Development and Characterization of a Novel Composite Hydrogel Biomaterial for Improved Mucoperiosteal Wound Repair.

Mucoperiosteal wound healing, as it occurs after pediatric cleft palate surgery, can be challenging due to the limitations of current treatments such as tissue flaps secured with sutures and fibrin glue. In this study, we characterized the in vitro performance of a novel composite hydrogel biomaterial designed to be employed as an in situ wound filler and enhance mucoperiosteal wound healing. We evaluated a range of photopolymerizable formulations containing methacrylated gelatin (GelMA), glycol chitosan, and bioglass microparticles. Our aim was to identify one or more formulations with an appropriate balance of properties against a set of functional requirements that we established for this application. To test the formulations against these criteria, we measured photopolymerization kinetics, mechanical properties, degradation rate, in vitro biocompatibility, and ex vivo tissue adhesion. All formulations polymerized in less than 90 s using violet light. In addition, we found that GelMA-based hydrogels were more adhesive to mucoperiosteal tissue than clinical standard fibrin glue. Inclusion of small amounts of bioglass in the formulation increased mechanical compatibility with mucoperiosteal tissue, enhanced cytoconductivity, and promoted cell proliferation. Taken together, our results support the suitability of these photopolymerized composite hydrogels as in situ mucoperiosteal wound fillers. Overall, this study lays the groundwork for investigating the in vivo, pre-clinical effectiveness of these composite hydrogels in improving mucoperiosteal wound healing outcomes.

Hdac3 deficiency limits periosteal reaction associated with Western diet feeding in female mice.

Diet-induced obesity is associated with enhanced systemic inflammation that limits bone regeneration. HDAC inhibitors are currently being explored as anti-inflammatory agents. Prior reports show that myeloid progenitor-directed Hdac3 ablation enhances intramembranous bone healing in female mice. In this study, we determined if Hdac3 ablation increased intramembranous bone regeneration in mice fed a high-fat/high-sugar (HFD) diet. Micro-CT analyses demonstrated that HFD-feeding enhanced the formation of periosteal reaction tissue of control littermates, reflective of suboptimal bone healing. We confirmed enhanced bone volume within the defect of Hdac3-ablated females and showed that Hdac3 ablation reduced the amount of periosteal reaction tissue following HFD feeding. Osteoblasts cultured in a conditioned medium derived from Hdac3-ablated cells exhibited a four-fold increase in mineralization and enhanced osteogenic gene expression. We found that Hdac3 ablation elevated the secretion of several chemokines, including CCL2. We then confirmed that Hdac3 deficiency increased the expression of Ccl2. Lastly, we show that the proportion of CCL2-positve cells within bone defects was significantly higher in Hdac3-deficient mice and was further enhanced by HFD. Overall, our studies demonstrate that Hdac3 deletion enhances intramembranous bone healing in a setting of diet-induced obesity, possibly through increased production of CCL2 by macrophages within the defect.

Clinical comprehensive of microfracture, autologous chondrocyte implantation, and periosteum-covered iliac bone grafting for Hepple stage IV-V lesions.

Chronic ankle pain significantly impairs daily activities and athletic performance with osteochondral lesions of the talus (OLT) in Hepple stages IV and V, which are often causative factors. This study aimed to assess the efficacy and safety of autologous osteochondral transplantation (AOT) for the treatment of these conditions. This retrospective study was conducted from May 2020 to May 2023 at Cangzhou Traditional Chinese and Western Medicine Combined Hospital, including patients with a diagnosis of Hepple stage IV or V OLT confirmed by magnetic resonance imaging (MRI) and arthroscopy. Surgical interventions involved arthroscopic debridement, followed by AOT or limited arthrotomy based on the location and size of the lesion. Preoperative and postoperative evaluations used the Visual Analog Scale, American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale, MRI-Based Cartilage Repair Tissue Scoring, and the International Knee Documentation Committee Knee Evaluation Form. Statistical analysis was conducted using paired-sample t tests to compare the preoperative and postoperative data. Twenty patients were included, revealing significant postoperative improvements in Visual Analog Scale, American Orthopedic Foot and Ankle Society, and MRI-based cartilage repair tissue scores (P < .05). The radiographic findings suggested effective cartilage regeneration. No adverse effects were observed in the donor knee sites, as confirmed by the stable pre- and postoperative International Knee Documentation Committee Knee Evaluation Form scores. Recovery of physical abilities was achieved on average within 7.3 weeks for daily activities and 13.4 weeks for sports activities. AOT effectively treats Hepple stage IV-V OLT, improves ankle function, promotes cartilage regrowth, and allows quick resumption of daily and athletic activities without compromising donor-site integrity.

