Update on the use of 45S5 bioactive glass in the treatment of bone defects in regenerative medicine.

Bone regeneration is a critical area in regenerative medicine, particularly in orthopedics, demanding effective biomedical materials for treating bone defects. 45S5 bioactive glass (45S5 BG) is a promising material because of its osteoconductive and bioactive properties. As research in this field continues to advance, keeping up-to-date on the latest and most successful applications of this material is imperative. To achieve this, we conducted a comprehensive search on PubMed/MEDLINE, focusing on English articles published in the last decade. Our search used the keywords "bioglass 45S5 AND bone defect" in combination. We found 27 articles, and after applying the inclusion criteria, we selected 15 studies for detailed examination. Most of these studies compared 45S5 BG with other cement or scaffold materials. These comparisons demonstrate that the addition of various composites enhances cellular biocompatibility, as evidenced by the cells and their osteogenic potential. Moreover, the use of 45S5 BG is enhanced by its antimicrobial properties, opening avenues for additional investigations and applications of this biomaterial.

Photobiomodulation Therapy Improves Repair of Bone Defects Filled by Inorganic Bone Matrix and Fibrin Heterologous Biopolymer.

Biomaterials are used extensively in graft procedures to correct bone defects, interacting with the body without causing adverse reactions. The aim of this pre-clinical study was to analyze the effects of photobiomodulation therapy (PBM) with the use of a low-level laser in the repair process of bone defects filled with inorganic matrix (IM) associated with heterologous fibrin biopolymer (FB). A circular osteotomy of 4 mm in the left tibia was performed in 30 Wistar male adult rats who were randomly divided into three groups: G1 = IM + PBM, G2 = IM + FB and G3 = IM + FB + PBM. PBM was applied at the time of the experimental surgery and three times a week, on alternate days, until euthanasia, with 830 nm wavelength, in two points of the operated site. Five animals from each group were euthanized 14 and 42 days after surgery. In the histomorphometric analysis, the percentage of neoformed bone tissue in G3 (28.4% ± 2.3%) was higher in relation to G1 (24.1% ± 2.91%) and G2 (22.2% ± 3.11%) at 14 days and at 42 days, the percentage in G3 (35.1% ± 2.55%) was also higher in relation to G1 (30.1% ± 2.9%) and G2 (31.8% ± 3.12%). In the analysis of the birefringence of collagen fibers, G3 showed a predominance of birefringence between greenish-yellow in the neoformed bone tissue after 42 days, differing from the other groups with a greater presence of red-orange fibers. Immunohistochemically, in all experimental groups, it was possible to observe immunostaining for osteocalcin (OCN) near the bone surface of the margins of the surgical defect and tartrate-resistant acid phosphatase (TRAP) bordering the newly formed bone tissue. Therefore, laser photobiomodulation therapy contributed to improving the bone repair process in tibial defects filled with bovine biomaterial associated with fibrin biopolymer derived from snake venom.

Use of Photobiomodulation Combined with Fibrin Sealant and Bone Substitute Improving the Bone Repair of Critical Defects.

In this preclinical protocol, an adjunct method is used in an attempt to overcome the limitations of conventional therapeutic approaches applied to bone repair of large bone defects filled with scaffolds. Thus, we evaluate the effects of photobiomodulation therapy (PBMT) on the bone repair process on defects filled with demineralized bovine bone (B) and fibrin sealant (T). The groups were BC (blood clot), BT (B + T), BCP (BC + PBMT), and BTP (B + T + PBMT). Microtomographically, BC and BCP presented a hypodense cavity with hyperdense regions adjacent to the border of the wound, with a slight increase at 42 days. BT and BTP presented discrete hyperdensing areas at the border and around the B particles. Quantitatively, BCP and BTP (16.96 ± 4.38; 17.37 ± 4.38) showed higher mean bone density volume in relation to BC and BT (14.42 ± 3.66; 13.44 ± 3.88). Histologically, BC and BCP presented deposition of immature bone at the periphery and at 42 days new bone tissue became lamellar with organized total collagen fibers. BT and BTP showed inflammatory infiltrate along the particles, but at 42 days, it was resolved, mainly in BTP. In the birefringence analysis, BT and BTP, the percentage of red birefringence increased (9.14% to 20.98% and 7.21% to 27.57%, respectively), but green birefringence was similar in relation to 14 days (3.3% to 3.5% and 3.5% to 4.2%, respectively). The number of osteocytes in the neoformed bone matrix proportionally reduced in all evaluated groups. Immunostaining of bone morphogenetic protein (BMP­2/4), osteocalcin (OCN), and vascular endothelial growth factor (VEGF) were higher in BCP and BTP when compared to the BC and BT groups (p < 0.05). An increased number of TRAP positive cells (tartrate resistant acid phosphatase) was observed in BT and BTP. We conclude that PBMT positively influenced the repair of bone defects filled with B and T.

