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Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/β-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.

This study evaluated how implant design features influence osseointegration. Two implant macrogeometries and surface treatments were evaluated: (1) progressive buttress threads with an SLActive surface (SLActive/BL), and (2) inner and outer trapezoidal threads with a nanohydroxyapatite coating over a dual acid-etched surface (Nano/U). Implants were placed in the right ilium of 12 sheep, and histologic and -metric analyses were conducted after 12 weeks. Percentages of bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within the threads were quantified. Histologically, the SLActive/BL group showed greater and more intimate BIC than the Nano/U group. In contrast, Nano/U group depicted woven bone formation within the healing chambers, between the osteotomy wall and implant threads, and bone remodeling was evident at the outer thread tip. Significantly higher BAFO was seen in the Nano/U group than the SLActive/BL group at 12 weeks (P < .042). Different implant design features influenced the osseointegration pathway, supporting further investigations to describe the differences and clinical performance. [ABSTRACT FROM AUTHOR]

The purpose of this in vitro study was to develop calcium sulfate (CS)-based disks infused with an antimicrobial drug, which can be used as a post-surgical treatment modality for osteomyelitis. CS powder was embedded with 10% antibiotic, amoxicillin (AMX) or moxifloxacin (MFX), to form composite disks 11 mm in diameter that were tested for their degradation and antibiotic release profiles. For the disk degradation study portion, the single drug-loaded disks were placed in individual meshes, subsequently submerged in phosphate-buffered saline (PBS), and incubated at 37 °C. The disks were weighed once every seven days and analyzed via Fourier-transform infrared spectroscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and scanning electron microscopy. During the antibiotic release analysis, composite disks were placed in PBS solution, which was changed every 3 days, and analyzed for antibiotic activity and efficacy. The antibacterial effects of these sustained-release composites were tested by agar diffusion assay using Streptococcus mutans (S. mutans) UA 159 as an indicator strain. The degradation data showed significant increases in the degradation of all disks with the addition of antibiotics. Following PBS incubation, there were significant increases in the amount of phosphate and decreases in the amount of sulfate. The agar diffusion assay demonstrated that the released concentrations of the respective antibiotics from the disks were significantly higher than the minimum inhibitory concentration exhibited against S. mutans over a 2–3-week period. In conclusion, CS-antibiotic composite disks can potentially serve as a resorbable, osteoconductive, and antibacterial therapy in the treatment of bone defects and osteomyelitis. [ABSTRACT FROM AUTHOR]

Periodontitis is a bacteria‐induced chronic inflammatory disease characterized by degradation of the supporting tissue and bone in the oral cavity. Treatment modalities seek to facilitate periodontal rehabilitation while simultaneously preventing further gingival tissue recession and potentially bone atrophy. The aim of this study was to compare two differently sourced membranes, a resorbable piscine collagen membrane and a porcine‐derived collagen membrane, in the repair of soft tissue defects utilizing a preclinical canine model. This in vivo component consisted of 10 beagles which were subjected to bilateral maxillary canine mucogingival flap defects, as well as bilateral soft tissue defects (or pouches) with no periodontal ligament damage in the mandibular canines. Defects received either a piscine‐derived dermal membrane, (Kerecis® Oral, Ísafjörður, Iceland) or porcine‐derived dermal membrane (Geistlich Mucograft®, Wolhusen, Switzerland) in a randomized fashion (to avoid site bias) and were allowed to heal for 30, 60, or 90 days. Statistical evaluation of tissue thickness was performed using general linear mixed model analysis of variance and least significant difference (LSD) post hoc analyses with fixed factors of time and membrane. Semi‐quantitative analysis employed for inflammation assessment was evaluated using a chi‐squared test along with a heteroscedastic t‐test and values were reported as mean and corresponding 95% confidence intervals. In both the mucogingival flap defects and soft tissue gingival pouches, no appreciable qualitative differences were observed in tissue healing between the membranes. Furthermore, no statistical differences were observed in the thickness measurements between piscine‐ and porcine‐derived membranes in the mucogingival flap defects (1.05 mm [±0.17] and 1.29 mm [±0.17], respectively [p =.06]) or soft tissue pouches (1.36 mm [±0.14] and 1.47 mm [±0.14], respectively [p =.27]), collapsed over time. Independent of membrane source (i.e., piscine or porcine), similar inflammatory responses were observed in both the maxilla and mandible at the three time points (p =.88 and p =.79, respectively). Histologic and histomorphometric evaluation results indicated that both membranes yielded equivalent tissue responses, remodeling dynamics and healing patterns for the mucogingival flap as well as the soft tissue gingival pouch defect models. [ABSTRACT FROM AUTHOR]

Purpose: To qualitatively and quantitatively evaluate histologic osseointegration parameters of implants designed with decompressing vertical chambers between the threads with two different surface treatments (TiO2 blasting + maleic acid vs TiO2 blasting + maleic + HCl) in a large translational animal model at 3 and 6 weeks in vivo. Materials and Methods: Nine female sheep were used, and 72 implants with trapezoidal threads and decompressing vertical chambers of 0.6 mm in diameter and 0.2 mm in depth were placed in the ilium crest. After 3 and 6 weeks, the animals were euthanized, and biomechanical and histomophometric analyses were performed. Results: Survey histologic evaluation indicated intimate contact between the bone and the implants independent of surface treatment at both times in vivo. Bone formation at both time points depicted an intramembranous-type healing pattern between the implant threads. The mean removal torque values for all groups showed a relative increase in removal torque from 3 to 6 weeks. In terms of bone area fraction occupancy analysis, significant differences were found at 6 weeks between surface treatments (P = .046), where the experimental surface yielded higher degrees of bone area fraction occupancy. Conclusion: Conical implants with decompressing vertical chambers between threads presented similar osseointegration parameters regarding bone-to-implant contact and torque-out test values irrespective of surface treatment. However, shifting from a minimally rough to a moderately rough surface (experimental surface with supplemental acid-etching) resulted in significantly improved bone area fraction occupancy at 6 weeks. [ABSTRACT FROM AUTHOR]

