Collagen Sponge Research Articles

Evaluation of Changes in the Palatal Mucosal Thickness Post-augmentation using a Xenogeneic Collagen MatrixAn Interventional Study

Introduction: Palatal augmentation is a unique approach that has been developed to increase the donor mucosal thickness and to procure sufficient dimensions of Connective Tissue Graft (CTG) during soft tissue augmentation around natural teeth and implants. Aim: To evaluate the relative changes in Palatal Mucosal Thickness (PMT) followed by augmentation with xenogeneic collagen sponge. Materials and Methods: This was an interventional study conducted on 16 subjects presenting with multiple gingival recession defects and also indicated for root coverage procedures at Department of Periodontology, SRM Dental College, Chennai, Tamil Nadu, India from June 2017 to March 2018. PMT was measured using a customised stent at eight standardised points with respect to Canine (C), Premolar-1 (PM1), Premolar-2 (PM2) and Molar 1 (M1) located at 4 mm and 8 mm from the gingival margin. Xenogeneic collagen sponge was implanted at the donor site and postoperatively reviewed for two months. Changes in PMT were analysed using Mann-Whitney U test. Results: A total of 16 patients (12 male and 4 female; mean age 36.81±7.27 years) were recruited in the study. At two months, statistically significant (p<0.05) increase in mean thickness of the palatal mucosa was observed at all the study points (at 4 mm: C- 5.24±0.43 mm to 4.82±0.39 mm, PM1- 5.47±0.71 mm to 4.88±0.48 mm, PM2- 5.71±0.58 mm to 5.06±0.65 mm and M1- 5.71±0.58 mm to 5.24±0.43 mm and at 8 mm C- 5.24±0.43 mm to 4.47±0.51 mm, PM1- 5.47±0.62 mm to 4.41±0.61 mm, PM2- 5.47±0.62 mm to 4.35±0.49 mm and M1- 5.65±0.60 mm to 4.76±0.43 mm). Conclusion: Xenogeneic collagen sponge implantation resulted in a significant increase in the thickness of palatal mucosa.

PLGA-collagen-BPNS Bifunctional composite mesh for photothermal therapy of melanoma and skin tissue engineering.

The treatment of melanoma requires not only the elimination of skin cancer cells but also skin regeneration to heal defects. To achieve this goal, a bifunctional composite scaffold of poly(DL-lactic-co-glycolic acid) (PLGA), collagen and black phosphorus nanosheets (BPNSs) was prepared by hybridizing a BPNS-embedded collagen sponge with a PLGA knitted mesh. The composite mesh increased the temperature under near-infrared laser irradiation. The incorporation of BPNSs provided the PLGA-collagen-BPNS composite mesh with excellent photothermal properties for the photothermal ablation of melanoma cells both in vitro and in vivo. The PLGA-collagen-BPNS composite mesh had high mechanical strength for easy handling. The PLGA-collagen-BPNS composite mesh facilitated the proliferation of fibroblasts, promoted the expression of angiogenesis-related genes and the genes of components of the extracellular matrix for skin tissue regeneration. The high mechanical strength, photothermal ablation capability and skin tissue regeneration effects demonstrate that the bifunctional PLGA-collagen-BPNS composite mesh is a versatile and effective platform for the treatment of melanoma and the regeneration of skin defects.

The use of collagen fleece for healing purposes

The collagen fleece is widely used biomaterial for healing in dental regeneration procedures. The aim of this work was to evaluate the regenerative potential of collagen sponge (collafleece®) in combination with other biomaterials being used in immediate implantation and sinus lift. For that reason, four patients were retrospectively analysed. The collagen fleece successfully supported the wound healing, controlled the bleeding, and assisted the healing of the Schneiderian membrane. The use of collafleece® led to successful treatment in combination with other biomaterials when used in immediate implantation and sinus lift.

Bone regeneration of induced pluripotent stem cells derived from peripheral blood cells in collagen sponge scaffolds.

