Absorbable Collagen Sponge Group Research Articles

Posterior open wound healing in immediate implant placement using reactive soft tissue versus absorbable collagen sponge: a retrospective cohort study

The soft and hard tissue healing of open wounds in immediate implant placement are yet to be explored. The aim of this study was to compare the clinical outcomes of open wound healing using reactive soft tissue (RST) and absorbable collagen sponge (ACS). Forty implants placed immediately in posterior sockets were included; autologous RST was used in 20 and ACS substitute was used in 20. Soft tissue healing was primarily assessed through a novel scoring system and the evaluation of gingival recession. The horizontal bone width (HBW) and interproximal marginal bone level (MBL) were measured on radiographs to observe the hard tissue healing. No significant difference in total soft tissue healing score was observed at 2 weeks postoperatively. Notably, the ACS group showed better tissue colour (P = 0.016) but worse fibrous repair (P = 0.043) scores than the RST group. Gingival recession levels were comparable in the two groups, both before tooth extraction and after placement of the restoration. Regarding hard tissue, HBW and MBL changes showed no intergroup differences. Within the limitations of this study, both RST and ACS seemed effective for open wound closure, achieving ideal soft and hard tissue healing in immediate implant placement.

BIOMIMETIC HEMATOMA: NOVEL CARRIER DELIVERS EXTREMELY LOW-DOSE RHBMP-2 FOR HIGHLY EFFECTIVE HEALING OF LARGE BONE DEFECTS IN GOATS

Our previous rat study demonstrated an ex vivo-created “Biomimetic Hematoma” (BH) that mimics the intrinsic structural properties of normal fracture hematoma, consistently and efficiently enhanced the healing of large bone defects at extremely low doses of rhBMP-2 (0.33 μg). The aim of this study was to determine if an extremely low dose of rhBMP-2 delivered within BH can efficiently heal large bone defects in goats.Goat 2.5 cm tibial defects were stabilized with circular fixators, and divided into groups (n=2-3): 2.1 mg rhBMP-2 delivered on an absorbable collagen sponge (ACS); 52.5 μg rhBMP-2 delivered within BH; and an empty group. BH was created using autologous blood with a mixture of calcium and thrombin at specific concentrations. Healing was monitored with X-rays. After 8 weeks, femurs were assessed using microCT.Using 2.1 mg on ACS was sufficient to heal 2.5 cm bone defects. Empty defects resulted in a nonunion after 8 weeks. Radiographic evaluation showed earlier and more robust callus formation with 97.5 % (52.5 μg) less of rhBMP-2 delivered within the BH, and all tibias were fully bridged at 3 weeks. The bone mineral density was significantly higher in defects treated with BH than with ACS. Defects in the BH group had smaller amounts of intramedullary and cortical trabeculation compared to the ACS group, indicating advanced remodeling.The results confirm that the delivery of rhBMP-2 within the BH was much more efficient than on an ACS. Not only did the large bone defects heal consistently with a 40x lower dose of rhBMP-2, but the quality of the defect regeneration was also superior in the BH group. These findings should significantly influence how rhBMP-2 is delivered clinically to maximize the regenerative capacity of bone healing while minimizing the dose required, thereby reducing the risk of adverse effects.

Efficacy of hyaluronic acid, absorbable collagen sponge, and their combination in minimizing bisphosphonate-related osteonecrosis of the jaws (BRONJ) after dental extraction: a preliminary animal histomorphometric study

