Next-generation personalized cranioplasty treatment.

Decompressive craniectomy (DC) is a surgical procedure, that is followed by cranioplasty surgery. DC is usually performed to treat patients with traumatic brain injury, intracranial hemorrhage, cerebral infarction, brain edema, skull fractures, etc. In many published clinical case studies and systematic reviews, cranioplasty surgery is reported to restore cranial symmetry with good cosmetic outcomes and neurophysiologically relevant functional outcomes in hundreds of patients. In this review article, we present a number of key issues related to the manufacturing of patient-specific implants, clinical complications, cosmetic outcomes, and newer alternative therapies. While discussing alternative therapeutic treatments for cranioplasty, biomolecules and cellular-based approaches have been emphasized. The current clinical practices in the restoration of cranial defects involve 3D printing to produce patient-specific prefabricated cranial implants, that provide better cosmetic outcomes. Regardless of the advancements in image processing and 3D printing, the complete clinical procedure is time-consuming and requires significant costs. To reduce manual intervention and to address unmet clinical demands, it has been highlighted that automated implant fabrication by data-driven methods can accelerate the design and manufacturing of patient-specific cranial implants. The data-driven approaches, encompassing artificial intelligence (machine learning/deep learning) and E-platforms, such as publicly accessible clinical databases will lead to the development of the next generation of patient-specific cranial implants, which can provide predictable clinical outcomes. STATEMENT OF SIGNIFICANCE: Cranioplasty is performed to reconstruct cranial defects of patients who have undergone decompressive craniectomy. Cranioplasty surgery improves the aesthetic and functional outcomes of those patients. To meet the clinical demands of cranioplasty surgery, accelerated designing and manufacturing of 3D cranial implants are required. This review provides an overview of biomaterial implants and bone flap manufacturing methods for cranioplasty surgery. In addition, tissue engineering and regenerative medicine-based approaches to reduce clinical complications are also highlighted. The potential use of data-driven computer applications and data-driven artificial intelligence-based approaches are emphasized to accelerate the clinical protocols of cranioplasty treatment with less manual intervention and shorter intraoperative time.

N-3 Polyunsaturated Fatty Acids Ameliorate Neurobehavioral Outcomes Post-Mild Traumatic Brain Injury in the Fat-1 Mouse Model.

Concussions and mild traumatic brain injury (m-TBI) have been identified as a consequential public health concern because of their potential to cause considerable impairments in physical, cognitive, behavioral, and social functions. Given their prominent structural and functional roles in the brain, n-3 polyunsaturated fatty acids (PUFA) have been identified as a potentially viable prophylactic agent that may ameliorate the deleterious effects of m-TBI on brain function. The purpose of the present pilot study was to investigate the effect of n-3 PUFA on neurologic function using a weight drop injury (WDI) model. Fat-1 mice, capable of synthesizing n-3 PUFA endogenously from n-6 PUFA, and their wild-type (WT) counterparts, were subjected to a mild low-impact WDI on the closed cranium, and recovery was evaluated using the neurological severity score (NSS) to assess the motor and neurobehavioral outcomes. In comparison to the WT mice, the fat-1 mice had a significantly (p ≤ 0.05) lower NSS at all time points post-WDI, and significantly greater neurological restoration measured as the time to first movement. Overall, these findings demonstrate the protective effect of n-3 PUFA against mild brain injury.

Violence in the first millennium BCE Eurasian steppe: Cranial trauma in three Turpan Basin populations from Xinjiang, China.