Stem cell-based regeneration therapy offers new therapeutic options for patients with bone defects because of significant advances in stem cell research. Although bone marrow mesenchymal stem cells are the ideal material for bone regeneration therapy using stem cell, they are difficult to obtain. Induced pluripotent stem cells (iPSCs) are now considered an attractive tool in bone tissue engineering. Recently, the efficiency of establishing iPSCs has been improved by the use of the Sendai virus vector, and it has become easier to establish iPSCs from several type of somatic cells. In our previous study, we reported a method to purify osteogenic cells from iPSCs.Objective:This study aimed to evaluate the osteogenic ability of iPSCs derived from peripheral blood cells.Methodology:Mononuclear cells (MNCs) were obtained from human peripheral blood. Subsequently, T cells were selectively obtained from these MNCs and iPSCs were established using Sendai virus vectors. Established iPSCs were evaluated by the expression of undifferentiated markers and teratoma formation assays. Osteoblasts were induced from these iPSCs and evaluated by the expression of osteoblast markers. Additionally, the induced osteoblasts were transplanted into rat critical size calvaria bone defect models with collagen sponge scaffolds. Samples were evaluated by radiographical and histological assessments.Results:Induced osteoblasts expressed several osteoblast-specific markers. The results of radiographical and histological assessments revealed that the cell transplant group had bone formations superior to those of the control group.Conclusions:This study suggests that peripheral blood MNCs have the potential to differentiate into osteoblasts. Although there are some hurdles in iPSC transplantation, osteoblasts obtained from MNC-iPSCs could be applied to bone regeneration therapy in the future.

Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite.

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing.

Biomimetic sponge using duck’s feet derived collagen and hydroxyapatite to promote bone regeneration

Collagen, a natural biomaterial derived from animal tissues, has attracted the attention of biomedical material researchers because of its excellent cell affinity and low rejection in vivo. In this study, collagen was extracted using livestock by-product flippers, and an experiment was performed to assess its application as a scaffold for bone tissue implantation. For this purpose, we fabricated 2%, and 3% duck's feet derived collagen (DC) sponges. We then compared them to hydroxyapatite (HAp)-coated DC sponges, and measured the porosity and pore size using scanning electron microscopy (SEM) to analyze the physical properties and morphology of DC and DC/HAp sponges. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were carried out to measure the proliferation of bone marrow stem cells (BMSCs) in DC and DC/HAp sponges. An alkaline phosphatase activity assay confirmed the osteogenic differentiation ability of BMSCs. Polymerase chain reaction (PCR) was performed to confirm the BMSC-specific genetic marker. The osteogenic potential was confirmed by the bone formation in an in vivo environment on the scaffold by histological and immunohistochemical analysis. Overall, this study shows that DC/HAp sponges have biocompatibility and good physical properties. Additionally, DC/HAp sponges show potential use as bone graft materials for tissue engineering applications.

Cost-effectiveness of 4 mg dibotermin alfa/absorbable collagen sponge versus iliac crest bone graft for lumbar degenerative disc disease in the United Kingdom

Aims To develop a model to evaluate the cost-effectiveness of 4 mg dibotermin alfa/absorbable collagen sponge (ACS) versus iliac crest bone graft (ICBG) in patients with lumbar degenerative disc disease in the United Kingdom. Materials & methods A Markov decision-analytic model was constructed to calculate costs and quality-adjusted life-years over a 4-year time horizon in each treatment group, from a United Kingdom National Health Service perspective. An individual patient data meta-analysis was undertaken to synthesize data from four randomized controlled trials and two single-arm studies concerning health-related quality of life and procedural resource use. Current cost data from the United Kingdom were then applied to determine the overall mean cost per patient in each group. One-way and probabilistic sensitivity analyses were undertaken to explore the impact of parameter uncertainty. Results The model predicted 4-year discounted cost savings of £192 per patient treated with dibotermin alfa/ACS, compared with ICBG, and a gain of 0.0114 QALYs per patient over the same time period. Sensitivity analyses indicated that the results were most sensitive to variability in the differences in health-related quality of life and secondary surgery rate, with dibotermin alfa/ACS having a 60% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY gained. Limitations There is uncertainty in the difference in cost and QALYs between the two groups. However, comprehensive sensitivity analyses were undertaken to explore this and present the results in a transparent manner. Conclusions Our results provide an economic case for the use of 4 mg dibotermin alfa/ACS versus iliac crest bone graft, with additional health benefits predicted at reduced overall cost.