IntroductionThere is no study on the effectiveness of hyaluronic acid (HA) placement either with or without absorbable collagen sponge (ACS) in reducing or preventing bisphosphonate-related osteonecrosis of the jaws (BRONJ). This preliminary animal study examined the efficacy of this clinically important treatment.MethodsFor simulating BRONJ, zoledronic acid was administered to 40 rats for 5 weeks. Two weeks later, a right first molar was extracted from each rat. The rats were randomized into four groups of socket treatments: control (empty extraction socket) or with sockets filled with ACS, HA, or HA+ACS (n=4×10). After 2 weeks, 5 rats in each group were sacrificed and subjected to histopathologic and histomorphometric evaluation. Eight weeks post-surgically, the rest of rats were euthanized and histologically examined. The Kruskal-Wallis test was used to compare the four treatments at each time point (α=0.05).ResultsSix rats were lost overall. In the second week, vascularization was higher in ACS group (P<0.05); osteoclast activity was not different between groups (P>0.05); empty lacunae were the most and fewest in control and HA+ACS groups, respectively (P<0.05); eosinophil infiltration was maximum in HA group (P<0.05); lymphocyte counts were maximum and minimum in the HA+ACS and ACS groups, respectively (P<0.05); the highest and lowest neutrophil counts were seen in ACS and control groups, respectively (P<0.05); and the extent of live bone did not differ between groups (P>0.05). In the eighth week, vascularization was not different in groups (P>0.05); the highest and lowest osteoclast activities were seen in the control and HA+ACS groups, respectively (P<0.05); empty lacunae were the most and fewest in control and HA+ACS, respectively (P<0.05); maximum and minimum numbers of eosinophils were in control and HA+ACS groups, respectively (P<0.05); HA and control groups exhibited the highest and lowest lymphocyte counts, respectively (P<0.05); the lowest and highest neutrophil counts were observed in HA+ACs and control groups, respectively (P<0.05); and the highest and lowest extents of the live bone were observed in HA+ACS and control groups, respectively (P<0.05).ConclusionsWithin the limitations of this preliminary animal study, HA and especially HA+ACS seem a proper method for preventing or treating BRONJ.

Bone Regeneration by Controlled Release of Bone Morphogenetic Protein-2: A Rabbit Spinal Fusion Chamber Molecular Study.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used in spine fusion surgery. However, high doses of rhBMP-2 delivered with absorbable collagen sponge (ACS) have led to inflammation-related adverse conditions. Polyelectrolyte complex (PEC) control release carrier can substantially reduce the rhBMP-2 dose and complication without compromising fusion. The molecular events underlying controlled release and their effects on spinal fusion remain unknown. In this study, a rabbit interbody spinal fusion chamber was designed to provide a controlled environment for profiling molecular events during the fusion process. Study groups included Group 1, PEC with 100 μg rhBMP-2; Group 2, ACS with 100 μg rhBMP-2; Group 3, ACS with 300 μg rhBMP-2; Group 4, autologous bone graft; and Group 5, empty chamber. Manual palpation, microcomputed tomography, and histological analysis showed that Group 1 and 3 achieved bone fusion, while the other groups showed no signs of fusion. Gene expression profiling showed robust induction of osteogenic markers in Groups 1 and 3, with modulated early induction of inflammatory genes in the PEC group. Delivery of 100 μg rhBMP-2 with ACS (Group 2) resulted in less upregulation of osteogenic genes, increased inflammatory genes expression, and upregulation of osteoclastic genes compared to Group 1. These results suggest that the manner of BMP-2 release at the interbody spinal defect site could dictate the balance of in-situ osteogenic and antiosteogenic activities, affecting fusion outcomes. The molecular evidence supports PEC for sustained release of BMP-2 for spinal interbody fusion, and the feasibility of employing this novel interbody spinal fusion chamber for future molecular studies. Impact Statement A radiolucent rabbit interbody spinal fusion chamber was developed to study the molecular events during spinal fusion process. The gene expression profile suggests that control release of bone morphogenetic protein-2 (BMP-2) resulted in lower inflammatory and osteoclastic activities, but elicited higher osteogenic activities, while burst release of BMP-2 resulted in predominantly inflammation and osteoclastogenesis with minimum osteogenic activity. This study provides the molecular evidence that underscores the regeneration outcomes from the two different BMP-2 delivery systems. This spinal fusion chamber could be used for future molecular studies to optimize carrier design for spinal fusion.

Local supplementation with plant-derived recombinant human FGF2 protein enhances bone formation in critical-sized calvarial defects.

Numerous studies have demonstrated the advantages of plant cell suspension culture systems in producing bioactive recombinant human growth factors. This study investigated the biological activity of recombinant basic human fibroblast growth factor (rhFGF2) protein produced by a plant culture system to enhance new bone formation in a bone defect mouse model. The human FGF2 cDNA gene was cloned into a plant expression vector driven by the rice α-amylase 3D promoter. The vector was introduced into rice calli (Oryza sativa L. cv. Dongjin), and the clone with the highest expression of rhFGF2 was selected. Maximum accumulation of rhFGF2 protein (approximately 28mg/l) was reached at 13day post-incubation. Male C57BL/6 mice underwent calvarial defect surgery and the defects were loaded with absorbable collagen sponge (ACS) only (ACS group) or ACS impregnated with 5μg of plant-derived rhFGF2 (p-FGF2) protein or E. coli-derived rhFGF2 (e-FGF2) protein. Similar to the effects of e-FGF2, local delivery with p-FGF2 enhanced bone healing in the damaged region to higher levels than the ACS group. Exogenous addition of p-FGF2 or e-FGF2 exhibited similar effects on proliferation, mineralization, and osteogenic marker expression in MC3T3-E1 cells. Together, the current findings support the usefulness of this plant-based expression system for the production of biologically active rhFGF2.