Biological Behavior of Xenogenic Scaffolds in Alcohol-Induced Rats: Histomorphometric and Picrosirius Red Staining Analysis.

In this experimental protocol, the objective was to evaluate the biological behavior of two xenogenic scaffolds in alcohol-induced rats through histomorphometric and Picrosirius Red staining analysis of non-critical defects in the tibia of rats submitted or not to alcohol ingestion at 25% v/v. Eighty male rats were randomly divided into four groups (n = 20 each): CG/B (water diet + Bio-Oss® graft, Geistlich Pharma AG, Wolhusen, Switzerland), CG/O (water diet + OrthoGen® graft, Baumer, Mogi Mirim, Brazil), AG/B (25% v/v alcohol diet + Bio-Oss® graft), and AG/O (25% v/v alcohol diet + OrthoGen® graft). After 90 days of liquid diet, the rats were surgically obtained, with a defect in the tibia proximal epiphysis; filled in according to their respective groups; and euthanized at 10, 20, 40 and 60 days. In two initial periods (10 and 20 days), all groups presented biomaterial particles surrounded by disorganized collagen fibrils. Alcoholic animals (AG/B and AG/O) presented, in the cortical and medullary regions, a reactive tissue with inflammatory infiltrate. In 60 days, in the superficial area of the surgical cavities, particles of biomaterials were observed in all groups, with new compact bone tissue around them, without complete closure of the lesion, except in non-alcoholic animals treated with Bio-Oss® xenograft (CG/B), where the new cortical interconnected the edges of the defect. Birefringence transition was observed in the histochemical analysis of collagen fibers by Picrosirius Red, in which all groups in periods of 10 and 20 days showed red-orange birefringence, and from 40 days onwards greenish-yellow birefringence, which demonstrates the characteristic transition from the formation of thin and disorganized collagen fibers initially to more organized and thicker later. In histomorphometric analysis, at 60 days, CG/B had the highest volume density of new bone (32.9 ± 1.15) and AG/O the lowest volume density of new bone (15.32 ± 1.71). It can be concluded that the bone neoformation occurred in the defects that received the two biomaterials, in all periods, but the Bio-Oss® was superior in the results, with its groups CG/B and AG/B displaying greater bone formation (32.9 ± 1.15 and 22.74 ± 1.15, respectively) compared to the OrthoGen® CG/O and AG/O groups (20.66 ± 2.12 and 15.32 ± 1.71, respectively), and that the alcoholic diet interfered negatively in the repair process and in the percentage of new bone formed.

Photobiomodulation Therapy on the Guided Bone Regeneration Process in Defects Filled by Biphasic Calcium Phosphate Associated with Fibrin Biopolymer.

The aim is to evaluate the effects of photobiomodulation therapy (PBMT) on the guided bone regeneration process (GBR) in defects in the calvaria of rats filled with biphasic calcium phosphate associated with fibrin biopolymer. Thirty male Wistar rats were randomly separated: BMG (n = 10), defects filled with biomaterial and covered by membrane; BFMG (n = 10), biomaterial and fibrin biopolymer covered by membrane; and BFMLG (n = 10), biomaterial and fibrin biopolymer covered by membrane and biostimulated with PBMT. The animals were euthanized at 14 and 42 days postoperatively. Microtomographically, in 42 days, there was more evident bone growth in the BFMLG, limited to the margins of the defect with permanence of the particles. Histomorphologically, an inflammatory infiltrate was observed, which regressed with the formation of mineralized bone tissue. In the quantification of bone tissue, all groups had a progressive increase in new bone tissue with a significant difference in which the BFMLG showed greater bone formation in both periods (10.12 ± 0.67 and 13.85 ± 0.54), followed by BFMG (7.35 ± 0.66 and 9.41 ± 0.84) and BMG (4.51 ± 0.44 and 7.11 ± 0.44). Picrosirius-red staining showed greater birefringence of collagen fibers in yellow-green color in the BFMLG, showing more advanced bone maturation. PBMT showed positive effects capable of improving and accelerating the guided bone regeneration process when associated with biphasic calcium phosphate and fibrin biopolymer.