OBJECTIVES: Violence affected daily life in prehistoric societies, especially at conflict zones where different peoples fought over resources and for other reasons. In this study, cranial trauma was analyzed to discuss the pattern of violence experienced by three Bronze to early Iron Age populations (1,000-100 BCE) that belonged to the Subeixi culture. These populations lived in the Turpan Basin, a conflict zone in the middle of the Eurasian Steppe. METHODS: The injuries on 129 complete crania unearthed from the Subeixi cemeteries were examined for crude prevalence rate (CPR), trauma type, time of occurrence, possible weapon, and direction of the blow. Thirty-three injuries identified from poorly preserved crania were also included in the analyses except for the CPR. Data was also compared between the samples and with four other populations that had violence-related backgrounds. RESULTS: Overall, 16.3% (21/129) of the individuals showed violence-induced traumatic lesions. Results also indicated that most of the injuries were perimortem (81.6%), and that women and children were more involved in conflict than the other comparative populations. Wounds from weapons accounted for 42.1% of the identified cranial injuries. Distribution analysis suggested no dominant handedness of the attackers, and that blows came from all directions including the top (17.1%). Wounds caused by arrowheads and a special type of battle-ax popular in middle and eastern Eurasian Steppe were also recognized. DISCUSSION: A comprehensive analysis of the skeletal evidence, historical records, and archeological background would suggest that the raiding to be the most possible conflict pattern reflected by the samples. The attackers were likely to have been nomadic invaders from the steppe (such as the Xiongnu from historical records), who attacked the residents in the basin more likely for their resources rather than territory or labor force.

Marine spongin incorporation into Biosilicate® for tissue engineering applications: An in vivo study.

Biomaterials and bone grafts, with the ability of stimulating tissue growth and bone consolidation, have been emerging as very promising strategies to treat bone fractures. Despite its well-known positive effects of biosilicate (BS) on osteogenesis, its use as bone grafts in critical situations such as bone defects of high dimensions or in non-consolidated fractures may not be sufficient to stimulate tissue repair. Consequently, several approaches have been explored to improve the bioactivity of BS. A promising strategy to reach this aim is the inclusion of an organic part, such as collagen, in order to mimic bone structure. Thus, the present study investigated the biological effects of marine spongin (SPG)-enriched BS composites on the process of healing, using a critical experimental model of cranial bone defect in rats. Histopathological and immunohistochemistry analyzes were performed after two and six weeks of implantation to investigate the effects of the material on bone repair (supplemental material-graphical abstract). Histological analysis demonstrated that for both BS and BS/SPG, similar findings were observed, with signs of material degradation, the presence of granulation tissue along the defect area and newly formed bone into the area of the defect. Additionally, histomorphometry showed that the control group presented higher values for Ob.S/BS (%) and for N.Ob/T.Ar (mm2) (six weeks post-surgery) compared to BS/SPG and higher values of N.Ob/T.Ar (mm2) compared to BS (two weeks post-surgery). Moreover, BS showed higher values for OV/TV (%) compared to BS/SPG (six weeks post-surgery). Also, VEGF immunohistochemistry was increased for BS (two weeks post-surgery) and for BS/SPG (six weeks) compared to CG. TGFb immunostaining was higher for BS compared to CG. The results of this study demonstrated that the BS and BS/SPG scaffolds were biocompatible and able to support bone formation in a critical bone defect in rats. Moreover, an increased VEGF immunostaining was observed in BS/SPG.

Silymarin effect on experimental bone defect repair in rat following implantation of the electrospun PLA/carbon nanotubes scaffold associated with Wharton's jelly mesenchymal stem cells.

In this study, the ability of silymarin to heal rat calvarial bone critical defects with mesenchymal stem cells isolated from human Wharton's jelly (HWJMSC) cultured on the electrospun scaffold of poly (lactic acid)/carbon nanotube (PLA/CNT) has been examined. In this study, 20 adult male Wistar rats were divided into four groups of five each. Under general anesthesia, 8 mm defects were created in the calvarial bone of the rats. Then, study groups were defined as no treatment group, the scaffold alone, the scaffold and HWJMSCs, and the scaffold/cells plus oral silymarin, respectively. The histomorphometric study was performed using H&E staining and Goldner's Masson trichrome as specific staining. The results of this study showed that the electrospun PLA/CNT scaffold is a biocompatible scaffold and HWJMSCs can considerably attach and proliferate on this scaffold, and the scaffold itself is also a suitable option for improving the bone repair process. The results of the histomorphometric analysis also showed a significantly higher amount of recently formed bone in the silymarin group plus scaffold/cells compared to the scaffold and cell group alone (p < .05). Utilizing silymarin plus HWJMSCs cultured on PLA/CNT scaffold can be used as a suitable method for the process of osteogenesis and bone repair.