Vascularized Femoral Myo-Periosteal Graft for Congenital Pseudarthrosis of the Tibia: A Case Report.

Pure vascularized periosteal transplants have been shown to be extremely effective at achieving rapid bone healing in children with biologically complex non-union. Free tibial and fibular periosteal transplants are generally indicated when large periosteal flaps are necessary. We report using a vascularized femoral myo-periosteal graft (VFMPG) to treat distal tibial osteotomy non-union in a six-year-old boy with congenital pseudarthrosis of the tibia. The graft consisted of a 9 cm myo-periosteal flap (after 50% of elastic retraction) that incorporated the vastus intermedius muscle and diaphyseal femoral periosteum nourished by the descending branch of the lateral circumflex femoral vessels. Plantaris medialis was used as a recipient vessel. Healing occurred 10 weeks after surgery. The patient resumed gait and sports activity without orthosis. No donor or recipient site complications occurred 17 months after surgery. Employing a VFMPG might be an alternative to other free or large vascularized periosteal flaps currently in use for complex pediatric non-unions.

Itm2a expression marks periosteal skeletal stem cells that contribute to bone fracture healing.

The periosteum contains skeletal stem/progenitor cells that contribute to bone fracture healing. However, the in vivo identity of periosteal skeletal stem cells (P-SSCs) remains unclear, and membrane protein markers of P-SSCs that facilitate tissue engineering are needed. Here, we identified integral membrane protein 2A (Itm2a) enriched in SSCs using single-cell transcriptomics. Itm2a+ P-SSCs displayed clonal multipotency and self-renewal and sat at the apex of their differentiation hierarchy. Lineage-tracing experiments showed that Itm2a selectively labeled the periosteum and that Itm2a+ cells were preferentially located in the outer fibrous layer of the periosteum. The Itm2a+ cells rarely expressed CD34 or Osx, but expressed periosteal markers such as Ctsk, CD51, PDGFRA, Sca1, and Gli1. Itm2a+ P-SSCs contributed to osteoblasts, chondrocytes, and marrow stromal cells upon injury. Genetic lineage tracing using dual recombinases showed that Itm2a and Prrx1 lineage cells generated spatially separated subsets of chondrocytes and osteoblasts during fracture healing. Bone morphogenetic protein 2 (Bmp2) deficiency or ablation of Itm2a+ P-SSCs resulted in defects in fracture healing. ITM2A+ P-SSCs were also present in the human periosteum. Thus, our study identified a membrane protein marker that labels P-SSCs, providing an attractive target for drug and cellular therapy for skeletal disorders.

HIF1 activation safeguards cortical bone formation against impaired oxidative phosphorylation.

Energy metabolism, through pathways such as oxidative phosphorylation (OxPhos) and glycolysis, plays a pivotal role in cellular differentiation and function. Our study investigates the impact of OxPhos disruption in cortical bone development by deleting mitochondrial transcription factor A (TFAM). TFAM controls OxPhos by regulating the transcription of mitochondrial genes. The cortical bone, constituting the long bones' rigid shell, is sheathed by the periosteum, a connective tissue layer populated with skeletal progenitors that spawn osteoblasts, the bone-forming cells. TFAM-deficient mice presented with thinner cortical bone, spontaneous midshaft fractures, and compromised periosteal cell bioenergetics, characterized by reduced ATP levels. Additionally, they exhibited an enlarged periosteal progenitor cell pool with impaired osteoblast differentiation. Increasing hypoxia-inducible factor 1a (HIF1) activity within periosteal cells substantially mitigated the detrimental effects induced by TFAM deletion. HIF1 is known to promote glycolysis in all cell types. Our findings underscore the indispensability of OxPhos for the proper accrual of cortical bone mass and indicate a compensatory mechanism between OxPhos and glycolysis in periosteal cells. The study opens new avenues for understanding the relationship between energy metabolism and skeletal health and suggests that modulating bioenergetic pathways may provide a therapeutic avenue for conditions characterized by bone fragility.