Photobiomodulation Therapy Associated with Heterologous Fibrin Biopolymer and Bovine Bone Matrix Helps to Reconstruct Long Bones.

Bone defects cause aesthetic and functional changes that affect the social, economic and especially the emotional life of human beings. This complication stimulates the scientific community to investigate strategies aimed at improving bone reconstruction processes using complementary therapies. Photobiomodulation therapy (PBMT) and the use of new biomaterials, including heterologous fibrin biopolymer (HFB), are included in this challenge. The objective of the present study was to evaluate the influence of photobiomodulation therapy on bone tibial reconstruction of rats with biomaterial consisting of lyophilized bovine bone matrix (BM) associated or not with heterologous fibrin biopolymer. Thirty male rats were randomly separated into three groups of 10 animals. In all animals, after the anesthetic procedure, a noncritical tibial defect of 2 mm was performed. The groups received the following treatments: Group 1: BM + PBMT, Group 2: BM + HFB and Group 3: BM + HFB + PBMT. The animals from Groups 1 and 3 were submitted to PBMT in the immediate postoperative period and every 48 h until the day of euthanasia that occurred at 14 and 42 days. Analyses by computed microtomography (µCT) and histomorphometry showed statistical difference in the percentage of bone formation between Groups 3 (BM + HB + PBMT) and 2 (BM + HFB) (26.4% ± 1.03% and 20.0% ± 1.87%, respectively) at 14 days and at 42 days (38.2% ± 1.59% and 31.6% ± 1.33%, respectively), and at 42 days there was presence of bone with mature characteristics and organized connective tissue. The µCT demonstrated BM particles filling the defect and the deposition of new bone in the superficial region, especially in the ruptured cortical. It was concluded that the association of PBMT with HFB and BM has the potential to assist in the process of reconstructing bone defects in the tibia of rats.

Evaluation of the Use of an Inorganic Bone Matrix in the Repair of Bone Defects in Rats Submitted to Experimental Alcoholism.

To assess the effects of chronic alcoholism on the repair of bone defects associated with xenograft. Forty male rats were distributed in: control group (CG, n = 20) and experimental group (EG, n = 20), which received 25% ethanol ad libitum after a period of adaptation. After 90 days of liquid diet, the rats were submitted to 5.0-mm bilateral craniotomy on the parietal bones, subdividing into groups: CCG (control group that received only water with liquid diet and the defect was filled with blood clot), BCG (control group that received only water with liquid diet and the defect was filled with biomaterial), CEG (alcoholic group that received only ethanol solution 25% v/v with liquid diet and the defect was filled with blood clot), and BEG (alcoholic group that received only ethanol solution 25% v/v with liquid diet and the defect was filled with biomaterial). In the analysis of body mass, the drunk animals presented the lowest averages in relation to non-drunk animals during the experimental period. Histomorphologically all groups presented bone formation restricted to the defect margins at 60 days, with bone islets adjacent to the BCG biomaterial particles. CEG showed significant difference compared to BEG only at 40 days (17.42 ± 2.78 vs. 9.59 ± 4.59, respectively). In the birefringence analysis, in early periods all groups showed red-orange birefringence turning greenish-yellow at the end of the experiment. The results provided that, regardless of clinical condition, i.e., alcoholic or non-alcoholic, in the final period of the experiment, the process of bone defect recomposition was similar with the use of xenograft or only clot.

Photobiomodulation Therapy (PBMT) Applied in Bone Reconstructive Surgery Using Bovine Bone Grafts: A Systematic Review.