Endemic violence in a pre-Hispanic Andean community: A bioarchaeological study of cranial trauma from the Majes Valley, Peru.

OBJECTIVES: This study examines violence-related cranial trauma frequencies and wound characteristics in the pre-Hispanic cemetery of Uraca in the lower Majes Valley, Arequipa, Peru, dating to the pre- and early-Wari periods (200-750 CE). Cranial wounds are compared between status and sex-based subgroups to understand how violence shaped, and was shaped by, these aspects of identity, and to reconstruct the social contexts of violence carried out by and against Uracans. MATERIALS AND METHODS: Presence, location, and characteristics (lethality, penetration, and post-traumatic sequelae) of antemortem and perimortem cranial fractures are documented for 145 crania and compared between subgroups. Cranial wounds are mapped in ArcGIS and the locational distribution of injuries is compared between male and female crania. RESULTS: Middle adult males were disproportionately interred at Uraca, particularly in the elite Sector I. The Uraca mortuary population presents the highest rate of cranial trauma reported for pre-Hispanic Peru: 67% of adults present trauma, and among those, 61.1% present more than one cranial injury. Males exhibit significantly more cranial trauma than females and present a higher mean number of injuries per person. Elite males show the highest mean number of injuries per person, more antemortem injuries, and are the only ones with perimortem cranial trauma, bladed injuries, penetrating injuries, and post-traumatic sequelae. Both sexes were most frequently injured on the anterior of the cranium, while the proportion of posterior injuries was higher for females. DISCUSSION: The rate, intensity, and locational patterns of cranial trauma suggests the community was engaged in raids and/or war with enemy groups, some of which may have increased physical violence between community members. Engaging in violence was likely a prerequisite for burial in the elite sector and was bound up with the generation and maintenance of social status differences linked to male social life.

Bioglass/PLGA associated to photobiomodulation: effects on the healing process in an experimental model of calvarial bone defect.

Bioactive glasses (BG) are known for their ability to bond to bone tissue. However, in critical situations, even the osteogenic properties of BG may be not enough to induce bone consolidation. Thus, the enrichment of BG with polymers such as Poly (D, L-lactic-co-glycolic) acid (PLGA) and associated to photobiomodulation (PBM) may be a promising strategy to promote bone tissue healing. The aim of the present study was to investigate the in vivo performance of PLGA supplemented BG, associated to PBM therapy, using an experimental model of cranial bone defect in rats. Rats were distributed in 4 different groups (Bioglass, Bioglass/PBM, Bioglas/PLGA and BG/PLGA/PBM). After the surgical procedure to induce cranial bone defects, the pre-set samples were implanted and PBM treatment (low-level laser therapy) started (808 nm, 100 mW, 30 J/cm2). After 2 and 6 weeks, animals were euthanized, and the samples were retrieved for the histopathological, histomorphometric, picrosirius red staining and immunohistochemistry analysis. At 2 weeks post-surgery, it was observed granulation tissue and areas of newly formed bone in all experimental groups. At 6 weeks post-surgery, BG/PLGA (with or without PBM) more mature tissue around the biomaterial particles. Furthermore, there was a higher deposition of collagen for BG/PLGA in comparison with BG/PLGA/PBM, at second time-point. Histomorphometric analysis demonstrated higher values of BM.V/TV for BG compared to BG/PLGA (2 weeks post-surgery) and N.Ob/T.Ar for BG/PLGA compared to BG and BG/PBM (6 weeks post-surgery). This current study concluded that the use of BG/PLGA composites, associated or not to PBM, is a promising strategy for bone tissue engineering.