On the Path to Thermo-Stable Collagen: Culturing the Versatile Sponge Chondrosia reniformis.

The collagen proteins family is sought-after in the pharmaceuticals, cosmetics, and food industries for various biotechnological applications. The most abundant sources of collagen are pigs and cows, but due to religious restrictions and possible disease transmission, they became less attractive. An alternative source can be found in marine invertebrates, specifically in sponges. Alas, two problems arise: (1). Growing sponges is complicated. (2). Sponge collagen has low heat tolerance, which can impose a problem for human biotechnological usage. To fill these gaps, we studied the collagen-abundant sponge Chondrosia reniformis. Two culture experiments were conducted: (1). A sea-based system examined the difference in growth rates of C. reniformis from different habitats, growing under natural seasonal conditions; (2). A land-based controlled system, which assessed the growth-rate of C. reniformis at different temperatures. The results reveal that C. reniformis from shallow habitats are growing larger and faster than individuals from colder, deeper habitats, and that the optimal temperature for C. reniformis growth is 25 °C. The results demonstrate that C. reniformis is highly fit for culture and can produce thermally stable collagen. Further research is needed to determine the best conditions for C. reniformis culture for collagen extract and other exciting materials for bioprospecting.

Comparison of the wound-healing efficacy of gelatin sponge dressings and that of artificial dermis using atelocollagen in a rat cranial periosteal defect model.

In oral surgery, tissue loss may occur in some cases, resulting in bone exposure and subsequent wound infection and possible scar formation during secondary healing. In this study, Terudermis® Artificial Dermis (AD-T), a dermal defect graft made from processed bovine dermis collagen and gelatin sponge (GS) were used as dressings on 100-mm2 wounds with exposed bone on the heads of rats. For the control group, the wound was left exposed. The wound-healing efficacy of the treatment was compared macroscopically and histologically among the three groups at 1, 2, and 4 weeks after surgery. Complete wound healing was achieved faster in the AD-T group than in the GS group, and osteoblasts appeared on the bone surface, indicating accelerated bone remodeling. Furthermore, in the AD-T group, there was an increased production of newly formed blood vessels, fibroblasts and osteoblasts positive for anti-cortactin antibodies, which are believed to contribute to wound healing. Our findings suggest that AD-T is better than GS as a wound dressing material.

Repairing Cartilage with Processed Chondrocyte Constructs: A 6-Month Study Using a Porcine Model.

Autologous chondrocyte implantation was the first cell-based therapy that used a tissue engineering process to repair cartilage defects. Recently improved approaches and tissue-engineered cell constructs have been developed for growing patient populations. We developed a chondrocyte construct using a collagen gel and sponge scaffold and physicochemical stimuli, implanted with a surgical adhesive. We conducted a proof-of-concept study of these improvements using a cartilage defect model in miniature swine. We implanted the autologous chondrocyte constructs into full-thickness chondral defects in the femoral condyle, compared those results with empty and acellular scaffold controls, and compared implantation techniques with adhesive alone and with partial adhesive with suture. Two weeks after the creation of the defects and implantation of the cellular or acellular constructs, we arthroscopically confirmed that the implanted constructs remained at the chondral defects. We evaluated the regenerated tissue macro- and microscopically 6 months after the cell constructs were implanted. The tissues were stained with Safranin-O and evaluated using Sellers' histology grading system. The defects implanted with processed cell constructs and acellular scaffolds were filled with chondrocyte-like round cells and with nearly normal tissue architecture that were significantly greater degree compared to empty defect control. Even with the adhesive alone and with suture alone, the cell construct was composed of the dense cartilaginous matrix that was found in the implantation using both the sutures and the adhesive. Implantation of cell constructs promoted regeneration and integration of articular cartilage at chondral defects in swine by 6 months.

