Collagen Sponge Research Articles

Development of fibroblast/endothelial cell-seeded collagen scaffolds for in vitro prevascularization.

The development of vascularized scaffolds remains one of the major challenges in tissue engineering, and co-culturing with endothelial cells is known as one of the possible approaches for this purpose. In this approach, optimization of cell culture conditions, scaffolds, and fabrication techniques is needed to develop tissue equivalents that will enable in vitro formation of a capillary network. Prevascularized equivalents will be more physiologically comparable to the native tissues and potentially prevent insufficient vascularization after implantation. This study aimed to culture human umbilical vein endothelial cells (HUVECs), alone or in co-culture with fibroblasts, on collagen scaffolds prepared by simple fabrication approaches for in vitro prevascularization. Different concentrations and ratios of HUVECs and fibroblasts seeded on collagen gel and sponge scaffolds under several culture conditions were examined. Cell viability, scaffolds morphology, and structure were analyzed. Collagen gel scaffolds showed good cell proliferation and viability, with higher proliferation rates for cells cultured in a 2:1 (fibroblasts: HUVECs) ratio and kept in endothelial cell growth medium. However, these matrices were unable to support endothelial cell sprouting. Collagen sponges were highly porous and showed good cell viability. However, they became fragile over time in culture, and they still lack signs of vascularization. Collagen scaffolds were a good platform for cell growth and viability. However, under the experimental conditions of this study, the HUVEC/fibroblast-seeded scaffolds were not suitable platforms to generate in vitro prevascularized equivalents. Our findings will be a valuable starting point to optimize culture microenvironments and scaffolds during fabrication of prevascularized scaffolds.

Carrier systems for bone morphogenetic proteins: An overview of biomaterials used for dentoalveolar and maxillofacial bone regeneration.

Different types of biomaterials have been used to fabricate carriers to deliver bone morphogenetic proteins (BMPs) in both dentoalveolar and maxillofacial bone regeneration procedures. Despite that absorbable collagen sponge (ACS) is considered the gold standard for BMP delivery, there is still some concerns regarding its use mainly due to its poor mechanical properties. To overcome this, novel systems are being developed, however, due to the wide variety of biomaterial combination, the heterogeneous assessment of newly formed tissue, and the intended clinical applications, there is still no consensus regarding which is more efficient in a particular clinical scenario. The combination of two or more biomaterials in different topological configurations has allowed specific controlled-release patterns for BMPs, improving their biological and mechanical properties compared with classical single-material carriers. However, more basic research is needed. Since the BMPs can be used in multiple clinical scenarios having different biological and mechanical needs, novel carriers should be developed in a context-specific manner. Thus, the purpose of this review is to gather current knowledge about biomaterials used to fabricate delivery systems for BMPs in both dentoalveolar and maxillofacial contexts. Aspects related with the biological, physical and mechanical characteristics of each biomaterial are also presented and discussed.

Methods of prevention and treatment of alveolar osteitis

Alveolar osteitis is an infectious complication after tooth extraction. They appear in two forms: serous, characterized by pain syndrome and decayed clot, purulent, which is identified by provoked pain and filling of alveoli, and chronic hypertrophic, in which body temperature decreases and general well-being improves.Aim. To explore different methods of preventing and treating alveolar osteitis.Alveolar osteitis usually occurs more frequently in young adults between the ages of 30 and 50 and is slightly more common in women than in men. Treatment methods for dry socket are quite limited, but there are a large number of drugs for treatment: eugenol-based drugs, chlorhexidine, antibiotics, analgesics and local anesthetics, enzymes, hemostatic agents, hormonal agents soaked in collagen sponges, pastes, gels, turundas, preparations based on biopolymers such as chitosan, and platelet-rich plasma.

Growth Factor-Free Vascularization of Marine-Origin Collagen Sponges Using Cryopreserved Stromal Vascular Fractions from Human Adipose Tissue.