METABOLIC, ENZYMATIC AND MINERAL MAINTENANCE OFREPARATIVE OSTEOGENESIS OF FACIAL CRANIUM INJURIES.

Aim - study of marker enzymes, hormonal and carbohydrate-protein indicators of the state of reparative osteogenesis in patients with complicated and uncomplicated course of injuries of facial cranium. The study included 81 patients with injuries of facial cranium, which were divided into 2 groups, depending on the presence of complications. The following enzyme indicators were studied: the level of excretion of hydroxyproline in daily urine; alkaline and acid phosphatase activity; the percentage of bone isoenzymes of alkaline phosphatase. To assess the mineral metabolism, the level of total and ionized calcium and inorganic phosphorus in the blood serum, as well as their excretion in the urine, were determined. To assess the state of metabolism, the concentration of glycosaminoglycans and their fractions in the blood serum were studied. To study the structural and functional state of the bone tissue the densitometry was performed. In patients with complicated course of injuries of facial cranium assosiated with traumatic brain injury there was revealed the increase (р<0,05) of: excretion of phosphorus, uronic acids and oxyproline, while the excretion of calcium was not disturbed (р>0,05), and excretion of magnesium was decreased (р<0,05). It was found out that the level of calcium of blood serum in patients with complicated course is significantly (р<0,05) lower than in the control group and does not depend on the presence of craniocerebral injury (р>0,05). The decrease of the level of ionized calcium content in blood serum can be the confirmation of lower metabolic activity of reparative osteogenesis processes, first of all at the expense of damage of central mechanisms. When studying the content of carbohydrate-protein metabolites by complicated course of injuries of facial cranium, the absolute increase (р<0,05) of concentration of chondroitin-6-sulfates was revealed, and during the analysis of results it was found out that in absolute values, as well as in structural indexes, the specific weight of various fractions changes, that can be the evidence of instability of mechanisms of osteogenesis and of damage of physiological mechanisms of reparative osteogenesis. Densitometric equivalents of forming of complicated course of injuries of facial cranium are the increase of broadband ultrasonic attenuation and the decrease of its spreading speed on the background of low levels of chondroitin-6-sulfates.

State of the art forensic techniques reveal evidence of interpersonal violence ca. 30,000 years ago.

The Cioclovina (Romania) calvaria, dated to ca. 33 cal ka BP and thought to be associated with the Aurignacian lithic industry, is one of the few relatively well preserved representatives of the earliest modern Europeans. Two large fractures on this specimen have been described as taphonomic modifications. Here we used gross and virtual forensic criteria and experimental simulations on synthetic bone models, to investigate their nature. Both forensic trauma pattern analysis and experimental models exclude a postmortem origin for the Cioclovina fractures. Rather, they indicate two incidents of blunt force trauma, the second clearly inflicted with a club-like object. The magnitude and extent of the lesions and the lack of signs of healing indicate a fatal injury. The Upper Paleolithic period is noted for intensified technological innovation, increased symbolic behavior, and cultural complexity. We show that the behavioural repertoire of the earliest modern Europeans also comprised violent inter-personal interactions and murder.

Bone Regeneration Effect of Hyperbaric Oxygen Therapy Duration on Calvarial Defects in Irradiated Rats.

OBJECTIVE: In this study, we evaluated changes in bone remodeling in an irradiated rat calvarial defect model according to duration of hyperbaric oxygen therapy. MATERIALS AND METHODS: The 28 rats were divided into four groups. Radiation of 12 Gy was applied to the skull, and 5-mm critical size defects were formed on both sides of the skull. Bone grafts were applied to one side of formed defects. From the day after surgery, HBO was applied for 0, 1, and 3 weeks. At 6 weeks after bone graft, experimental sites were removed and analyzed for radiography, histology, and histomorphometry. RESULTS: Micro-CT analysis showed a significant increase in new bone volume in the HBO-3 group, with or without bone graft. When bone grafting was performed, BV, BS, and BS/TV all significantly increased. Histomorphometric analysis showed significant increases in %NBA and %BVN in the HBO-1 and HBO-3 groups, regardless of bone graft. CONCLUSION: Hyperbaric oxygen therapy was effective for bone regeneration with only 1 week of treatment.