Bone marrow mesenchymal stem cells with low dose bone morphogenetic protein 2 enhances scaffold-based spinal fusion in a porcine model.

High doses bone morphogenetic protein 2 (BMP-2) have resulted in a series of complications in spinal fusion. We previously established a polyelectrolyte complex (PEC) carrier system that reduces the therapeutic dose of BMP-2 in both rodent and porcine spinal fusion models. This study aimed to evaluate the safety and efficacy of the combination of bone marrow mesenchymal stem cells (BMSCs) and low dose BMP-2 delivered by PEC for bone regeneration in a porcine model of anterior lumbar interbody spinal fusion (ALIF) application. Six Yorkshire pigs underwent a tri-segmental (L2/L3; L3/L4; L4/L5) ALIF in four groups, namely: (a) BMSCs+25μg BMP-2/PEC (n=9), (b) 25μg BMP-2/PEC (n=3), (c) BMSCs (n=3), and (d) 50μg BMP-2/absorbable collagen sponge (n=3). Fusion outcomes were evaluated by radiography, biomechanical testing, and histological analysis after 12weeks. Mean radiographic scores at 12weeks were 2.7, 2.0, 1.0, and 1.0 for Groups 1 to 4, respectively. μ-CT scanning, biomechanical evaluation, and histological analysis demonstrated solid fusion and successful bone regeneration in Group 1. In contrast, Group 2 showed inferior quality and slow rate of fusion, and Groups 3 and 4 failed to fuse any of the interbody spaces. There was no obvious evidence of seroma formation, implant rejection, or any other complications in all groups. The results suggest that the combination of BMSCs and low dose BMP-2/PEC could further lower down the effective dose of the BMP-2 and be used as a bone graft substitute in the large animal ALIF model.

Local Antibiotic Delivery Systems in Diabetic Foot Osteomyelitis: A Brief Review.

Diabetic foot osteomyelitis (DFO) is a severe, difficult to treat infection. Local antibiotic delivery has been studied as a potential therapeutic adjunct following surgery for DFO. This review aims to summarize the evidence on local antibiotic delivery systems in DFO. PubMed database was searched up to March 2020. Overall, 16 studies were identified and included: 3 randomized controlled trials (RCTs), 3 retrospective studies (RSs), and 10 case series. In the RCTs, gentamicin-impregnated collagen sponges significantly improved clinical healing rates and slightly improved duration of hospitalization. In the RSs, antibiotic-impregnated calcium sulfate beads non-significantly improved all healing parameters, but did not reduce post-operative amputation rates or time of healing. The majority of case series used calcium sulfate beads, achieving adequate rates of healing and eradication of infection. In conclusion, evidence for add-on local antibiotic delivery in DFO is still limited; more data are needed to assess this therapeutic measure.

Analysis of the Curative Effect and Influencing Factors of Collagen Sponge Combined with Autologous Skin Graft in the Treatment of Deep Burn Patients.

Burn is one of the common traumatic diseases in clinics. After deep burn, the complicated changes of the condition are caused by the burn wound, which ends with the repair of the wound. For patients with deep burns, whether the wound can be repaired as soon as possible is the key to the success of clinical treatment. For patients with deep burns, due to the lack of an autologous skin source, scar hyperplasia at donor site, skin graft repair at donor site, postoperative flap necrosis, and other problems in traditional surgical procedures, the method of improving function only by an autologous skin source has been unable to perform the later function reconstruction in patients with deep burns. In this study, collagen sponge combined with autologous skin graft was used to treat patients with deep burn, and the clinical efficacy of the patients was observed, and the related factors affecting the efficacy of the patients were analyzed. The results showed that collagen sponge combined with autologous skin graft was effective in the treatment of deep burn patients, and it was worth popularizing. Deep III-IV degree burns, wound infection, and hospital stay >3 months are all risk factors affecting the postoperative curative effect of patients. Therefore, in the clinical work, we should focus on patients with deep III-IV degree burns, perform surgery as soon as possible, and actively deal with wounds to prevent infection, which is beneficial to improve the curative effect.