The use of low-level laser therapy (LLLT) with biomodulatory effects on biological tissues, currently called photobiomodulation therapy (PBMT), assists in healing and reduces inflammation. The application of biomaterials has emerged in bone reconstructive surgery, especially the use of bovine bone due to its biocompatibility. Due to the many benefits related to the use of PBMT and bovine bones, the aim of this research was to review the literature to verify the relationship between PBMT and the application of bovine bone in bone reconstruction surgeries. We chose the PubMed/MEDLINE, Web of Science, and Scopus databases for the search by matching the keywords: "Bovine bone AND low-level laser therapy", "Bovine bone AND photobiomodulation therapy", "Xenograft AND low-level laser therapy", and "Xenograft AND photobiomodulation therapy". The initial search of the three databases retrieved 240 articles, 18 of which met all inclusion criteria. In the studies concerning animals (17 in total), there was evidence of PBMT assisting in biomaterial-related conduction, formation of new bone, bone healing, immunomarker expression, increasing collagen fibers, and local inflammation reduction. However, the results disagreed with regard to the resorption of biomaterial particles. The only human study showed that PBMT with bovine bone was effective for periodontal regeneration. It was concluded that PBMT assists the process in bone reconstruction when associated with bovine bone, despite divergences between applied protocols.

Unique heterologous fibrin biopolymer with hemostatic, adhesive, sealant, scaffold and drug delivery properties: a systematic review.

Fibrin biopolymers, previously referred as "fibrin glue" or "fibrin sealants", are natural biomaterials with diverse applications on health. They have hemostatic, adhesive, sealant, scaffold and drug delivery properties and have become widely used in medical and dental procedures. Historically, these biomaterials are produced from human fibrinogen and human or animal thrombin, and the possibility of transmission of infectious diseases by human blood is not ruled out. In the 1990s, to overcome this problem, a new heterologous biomaterial composed of a thrombin-like enzyme purified from Crotalus durissus terrificus venom and a cryoprecipitate rich in fibrinogen extracted from buffaloes Bubalus bubalis blood has been proposed. Therefore, a systematic review of studies on exclusively heterologous fibrin sealants published between 1989 and 2018 was carried out using the following databases: PubMed, SciELO and Google Scholar. The keyword used was "heterologous fibrin sealant". The search resulted in 35 scientific papers in PubMed, four in SciELO and 674 in Google Scholar. After applying the inclusion/exclusion criteria and complete reading of the articles, 30 studies were selected, which formed the basis of this systematic review. It has been observed that the only completely heterologous sealant is the one produced by CEVAP/UNESP. This heterologous biopolymer is proven effective by several studies published in refereed scientific journals. In addition, clinical trials phase I/II for the treatment of chronic venous ulcers authorized by the Brazilian Health Regulatory Agency (ANVISA) were completed. Preliminary results have indicated a safe and promising effective product. Phase III clinical trials will be proposed and required to validate these preliminary findings.

Fibrin Sealant Derived from Human Plasma as a Scaffold for Bone Grafts Associated with Photobiomodulation Therapy.

Fibrin sealants derived from human blood can be used in tissue engineering to assist in the repair of bone defects. The objective of this study was to evaluate the support system formed by a xenograft fibrin sealant associated with photobiomodulation therapy of critical defects in rat calvaria. Thirty-six rats were divided into four groups: BC (n = 8), defect filled with blood clot; FSB (n = 10), filled with fibrin sealant and xenograft; BCPBMT (n = 8), blood clot and photobiomodulation; FSBPBMT (n = 10), fibrin sealant, xenograft, and photobiomodulation. The animals were killed after 14 and 42 days. In the histological and microtomographic analysis, new bone formation was observed in all groups, limited to the defect margins, and without complete wound closure. In the FSB group, bone formation increased between periods (4.3 ± 0.46 to 6.01 ± 0.32), yet with lower volume density when compared to the FSBPBMT (5.6 ± 0.45 to 10.64 ± 0.97) group. It was concluded that the support system formed by the xenograft fibrin sealant associated with the photobiomodulation therapy protocol had a positive effect on the bone repair process.