Integrating molecular-caged nano-hydroxyapatite into post-crosslinked PVA nanofibers for artificial periosteum.

Artificial periosteum is deemed a novel strategy for inducing endogenous bone regeneration, but ideal periosteum substitutes achieved by orchestrating a biomimetic microenvironment for bone regeneration remain a significant challenge. Here, we design and fabricate a hybridized nanofiber-based artificial periosteum with boosted osteoinduction properties. Via a "molecular cage" biomineralization strategy, nano-hydroxyapatite (nano-HAp) with a controllable size (∼22 nm) and excellent dispersion serves as unique nano-additives for water-soluble polyvinyl-alcohol (PVA)-based artificial periosteum. The PVA/HAp composite is electrospun into nanofibers to replicate the extracellular-matrix-inspired nanostructure for inducing cell adhesion, proliferation, and fate manipulation. A simple post-crosslinking treatment is subsequently applied to further booster its mechanical strength (6.6 MPa) and swelling stability. The optimized sample of C-PVA/HAp (10 wt% nano-HAp) artificial periosteum features excellent biocompatibility and remarkable in vitro mineralization. Cell experiments demonstrate that its effectively boasted cell modulation for enhanced osteogenesis without the aid of growth factors, showing a possible activation of the ERK/MAPK signaling pathway. This work provides an effective strategy for designing novel HAp nano-additives and expands the possibility of biomimetic fabrication for more advanced nanofiber-based artificial periosteum.

Clinical outcomes of gingivoperiosteoplasty for unilateral cleft lip and palate performed in early childhood.

Conventional gingivoperiosteoplasty (GPP) performed during infancy adversely affects maxillary development. However, the outcomes of this procedure in early childhood have rarely been reported. Therefore, we examined the postoperative outcomes of GPP conducted in patients aged 1.5 years with unilateral cleft lip and palate (UCLP). This study included 87 non-syndromic patients with complete UCLP who had undergone early two-stage palatoplasty during the 1999-2004 period. The protocol comprised soft palate plasty at 1 year of age and hard palate closure at 1.5 years of age. In the GPP group (n = 34), we introduced the GPP procedure during hard palate closure; in the non-GPP group (n = 53), the labial side of the alveolar cleft remained intact. We examined computed tomography images taken at 8 years of age to observe bone formation at the alveolar cleft site. We also conducted cephalometric analysis to examine maxillary development at 12 years of age. Bone bridges at the alveolar cleft site were observed in 92% and 5.6% of the GPP and non-GPP groups, respectively. Moreover, 56% of the GPP group did not require secondary alveolar bone grafting (sABG), whereas all the patients in the non-GPP group underwent sABG. No statistically significant differences were noted in the maxillary anteroposterior length (GPP: 45.5 ± 3.7 mm, non-GPP: 45.9 ± 3.5 mm, p = 0.67) and sella-nasion-point A angle (GPP: 75.6 ± 4.5°, non-GPP: 73.8 ± 12.6°, p = 0.49). This study's findings suggest that GPP performed at 1.5 years of age minimises the necessity of sABG and does not exert a negative influence on maxillofacial development.

Developing long bones respond to surrounding tissues by trans-pairing of periosteal osteoclasts and endocortical osteoblasts.

Developing long bones alter their shape while maintaining uniform cortical thickness via coordinated activity of bone-forming osteoblasts and bone-resorbing osteoclasts at periosteal and endosteal surfaces, a process we designate trans-pairing. Two types of trans-pairing shift cortical bone in opposite orientations: peri-forming trans-pairing (peri-t-p) increases bone marrow space and endo-forming trans-pairing (endo-t-p) decreases it, via paired activity of bone resorption and formation across the cortex. Here, we focused on endo-t-p in growing bones. Analysis of endo-t-p activity in the cortex of mouse fibulae revealed osteoclasts under the periosteum compressed by muscles, and expression of RANKL in periosteal cells of the cambium layer. Furthermore, mature osteoblasts were localized on the endosteum, while preosteoblasts were at the periosteum and within cortical canals. X-ray tomographic microscopy revealed the presence of cortical canals more closely associated with endo- than with peri-t-p. Sciatic nerve transection followed by muscle atrophy and unloading induced circumferential endo-t-p with concomitant spread of cortical canals. Such canals likely supply the endosteum with preosteoblasts from the periosteum under endo-t-p, allowing bone shape to change in response to mechanical stress or nerve injury.