The successful integration of transplanted three-dimensional tissue engineering (TE) constructs depends greatly on their rapid vascularization. Therefore, it is essential to address this vascularization issue in the initial design of constructs for perfused tissues. Two of the most important variables in this regard are scaffold composition and cell sourcing. Collagens with marine origins overcome some issues associated with mammal-derived collagen while maintaining their advantages in terms of biocompatibility. Concurrently, the freshly isolated stromal vascular fraction (SVF) of adipose tissue has been proposed as an advantageous cell fraction for vascularization purposes due to its highly angiogenic properties, allowing extrinsic angiogenic growth factor-free vascularization strategies for TE applications. In this study, we aimed at understanding whether marine collagen 3D matrices could support cryopreserved human SVF in maintaining intrinsic angiogenic properties observed for fresh SVF. For this, cryopreserved human SVF was seeded on blue shark collagen sponges and cultured up to 7 days in a basal medium. The secretome profile of several angiogenesis-related factors was studied throughout culture times and correlated with the expression pattern of CD31 and CD146, which showed the formation of a prevascular network. Upon in ovo implantation, increased vessel recruitment was observed in prevascularized sponges when compared with sponges without SVF cells. Immunohistochemistry for CD31 demonstrated the improved integration of prevascularized sponges within chick chorioalantoic membrane (CAM) tissues, while in situ hybridization showed human cells lining blood vessels. These results demonstrate the potential of using cryopreserved SVF combined with marine collagen as a streamlined approach to improve the vascularization of TE constructs.

Evaluation of Topology Optimization Using 3D Printing for Bioresorbable Fusion Cages: A Biomechanical Study in a Porcine Model.

Preclinical biomechanical study of topology optimization versus standard ring design for bioresorbable poly-ε-caprolactone (PCL) cervical spine fusion cages delivering bone morphogenetic protein-2 (BMP-2) using a porcine model. The aim was to evaluate range of motion (ROM) and bone fusion, as a function of topology optimization and BMP-2 delivery method. 3D printing technology enables fabrication of topology-optimized cages using bioresorbable materials, offering several advantages including customization, and lower stiffness. Delivery of BMP-2 using topology optimization may enhance the quality of fusion. Twenty-two 6-month-old pigs underwent anterior cervical discectomy fusion at one level using 3D printed PCL cages. Experimental groups (N=6 each) included: Group 1: ring design with surface adsorbed BMP-2, Group 2: topology-optimized rectangular design with surface adsorbed BMP-2, and Group 3: ring design with BMP-2 delivery via collagen sponge. Additional specimens, two of each design, were implanted without BMP-2, as controls. Complete cervical segments were harvested six months postoperatively. Nanocomputed tomography was performed to assess complete bony bridging. Pure moment biomechanical testing was conducted in all three planes, separately. Continuous 3D motions were recorded and analyzed. Three subjects suffered early surgical complications and were not evaluated. Overall, ROM for experimental specimens, regardless of design or BMP-2 delivery method, was comparable, with no clinically significant differences among groups. Among experimental specimens at the level of the fusion, ROM was <1.0° in flexion and extension, indicative of fusion, based on clinically applied criteria for fusion of <2 to 4°. Despite the measured biomechanical stability, using computed tomography evaluation, complete bony bridging was observed in 40% of the specimens in Group 1, 50% of Group 2, 100% of Group 3, and none of the control specimens. A topology-optimized PCL cage with BMP-2 is capable of resulting in an intervertebral fusion, similar to a conventional ring-based design of the same bioresorbable material.

Preparation of methacrylated hyaluronate/methacrylated collagen sponges with rapid shape recovery and orderly channel for fast blood absorption as hemostatic dressing

Uncontrolled hemorrhage of deep, narrow, and non-compressible perforating wounds is responsible for many trauma deaths. In this study, a rapid hemostatic sponge with an orderly channel based on methacrylated collagen (ColMA) was prepared via directional freeze-drying technology. The methacrylated hyaluronate (HAMA) was added to further enhance the mechanical properties of the sponge. The sponge presents excellent mechanical strength, rapid shape recovery, and absorption speed, which was faster than those of many reported natural polymer hemostatic sponges. Moreover, ColMA/HAMA sponge showed much better blood-clotting capacity and superior hemostasis performance than commercially available collagen sponges in vitro and in the rat-liver injury model. This study demonstrated a feasible strategy to construct the rapid hemostatic sponge with an orderly channel for the deep and non-compressible perforating wound.

Tissue origin matters: Maintenance of tenogenic phenotype on the tendon and not skin collagen‐derived devices

AbstractRecent data suggest that collagen retains the memory of the tissue that it derives from. With this in mind, collagen (from bovine skin and tendon) sponges were fabricated with different crosslinking densities, and their physicochemical and biological properties were assessed. As the crosslinking density was increased, the resistance to collagenase digestion, denaturation temperature, compressive stress, and compressive modulus was significantly increased and the free amine content, % swelling, and human dermal fibroblast cytocompatibility were significantly reduced. The tendon‐collagen‐derived scaffolds exhibited significantly higher compressive stress and compressive modulus values and induced significantly higher human tenocyte DNA concentration and metabolic activity than the skin‐collagen‐derived scaffolds. In human tenocyte cultures on day 14, the 1 mM 4‐arm polyethylene‐glycol succinimidyl glutarate tendon‐collagen‐derived collagen sponges induced significantly higher collagen type III synthesis (as expected at early stages of physiological tendon healing) and downregulated actin alpha 2 (associated with myofibroblast differentiation) and the skin‐collagen‐derived collagen sponges induced significantly higher collagen type IV synthesis (found primarily at the dermal‐epidermal junction) and upregulated prolyl 4‐hydroxylase subunit alpha‐1 (associated with collagen biosynthesis and constitutes a target for antifibrotic compounds). Our data indicate that the tissue from which collagen is extracted should be considered in the development of medical devices.