Electrical stimulation: Complementary therapy to improve the performance of grafts in bone defects?

The limitations of bone reconstruction techniques have stimulated the tissue engineering for the repair of large bone defects using osteoconductive materials and osteoinductive agents. This study evaluated the effects of low intensity electric current on the inorganic bovine graft in calvaria defects. Bone defects were performed with piezoelectric system in the calvaria of Wistar rats divided into four groups (n = 24): (C) without grafting and without electrical stimulation; (E) with grafting; (MC) without grafting and submitted to electrical stimulation; (MC + E) with grafting and submitted to electrical stimulation. Inflammatory, angiogenic and osteogenic events during bone repair at the 10th, 30th, 60th, and 90th days were considered. Several inflammatory markers demonstrated the efficacy of grafting in reducing inflammation, particularly when subjected to electrical stimulation. Angiogenesis and collagen organization were more evident by electrical stimulation application on the grafts. Moreover, the osteogenic cell differentiation process indicated that the application of microcurrent on grafting modulated the homeostasis of bone remodeling. It is concluded that microcurrent favored the performance of grafts in calvarial rat model. Low-intensity electrical current might improve the osteoconductive property of grafting in bone defects. Therefore, electrical current becomes an option as complementary therapy in clinical trials involving bone surgeries and injuries. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 924-932, 2019.

Earliest Animal Cranial Surgery: from Cow to Man in the Neolithic.

The earliest cranial surgery (trepanation) has been attested since the Mesolithic period. The meaning of such a practice remains elusive but it is evident that, even in prehistoric times, humans from this period and from the Neolithic period had already achieved a high degree of mastery of surgical techniques practiced on bones. How such mastery was acquired in prehistoric societies remains an open question. The analysis of an almost complete cow cranium found in the Neolithic site of Champ-Durand (France) (3400-3000 BC) presenting a hole in the right frontal bone reveals that this cranium underwent cranial surgery using the same techniques as those used on human crania. If bone surgery on the cow cranium was performed in order to save the animal, Champ-Durant would provide the earliest evidence of veterinary surgical practice. Alternatively, the evidence of surgery on this cranium can also suggest that Neolithic people practiced on domestic animals in order to perfect the technique before applying it to humans.

A Novel Secretome Biotherapeutic Influences Regeneration in Critical Size Bone Defects.

Severe traumatic injuries often result in critical size bone defects, which are unable to heal without treatment. Autologous grafting is the standard of care but requires additional surgeries for graft procurement. Amnion-derived multipotent progenitor cells release a secretome of biomolecules identified as integral to the process of bone regeneration and angiogenesis. This secretome is currently under development as a biotherapeutic. The efficacy of this secretome biotherapeutic was evaluated in vitro on the proliferation and migration of mesenchymal stem cells and osteoprogenitor cells as well as in vivo using a critical size rat calvarial defect model. The secretome biotherapeutic was loaded onto a collagen scaffold and placed into the defect, which was allowed to heal for 4 and 12 weeks. The secretome biotherapeutic enhanced the proliferation and migration of mesenchymal stem cells and proliferation of osteoprogenitor cells. Further, the secretome biotherapeutic improved new bone volume and connectivity by 12 weeks and significantly improved angiogenesis at 4 weeks and bone density at 4 and 12 weeks with no deleterious effects. The improvement in new bone volume, connectivity, and angiogenesis suggests that the secretome biotherapeutic has beneficial effects for bone healing and a higher dose of the secretome biotherapeutic may further improve regeneration.

* Early and Marked Enhancement of New Bone Quality by Alendronate-Loaded Collagen Sponge Combined with Bone Morphogenetic Protein-2 at High Dose: A Long-Term Study in Calvarial Defects in a Rat Model.

