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Keywords = recalcitrant nonunions

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10 pages, 5031 KB  
Case Report
Double Microsurgical Corticoperiosteal Free Flap from Bilateral Medial Femoral Condyles for the Treatment of Forearm Nonunions: A Case Report
by Matteo Guzzini, Alice Patrignani and Susanna Pagnotta
Surgeries 2026, 7(2), 74; https://doi.org/10.3390/surgeries7020074 - 18 Jun 2026
Viewed by 482
Abstract
Background: Forearm nonunions represent a challenging clinical condition that significantly impairs upper limb function. Various surgical techniques have been proposed, including vascularized bone grafts. Although these procedures are not considered first-line treatment, they play a crucial role in complex or recalcitrant cases, particularly [...] Read more.
Background: Forearm nonunions represent a challenging clinical condition that significantly impairs upper limb function. Various surgical techniques have been proposed, including vascularized bone grafts. Although these procedures are not considered first-line treatment, they play a crucial role in complex or recalcitrant cases, particularly after failure of conventional methods, where their superior biological potential can significantly enhance bone healing. Despite the widespread use of the medial femoral condyle corticoperiosteal flap, simultaneous bilateral harvest has not been previously described in the literature. Case Presentation: We report the case of a 50-year-old male presenting with persistent nonunions of both the radius and ulna following previous osteosynthesis and revision surgery with iliac crest bone graft. The patient was successfully treated using bilateral vascularized corticoperiosteal free flaps harvested from both medial femoral condyles. Conclusions: Double vascularized corticoperiosteal free flaps may represent an effective and reliable option for the treatment of complex forearm nonunions, especially in cases with multiple previous surgical failures. To the best of our knowledge, this case represents the first report of simultaneous bilateral medial femoral condyle corticoperiosteal flap harvest. Full article
(This article belongs to the Section Hand Surgery and Research)
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15 pages, 11419 KB  
Article
Reconstructive Strategies in Post-Traumatic Osteomyelitis of the Lower Limb: A Case Series and Surgical Algorithm Analysis
by Marta Jagosz, Piotr Węgrzyn, Michał Chęciński, Maja Smorąg, Jędrzej Króliński, Szymon Manasterski, Patryk Ostrowski and Ahmed Elsaftawy
J. Clin. Med. 2025, 14(19), 6746; https://doi.org/10.3390/jcm14196746 - 24 Sep 2025
Cited by 4 | Viewed by 4332
Abstract
Background: Post-traumatic osteomyelitis (PTO) of the lower extremity is among the most demanding problems in orthoplastic reconstructive surgery. It typically follows open fractures, failed osteosynthesis, or implant infection. Effective management requires coordinated infection control, stable skeletal fixation, and timely vascularized soft-tissue coverage. Methods: [...] Read more.
Background: Post-traumatic osteomyelitis (PTO) of the lower extremity is among the most demanding problems in orthoplastic reconstructive surgery. It typically follows open fractures, failed osteosynthesis, or implant infection. Effective management requires coordinated infection control, stable skeletal fixation, and timely vascularized soft-tissue coverage. Methods: We conducted a retrospective case series of 20 consecutive patients with PTO of the lower limb treated between 2021 and 2024 at a tertiary orthoplastic center. All patients underwent radical debridement, culture-directed intravenous antibiotic administration, and soft-tissue reconstruction using local muscle, fasciocutaneous, or free flaps; vascularized bone flaps were used to select nonunion cases. The primary outcomes were flap survival, complications, infection resolution, and limb salvage. Exploratory analyses included descriptive subgroup summaries by flap category. Results: Among 20 patients (15 men, 5 women; mean age 53.6 years), reconstructions included reverse/pedicled sural flaps (n = 9), hemisoleus muscle flaps (n = 7), medial gastrocnemius muscle flaps (n = 2), peroneus brevis muscle flaps (n = 2), and free flaps (n = 6), which comprised anterolateral thigh (ALT), medial femoral condyle (MFC) osteoperiosteal, deep circumflex iliac artery (DCIA) osteocutaneous, and radial forearm free flaps (RFFFs). Single-flap reconstructions were performed in 13 cases, whereas multistage/multiflap strategies were used in 7. Overall flap survival was 90%. Major flap complications comprised partial necrosis in two reverse sural flaps and one complete loss of a reverse sural flap; two patients had minor wound dehiscence. Infection resolved in 18/20 patients (90%; 95% CI ≈ 0.70–0.97). One patient