reported outcome measures were also assessed. Mixed-modelling regression analyses were used for statistical comparisons. At 6months, the mRC of the CCM + rhPDGF and CCM alone groups were 88.25% and 77.72%, respectively (p=.02). A significant gain in GT was consistently observed for both treatment arms, and more so for the patients receiving the matrix containing rhPDGF through time (0.51 vs. 0.80 mm, on average, p=.01). The rhPDGF + CCM treated patients presented greater volume gain, higher soft tissue thickness, and a superior aesthetic score. rhPDGF enhances the clinical, volumetric, and aesthetic outcomes of MAGRs above the results achieved with CAF + CCM alone (ClinicalTrials.gov NCT04462237).

Management of single tooth gingival recession using free gingival grafting followed by coronally advanced flap with cross-linked collagen matrix: A case report

Gingival recession is the exposure of root surfaces due to apical migration of the gingival margins beyond the cementoenamel junction and is considered as one of the most common esthetic concerns associated with periodontal tissues. Insufficient gingival thickness and lack of adequate width of attached gingiva are considered to be the most common reason for progressive gingival recession. This case report presented the management of gingival recession in the lower anterior tooth using two-stage recession coverage technique. In the first stage, free gingival grafting was performed which was followed by coronally advanced flap in combination with cross-linked collagen matrix (Fibro-Gide, Geistlich Biomaterials, Switzerland) for recession coverage and enhancement of gingival thickness. Three-month follow-up of the case reported significant enhancement in clinical parameters with improvement in patient’s esthetic demand.

Effect of Dialdehyde Carboxymethyl Cellulose Cross-Linking on the Porous Structure of the Collagen Matrix.

Porous structures are essential for some collagen-based biomaterials and can be regulated by crosslinkers. Herein, dialdehyde carboxymethyl cellulose (DCMC) crosslinkers with similar size but different aldehyde group contents were prepared through periodate oxidation of sodium carboxymethyl cellulose with varying degrees of substitution (DS). They can penetrate into the hierarchy of fibril and form inter-molecular and intra-fibril cross-linking within the collagen matrix due to their nanoscale sizes and reactive aldehyde groups. The collagen matrices possessed higher porosity, significantly greater proportion of large pores (Φ > 10 μm), and shorter D-periodicity after cross-linking, showing greater potential for biomedical applications. In addition, the crosslinked collagen matrices showed satisfactory biocompatibility and biodegradation. The decreased DS of carboxymethyl cellulose, which led to the increased aldehyde content of corresponding DCMC, brought about an enhanced cross-linking degree, porosity, and proportion of large pores of the crosslinked collagen matrix. DCMC dosage of 6% was sufficient for cross-linking and pore formation. Excess DCMC would physically deposit in the matrix and decrease the porosity instead. Therefore, the desired pore properties of the collagen matrix could be obtained by regulating the structure of DCMC and thereby achieving the required functions of the biomaterial.

Dimensional ridge changes in conjunction with four implant timing protocols and two types of soft tissue grafts: A pilot pre‐clinical study

To determine the effect of (1) implant placement timing and (2) the type of soft tissue graft in terms of ridge profile changes. Four implant treatment modalities were applied in the mesial root areas of the third and fourth mandibular premolars of 10 mongrel dogs alongside connective-tissue graft (CTG) and volume-stable cross-linked collagen matrix (VCMX): immediate, early, and delayed placement (DP), and DP following alveolar ridge preservation (ARP). All dogs were sacrificed 3months after soft tissue augmentation. Standard Tessellation Language files from designated time points were analysed. Compared with the pre-extraction situation, the median width of the ridge demontstrated a linear increase only in group ARP/CTG (0.07 mm at the 2-mm level), whereas all other groups showed a reduction (between -1.87and -0.09 mm, p > .05). Groups ARP/CTG (0.17 mm) and DP/CTG (0.05 mm) exhibited a profilometric tissue gain in a set region of interest (p > .05). The net effect of CTG and VCMX ranged from 0.14 to 0.79 mm. Dimensional ridge changes varied between treatment protocols. ARP with CTG led to the smallest difference in ridge profile between the pre-extraction and the study end time point. Both CTG and VCMX enhanced the ridge contour.