Tissue Adhesion-Anisotropic Polyrotaxane Hydrogels Bilayered with Collagen

Hydrogels are promising materials in tissue engineering scaffolds for healing and regenerating damaged biological tissues. Previously, we developed supramolecular hydrogels using polyrotaxane (PRX), consisting of multiple cyclic molecules threaded by an axis polymer for modulating cellular responses. However, since hydrogels generally have a large amount of water, their adhesion to tissues is extremely weak. Herein, we designed a bilayered hydrogel with a PRX layer and a collagen layer (PRX/collagen hydrogel) to achieve rapid and strong adhesion to the target tissue. The PRX/collagen hydrogel was fabricated by polymerizing PRX crosslinkers in water with placement of a collagen sponge. The differences in components between the PRX and collagen layers were analyzed using Fourier transform infrared spectroscopy (FT-IR). After confirming that the fibroblasts adhered to both layers of the PRX/collagen hydrogels, the hydrogels were implanted subcutaneously in mice. The PRX hydrogel without collagen moved out of its placement site 24 h after implantation, whereas the bilayer hydrogel was perfectly adherent at the site. Together, these findings indicate that the bilayer structure generated using PRX and collagen may be a rational design for performing anisotropic adhesion.

Bone Tissue Regeneration by Collagen Scaffolds with Different Calcium Phosphate Coatings: Amorphous Calcium Phosphate and Low-Crystalline Apatite.

Surface-mineralized collagen sponges have attracted much attention as scaffolds for bone tissue engineering. Recently, we developed amorphous calcium phosphate (ACP) and low-crystalline apatite coating processes on collagen sponges. In the present study, we applied these coating processes to granular collagen sponges (referred to as Col) to compare the bone tissue regeneration capabilities of ACP-coated and apatite-coated Col (referred to as Col-ACP and Col-Ap, respectively) using a rat cranial bone defect model. According to micro-CT and histological analyses, Col-Ap enhanced bone tissue regeneration compared to Col, whereas Col-ACP did not. These results not only demonstrated the superior bone tissue regeneration capability of Col-Ap, but also indicated limitations of the in vitro simulated body fluid (SBF) test used in our previous study. Despite the apatite-forming ability of Col-ACP in SBF, it was ineffective in improving bone tissue regeneration in vivo, unlike Col-Ap, most likely due to the quick resorption of the ACP coating in the defect site. The present results clarified the importance of the coating stability in vivo and revealed that the low-crystalline apatite coating was more beneficial than the ACP coating in the fabrication of surface-mineralized collagen sponges for use as bone tissue engineering scaffolds.

Potential Biomedical Applications of Collagen Filaments derived from the Marine Demosponges Ircinia oros (Schmidt, 1864) and Sarcotragus foetidus (Schmidt, 1862)

Collagen filaments derived from the two marine demosponges Ircinia oros and Sarcotragus foetidus were for the first time isolated, biochemically characterised and tested for their potential use in regenerative medicine. SDS-PAGE of isolated filaments revealed a main collagen subunit band of 130 kDa in both of the samples under study. DSC analysis on 2D membranes produced with collagenous sponge filaments showed higher thermal stability than commercial mammalian-derived collagen membranes. Dynamic mechanical and thermal analysis attested that the membranes obtained from filaments of S. foetidus were more resistant and stable at the rising temperature, compared to the ones derived from filaments of I. oros. Moreover, the former has higher stability in saline and in collagenase solutions and evident antioxidant activity. Conversely, their water binding capacity results were lower than that of membranes obtained from I. oros. Adhesion and proliferation tests using L929 fibroblasts and HaCaT keratinocytes resulted in a remarkable biocompatibility of both developed membrane models, and gene expression analysis showed an evident up-regulation of ECM-related genes. Finally, membranes from I. oros significantly increased type I collagen gene expression and its release in the culture medium. The findings here reported strongly suggest the biotechnological potential of these collagenous structures of poriferan origin as scaffolds for wound healing.