Free vascularized medial femoral condyle periosteal flaps in the ankle and foot region: A narrative review.

OBJECTIVES: The objective of this study was to determine the role and reliability of the free medial femoral condyle (MFC) flap (MFCF) in demanding foot and ankle reconstruction procedures. MATERIALS AND METHODS: A search of the MEDLINE, PubMed, and Embase electronic databases was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines between January 2008 and September 2023. Articles concerning free MFC bone flaps for reconstruction of the foot and ankle regions were included. Outcomes of interest included flap failure, complications, union rate, time to union, and functional scores. RESULTS: Twenty studies involving 131 patients met the inclusion criteria. The most common clinical indications for the free MFCF were nonunion, avascular necrosis, and osteomyelitis. The most common sites of nonunion were tibiotalar arthrodesis (50%) and subtalar arthrodesis (33%). Overall, the bony union rate was 93.1%, with a mean time to union of 14.6±0.1 weeks. There were no flap failures reported. Postoperative complications were observed in 39 (29.7%) cases (e.g., delayed donor site wound healing, flap debulking, medial condyle osteonecrosis, and donor site numbness), with 21 (16%) patients requiring further operative intervention. No major donor or recipient site morbidity occurred, except for one case. CONCLUSION: Free MFCFs offer a versatile and dependable choice for cases of foot and ankle reconstruction, displaying favorable rates of bone fusion and acceptable complication rates. Existing literature indicates that MFC reconstruction in the foot and ankle is not associated with significant morbidity at the donor or recipient sites. The pooled data demonstrated a 93% success rate in achieving bone fusion in the foot and ankle region, supporting the view that it can be considered another option of treatment.

Laser-assisted bioprinting of targeted cartilaginous spheroids for high density bottom-up tissue engineering.

Multicellular spheroids such as microtissues and organoids have demonstrated great potential for tissue engineering applications in recent years as these 3D cellular units enable improved cell-cell and cell-matrix interactions. Current bioprinting processes that use multicellular spheroids as building blocks have demonstrated limited control on post printing distribution of cell spheroids or moderate throughput and printing efficiency. In this work, we presented a laser-assisted bioprinting approach able to transfer multicellular spheroids as building blocks for larger tissue structures. Cartilaginous multicellular spheroids formed by human periosteum derived cells (hPDCs) were successfully bioprinted possessing high viability and the capacity to undergo chondrogenic differentiation post printing. Smaller hPDC spheroids with diameters ranging from ∼100 to 150µm were successfully bioprinted through the use of laser-induced forward transfer method (LIFT) however larger spheroids constituted a challenge. For this reason a novel alternative approach was developed termed as laser induced propulsion of mesoscopic objects (LIPMO) whereby we were able to bioprint spheroids of up to 300µm. Moreover, we combined the bioprinting process with computer aided image analysis demonstrating the capacity to 'target and shoot', through automated selection, multiple large spheroids in a single sequence. By taking advantage of target and shoot system, multilayered constructs containing high density cell spheroids were fabricated.

Periosteal expansion osteogenesis using a tubular dynamic frame device: An experimental study in rats.

Periosteal expansion osteogenesis (PEO) is a technique for augmenting bone by creating a gradual separation between the bone and periosteum. This study assessed PEO-induced bone formation around the femurs of rats using a dynamic frame device (DFD), consisting of a shape memory membrane made of polyethylene terephthalate (PET) formed into a tubular shape. The DFDs, consisting of a PET membrane coated with hydroxyapatite (HA)/gelatin on the bone-contact surface, were inserted between the periosteum and bone of the femurs of rats. In the experimental group, DFDs were suture-fixed to the femur with 4-0 Vicryl Rapid; in the control group, 4-0 silk thread was used for fixation. Five rats per group were euthanized at intervals of 3, 5, and 8 weeks postoperatively. Bone formation was evaluated via micro-CT imaging, histomorphometry, and histological analysis. Morphological analysis revealed new bone between the femur and the periosteum, expanded by the DFD, in all groups. The mean values of new bone were 0.30 mm2 proximally, 0.18 mm2 centrally, and 0.82 mm2 distally in the control group, compared to 1.05 mm2 proximally, 0.27 mm2 centrally, and 0.84 mm2 distally in the experimental group. A significant difference in new bone was observed in the proximal region of the experimental group. Histological examination showed that a single layer of newly formed neoplastic bone was noted on the cortical bone surface across all sites. The proximal portion displayed a bone marrow cavity at the center, encircled by a thick bone cortex with a layered structure. New bone formation was notable between existing cortical bone and the periosteum, particularly at both ends of the DFD. The use of PET in PEO was a viable option for achieving ideal bone morphology.