requested below-knee amputation due to persistent nonunion associated with a pathological fracture. At a mean 10-month follow-up, all limb-salvaged patients were ambulatory. Conclusions: Effective reconstruction of PTO is improved by using a patient-specific algorithm that considers the defect location, vascular status, and host comorbidities. Local muscle and fasciocutaneous flaps remain dependable for most defects, with free or vascularized bone flaps reserved for composite or recalcitrant cases. Early referral to high-volume centers, radical debridement, and orthoplastic collaboration are critical for optimizing limb salvage. Our findings should be interpreted in light of the study’s retrospective design and small sample size. Full article
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20 pages, 3629 KB  
Article
An Autologous Human Adipose Stem Cell-Derived 3D Osteogenic Implant for Bone Grafting: From Development to First-in-Human Experience
by Torsten Gerich, Pierre-Louis Docquier, John A. Carrino, Mikael Boesen, Nadine Schmid, Ginny Hsu, Ji-Hye Yea, Aaron James, Judy Ashworth, Hara Episkopou and Denis Dufrane
J. Clin. Med. 2025, 14(18), 6436; https://doi.org/10.3390/jcm14186436 - 12 Sep 2025
Cited by 1 | Viewed by 1505
Abstract
Background: NVD003 is an autologous, adipose tissue-derived stem cell-based tissue-engineered bone graft substitute with pro-osteogenic, anti-resorptive, and pro-angiogenic properties. Here, we describe highlights from the NVD003 preclinical development program as well as early clinical experience. Methods: NVD003 is produced in a Good Manufacturing [...] Read more.
Background: NVD003 is an autologous, adipose tissue-derived stem cell-based tissue-engineered bone graft substitute with pro-osteogenic, anti-resorptive, and pro-angiogenic properties. Here, we describe highlights from the NVD003 preclinical development program as well as early clinical experience. Methods: NVD003 is produced in a Good Manufacturing Practice-controlled process from adipose stem cells collected during a minimally invasive liposuction procedure. The final implant is a ready-to-use moldable putty with fixed mineral content and predefined physiologic ranges of osteogenic cells and bioactive growth factors. Preclinical pharmacology studies were conducted in nude rats using a paravertebral implantation model, and subsequently, in a femoral critical-sized bone defect (CSBD) model. In a first-in-human Phase 1b/2a study, NVD003 was used for fracture osteosynthesis with classical fixation material in nine adults with recalcitrant lower limb non-union. NVD003 was also used at the discretion of treating physicians in four pediatric patients surgically treated for congenital pseudarthrosis of the tibia (CPT) with the Masquelet technique. Efficacy was evaluated as clinical healing and in terms of bone formation, bone union, and bone remodeling on radiographs and computed tomography using the extended Lane and Sandhu Scale. Results: Preclinical studies indicated that NVD003 requires cellularity for its bioactivity and moreover facilitates bone union when used as a graft material in femoral CSBD. In the clinical study, nine adult participants were successfully grafted with NVD003 and completed study follow-up to 24 months, with extended safety follow-up to 5 years ongoing. No adverse events were considered related to NVD003. Maximal bone formation occurred between 3 and 12 months post-implantation; the mean time to clinical healing was 6 months and the mean time to radiological union was 17 months. Ultimately, 89% (8/9) of patients achieved bone union without refracture. All four pediatric patients with CPT also achieved lasting bone union following grafting with NVD003. No safety signals were observed over a mean follow-up of 62.1 months. Conclusions: NVD003 represents a safe, autologous bone graft substitute product without side effects of heterotopic ossification or bone resorption. NVD003 facilitated bone union in adult and pediatric patients even under severe pathophysiological conditions. Full article
(This article belongs to the Special Issue Clinical Therapeutic Advances in Bone Fractures)
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455 KB  
Article
Treatment of Recalcitrant Isolated Congenital Fibular Pseudarthrosis: Fibular Segment Transfer and Tibiofibular Synostosis with Unilateral External Fixator
by Damla Fidan Yamanel, Bedri Karaismailoglu and Turgut Nedim Karaismailoglu
J. Am. Podiatr. Med. Assoc. 2023, 113(6), 21255; https://doi.org/10.7547/21-255 - 1 Nov 2023
Cited by 1 | Viewed by 136
Abstract
Isolated congenital pseudarthrosis of the fibula is a rare entity with a limited number of cases reported in the literature. Treatment is challenging because of recalcitrant nonunion and because no consensus about the best treatment plan exists. We report a case of isolated [...] Read more.