Bone Morphogenetic Protein as Bone Additive around Dental Implant and its Impact on Osseointegration: a Systematic Review.

Bone morphogenetic protein (BMP), a potential osteoinductive agent, was systematically reviewed for merits and demerits when used as a bone additive that was intervened during the surgical phase of dental implant placement; and suitable drug carriers that could withstand the functional load and deliver BMP at its lowest concentration. To identify the carriers and concentration of BMP acceptable during surgical phase of implant placement and evaluate its efficacy in bone gain and osseointegration. The study design was systematic review. Literature search as per PICO format was carried out within a time range from 2000 to July 2021. The review fol-lowed PRISMA guidelines and registered with the PROSPERO (CRD42020171667). The focus question included the population with an intra-oral implant placed in both animal and human models that were intervened with BMP-2 as an external additive biomaterial during the surgical phase. 2631 articles selected from the initial search were systematically filtered and yielded 16 articles that were qualitatively analysed. The inter-rater reliability and level of agreement were 93.71%, κ(Kappa)>0.81 re-spectively. Results revealed the collagen carrier was commonly used for BMP delivery but lacked the property to withstand functional load and sustained release. BMP concentration varied in the range of 0.215μg to 0.8mg and the study revealed significantly indifferent out-come with low dose compared to the highest dose. BMP supplement showed better osseointe-gration in comparison with non-supplemented sites during the early period (within 6 months). BMP at lower concentrations and with appropriate carriers, collagen sponge, hydroxyapatite/tricalcium phosphate (HA/TCP) with a bio ceramic bulking agent, and poly (D, L-lactide-co-glycolic acid) (PLGA) reinforced with gelatin/HA/TCP accelerated bone growth during the initial stages of healing. Further long-term clinical trials for dental implant, analysing the sustained release of BMP with biodegradable and load-bearing carriers should be considered.

Characterization and assessment of lung and bone marrow derived endothelial cells and their bone regenerative potential.

Angiogenesis is important for successful fracture repair. Aging negatively affects the number and activity of endothelial cells (ECs) and subsequently leads to impaired bone healing. We previously showed that implantation of lung-derived endothelial cells (LECs) improved fracture healing in rats. In this study, we characterized and compared neonatal lung and bone marrow-derived endothelial cells (neonatal LECs and neonatal BMECs) and further asses3sed if implantation of neonatal BMECs could enhance bone healing in both young and aged mice. We assessed neonatal EC tube formation, proliferation, and wound migration ability in vitro in ECs isolated from the bone marrow and lungs of neonatal mice. The in vitro studies demonstrated that both neonatal LECs and neonatal BMECs exhibited EC traits. To test the function of neonatal ECs in vivo, we created a femoral fracture in young and aged mice and implanted a collagen sponge to deliver neonatal BMECs at the fracture site. In the mouse fracture model, endochondral ossification was delayed in aged control mice compared to young controls. Neonatal BMECs significantly improved endochondral bone formation only in aged mice. These data suggest BMECs have potential to enhance aged bone healing. Compared to LECs, BMECs are more feasible for translational cell therapy and clinical applications in bone repair. Future studies are needed to examine the fate and function of BMECs implanted into the fracture sites.

P9. Sex differences in response to recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat posterolateral fusion spine model