The performance of hydroxyapatite-sugar cross linked collagen matrix during immediate single-tooth implant placement in the aesthetic zone

The immediate single-tooth implant placement in the aesthetic zone represents a clinical challenge for preserving the bone contour. Aim of this clinical case was to observe the effect of grafting the buccal bone gap during immediate implant placement. The buccal bone gap was filled with a new hydroxyapatite-sugar cross linked collagen matrix to preserve the mucosal contour. At re-entry surgery, partial preservation of the buccal bone wall was observed after 6 months of healing and stable peri-implant bone was present. Such treatment during immediate single-tooth implant placement in the aesthetic zone may provide buccal contour stability.

Positive Effects of Three-Dimensional Collagen-Based Matrices on the Behavior of Osteoprogenitors.

Recent research has demonstrated that reinforced three-dimensional (3D) collagen matrices can provide a stable scaffold for restoring the lost volume of a deficient alveolar bone. In the present study, we aimed to comparatively investigate the migratory, adhesive, proliferative, and differentiation potential of mesenchymal stromal ST2 and pre-osteoblastic MC3T3-E1 cells in response to four 3D collagen-based matrices. Dried acellular dermal matrix (DADM), hydrated acellular dermal matrix (HADM), non-crosslinked collagen matrix (NCM), and crosslinked collagen matrix (CCM) did all enhance the motility of the osteoprogenitor cells. Compared to DADM and NCM, HADM and CCM triggered stronger migratory response. While cells grown on DADM and NCM demonstrated proliferative rates comparable to control cells grown in the absence of a biomaterial, cells grown on HADM and CCM proliferated significantly faster. The pro-proliferative effects of the two matrices were supported by upregulated expression of genes regulating cell division. Increased expression of genes encoding the adhesive molecules fibronectin, vinculin, CD44 antigen, and the intracellular adhesive molecule-1 was detected in cells grown on each of the scaffolds, suggesting excellent adhesive properties of the investigated biomaterials. In contrast to genes encoding the bone matrix proteins collagen type I (Col1a1) and osteopontin (Spp1) induced by all matrices, the expression of the osteogenic differentiation markers Runx2, Alpl, Dlx5, Ibsp, Bglap2, and Phex was significantly increased in cells grown on HADM and CCM only. Short/clinically relevant pre-coating of the 3D biomaterials with enamel matrix derivative (EMD) or recombinant bone morphogenetic protein-2 (rBMP-2) significantly boosted the osteogenic differentiation of both osteoprogenitor lines on all matrices, including DADM and NCM, indicating that EMD and BMP-2 retained their biological activity after being released from the matrices. Whereas EMD triggered the expression of all osteogenesis-related genes, rBMP-2 upregulated early, intermediate, and late osteogenic differentiation markers except for Col1a1 and Spp1. Altogether, our results support favorable influence of HADM and CCM on the recruitment, growth, and osteogenic differentiation of the osteoprogenitor cell types. Furthermore, our data strongly support the biofunctionalization of the collagen-based matrices with EMD or rBMP-2 as a potential treatment modality for bone defects in the clinical practice.

Healing hard-to-heal diabetic foot ulcers: the role of dehydrated amniotic allograft with cross-linked bovine-tendon collagen and glycosaminoglycan matrix.

The treatment of diabetic foot ulcers is complex and costly with an increased risk for infection, which may even lead to amputation. This prospective case series aims to assess the effectiveness of a dehydrated amniotic membrane allograft combined with a bilayer dermal matrix for healing complicated foot ulcers in patients with comorbidities. A total of six patients with complicated full-thickness ulcers and comorbidities, such as diabetes and peripheral vascular disease were treated with this technique. Each wound was measured intraoperatively just before graft application, at 14 days after application, and then at weeks 4, 8, and 12. Changes in wound volume and area were compared over time. One patient had complete wound closure by week eight, a second patient by week 12. The other four patients had wounds that decreased in size during the course of 12 weeks. The mean decrease in wound volume was 73.5% post-removal of the bilayer dermal matrix after two weeks of application. At week 12, the mean decrease in wound area and volume were 93.2% and 97.1%, respectively. This case series provides initial evidence that the combination of dehydrated amniotic membrane allograft with bilayer dermal matrix promotes complete wound closure in patients with comorbidities that may impede wound healing. Further clinical trials are needed to confirm these results.