Choice of appropriate biomaterial is a key factor for the success of recombinant human bone morphogenetic protein (rhBMP)-2 therapy. Inspired by osteogenic cell-differentiating and osteoclast-suppressing capabilities of alendronate (ALN), we manufactured a composite type of ALN-loaded collagen sponge (ALN-CS), which controls the early detrimental effect of high-dose rhBMP-2. This study aimed to evaluate ALN-CS as a high-dose rhBMP-2 carrier by investigating its initial biomolecular effect and efficacy on intramembranous ossification at 1, 4, 8, and 24 weeks using a rat calvarial defect model compared with nonloaded CS. The in vitro rhBMP-2 release in the ALN-CS showed a low initial burst and steady release phase during the rest period despite lack of calcium compared with that in CS alone. ALN release showed the same tendency as rhBMP-2 release. In vitro characterization showed that osteoblast differentiation and mineralization of mesenchymal stromal cells were more enhanced with ALN-CS. The ALN-CS-BMP group showed higher expression of bone-forming and -resorbing markers in vivo than the CS-BMP group after the first 7 days, which might be attributable to the relatively large amount of rhBMP-2 remaining. However, osteoclast activation in the ALN-CS-BMP group was significantly reduced compared with the CS-BMP group. Radiological and histological analyses revealed that ALN-CS-BMP promoted early and dense ossification at the initial defect, with 100% greater bone mass, 20% greater bone density, and less fatty marrow tissue than CS-BMP, which continued during the whole healing period. However, CS or ALN-CS alone failed to show complete defect closure even at the 24-week healing interval. Our results demonstrate that ALN-CS has remarkable advantages over CS alone in high-dose BMP-2 delivery, with potent suppression of resorption, early and dense ossification at the target area with less fatty marrow formation, and continuation of bone quality over the long term, which highlights its great clinical potential as a rhBMP carrier for bone regeneration at intramembranous ossification sites.

Prehistoric massacre revealed. Perimortem cranial trauma from Potocani, Croatia.

ABSTRACT: During archaeological rescue excavations carried out in 2007 at Potocani in continental Croatia, a pit containing numerous human skeletal remains (MNI = 41) was discovered. The remains were mostly articulated but also commingled and showed no clear pattern of organization. There were no associated artifacts, just a few pottery fragments probably belonging to the Copper Age Lasinja Culture (c. 4300 to 3950 BCE). Anthropological analyses suggest the presence of individuals of all ages and both sexes with many crania exhibiting various perimortem injuries. Three human bone samples from different layers were dated to around 4100 cal BCE by radiocarbon analysis. These radiocarbon dates combined with other aspects of archaeological context, indicate that the deposition was a single episode rather than a long-term accumulation. All this suggests a single violent encounter (massacre). Here we present results of the bioarchaeological analysis of four adult crania with clear signs of perimortem trauma. These include blunt force trauma as well as cuts and penetrating injuries indicating the use of different weapons/tools.

Immunohistochemical response in rats of beta-tricalcium phosphate (TCP) with or without BMP-2 in the production of collagen matrix critical defects.

This study aimed to assess the biological response of BMP-2 (bone morphogenetic protein-2) in supplementation with ß-tricalcium phosphate (TCP) as a carrier in the bone healing of surgical defects in rats' calvaria. A critical-size defect (5mm in diameter) was filled with ß-TCP alone or added with that plus 5mg of BMP-2 at 5, 15, and 30 postoperative days. Histomorphometric and immunohistochemical (osteocalcin, collagen type I, and metalloproteinase-9) analysis was performed to assess the features of bone healing. Histological behavior and collagen type I labeling showed increased formation of the collagen matrix, leading to a higher percentage of newly formed bone and biomaterial for tissue and more total mineralization of pure TCP when compared to the other groups. The supplementation with BMP-2 promoted faster TCP remodeling; however, there was no statistically significant difference for the bone formed in both groups (P>0.05). Collagen-matrix formation and new bone formation reached maximum levels when the defects were filled with pure TCP, even exceeding the levels from BMP-2 supplementation.