<h3>BACKGROUND CONTEXT</h3> Estrogen modulates bone activity largely through inhibition of osteoclast bone resorption and bone morphogenetic protein-2 (BMP-2) signaling pathways in osteoblasts. Minimal data exist concerning potential sex-dependent differences in BMP-2-mediated bone regeneration. Here, we aimed to quantify sex-dependent differences in the bone healing response to recombinant human BMP-2 (rhBMP-2) treatment in a rat posterolateral spinal fusion model. <h3>METHODS</h3> A total of 48 female and male Sprague-Dawley rats (N=24/group), underwent L4-L5 posterolateral fusion with bilateral placement of absorbable collagen sponges, loaded with 5 µg of rhBMP-2 (10 µg/animal). At 8 weeks postoperatively, 10 specimens of each sex were tested in flexion-extension with quantification of range of motion (ROM) and stiffness. The remaining specimens were evaluated for new bone growth and fusion via radiography, blinded manual palpation and microcomputed tomography (microCT). Laboratory microCT quantified bone microarchitecture and synchrotron microCT examined bone microstructure. On histology, the number of adipocytes within a standardized field of view was counted for both male and female fusion masses. <h3>RESULTS</h3> Manual palpation scores differed significantly between sexes, with mean fusion scores of 2.4±0.4 in females vs 3.1±0.6 in males, p < 0.001. Biomechanical stiffness did not differ between sexes, but ROM was significantly greater and more variable for females vs males (3.7°±5.6° vs 0.27°±0.15°,p < 0.005, respectively. Laboratory microCT showed significantly smaller volumes of fusion masses in females vs males (262±87 mm³ vs 732±238 mm³, respectively, p < 0.001) but significantly higher bone volume fraction (0.27±0.08 vs 0.12±0.05, respectively, p < 0.001). Mean trabecular thickness was not different, but trabecular number was significantly greater in females (3.1±0.5 mm-1vs 1.5±0.4 mm-1, respectively, p<0.001). Synchrotron microCT showed fine bone structures developing in both sexes at the 8-week time point. Adipocyte density was found to be significantly higher in male fusion masses than in female fusion masses. <h3>CONCLUSIONS</h3> This study demonstrates that sex-based factors may influence both the quantity and quality of bone formation in patients receiving rhBMP-2 for a variety of orthopedic applications. We found that male rats had significantly higher fusion scores, greater fusion-mass volume, and lower ratio of new bone volume to total volume compared to female rats. Male and female mean trabecular thicknesses were equal, but the female fusion masses were more densely filled with trabeculae (higher trabecular number) than those of males. MicroCT results suggested that the male trabeculae were more rod-like and the female more plate-like, although the methods that were used are generally considered less accurate for trabecular bone, which has a high degree of concavity. The incomplete fusions on three female rats, evidenced by high ROM and small gaps on microCT, suggest that females may have a more variable response to rhBMP-2. Investigation into whether these sex-based differences are specific to rhBMP-2-induced bone formation or are more general to bone regeneration/healing is prudent. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

P7. Percutaneous delivery of recombinant human bone morphongenetic protein-2 augments fusion in a nicotine impaired rabbit fusion model

<h3>BACKGROUND CONTEXT</h3> Several experiments have shown that delivery of BMP-2 in a delayed fashion from initial surgery may be superior for optimal bone growth. Studies of posterolateral spinal fusion in rabbits have shown that BMP-2 expression physiologically peaks from 4-6 weeks out from surgery. The hypothesis of this experiment was that delayed delivery of ACS/BMP-2 would augment bone growth in a rabbit spine fusion model. By percutaneously delivering ACS/BMP-2 we would be able to deliver osteoinductive material at an optimal time point away from the typical time of surgery application. <h3>PURPOSE</h3> To determine if controlled delivery of morselized absorbable collagen sponge (ACS) Rh-BMP2 in a delayed manner postsurgery would allow for increased fusion mass in a rabbit spine fusion model. <h3>STUDY DESIGN/SETTING</h3> A nicotine-impaired spinal fusion rabbit model. <h3>PATIENT SAMPLE</h3> Sixteen male one-year-old rabbits. <h3>OUTCOME MEASURES</h3> Histologic, radiologic (radiographic, CT scans) and palpation examinations were performed to determine fusion status and the volume of bone formed. <h3>METHODS</h3> Sixteen male one-year-old rabbits underwent a posterolateral spinal fusion with iliac crest bone graft at L5-L6 while being given nicotine to prevent spinal fusion as previously published. Eight were controls while 8 had morselized RhBMP-2 (4.2mg) injected at the fusion site at 4 weeks postoperatively. At 12 weeks, the rabbits were sacrificed. Histologic, radiologic (radiographic, CT scans) and palpation examinations were performed to determine fusion status and the volume of bone formed. Hematoxylin and eosin (H&E) stain were used for histology. There were 4 of 8 rabbits in the control cohort with bilateral fusion and 6 of 8 rabbits in the BMP-DDC that had bilateral fusion based on CT scan analysis. A student's t-test was used to compare the CT scan measured volume of bone created between control (CC) and RhBMP-2 delayed delivery cohorts (BMP-DDC). <h3>RESULTS</h3> Seven of 8 rabbits in the BMP-DDC and 5 of 8 rabbits in the CC formed definitive fusion with a positive palpation exam, bridging bone between transverse processes on CT scan and an x-ray showing fusion. Histologic analysis revealed new remodeled bone within the BMP-DDC. There was increased average volume of bone formed within the BMP-DDC vs the CC (22.6±13.1 vs 11.1±3.6 cm^3, p=0.04) <h3>CONCLUSIONS</h3> Our study shows that injectable morselized ACS/RhBMP-2 can create twice as much bone within a nicotine-impaired rabbit spine fusion model when delivered 4 weeks out from time of surgery. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