Testing a novel nanofibre scaffold for utility in bone tissue regeneration.

Many variables serve to alter the process of bone remodelling and diminish regeneration including the size and nature of the wound bed and health status of the individual. To overcome these inhibitory factors, tissue-engineered osteoconductive scaffolds paired with various growth factors have been utilized clinically. However, many limitations still remain, for example, bone morphogenetic protein 2 (BMP2) can lead to rampant inflammation, ectopic bone formation, and graft failure. Here, we studied the ability for a nanofiber scaffold (Talymed) to accelerate BMP2 growth factor-induced bone healing compared with the traditional absorbable collagen sponge (ACS) delivery system. One hundred fifty-five adult wild type mice were arranged in 16 groups by time, 4 and 8weeks, and treatment, ACS or Talymed, loaded with control, low, medium, or high dosages of BMP2. Skulls were subjected to microCT, biomechanical, and histological analysis to assess bone regeneration. The use of Talymed within the defect site was found to decrease the bone volume, bone formation rate, and alkaline phosphatase activity compared with ACS/BMP2 combinations. Interestingly, though Talymed regenerated less bone, the regenerate was found to have a greater hardness value than that of bone within the ACS groups. However, the difference in bone hardness between scaffolds was not detectable by 8weeks. Based on these results, we found that the nanofiber scaffold generated a better quality of bone regenerate at 4weeks but, due to the lack of overall bone formation and the inhibition of normal remodelling processes, was not as efficacious as the current clinical standard ACS/BMP2 therapy.

Vertical Bone Augmentation Using Deproteinized Bovine Bone Mineral, Absorbable Collagen Sponge, and Recombinant Human Bone Morphogenetic Protein-2: An In Vivo Study in Rabbits.

The objective of this investigation was to assess vertical bone augmentation using deproteinized bovine bone mineral (DBBM) infused or not with recombinant human bone morphogenetic protein (rhBMP-2) in rabbit tibiae. A total of 18 female rabbits (New Zealand) received two blocks of DBBM in each tibia. The DBBM blocks were randomly assigned into four experimental groups: DBBM (only the bone graft); DBBM associated with absorbable collagen sponge (ACS); DBBM plus rhBMP-2 (1.5 mg/mL); and DBBM infused with rhBMP-2 (1.5 mg/mL) in an ACS carrier. Animals were sacrificed after 12 weeks, and the tibiae containing the DBBM blocks were dissected and analyzed radiographically (microcomputed tomography [micro-CT]), histologically, and immunohistochemically. Micro-CT analysis showed a considerable increase in bone volume (BV) and BV/tissue volume in the rhBMP-2/ACS group compared with all the others. Trabeculae thickness also increased in the rhBMP-2/ACS group compared with the DBBM/ACS group. Trabecular number, separation, and bone mineral density were not different among groups. Histomorphometric evaluation showed increased newly formed bone in the rhBMP-2/ACS group compared with the DBBM and DBBM/ACS groups. The amount of residual bone graft was statistically higher in the rhBMP-2 groups compared with the DBBM/ACS group. Immunohistochemical analysis showed that the vascular endothelial growth factor (VEGF) expression was more intense in the rhBMP-2/ACS group compared with the DBBM/ACS group. The immunopositivity for type 1 collagen tended to be higher in the two groups with rhBMP-2. Collectively, the results of this study suggest that the addition of rhBMP-2 in an ACS carrier placed on top of the DBBM graft enhanced bone formation in this animal model.

Local rhBMP-12 on an Absorbable Collagen Sponge as an Adjuvant Therapy for Rotator Cuff Repair-A Phase 1, Randomized, Standard of Care Control, Multicenter Study: Part 2-A Pilot Study of Functional Recovery and Structural Outcomes.