The Effects of Nigella Sativa Seed Extract on Bone Healing in an Experimental Model.

The purpose of this study was to histologically evaluate the effects on bone healing of nigella sativa seed extract applied on calvarial defects in an ovariectomized rat model. The study included 32 female rats weighing 280 to 310 g with an average age of 3 months. A defect was created with a trephine burr on each rat calvarium. The rats were divided into 2 groups (control and study) of 8 animals each. All the defects were grafted with a gelatin sponge mixed with normal saline. In the study group, nigella sativa seed extract was applied systemically using an oro-gastric tube. Half of the animals in each group were sacrificed after 2 weeks, and the others after 4 weeks. In the control groups, the defects were not completely filled with regenerated bone. Osteoblast cells were observed more in the study groups. A higher rate of osteoclasts was determined in the control groups. In addition, the nigella sativa group had a statistically greater amount of bone formation than the others group at both 2 weeks and 4 weeks (P <0.05). The systemic application of nigella sativa seed extract demonstrated incredibly positive effects on enhanced bone healing in this experimental osteoporotic model.

The facilitatory effects of hyperbaric oxygen treatment on membrane bone wound healing in a rat calvarial defect model.

We examined the effect of hyperbaric oxygen (HBO2) treatment on bone wound healing in a rat calvarial defect. Critical-sized defects were created in the calvaria of adult Wistar rats. The animals were divided into four groups--HBO2, normobaric oxygen, hyperbaric air, and no treatment. Treatments were performed five days a week, for two weeks. Micro-computerized tomography and histological analysis were used to evaluate the bone defects. Regenerated bone areas were calculated as the percentage of new bone in the cross-sectional area of defect. The new bone cross-sectional area was significantly greater in the HBO2 group than in the other groups. There were no significant differences in the numbers of nucleated cells in the new bone areas. Although new bone volume per defect volume was significantly greater in the HBO2 group than in the other groups, no significant differences in bone mineral density in the new bone area were observed. These findings indicate the facilitatory role of HBO2 treatment on bone wound healing in the rat calvarial bone defect, and it does not appear to have any negative effects on bone maturity. We propose that HBO2 treatment would be useful in promoting bone regeneration following injury in the orofacial region.

Craniofacial Wound Healing with Photobiomodulation Therapy: New Insights and Current Challenges.

The fundamental pathophysiologic response for the survival of all organisms is the process of wound healing. Inadequate or lack of healing constitutes the etiopathologic basis of many oral and systemic diseases. Among the numerous efforts to promote wound healing, biophotonics therapies have shown much promise. Advances in photonic technologies and a better understanding of light-tissue interactions, from parallel biophotonics fields such as in vivo optical imaging and optogenetics, are spearheading their popularity in biology and medicine. Use of high-dose lasers and light devices in dermatology, ophthalmology, oncology, and dentistry are now popular for specific clinical applications, such as surgery, skin rejuvenation, ocular and soft tissue recontouring, and antitumor and antimicrobial photodynamic therapy. However, a less well-known clinical application is the therapeutic use of low-dose biophotonics termed photobiomodulation (PBM) therapy, which is aimed at alleviating pain and inflammation, modulating immune responses, and promoting wound healing and tissue regeneration. Despite significant volumes of scientific literature from clinical and laboratory studies noting the phenomenological evidence for this innovative therapy, limited mechanistic insights have prevented rigorous and reproducible PBM clinical protocols. This article briefly reviews current evidence and focuses on gaps in knowledge to identify potential paths forward for clinical translation with PBM therapy with an emphasis on craniofacial wound healing. PBM offers a novel opportunity to examine fundamental nonvisual photobiological processes as well as develop innovative clinical therapies, thereby presenting an opportunity for a paradigm shift from conventional restorative/prosthetic approaches to regenerative modalities in clinical dentistry.