Osteoperiosteal fibular strut grafting - A technique to improve union rates.

PURPOSE: Gap non-union of long bones are challenging problems in orthopaedic patients. Non-vascularized fibular grafting is a simple, cost effective, single stage procedure and is an accepted method of reconstruction for gap non unions in children. However, there is a risk of non-union when a long avascular strut of fibula is used. The periosteum, by itself has high biological activity and is helpful in osteointegration. Harvesting the fibula with the periosteum gives the advantage of mechanical and biological support in a gap non-union. METHODS: During 2020 to 2022, 13 patients presented to us with gap nonunion of long bones due to various aetiology. The mean age of the patients was six years with a mean bone gap of 4.2 cm. A modified technique of harvesting the fibula with the periosteum is described. The graft was stabilized with the recipient bone by intra medullary or extra medullary implants. RESULTS: Union occurred in average 12.7 weeks in all except one patient with congenital pseudoarthrosis of tibia. The fibula on the harvest site regenerated completely in all other patients. One patient had a superficial infection. Children were followed were an average of 17.5 months and there was no incidence of graft resorption or fracture. Osteoperiosteal fibula graft is a simple, effective and cost-effective procedure for the treatment of gap non-unions in children. It offers the advantage of both biological and mechanical support, with high union rates and low complication rates.

Personalized PLGA/BCL Scaffold with Hierarchical Porous Structure Resembling Periosteum-Bone Complex Enables Efficient Repair of Bone Defect.

Using bone regeneration scaffolds to repair craniomaxillofacial bone defects is a promising strategy. However, most bone regeneration scaffolds still exist some issues such as a lack of barrier structure, inability to precisely match bone defects, and necessity to incorporate biological components to enhance efficacy. Herein, inspired by a periosteum-bone complex, a class of multifunctional hierarchical porous poly(lactic-co-glycolic acid)/baicalein scaffolds is facilely prepared by the union of personalized negative mold technique and phase separation strategy and demonstrated to precisely fit intricate bone defect cavity. The dense up-surface of the scaffold can prevent soft tissue cell penetration, while the loose bottom-surface can promote protein adsorption, cell adhesion, and cell infiltration. The interior macropores of the scaffold and the loaded baicalein can synergistically promote cell differentiation, angiogenesis, and osteogenesis. These findings can open an appealing avenue for the development of personalized multifunctional hierarchical materials for bone repair.

[Isolation and characterization of normal mandibular periosteal stem cells from human and macaca mulatta and cross-species single-cell analysis].

Objective: To investigate the presence of a distinct stem cell populations different from mesenchymal stem cells in the mandibular periosteum of both human and non-human primates (macaca mulatta), to explore its properties during intramembranous osteogenesis and to establish standard protocols for the isolation, culturing and expanding of mandibular periosteal stem cells (PSC) distinguished from other PSCs in other anatomical regions. Methods: Periosteum was harvested from the bone surface during flap bone removal in patients aged 18-24 years undergoing third molar extraction and from the buccal side of the mandibular premolar region of 6-year-old macaca mulatta respectively, and then subjected to single-cell sequencing using the Illumina platform Novaseq 6000 sequencer. Cross-species single-cell transcriptome sequencing results were compared using homologous gene matching. PSC were isolated from primary tissues using two digestion methods with body temperature and low temperature, and their surface markers (CD200, CD31, CD45 and CD90) were identified by cell flow cytometry. The ability of cell proliferation and three-lineage differentiation of PSC expanded to the third generation in vitro in different species were evaluated. Finally, the similarities and differences in osteogenic properties of PSC and bone marrow mesenchymal stem cells (BMSC) were compared. Results: The single-cell sequencing results indicated that 18 clusters of cell populations were identified after homologous gene matching for dimensionality reduction, and manual cellular annotation was conducted for each cluster based on cell marker databases. The comparison of different digestion protocols proved that the low-temperature overnight digestion protocol can stably isolate PSC from the human and m. mulatta mandibular periosteum and the cells exhibited a fibroblast-like morphology. This research confirmed that PSC of human and m. mulatta had similar proliferation capabilities through the cell counting kit-8 assay. Flow cytometry analysis was then used to identify the cells isolated from the periosteum expressed CD200(+), CD31(-), CD45(-), CD90(-). Then, human and m. mulatta PSC were induced into osteogenesis, adipogenesis, and chondrogenesis to demonstrate their corresponding multi-lineage differentiation capabilities. Finally, comparison with BMSC further clarified the oesteogenesis characteristics of PSC. The above experiments proved that the cells isolated from the periosteum were peiosteal cells with characteristics of stem cells evidenced by their cell morphology, proliferation ability, surface markers, and differentiation ability, and that this group of PSC possessed characteristics different from traditional mesenchymal stem cells. Conclusions: In this study, normal mandibular PSC from humans and m. mulatta were stably isolated and identified for the first time, providing a cellular foundation for investigating the mechanism of mandibular intramembranous osteogenesis, exploring ideal non-human primate models and establishing innovative strategies for clinically mandibular injury repair.