Unique heterologous fibrin biopolymer with hemostatic, adhesive, sealant, scaffold and drug delivery properties: a systematic review

Fibrin biopolymers, previously referred as "fibrin glue" or "fibrin sealants", are natural biomaterials with diverse applications on health. They have hemostatic, adhesive, sealant, scaffold and drug delivery properties and have become widely used in medical and dental procedures. Historically, these biomaterials are produced from human fibrinogen and human or animal thrombin, and the possibility of transmission of infectious diseases by human blood is not ruled out. In the 1990s, to overcome this problem, a new heterologous biomaterial composed of a thrombin-like enzyme purified from Crotalus durissus terrificus venom and a cryoprecipitate rich in fibrinogen extracted from buffaloes Bubalus bubalis blood has been proposed. Therefore, a systematic review of studies on exclusively heterologous fibrin sealants published between 1989 and 2018 was carried out using the following databases: PubMed, SciELO and Google Scholar. The keyword used was "heterologous fibrin sealant". The search resulted in 35 scientific papers in PubMed, four in SciELO and 674 in Google Scholar. After applying the inclusion/exclusion criteria and complete reading of the articles, 30 studies were selected, which formed the basis of this systematic review. It has been observed that the only completely heterologous sealant is the one produced by CEVAP/UNESP. This heterologous biopolymer is proven effective by several studies published in refereed scientific journals. In addition, clinical trials phase I/II for the treatment of chronic venous ulcers authorized by the Brazilian Health Regulatory Agency (ANVISA) were completed. Preliminary results have indicated a safe and promising effective product. Phase III clinical trials will be proposed and required to validate these preliminary findings.(AU)

Photobiomodulation Therapy (PBMT) in Peripheral Nerve Regeneration: A Systematic Review.

Photobiomodulation therapy (PBMT) has been investigated because of its intimate relationship with tissue recovery processes, such as on peripheral nerve damage. Based on the wide range of benefits that the PBMT has shown and its clinical relevance, the aim of this research was to carry out a systematic review of the last 10 years, ascertaining the influence of the PBMT in the regeneration of injured peripheral nerves. The search was performed in the PubMed/MEDLINE database with the combination of the keywords: low-level laser therapy AND nerve regeneration. Initially, 54 articles were obtained, 26 articles of which were chosen for the study according to the inclusion criteria. In the qualitative aspect, it was observed that PBMT was able to accelerate the process of nerve regeneration, presenting an increase in the number of myelinated fibers and a better lamellar organization of myelin sheath, besides improvement of electrophysiological function, immunoreactivity, high functionality rate, decrease of inflammation, pain, and the facilitation of neural regeneration, release of growth factors, increase of vascular network and collagen. It was concluded that PBMT has beneficial effects on the recovery of nerve lesions, especially when related to a faster regeneration and functional improvement, despite the variety of parameters.

Stimulation of morphofunctional repair of the facial nerve with photobiomodulation, using the end-to-side technique or a new heterologous fibrin sealant.

This research evaluated the influence of Photobiomodulation Therapy (PBMT) on lesions of the facial nerve repaired with the end-to-side technique or coaptation with a new heterologous fibrin sealant. Thirty-two Wistar rats were separated into 5 groups: Control group (CG), where the buccal branch of the facial nerve was collected; Experimental Suture Group (ESG) and Experimental Fibrin Group (EFG), in which the buccal branch was end-to-side sutured to the zygomatic branch on the right side of the face or coaptated with fibrin sealant on the left side; Experimental Suture Laser Group (ESLG) and Experimental Fibrin Laser Group (EFLG), in which the same procedures were performed as the ESG and EFG, associated with PBMT (wavelength of 830nm, energy density 6.2J/cm2, power output 30mW, beam area of 0.116cm2, power density 0.26W/cm2, total energy per session 2.16J, cumulative dose of 34.56J). The laser was applied for 24s/site at 3 points on the skin's surface, for a total application time of 72s, performed immediately after surgery and 3 times a week for 5weeks. A statistically significant difference was observed in the fiber nerve area between the EFG and EFLG (57.49±3.13 and 62.52±3.56µm2, respectively). For the area of the axon, fiber diameter, axon diameter, myelin sheath area and myelin sheath thickness no statistically significant differences were found (p<0.05). The functional recovery of whisker movement occurred faster in the ESLG and EFLG, which were associated with PBMT, with results closer to the CG. Therefore, PBMT accelerated morphological and functional nerve repair in both techniques.