Background:The high failure rate of rotator cuff repairs requires the development of methods to enhance healing at the tendon-bone junction of the repair site.Purpose:To assess functional recovery and structural outcomes in detail after implanting recombinant human bone morphogenetic protein–12 (rhBMP-12)/absorbable collagen sponge (ACS) as adjuvant treatment during open rotator cuff repair in patients over a 1-year postoperative follow-up.Study Design:Randomized controlled trial; Level of evidence, 2.Methods:A total of 20 patients were randomized into 2 groups, rhBMP-12/ACS and standard-of-care (SOC) control, with 16 and 4 patients, respectively. The patients underwent open repair of a rotator cuff tear at least 2 to 4 cm wide; in the rhBMP-12/ACS group, this was augmented with a bioscaffold containing rhBMP-12. Follow-up assessments were conducted with a 100-mm visual analog scale (VAS) for pain and active and passive ranges of motion (ROMs) including forward flexion, elevation in the scapular plane, abduction, and external rotation at 12, 16, 26, 39, and 52 weeks after surgery; isometric strength in scapular abduction and external rotation at 16, 26, 39, and 52 weeks; and magnetic resonance imaging (MRI) at 12 and 52 weeks.Results:The mean VAS score decreased from 37.9 mm preoperatively to 13.8 mm at week 52, and ROM and isometric strength recovered at week 52 in the rhBMP-12/ACS group. The mean VAS score decreased from 48.3 mm preoperatively to 1.5 mm at week 52, and ROM (excluding external rotation) and isometric strength recovered by week 52 in the SOC control group. Of the 16 patients in the rhBMP-12/ACS group, 14 showed an intact repair at week 12; the MRI scans of the other 2 patients could not be evaluated because of artifacts. In the SOC control group, 1 patient showed repair failure. At week 52, 14 repairs in the rhBMP-12/ACS group and 2 repairs with available MRI scans in the SOC control group remained intact.Conclusion:Functional recovery and structural outcomes in patients in whom rhBMP-12/ACS was used as adjuvant therapy in rotator cuff repair justify conducting future, larger, multicenter, prospective studies.Registration:NCT00936559, NCT01122498 (ClinicalTrials.gov identifier).

Recombinant human IGF-1 produced by transgenic plant cell suspension culture enhances new bone formation in calvarial defects

Transgenic plant cell suspension culture systems have been utilized extensively as convenient and efficient expression systems for the production of recombinant human growth factors. We produced insulin-like growth factor-1 using a plant suspension culture system (p-IGF-1) and explored its effect on new bone formation in calvarial defects. We also compared the bone regenerating potential of p-IGF-1 with commercial IGF-1 derived from Escherichia coli (e-IGF-1). Male C57BL/6 mice underwent calvarial defect surgery, and the defects were loaded with absorbable collagen sponge (ACS) only (ACS group) or ACS impregnated with 13μg of p-IGF-1 (p-IGF-1 group) or e-IGF-1 (e-IGF-1 group). The sham group did not receive any treatment with ACS or IGFs after surgery. Live μCT and histological analyses showed critical-sized bone defects in the sham group, whereas greater bone formation was observed in the p-IGF-1 and e-IGF-1 groups than the ACS group both 5 and 10weeks after surgery. Bone mineral density, bone volume, and bone surface values were also higher in the IGF groups than in the ACS group. Local delivery of p-IGF-1 or e-IGF-1 more greatly enhanced the expression of osteoblast-specific markers, but inhibited osteoclast formation, in newly formed bone compared with ACS control group. Specifically, p-IGF-1 treatment induced higher expression of alkaline phosphatase, osteocalcin, and osteopontin in the defect site than did e-IGF-1. Furthermore, treatment with p-IGF-1, but not e-IGF-1, increased mineralization of MC3T3-E1 cells, with the attendant upregulation of osteogenic marker genes. Collectively, our findings suggest the potential of p-IGF-1 in promoting the processes required for bone regeneration.

Comparison of recombinant human bone morphogenetic protein-2-infused absorbable collagen sponge, recombinant human bone morphogenetic protein-2-coated tricalcium phosphate, and platelet-rich fibrin-mixed tricalcium phosphate for sinus augmentation in rabbits