Dynamic Transcriptome Analysis of SFRP Family in Guided Bone Regeneration With Occlusive Periosteum in Swine Model.

BACKGROUND: A variety of congenital or acquired conditions can cause craniomaxillofacial bone defects, resulting in a heavy financial burden and psychological stress. Guided bone self-generation with periosteum-preserved has great potential for reconstructing large bone defects. METHODS: A swine model of guided bone regeneration with occlusive periosteum was established, the rib segment was removed, and the periosteum was sutured to form a closed regeneration chamber. Hematoxylin and eosin staining, Masson's staining, and Safranine O-Fast Green staining were done. Nine-time points were chosen for collecting the periosteum and regenerated bone tissue for gene sequencing. The expression level of each secreted frizzled-related protein (SFRP) member and the correlations among them were analyzed. RESULTS: The process of bone regeneration is almost complete 1 month after surgery, and up to 1 week after surgery is an important interval for initiating the process. The expression of each SFRP family member fluctuated greatly. The highest expression level of all members ranged from 3 days to 3 months after surgery. The expression level of SFRP2 was the highest, and the difference between 2 groups was the largest. Secreted frizzled-related protein 2 and SFRP4 showed a notable positive correlation between the control and model groups. Secreted frizzled-related protein 1, SFRP2, and SFRP4 had a significant spike in fold change at 1 month postoperatively. Secreted frizzled-related protein 1 and SFRP2 had the strongest correlation. CONCLUSIONS: This study revealed the dynamic expression of the SFRP family in guided bone regeneration with occlusive periosteum in a swine model, providing a possibility to advance the clinical application of bone defect repair.

An enhanced tri-layer bionic periosteum with gradient structure loaded by mineralized collagen for guided bone regeneration and in-situ repair.

Severe fracture non-union often accompanied by damaged or even absent periosteum remains a significant challenge. This paper presents a novel tri-layer bionic periosteum with gradient structure and mineralized collagen (MC) mimics natural periosteum for in-situ repair and bone regeneration. The construct with ultrasonic polylactic acid as the loose outer fibrous layer (UPLA), poly(ε-caprolactone) as the intermediate barrier layer (PCL-M), and poly(ε-caprolactone)/MC as the inner osteoblastic layer (PM) was prepared. The physicochemical properties of layers were investigated. UPLA/PCL-M/PM exhibited a tensile strength (3.55 ± 0.23 MPa) close to that of natural periosteum and excellent adhesion between the layers. In vitro experiments demonstrated that all layers had no toxicity to cells. UPLA promoted inward growth of mouse fibroblasts. PCL-M with a uniform pore size (2.82 ± 0.05 µm) could achieve a barrier effect against fibroblasts according to the live/dead assay. Meanwhile, PM could effectively promote cell migration with high alkaline phosphatase expression and significant mineralization of the extracellular matrix. Besides, in vivo experiments showed that UPLA/PCL-M/PM significantly promoted the regeneration of bone and early angiogenesis. Therefore, this construct with gradient structure developed in this paper would have great application potential in the efficient and high-quality treatment of severe fractures with periosteal defects.

Dissolving magnesium hydroxide implants enhance mainly cancellous bone formation whereas degrading RS66 implants lead to prominent periosteal bone formation in rabbits.