8. Controlling the rate of presentation of BMP-2 from a highly structured composite for interbody fusion

<h3>BACKGROUND CONTEXT</h3> Clinical outcomes for patients with intervertebral disc injury or disease could be enhanced by a new generation of regenerative matrices that create tissue environments to control angiogenesis, chondrogenesis and bone formation. Regenerative matrices are a new class of controlled release biomaterials that use surface chemistry, materials architecture, and drug delivery kinetics to create optimised conditions for cell interactions that result in high quality tissue formation. A novel biodegradable polymer matrix that releases bone morphogenetic protein 2 (BMP-2) over a period of one month with a low Cmax and sustained presentation of active protein is investigated in this study. <h3>PURPOSE</h3> BMP-2 release kinetics and protein activity from a new regenerative matrix was quantified to develop an implant with 1-month release of the drug within a macroporous matrix. A rabbit posterolateral (PLF) vertebral fusion model was performed to assess bone formation and fusion outcomes as a function of dose and source of BMP-2 (E coli and CHO cells). <h3>STUDY DESIGN/SETTING</h3> The study was designed to investigate the effect of various biomaterial design factors and manufacturing methods on the rate of release of BMP-2, the activity of BMP-2 and the extent of in vivo bone formation. <h3>PATIENT SAMPLE</h3> This study did not involve patients. <h3>OUTCOME MEASURES</h3> Outcome measures were the mechanical properties of the regenerative matrix, the architecture and porosity of the matrix, BMP-2 release kinetics, BMP-2 activity as a function of release time and bone formation. <h3>METHODS</h3> BMP-2 activity was tested using two in vitro cell-based assays. BMP-2 solutions and regenerative matrix extracts were tested for their ability to induce alkaline phosphatase (ALP) activity in W-20-17 stromal cells using a modified version of the ASTM standard protocol for in vitro biological activity of recombinant human BMP-2 (F2131-02). Cells were exposed to serial dilutions of BMP-2 for 24 h, assayed for ALP activity and EC50s calculated allowing the relative potency to NIBSC WHO BMP-2 standard to be calculated. BMP-2 release was assessed with an in vitro assay of ALP activity in the mouse muscle myoblast cell line C2C12. Formulations were suspended above a C2C12 monolayer in an insert with a porous (8 µm) PET membrane. Following 3-4 days of exposure, the inserts containing LDGraft were transferred to fresh cells for a further 3-4 days. Cells exposed to LDGraft in this manner were assayed for ALP activity (normalised to protein content) once the inserts had been transferred to fresh cells. Fusion rate and new bone formation were compared to INFUSE in a single-level lumbar (L4-L5) posterolateral (PLF) vertebral fusion model in the New Zealand White rabbit based on standard protocols (Boden et al, 1995, ASTM F3207). Pre-formed implants (3 cc) of INFUSE (rhBMP-2 and absorbable collagen sponge) were implanted on decorticated dorsal surfaces of the transverse processes of L4 and L5 adjacent to the laminae. Fusion was assessed by radiograph at 6 weeks and by manual palpation, radiography and microCT at 12 weeks. <h3>RESULTS</h3> BMP-2 activity was retained over one month of release with the addition of protectants in the formulation and precise control of manufacturing processes. The matrix had a porosity of >70% with a high proportion of macropores (>200 micron diameter). Low doses of E. coli-produced BMP-2 induced fusion in the PLF model. <h3>CONCLUSIONS</h3> A one-month releasing BMP-2 formulation is described. This new regenerative matrix had internal architecture designed to host angiogenesis. Manufacturing and design challenges can be overcome to retain high biologic activity throughout the release period. <h3>FDA DEVICE/DRUG STATUS</h3> BMP-2, not approved for this indication.

Sex-based Difference in Response to Recombinant Human Bone Morphogenetic Protein-2 in a Rat Posterolateral Fusion Model.