Background/purposeNumerous grafting materials have been used in the bone regeneration of maxillary sinus to obtain a sufficient amount of new bone in implant dentistry. The objective of this study was to compare the potentials of Type I absorbable collagen sponge (ACS) impregnated with recombinant human bone morphogenetic protein (rhBMP)-2, rhBMP-2-coated tricalcium phosphate (TCP), platelet-rich fibrin-mixed TCP for enhancing bone regeneration in sinus augmentation in rabbits. Materials and methodsThe sinus defects were grafted with rhBMP-2+ACS (Group A), rhBMP-2-coated TCP (Group B), and platelet-rich fibrin-mixed TCP (Group C). The specimens underwent decalcification, and were stained for histomorphometric analysis. ResultsThere were no significant differences in inflammatory features among the groups 1-week postoperation. In a histomorphometric analysis, the new bone formation ratio showed significant differences between groups at 2 weeks. rhBMP-2+ACS showed a larger and more rapid bone formation area at 2 weeks than those of Groups B and C. ConclusionOur histological evaluation demonstrates that Type I ACS can be used as a carrier of rhBMP-2, and rhBMP-2+ACS showed rapid bone formation, remodeling, and calcification at Week 2 in rabbit.

Heparin-Based Polyelectrolyte Complex Enhances the Therapeutic Efficacy of Bone Morphogenetic Protein-2 for Posterolateral Fusion in a Large Animal Model.

The study was based on porcine posterolateral fusion model. The study aims to prove that polyelectrolyte complex (PEC) carrier could enhance the efficacy and safety profile of bone morphogenetic protein-2 (BMP-2). BMP-2 was introduced to enhance posterolateral fusion; however, extremely high doses of this molecule were often used which contributed to various complications. This was attributed to the poor modulation capacity of the traditional carrier absorbable collagen sponge (ACS). To reduce the efficacious dose of BMP-2 and its associated complications, heparin-based PEC was introduced. L3/L4 and L5/L6 two-level posterolateral spinal fusion was performed on six pigs using two doses of BMP-2 with PEC or ACS: (1) PEC with 800 μg BMP-2 (n = 2); (2) PEC with 400 μg BMP-2 (n = 2); (3) ACS with 800 μg BMP-2 (n = 1); (4) ACS with 400 μg of BMP-2 (n = 1). The construct was loaded into a rigid bioabsorbable cage for implantation. Fusion rate and quality were assessed 2 months after operation. Manual palpation revealed successful fusion in all groups. Radiological fusion score of PEC groups was, however, higher than that of ACS groups. The newly formed bone in PEC groups appeared to be well integrated into the native bone with no overgrowth into the adjacent structure. On comparison, in ACS groups, large gaps were observed between the newly formed bone and the fusion bed with heterotopic ossification into the psoas muscle. The microarchitecture on the newly formed bone in PEC groups was superior to that in ACS groups, which was demonstrated by higher three-dimensional parameters. The present study demonstrated that BMP-2 delivered by PEC induced successful posterolateral fusion in porcine model. The efficacy of BMP-2 was improved and bony overgrowth was reduced. The microarchitecture of BMP-2-induced bone tissue was also enhanced by PEC. N/A.

Bone Regenerative Efficacy of Limited-Dose Escherichia Coli-Derived rhBMP-2 With Biphasic Calcium Phosphate Carrier in Rabbit Calvarial Defect Model.

The aim of this study was to characterize the healing in rabbit calvarial bone defects after delivery of limited-dose (1.5 μg) Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2), and evaluate biphasic calcium phosphate (BCP) as a carrier. Four 8-mm diameter circular calvarial bone defects were made in 16 rabbits and filled with one of the following: (1) nothing, (2) BCP alone, (3) ErhBMP-2-loaded absorbable collagen sponge (ACS), or (4) ErhBMP-2-loaded BCP. The animals were allowed to heal for either 2 or 8 weeks and were evaluated in clinical, microcomputed tomographic, histological, and histomorphometric analyses. Microcomputed tomography revealed extensive new bone formation in both of the limited-dose ErhBMP-2-loaded groups. However, bony collapse of the upper defect borders was found in the ErhBMP-2-loaded ACS group. Histomorphometric examination revealed significantly greater new bone formation at 8 weeks than at 2 weeks in all 4 groups (P < 0.05). Both new bone formation and the size of the augmented area differed significantly between the ErhBMP-2-loaded BCP group (6.88 ± 0.74 and 19.62 ± 0.77) and the ErhBMP-2-loaded ACS group (3.04 ± 0.27 and 5.41 ± 0.43) at 8 weeks of healing. ErhBMP-2 promotes bone regeneration in rabbit calvarial defects, even at a limited dose (1.5 μg). The results of this study suggest that BCP is the more efficient carrier for this protein than ACS.

Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects.