Locally Delivered Ascorbic Acid and β-Glycerophosphate Augment Local Bone Graft in a Murine Model of 2-Level Posterior Spinal Fusion.

Ascorbic acid is involved in collagen biosynthesis and upregulates alkaline phosphatase, potentially alleviating cell senescence and stimulating mesenchymal stem cell proliferation and differentiation into osteoblasts. We hypothesized locally delivered ascorbic acid and β-glycerophosphate act as a bone graft extender to increase the volume of new bone formed in a murine model of posterior lumbar fusion. Collagen sponges were used as delivery vehicles. Sponges were prepared with primary media alone or with the addition of ascorbic acid and β-glycerophosphate. Fresh morselized bone graft from 12 donor mice was used. Twenty-four healthy male C57BL/6 mice underwent an uninstrumented posterior L3-L5 lumbar fusion. One control group received morselized bone only. A second "sponge control" group received morselized bone with the control collagen sponge. The third group received morselized bone and a collagen sponge with ascorbic acid and β-glycerophosphate. Three months postoperatively, the lumbar spine underwent high-resolution micro-computed tomography for analysis of bone formation, density, and bridging fusion. Animals receiving ascorbic acid and β-glycerophosphate had a statistically significant increase in corrected bone volume compared with control and sponge groups, with a 56.3% and 25.4% increase, respectively. Mineralized bone fraction was statistically significantly decreased for animals in the ascorbic acid group compared with control and sponge groups. There was no significant difference in fusion rate between test groups. Locally delivered ascorbic acid and β-glycerophosphate in a murine model of posterior spinal fusion yielded statistically significant increases in new bone formation in the lumbar spine but statistically significant decreases in mineralized bone fraction. Differences in fusion rate were not statistically significant. This study provides early data suggesting that delivery of ascorbic acid to a spinal fusion site may be beneficial but does not yet establish an indication for clinical use. Further studies are needed to determine optimal dose and delivery of ascorbic acid.

Comparative Evaluation of Efficacy between Recombinant Human Bone Morphogenetic Protein-2 Impregnated with Absorbable Sponge and Platelet-Rich Fibrin in the Treatment of Grade II Furcation Defects: A Randomized Controlled Trial.

Aim and Objectives:The objective of the study was to clinically and radiographically compare and evaluate the regenerative potential of recombinant human bone morphogenetic protein-2 (RhBMP-2) impregnated with absorbable collagen sponge and platelet-rich fibrin (PRF) in the treatment of Grade II furcation defects.Patients and Methods:Thirty-two subjects were randomly assigned to each of the following groups: bone morphogenetic protein (BMP) group and PRF group, with one defect/subject. Sixteen Grade II furcation defects were treated with RhBMP-2 impregnated with absorbable collagen sponge in the BMP group and the remaining 16 defects were treated with PRF in the PRF group. Clinical and radiographic parameters which were evaluated at baseline, postoperative 1 week, 3 months, and 6 months were probing pocket depth, clinical attachment level, scoring of plaque index, and gingival index, and the bone fill was evaluated using Digital Subtraction technique and morphometric area analysis with ImageJ® software.Results:RhBMP-2 in absorbable collagen sponge was effective in increasing the bone fill in Grade II furcation defects when compared to PRF alone (P = 0.05). In relation to clinical parameters, both the groups showed no statistical significance between them.Conclusion: The unique regenerative potential of RhBMP-2 impregnated with absorbable collagen sponge makes it a potential agent to be used as a graft material for the treatment of Grade II furcation defects.