Buccal Pedicle Flap Combined With Porcine Collagen Matrix: A Follow‐Up of 2 Years on 40 Consecutive Cases

A thick peri-implant mucosa is of importance to prevent recession, color alterations, bone remodeling and promote "creeping attachment." A volume stable porcine cross-linked collagen matrix has been recently introduced for soft tissue regeneration and volume maintenance. The aim of this study was to investigate peri-implant soft tissue healing and stability on 40 consecutive patients treated with buccal pedicle flap combined with the use of the collagen matrix. The buccal pedicle flap combined with a volume stable collagen matrix was executed at second stage surgery. The average initial mucosa thickness was 1.32 mm whereas the average band of keratinized mucosa was 1.65 mm and the height 1.3 mm. Four months after surgical procedure and before delivering the final restoration, the peri-implant soft tissue measurements were significantly increased: the average band of keratinized mucosa was 5.10 mm, the mucosa thickness was 3.27 mm, and the mucosa height was 3.32 mm. After 2 years of follow-up, the superimposition of 3D models described an overall volumetric stability of the augmented mucosa with no signs of soft tissue collapse. The proposed modified buccal pedicle flap was demonstrated to perform well in terms of decreased morbidity, maintenance of blood supply, stabilization of the pedicle, superior haemostasis, and speed of treatment. No significant variations of the keratinized tissue were registered when the buccal pedicle flap was executed in conjunction with the collagen matrix that however provided color match with the surrounding tissue as well as an increased mucosa thickness.

Buccal tissue augmentation with a sugar cross‐linked collagen matrix: a case series study

Background: The thickness of buccal hard and soft tissue has been claimed to be of great clinical relevance in terms of aesthetics and health around implants. To improve such condition several surgical techniques have been proposed and several biomaterials have been used. Collagen products, cross-linked through the use of sugar according to GLYMATRIX technology, have shown their ability to undergo ossification in both animal and human studies, maintaining space for regeneration for long time. Aim/Hypothesis: To evaluate, through a series of consecutively treated patients, the ability of a GLYMATRIX collagen scaffold to improve buccal tissue thickness when used simultaneously to implant positioning in native bone. Materials and Methods: 16 patients, pre-operatively showing adequate bone for implant placement in a CBCT and flat\concave horizontal profile of the ridge in a clinical evaluation, were included in the study. Preoperative virtual models were developed using an intraoral scanner and a dedicated software. All patients received one or two implants and a cross-linked collagen scaffold (OSSIX Volumax, Datum Dental) was placed on the buccal bone plate at the same time. Flaps were repositioned to cover the matrix and sutured around a healing cap. After a conventional healing protocol (post-operative home care, suture removal, clinical and radiographic follow up visits) implants were loaded at 6 months and a new virtual model was obtained with the procedure of above. Gain in tissue thickness buccally to the implant was measured, by means of a computed superimposition of pre- and 6-month virtual models, as the largest improvement along the first 5 mm vertically measured from the gingival margin. Results: 20 implants with sugar cross-linked collagen matrix on the buccal side were consecutively placed in 16 patients. The mean buccal tissue gain at 6 months was 2.4 mm (SD = 0.7 mm). Conclusions and Clinical Implications: The use of a sugar cross-linked collagen matrix showed very promising results in improving buccal tissue thickness around implants. Such ability could be of high clinical relevance to improve this clinical parameter so important for health and esthetics with no needs for major procedures for augmentation. Keywords: Buccal tissue thickness, Tissue augmentation, Cross linked collagen matrix