The aim of this study was to examine the effects of recombinant human BMP-9 (rhBMP-9) with chitosan sponge (ChiS) or absorbable collagen sponge (ACS) on bone formation in rat calvarial defects. The defects were treated by one of the following implantations: ChiS, rhBMP-9/ChiS, ACS, rhBMP-9/ACS and no implantation. The animals were euthanized at 8 weeks for histological evaluation. The percentage of defect closure (DC) in the rhBMP-9/ACS group was significantly greater than that in the ACS group. The rhBMP-9/ACS group demonstrated the highest level of DC among all the groups. The newly formed bone area (NBA) and NBA/total area in the ChiS-implanted groups and in the rhBMP-9/ACS group were significantly greater compared with those in the ACS group. It can be concluded that rhBMP-9/ACS has a potential to induce bone formation in rat calvarial defects. Further studies are required to elucidate the mechanism of bone formation induced by rhBMP-9.

Local rhBMP-12 on an Absorbable Collagen Sponge as an Adjuvant Therapy for Rotator Cuff Repair— A Phase 1, Randomized, Standard of Care Control, Multicenter Study

Background: Recombinant human bone morphogenetic protein–12 (rhBMP-12) has been shown to induce tendon and ligament formation in rats and to improve tendon healing; however, the safety and feasibility of implanting rhBMP-12/absorbable collagen sponge (ACS) in humans are not known. Purpose: To investigate the safety and feasibility of rhBMP-12 on an ACS as an adjuvant therapy in open rotator cuff repair. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: This study consisted of 20 patients with full-thickness rotator cuff tears. Patients were randomized either to standard of care (SOC) treatment (open rotator cuff repair) or to receive 0.015 mg/mL rhBMP-12/ACS and SOC treatment during their open rotator cuff repair (rhBMP-12/ACS group) at a rate of 1/4 SOC/rhBMP-12/ACS. The feasibility of implanting the product and the safety of the product were evaluated during the 1-year follow-up period. The evaluation involved up to 10 postoperative visits, which included physical examinations, radiographs, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans with an emphasis on heterotopic ossification (HO), pharmacokinetics, immunogenicity, laboratory evaluations, and local and systemic adverse events at specified time points. Results: Small amounts of HO were seen on follow-up CT scans in 10 of 16 patients in the rhBMP-12/ACS group and in 2 of 3 patients in the SOC group. HO did not increase at 26 weeks and was not associated with any adverse events or unsatisfactory clinical outcomes. Pharmacokinetics demonstrated that circulating levels of rhBMP-12 were not detectable after administration. Five of 16 patients showed a postoperative immunogenic response but did not show any correlating adverse events. Complete healing of the rotator cuff was observed in 14 of 16 patients; 2 of 16 imaging results could not be analyzed because of artifacts in the rhBMP-12 group on MRI scans. In the SOC group, 1 of 4 patients showed a retear at 12 weeks after surgery. Conclusion: The use of rhBMP-12/ACS has been shown to be feasible and safe in a concentration of 0.015 mg/mL when used in open rotator cuff repair. Higher dose concentrations of rhBMP-12 should be evaluated in the future to evaluate their safety and potential to increase rotator cuff healing after open surgical repair.

Bone morphogenetic protein 2–mediated mandible reconstruction successfully heals bony defects but inhibits concurrent inferior alveolar nerve grafting: a rabbit experimental model.

Bone morphogenetic protein 2 (BMP-2) has been used to reconstruct mandibular defects. An elegant addition to this reconstruction method would be incorporation of a nerve graft wrapped in a BMP-2 carrier to reconstitute the inferior alveolar nerve (IAN) and restore sensation to the lower face. We developed a rabbit model to determine the effect BMP-2 has on nerve regeneration following neurorrhaphy. An inferior border mandibulectomy was created in 16 adult New Zealand white rabbits. The IAN was protected, divided, and repaired with either primary neurorrhaphy or reverse autografts. Bone defects were treated with no treatment controls (n = 2), absorbable collagen sponge (ACS) (vehicle controls) (n = 7), and ACS soaked in BMP-2 (treatment group) (n = 7). Animals underwent computed tomography (CT) 2 days and 6 weeks postoperatively. The percent bone defect healing was calculated using Amira 3D imaging software. At 6 weeks, IANs were harvested mesial to the reconstruction and were evaluated with toluidine blue histology to identify myelinated axons. Reconstructed mandible segments were evaluated with micro-CT and hematoxylin-eosin histology. Bone morphogenetic protein 2-treated animals demonstrated significantly more bone healing than did the ACS and empty defect groups (82%, 38%, 44%, respectively; P < 0.01). One hundred percent of ACS-treated nerves (n = 4) demonstrated axon regrowth, whereas only 25% of BMP-2-treated nerves (n = 4) did. Micro-CT and histology showed BMP-2 caused bone growth around the IAN, but regenerated bone infiltrated the repair site and created a physical barrier to axon growth. Bone morphogenetic protein 2 can successfully heal bone defects in the rabbit mandible, but ectopic bone growth can inhibit IAN recovery after repair. Level of Evidence: Not gradable.