This was a preclinical study. Evaluate sex-dependent differences in the bone healing response to recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat posterolateral spinal fusion model. Minimal and conflicting data exist concerning potential sex-dependent differences in rhBMP-2-mediated bone regeneration in the context of spinal fusion. Forty-eight female and male Sprague-Dawley rats (N=24/group), underwent L4-L5 posterolateral fusion with bilateral placement of an absorbable collagen sponge, each loaded with 5µg of bone morphogenetic protein-2 (10µg/animal). At eight weeks postoperative, 10 specimens of each sex were tested in flexion-extension with quantification of range of motion and stiffness. The remaining specimens were evaluated for new bone growth and successful fusion via radiography, blinded manual palpation and microcomputed tomography (microCT). Laboratory microCT quantified bone microarchitecture, and synchrotron microCT examined bone microstructure at the 1µm level. Manual palpation scores differed significantly between sexes, with mean fusion scores of 2.4±0.4 in females versus 3.1±0.6 in males ( P <0.001). Biomechanical stiffness did not differ between sexes, but range of motion was significantly greater and more variable for females versus males (3.7±5.6° vs. 0.27±0.15°, P <0.005, respectively). Laboratory microCT showed significantly smaller volumes of fusion masses in females versus males (262±87 vs. 732±238mm 3 , respectively, P <0.001) but significantly higher bone volume fraction (0.27±0.08 vs. 0.12±0.05, respectively, P <0.001). Mean trabecular thickness was not different, but trabecular number was significantly greater in females (3.1±0.5 vs. 1.5±0.4mm -1 , respectively, P <0.001). Synchrotron microCT showed fine bone structures developing in both sexes at the eight-week time point. This study demonstrates sex-dependent differences in bone regeneration induced by rhBMP-2. Further investigation is needed to uncover the extent of and mechanisms underlying these sex differences, particularly at different doses of rhBMP-2.

Extended Release of Bupivacaine from Temperature-responsive Hydrogels Provides Multi-day Analgesia for Postoperative Pain.

A local anesthetic that provides analgesia lasting at least three days could significantly improve postoperative pain management. This study evaluated the analgesic efficacy and safety of an extended-release formulation of bupivacaine based on the injectable hydrogel carrier poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) (PNDJ). The efficacy of PNDJ containing 4% bupivacaine (SBG004) given by peri-incisional subcutaneous injection (SBG004 SC) or wound filling instillation (SBG004 WF) was evaluated compared to saline, liposomal bupivacaine, bupivacaine collagen sponge, bupivacaine-meloxicam polyorthoester, and bupivacaine HCl in a porcine skin and muscle incision model. Mechanical allodynia was assessed by withdrawal from application of von Frey filaments, and local tolerance was evaluated by histology. Bupivacaine pharmacokinetics for SBG004 SC were measured in rabbits (16.5 mg bupivacaine/kg). Animals demonstrated less mechanical allodynia at incisions receiving SBG004 SC for up to 96 hours postoperatively. Incisions treated with SBG004 SC tolerated more force without a withdrawal indicative of pain compared to saline for 96 hours, and compared to SBG004 WF and all active controls at 24, 48, and 72 hours except bupivacaine-meloxicam polyorthoester at 72 hours. By 49 days, SBG004 was histologically absent and was replaced with granulation tissue infiltrated with immune cells in some areas. In rabbits, Cmax was 41.6 ± 9.7 ng/mL with t1/2 82.0 ± 35.8 hours (mean ± SD). Peri-incisional SBG004 SC provided extended release of bupivacaine sufficient to reduce sensation of incisional pain for 96 hours, in vivo bupivacaine delivery for at least 7 days, and a favorable local and systemic toxicity profile.

Double Transcrestal Sinus Lift Procedure with Collagen as Bone Void Filler Alone in Atrophic Maxilla: 5 Years Retrospective Radiological Study

Objectives: The present study aimed to investigate the effectiveness of transcrestal double-elevation of the maxillary sinus (TSFE) with an implant placement during the second-stage surgery in the maxillary areas with a residual alveolar bone less than 3mm. Materials and Methods: Patients with long-standing edentulous areas underwent double TSFE surgery involving a first transcrestal maxillary sinus floor augmentation with a collagen sponge to fill the intrabony cavity and a second osteotome-mediated sinus floor elevation by using an electromagnetic device and immediate implant placement. The radiographic changes in bone heightwere measured and compared during the different time intervals by nonparametric statistics with p &lt; 0.01. Results: Twenty-eight patients were retrospectively selected for the study. A total of 42 implants were positioned in 28 augmented sinuses. After the first TSFE surgery, no minor swelling of gingival mucosa, no mucositis, or flap dehiscence with suppuration was found. After three months a second TSFE with simultaneous implant placement was performed; four patients experienced minor nasal bleeding. Significant increases in the bone height had been respectively reported for the first (from 2.3±0.2 to 9.5 ± 0.3 mm) and second surgeries with p-values less than 0.0001 and an overall bone height measured 5 years after the first surgery of 12.2±0.3 mm. Conclusion: The present study suggested to clinicians the possibility of osteotome double sinus lifting and grafting with highly absorbable collagen material, generally used as a haemostatic agent alone in case of residual bone height less than 3 mm.