A Collagen-Conducting Polymer Composite with Enhanced Chondrogenic Potential.

Conducting polymers (CPs) have demonstrated promise for promoting tissue repair, yet their ability to facilitate cartilage regeneration has yet to be thoroughly investigated. Integrating CPs into common scaffolds for tissue regeneration, such as collagen, would enable mechanistic studies on the potential for CPs to promote cartilage repair. Here, we combine absorbable collagen sponges (ACS) with the CP PEDOT-S and show that the PEDOT-S-collagen composite (PEDOT-ACS) has enhanced chondrogenic potential compared to the collagen sponge alone. PEDOT-S was incorporated through a simple incubation process. Changes to scaffold topography, elastic modulus, swelling ratio, and surface charge were measured to analyze how PEDOT-S affected the material properties of the scaffold. Changes in rat bone marrow mesenchymal stem cell (rBMSC) functionality were assessed with cell viability and glycosaminoglycan production assays. Macrostructure and microstructure of the scaffold remained largely unaffected by PEDOT-S modification, as observed through SEM images and quantification of scaffold porosity. Zeta potential, swelling ratio, and dry elastic modulus of the collagen scaffold were significantly changed by the incorporation of PEDOT-S. Seeding cells on PEDOT-ACS improved cell viability and enhanced glycosaminoglycan production. We demonstrate a practical approach to generate PEDOT-S composites with comparable physical properties to pristine collagen scaffolds. We show that PEDOT-ACS can influence cell functionality and serve as a promising model system for mechanistic investigations on the roles of bioelectronic signaling in the repair of cartilage and other tissue types.

Bone Morphogenetic Protein-2 Rapidly Heals Two Distinct Critical Sized Segmental Diaphyseal Bone Defects in a Porcine Model.

Segmental bone defects (SBDs) are devastating injuries sustained by warfighters and are difficult to heal. Preclinical models that accurately simulate human conditions are necessary to investigate therapies to treat SBDs. We have developed two novel porcine SBD models that take advantage of similarities in bone healing and immunologic response to injury between pigs and humans. The purpose of this study was to investigate the efficacy of Bone Morphogenetic Protein-2 (BMP-2) to heal a critical sized defect (CSD) in two novel porcine SBD models. Two CSDs were performed in Yucatan Minipigs including a 25.0-mm SBD treated with intramedullary nailing (IMN) and a 40.0-mm SBD treated with dual plating (ORIF). In control animals, the defect was filled with a custom spacer and a bovine collagen sponge impregnated with saline (IMN25 Cont, n = 8; ORIF40 Cont, n = 4). In experimental animals, the SBD was filled with a custom spacer and a bovine collage sponge impregnated with human recombinant BMP-2 (IMN25 BMP, n = 8; ORIF40 BMP, n = 4). Healing was quantified using monthly modified Radiographic Union Score for Tibia Fractures (mRUST) scores, postmortem CT scanning, and torsion testing. BMP-2 restored bone healing in all eight IMN25 BMP specimens and three of four ORIF40 BMP specimens. None of the IMN25 Cont or ORIF40 Cont specimens healed. mRUST scores at the time of sacrifice increased from 9.2 (±2.4) in IMN25 Cont to 15.1 (±1.0) in IMN25 BMP specimens (P < .0001). mRUST scores increased from 8.2 (±1.1) in ORIF40 Cont to 14.3 (±1.0) in ORIF40 BMP specimens (P < .01). CT scans confirmed all BMP-2 specimens had healed and none of the control specimens had healed in both IMN and ORIF groups. BMP-2 restored 114% and 93% of intact torsional stiffness in IMN25 BMP and ORIF40 BMP specimens. We have developed two porcine CSD models, including fixation with IMN and with dual-plate fixation. Porcine models are particularly relevant for SBD research as the porcine immunologic response to injury closely mimics the human response. BMP-2 restored healing in both CSD models, and the effects were evident within the first month after injury. These findings support the use of both porcine CSD models to investigate new therapies to heal SBDs.