Bone fractures often require internal fixation using plates or screws. Normally, these devices are made of permanent metals like titanium providing necessary strength and biocompatibility. However, they can also cause long-term complications and may require removal. An interesting alternative are biocompatible degradable devices, which provide sufficient initial strength and then degrade gradually. Among other materials, biodegradable magnesium alloys have been developed for craniofacial and orthopaedic applications. Previously, we tested implants made of magnesium hydroxide and RS66, a strong and ductile ZK60-based alloy, with respect to biocompatibility and degradation behaviour. Here, we compare the effects of dissolving magnesium hydroxide and RS66 cylinders on bone regeneration and bone growth in rabbit condyles using microtomographical and histological analysis. Both magnesium hydroxide and RS66 induced a considerable osteoblastic activity leading to distinct but different spatio-temporal patterns of cancellous and periosteal bone growth. Dissolving RS66 implants induced a prominent periosteal bone formation on the medial surface of the original condyle whereas dissolving magnesium hydroxide implants enhance mainly cancellous bone formation. Especially periosteal bone formation was completed after 6 and 8 weeks, respectively. The observed bone promoting functions are in line with previous reports of magnesium stimulating cancellous and periosteal bone growth and possible underlying signalling mechanisms are discussed. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium based implants are promising candidates for use in orthopedic and traumatic surgery. Although these implants are in the scientific focus for a long time, comparatively little is known about the interactions between degrading magnesium and the biological environment. In this work, we investigated the effects of two degrading cylindrical magnesium implants (MgOH2 and RS66) both on bone regeneration and on bone growth. Both MgOH2 and RS66 induce remarkable osteoblastic activities, however with different spatio-temporal patterns regarding cancellous and periosteal bone growth. We hypothesize that degradation products do not diffuse directionless away, but are transported by the restored blood flow in specific spatial patterns which is also dependent on the used surgical technique.

Reconstruction of congenital pseudarthrosis of the radius with a vascularized tibial periosteal transplant: A case report.

Congenital pseudarthrosis of the forearm poses a considerable challenge because of its rarity. The objective of this report is to introduce a novel surgical technique for its treatment. Here, we document a case of congenital pseudarthrosis of the radius in a 3-year-old boy diagnosed with type-1 neurofibromatosis. The surgical treatment involved the excision of approximately 9 cm of native radial periosteum and a bifocal radius osteotomy, which was supplemented with a vascularized tibial periosteal transplant to facilitate bone healing. Anastomosis between the anterior tibial vessels and radial vessels was performed. No immediate or late postoperative complications were observed. After 3 weeks, a robust callus formation was observed, and during a follow-up examination 3 years and 4 months later, a wide range of active forearm rotation was noted. This report suggests that vascularized periosteal flaps show promise as a viable treatment option for congenital pseudarthrosis of the forearm. They offer an alternative to vascularized fibular grafts or single-bone forearm constructs.

In Vitro Cell Surface Marker Expression on Mesenchymal Stem Cell Cultures does not Reflect Their Ex Vivo Phenotype.

Cell surface marker expression is one of the criteria for defining human mesenchymal stem or stromal cells (MSC) in vitro. However, it is unclear if expression of markers including CD73 and CD90 reflects the in vivo origin of cultured cells. We evaluated expression of 15 putative MSC markers in primary cultured cells from periosteum and cartilage to determine whether expression of these markers reflects either the differentiation state of cultured cells or the self-renewal of in vivo populations. Cultured cells had universal and consistent expression of various putative stem cell markers including > 95% expression CD73, CD90 and PDPN in both periosteal and cartilage cultures. Altering the culture surface with extracellular matrix coatings had minimal effect on cell surface marker expression. Osteogenic differentiation led to loss of CD106 and CD146 expression, however CD73 and CD90 were retained in > 90% of cells. We sorted freshly isolated periosteal populations capable of CFU-F formation on the basis of CD90 expression in combination with CD34, CD73 and CD26. All primary cultures universally expressed CD73 and CD90 and lacked CD34, irrespective of the expression of these markers ex vivo indicating phenotypic convergence in vitro. We conclude that markers including CD73 and CD90 are acquired in vitro in most 'mesenchymal' cells capable of expansion. Overall, we demonstrate that in vitro expression of many cell surface markers in plastic-adherent cultures is unrelated to their expression prior to culture.