Clinical effectiveness of a new collagen-based drug with lincomycin for the prevention and treatment of jaw alveolitis

BACKGROUND: Alveolitis is the most common complication that occurs after tooth extraction. Among preventive and therapeutic methods, pharmacological agents for the dry socket treatment have been proposed. However, the gold standard for the prevention and treatment of alveolitis has not been defined.&#x0D; AIM: The study aimed to conduct a comparative analysis of the effectiveness of a collagen sponge with lincomycin and an iodoform tampon for the prevention of the development and treatment of alveolitis.&#x0D; MATERIAL AND METHODS: The study included 75 patients with jaw alveolitis and patients with teething disorders and chronic periodontitis who underwent planned tooth extraction. The patients were divided into two groups: group 1 underwent a socket revision, whereas group 2 had a tooth extraction. The patients of each group were divided into two subgroups: subgroup A used a collagen sponge with lincomycin and subgroup B used an iodoform tampon. The intensity of pain syndrome, severity of mucosal hyperemia, and collateral edema were assessed, and the epithelialization time of the sockets was recorded.&#x0D; RESULTS: The clinical study of the effectiveness of a collagen sponge with lincomycin in comparison with an iodoform tampon demonstrated some advantages of a collagen sponge, including a more comfortable postoperative period, mild pain, less pronounced edema and hyperemia, epithelialization of the extracted teeth sockets 1.5 days earlier.&#x0D; CONCLUSION: For the prevention and treatment of alveolitis, especially in patients in whom the use of iodine compounds is contraindicated, the use of Alvanes collagen sponge with lincomycin is preferable to an iodoform tampon.

Tips and Tricks and Clinical Outcome of Cryopreserved Human Amniotic Membrane Application for the Management of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Pilot Study.

Medication-related osteonecrosis of the jaw (MRONJ) is a complication of certain pharmacological treatments such as bisphosphonates, denosumab, and angiogenesis inhibitors. There are currently no guidelines on its management, particularly in advanced stages. The human amniotic membrane (hAM) has low immunogenicity and exerts anti-inflammatory, antifibrotic, antimicrobial, antiviral, and analgesic effects. It is a source of stem cells and growth factors promoting tissue regeneration. hAM acts as an anatomical barrier with suitable mechanical properties (permeability, stability, elasticity, flexibility, and resorbability) to prevent the proliferation of fibrous tissue and promote early neovascularization at the surgical site. In oral surgery, hAM stimulates healing and facilitates the proliferation and differentiation of epithelial cells in the oral mucosa and therefore its regeneration. We proposed using cryopreserved hAM to eight patients suffering from cancer (11 lesions) with stage 2–3 MRONJ on a compassionate use basis. A collagen sponge was added in some cases to facilitate hAM grafting. One or three hAMs were applied and one patient had a reapplication. Three patients had complete closure of the surgical site with proper epithelialization at 2 weeks, and two of them maintained it until the last follow-up. At 1 week after surgery, three patients had partial wound dehiscence with partial healing 3 months later and two patients had complete wound dehiscence. hAM reapplication led to complete healing. All patients remained asymptomatic with excellent immediate significant pain relief, no infections, and a truly positive impact on the patients’ quality of life. No adverse events occurred. At 6 months of follow-up, 80% of lesions had complete or partial wound healing (30 and 50%, respectively), while 62.5% of patients were in stage 3. Radiological evaluations found that 85.7% of patients had stable bone lesions (n = 5) or new bone formation (n = 1). One patient had a worsening MRONJ but remained asymptomatic. One patient did not attend his follow-up radiological examination. For the first time, this prospective pilot study extensively illustrates both the handling and surgical application of hAM in MRONJ, its possible association with a collagen sponge scaffold, its outcome at the site, the application of multiple hAM patches at the same time, and its reapplication.