Bone tissue has the capacity to regenerate under healthy conditions, but complex cases like critically sized defects hinder natural bone regeneration, necessitating surgery, and use of a grafting material for rehabilitation. The field of bone tissue engineering (BTE) has pioneered ways to address such issues utilizing different biomaterials to create a platform for cell migration and tissue formation, leading to improved bone reconstruction. One such approach involves 3D‐printed patient‐specific scaffolds designed to aid in regeneration of boney defects. This study aimed to develop and characterize 3D printed scaffolds composed of type I collagen augmented with β‐tricalcium phosphate (COL/β‐TCP). A custom‐built direct inkjet write (DIW) printer was used to fabricate β‐TCP, COL, and COL/β‐TCP scaffolds using synthesized colloidal gels. After chemical crosslinking, the scaffolds were lyophilized and subjected to several characterization techniques, including light microscopy, scanning electron microscopy, and x‐ray diffraction to evaluate morphological and chemical properties. In vitro evaluation was performed using human osteoprogenitor cells to assess cytotoxicity and proliferative capacity of the different scaffold types. Characterization results confirmed the presence of β‐TCP in the 3D printed COL/β‐TCP scaffolds, which exhibited crystals that were attributed to β‐TCP due to the presence of calcium and phosphorus, detected through energy dispersive x‐ray spectroscopy. In vitro studies showed that the COL/β‐TCP scaffolds yielded more favorable results in terms of cell viability and proliferation compared to β‐TCP and COL scaffolds. The novel COL/β‐TCP scaffold constructs hold promise for improving BTE applications and may offer a superior environment for bone regeneration compared with conventional COL and β‐TCP scaffolds. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to qualitatively and quantitatively assess the effect of osteotomy preparation by conventional, subtractive, or osseodensification instrumentation on osteotomies, treated with or without endosteal implants, and healing capacity. Materials and Methods: Seven sheep were used, and 56 osteotomies were made in the left and right ilium of the sheep (n = 8/sheep [4 per side/time point (3 and 6 weeks)]). Two different instrumentation techniques were used: (1) conventional/regular drilling in a three-step series of a 2-mm pilot and 3.2-mm and 3.8-mm twist drills and (2) osseodensification drilling with a Densah Bur 2.0-mm pilot and 2.8-mm and 3.8-mm multi-fluted tapered burs. Drilling was performed at 1,100 rpm with saline irrigation. Results: Qualitative histomorphometric evaluation of the osteotomies after 3 and 6 weeks did not indicate any healing impairment due to the instrumentation. In all samples, histologic examination suggested bone remodeling and growth (empty and treated with an implant), irrespective of preparation technique. Osteotomies prepared using the osseodensification instrumentation showed the existence of bone chips autografted into the trabecular spaces along the length of the osteotomy wall. Conclusion: The osseodensification group yielded higher osseointegration rates, as distinguished through qualitative assessment, bone-to-implant contact, and bone-areafraction occupancy, indicating an increased osteogenic potential in osteotomies prepared using the osseodensification technique. [ABSTRACT FROM AUTHOR]

This study sought to qualitatively and quantitatively evaluate the effect of osteotomy preparation by conventional (control group) or OD (OD group) instrumentation on osteotomy healing. An incision of 10 cm was made in the anteroposterior direction over the hip in five sheep, and 15 osteotomies were prepared in the left ilium of the sheep (n = 3/sheep). Three different instrumentation techniques were utilized: (1) conventional/regular drilling (R [recommended by manufacturer]) in a 3-step series of a 2-mm pilot, 3.2-mm, and 3.8-mm twist drills; (2) OD clockwise (OD-CW) drilling with Densah Bur (Versah) 2.0-mm pilot, 2.8-mm, and 3.8-mm multi-fluted tapered burs; and (3) OD counterclockwise (OD-CCW) drilling with Densah Bur 2.0-mm pilot, 2.8-mm, and 3.8-mm multifluted tapered burs. Drilling was performed at 1,100 rpm with saline irrigation. Qualitative histomorphometric analysis of the osteotomies after 6 weeks did not show any healing impairment due to the instrumentation. Histologic analysis shows bone remodeling and growth in all samples, irrespective of osteotomy preparation technique, with the presence of bone chips observed along the length of the osteotomy wall in sites subjected to osseodensification drilling. [ABSTRACT FROM AUTHOR]

The field of additive manufacturing, 3D printing (3DP), has experienced an exponential growth over the past four decades, in part due to increased accessibility. Developments including computer‐aided design and manufacturing, incorporation of more versatile materials, and improved printing techniques/equipment have stimulated growth of 3DP technologies within various industries, but most specifically the medical field. Alternatives to metals including ceramics and polymers have been garnering popularity due to their resorbable properties and physiologic similarity to extracellular matrix. 3DP has the capacity to utilize an assortment of materials and printing techniques for a multitude of indications, each with their own associated benefits. Within the field of medicine, advances in medical imaging have facilitated the integration of 3DP. In particular, the field of orthopedics has been one of the earliest medical specialties to implement 3DP. Current indications include education for patients, providers, and trainees, in addition to surgical planning. Moreover, further possibilities within orthopedic surgery continue to be explored, including the development of patient‐specific implants. This review aims to highlight the use of current 3DP technology and materials by the orthopedic community, and includes comments on current trends and future direction(s) within the field. [ABSTRACT FROM AUTHOR]