Bone Healing Properties of Autoclaved Autogenous Bone Grafts Incorporating Recombinant Human Bone Morphogenetic Protein-2 and Comparison of Two Delivery Systems in a Segmental Rabbit Radius Defect

Purpose:This study aims to validate the effect of autoclaved autogenous bone (AAB), incorporating Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2), on critical-sized, segmental radius defects in rabbits. Delivery systems using absorbable collagen sponge (ACS) and fibrin glue (FG) were also evaluated.Methods:Radius defects were made in 12 New Zealand white rabbits. After autoclaving, the resected bone was reinserted and fixed. The animals were classified into three groups: only AAB reinserted (group 1, control), and AAB and ErhBMP-2 inserted using an ACS (group 2) or FG (group 3) as a carrier. Animals were sacrificed six or 12 weeks after surgery. Specimens were evaluated using radiology and histology.Results:Micro-computed tomography images showed the best bony union in group 2 at six and 12 weeks after operation. Quantitative analysis showed all indices except trabecular thickness were the highest in group 2 and the lowest in group 1 at twelve weeks. Histologic results showed the greatest bony union between AAB and radial bone at twelve weeks, indicating the highest degree of engraftment.Conclusion:ErhBMP-2 increases bony healing when applied on AAB graft sites. In addition, the ACS was reconfirmed as a useful delivery system for ErhBMP-2.

Efficacy of rhBMP-2 Versus Iliac Crest Bone Graft for Posterior C1–C2 Fusion in Patients Older Than 60 Years

Few studies have specifically examined the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) in posterolateral lumbar spine fusion. The purpose of this study was to report the clinical outcomes in elderly patients treated with posterior C1-C2 fusion with iliac crest bone graft (ICBG) plus rhBMP-2/ACS vs ICBG alone. One hundred forty patients older than 60 years were enrolled in this prospective, randomized trial and underwent instrumented C1- C2 fusion. Patients were divided into 2 groups based on fusion material. The ICBG group comprised patients who received ICBG alone, and the rhBMP-2/ACS group comprised patients who received ICBG plus rhBMP-2/ACS. The groups were compared based on operative time, estimated blood loss, hospital length of stay, clinical results, perioperative complications, fusion rate, fusion time, and revision rate. There were no significant differences in operative time, estimated blood loss, length of stay, and intraoperative complications between the 2 groups. Improvements in visual analog scale scores and Japanese Orthopaedic Association scores over the 2-year follow-up period were similar between groups. The fusion rate was 82.4% (56 of 68) in the rhBMP-2/ACS group and 78.7% (52 of 66) in the ICBG group (P=.782). Mean fusion time was 11 days shorter in the rhBMP-2/ACS group (81.8±29.4 days) than in the ICBG group (92.9±23.7 days) (P=.034). There were more wound complications requiring treatment in the rhBMP-2/ACS group (n=6; 8.8%) than in the ICBG group (n=2; 3.0%), although this was not statistically significant (P=.118). The use of rhBMP-2/ACS for posterior C1-C2 fusion appears to result in a relatively shorter fusion time, but there may be an increased risk of posterior cervical wound complications.