Effectiveness of different epidural coverage materials for preventing postoperative scar hyperplasia and dural adhesion in spine

Objective: To analyze the effects and mechanisms of three commonly used epidural coverings, gelatin sponge, bovine Achilles tendon extract collagen and polyester urethane fiber, in preventing epidural scar adhesions after laminectomy in rats. Methods: Forty-eight adult Wistar rats were excised from L2 to L5 lamina to establish laminectomy models, and were divided into four groups with random number table according to different covering materials (12 rats in each group): blank group (group A), gelatin sponge group (absorbable, group B), polyester urethane fiber group (non-absorbable, group C) and bovine Achilles tendon extract collagen group (absorbable, group D). At 4 and 12 weeks postoperatively, the spinal tissues of the operated area were taken for gross observation (Rydell scar adhesion rating criteria) and histological observation (Nussbaum criteria); and the expression of three scar proliferation-related cytokines, basic fibroblast growth factor (bFGF), growth transforming factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF), were measured in the peridural tissues. The differences between the indices in each group were analyzed and compared. Results: All 48 rats survived, and gross and histological findings at 4 and 12 weeks showed no dural adhesions in the gelatin sponge and bovine Achilles tendon extract collagen groups, adhesions in the polyester urethane fiber group, and heavy adhesions and spinal cord compression in the blank control group. There were significant differences in the Rydell grade and Nussbaum histological score between the absorbable material group and the non-absorbable group (both P<0.05). Western protein blotting at 4 and 12 weeks confirmed that the expression levels of three cytokines, including bFGF, TGF-β1, and VEGF, were lower in the absorbable material group than those in the non-absorbable group (all P<0.01). Immunofluorescence tests at 12 weeks confirmed that the expression of bFGF, TGF-β1 and VEGF were all lower in the gelatin sponge group (9.81±0.81, 12.42±2.35, 8.63±1.76) and the bovine Achilles tendon extract collagen group (12.70±2.02, 8.23±1.03, 10.19±2.67) than those in the polyester urethane fiber group (33.94±2.03, 30.29±2.76, 25.79±1.21) (all P<0.01). Conclusions: Bovine achilles tendon extract collagen and gelatin sponge can effectively reduce the hyperplasia of scar and dural adhesions after spinal surgery.

Local administration of low doses of exogenous BMP2 and leptin promotes ectopic bone regeneration in leptin-deficient mice.

Obesity and leptin deficiency are associated with compromised bone regeneration. This study aims to investigate the role of locally administrated low-dose BMP2+leptin on bone regeneration in leptin-deficient obese (ob/ob) mice. Wildtype (WT) and ob/ob mice were divided into 3 groups (4mice/group): BMP2 (5μg) group, BMP2+low-dose leptin (1μg) group, and BMP2+high-dose leptin (2.5μg) group. WT mice were used as control mice. An equal size absorbable collagen sponge was prepared by loading the BMP2 or/and leptin and implanted subcutaneously. After 19 days, samples were collected and analyzed by micro-CT and H&E staining. No significant difference in bone regeneration among the three groups in WT mice. Quantification of newly formed bone parameters from micro-CT and H&E staining showed that low-dose BMP2 treatment formed less new bone in ob/ob mice compared to WT. BMP2+low-dose leptin treatment substantially rescued the compromised bone regeneration in ob/ob mice up to the level in WT mice. However, the BMP2 and high dose of leptin failed to rescue the compromised bone regeneration in ob/ob mice. Our findings suggest that a combination of the low-dose BMP2 and leptin could be a strategy to promote osteogenesis in obese populations with leptin deficiency.

Effect of Gentamicin Collagen Sponge on Wound Healing: In Vivo Study and Assessment of Its Effectiveness against Nosocomial Bacteria

Background: Gentamicin collagen sponge (Genta-Coll) reportedly has a hemostatic effect and promotes wound healing. However, it may also interfere with wound healing by causing foreign body reactions. We planned to analyze the effect of Genta-Coll on wound healing by inducing muscle defects in the rectus abdominis muscle of rats. We also assessed the effectiveness of Genta-Coll in preventing surgical site infections (SSIs) using the zone of inhibition tests to determine the sensitivity of pathogenic bacteria.Methods: We created an 8×8-mm muscle defect in both recti abdominis of 15 white Sprague-Dawley rats and distributed them into the control group (no care) and group A (Genta-Coll). Three biopsies were performed for histologic analysis (on days 3, 7, and 27). In the second study, we placed Genta-Coll on Mueller–Hinton agar plates seeded with pathogenic microorganisms commonly responsible for SSIs. The zone of inhibition was measured after 24 and 48 hours of incubation.Results: Group A showed a slightly higher score for foreign body giant cells and inflammation, with no significant difference. Granulation and neovascularization were constantly high in group A, and muscle regeneration was also high in group A. Extracellular matrix formation advanced at a similar pace in both groups. Genta-Coll created a zone of inhibition against all microorganisms except for Candida albicans. The effect lasted without change between 24 and 48 hours.Conclusion: While foreign body reactions and inflammation increased in group A, wound healing was unaffected. Genta-Coll can promote faster wound healing with an anti-bactericidal effect against SSI pathogens.