Characterizing the Host Response to rhBMP-2 in a Rat Spinal Arthrodesis Model

Prospective, randomized, controlled preclinical trial. This study seeks to characterize the localized and systemic host response to recombinant human bone morphogenetic protein-2 (rhBMP-2) in a well established rodent spine arthrodesis model utilizing cytokine analysis and magnetic resonance imaging (MRI). Although high fusion rates are achieved with rhBMP-2 in the spine, several complications have also been reported, including a localized response leading to radiculitis and seroma formation. The mechanism in which this occurs clinically is yet unknown. One hundred female Fischer rats underwent a posterolateral intertransverse lumbar spinal fusion, with paraspinal muscle tissue resection, using iliac crest autograft, type I absorbable collagen sponge (ACS), 10- or 100-μg rhBMP-2/ACS. The animals underwent magnetic resonance imaging evaluation, serum cytokine analysis, manual palpation, and gross tissue inspection at 2, 4, 7, 10, and 21 days, postoperatively. Qualitative evaluation of MR images demonstrated a transient fluid collection at the surgery site in the rhBMP-2 animals as early as 4 and 7 days that was greater than the autograft or ACS groups. Quantitative analysis on T2-weighted axial images demonstrated greater signal intensity in the rhBMP-2 animals compared with the ACS and autograft groups in a time-dependent fashion. Higher concentrations of several cytokines were also detected at 2, 4, and 7 days, including interleukin 1β, interleukin 18, tumor necrosis factor α, macrophage inflammatory protein 1α, and monocyte chemotactic protein 1 in animals treated with rhBMP-2/ACS relative to ACS alone. Our data suggest that the in vivo host response to rhBMP-2 in an animal model may be associated with circulating proinflammatory and osteoclastic cytokines.

Novel Animal Model of Calvarial Defect

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to be an effective therapy in the acute calvarial defect wound and in calvarial defects complicated by chronic scar and radiation. The authors assessed the effectiveness of rhBMP-2-mediated bone regeneration in calvarial defects complicated by durectomy. Sixteen adult New Zealand White rabbits underwent subtotal calvariectomy and dural removal, followed by dural repair and reconstruction in one of four groups: empty (n = 3), vehicle (buffer solution on an absorbable collagen sponge, n = 2), autologous graft (n = 3), or rhBMP-2 repair (rhBMP-2/absorbable collagen sponge, n = 8). Animals underwent computed tomographic imaging at 0, 2, 4, and 6 weeks postoperatively, followed by euthanasia and histologic analysis. Percent healing was determined by three-dimensional analysis. A 4 × 3 mixed model analysis of variance was performed on healing versus treatment group/postoperative time. The rhBMP-2/absorbable collagen sponge and autograft repair groups had 51.4 and 37.3 percent healing, respectively, at 6 weeks; empty and vehicle control groups had 7.8 and 17.9 percent healing, respectively, at 6 weeks. Compared with immediate favorable reconstruction (96.8 percent healing), rhBMP-2 in this setting was significantly less effective (p = 0.001). Bone in the rhBMP-2/absorbable collagen sponge group was compact and cellular but appeared only over the intact sagittal sinus and irregularly within the absorbable collagen sponge. Although promising in the acute calvarial wound and other complex defects, rhBMP-2 therapy is less effective in reconstruction following dural compromise. Future studies using additional growth factors and cell therapy may improve results in this especially difficult scenario.

Bone Tissue Engineering in Oral Surgery: A New Method of Bone Development in Periodontal Surgery

This article describes the development of a new surgical approach to periodontal treatment. Twenty patients who suffered from bone defects without existing bony walls due to adult periodontitis were treated in three different groups using methods of bone tissue engineering. At that time no surgical technique existed that could be applied to those patients to generate new bone. The periodontal surgeries were performed between 2004 and 2008. All patients received follow-up examinations at 6, 12, and 24 months after surgical procedure. Measured parameters were compared to baseline. The surgical approach and the augmentation material have been improved based on the results of the previous group. This strategy was applied because of the ethical fact that a medical treatment of patients has to be carried out with the knowledge and experience of previous settings. All groups received recombinant human bone morphogenetic protein 2 and platelet-rich plasma. The above-mentioned procedure had been approved in other indications in the field of oral and maxillofacial surgery. The first group underwent conventional muco-periosteal flap technique and obtained an augmentation with absorbable collagen sponge (ACS). The second and third groups were treated using endoscopically assisted microsurgery due to wound healing disturbances that appeared in the first group. The augmentation was carried out with demineralized bone matrix (DBM) instead of ACS (group 2) or tricalciumphosphate as a further development instead of DBM (group 3). The radiological control 12 months (group 1), 18 months (group 2), and 2 years (group 3) after surgery proved the following results-first group: 1.7 mm (average) vertical bone development (VBD); second group: 2.5 mm (average) VBD; third group: 3.2 mm (average) VBD. These results of single patient treatment open new ways into periodontal surgery. They have to be confirmed by prospective case series and multicenter studies.