Isolated congenital pseudarthrosis of the fibula is a rare entity with a limited number of cases reported in the literature. Treatment is challenging because of recalcitrant nonunion and because no consensus about the best treatment plan exists. We report a case of isolated congenital fibular pseudarthrosis with valgus deformity of the ankle. The patient had a history of two failed operations. We used a novel surgical plan that combined tibiofibular synostosis with fibular segment transfer through a unilateral external fixator. The patient showed good early results with fibular union. We advocate the combination of tibiofibular synostosis and fibular segment transfer to restore the integrity and stability of the ankle in recalcitrant isolated congenital fibular pseudarthrosis cases with a history of failed surgery. Full article
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11 pages, 900 KB  
Review
Bone Healing Materials in the Treatment of Recalcitrant Nonunions and Bone Defects
by Emérito Carlos Rodríguez-Merchán
Int. J. Mol. Sci. 2022, 23(6), 3352; https://doi.org/10.3390/ijms23063352 - 20 Mar 2022
Cited by 77 | Viewed by 6749
Abstract
The usual treatment for bone defects and recalcitrant nonunions is an autogenous bone graft. However, due to the limitations in obtaining autogenous bone grafts and the morbidity associated with their procurement, various bone healing materials have been developed in recent years. The three [...] Read more.
The usual treatment for bone defects and recalcitrant nonunions is an autogenous bone graft. However, due to the limitations in obtaining autogenous bone grafts and the morbidity associated with their procurement, various bone healing materials have been developed in recent years. The three main treatment strategies for bone defects and recalcitrant nonunions are synthetic bone graft substitutes (BGS), BGS combined with bioactive molecules, and BGS and stem cells (cell-based constructs). Regarding BGS, numerous biomaterials have been developed to prepare bone tissue engineering scaffolds, including biometals (titanium, iron, magnesium, zinc), bioceramics (hydroxyapatite (HA)), tricalcium phosphate (TCP), biopolymers (collagen, polylactic acid (PLA), polycaprolactone (PCL)), and biocomposites (HA/MONs@miR-34a composite coating, Bioglass (BG)-based ABVF-BG (antibiotic-releasing bone void filling) putty). Bone tissue engineering scaffolds are temporary implants that promote tissue ingrowth and new bone regeneration. They have been developed to improve bone healing through appropriate designs in terms of geometric, mechanical, and biological performance. Concerning BGS combined with bioactive molecules, one of the most potent osteoinductive growth factors is bone morphogenetic proteins (BMPs). In recent years, several natural (collagen, fibrin, chitosan, hyaluronic acid, gelatin, and alginate) and synthetic polymers (polylactic acid, polyglycolic acid, polylactic-coglycolide, poly(e-caprolactone) (PCL), poly-p-dioxanone, and copolymers consisting of glycolide/trimethylene carbonate) have been investigated as potential support materials for bone tissue engineering. Regarding BGS and stem cells (cell-based constructs), the main strategies are bone marrow stromal cells, adipose-derived mesenchymal cells, periosteum-derived stem cells, and 3D bioprinting of hydrogels and cells or bioactive molecules. Currently, significant research is being performed on the biological treatment of recalcitrant nonunions and bone defects, although its use is still far from being generalized. Further research is needed to investigate the efficacy of biological treatments to solve recalcitrant nonunions and bone defects. Full article
(This article belongs to the Special Issue Research on Bone Healing Materials)
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14 pages, 297 KB  
Review
A Review of Recent Developments in the Molecular Mechanisms of Bone Healing
by Emerito Carlos Rodríguez-Merchán
Int. J. Mol. Sci. 2021, 22(2), 767; https://doi.org/10.3390/ijms22020767 - 14 Jan 2021
Cited by 46 | Viewed by 8434
Abstract
Between 5 and 10 percent of fractures do not heal, a condition known as nonunion. In clinical practice, stable fracture fixation associated with autologous iliac crest bone graft placement is the gold standard for treatment. However, some recalcitrant nonunions do not resolve satisfactorily [...] Read more.
Between 5 and 10 percent of fractures do not heal, a condition known as nonunion. In clinical practice, stable fracture fixation associated with autologous iliac crest bone graft placement is the gold standard for treatment. However, some recalcitrant nonunions do not resolve satisfactorily with this technique. For these cases, biological alternatives are sought based on the molecular mechanisms of bone healing, whose most recent findings are reviewed in this article. The pro-osteogenic efficacy of morin (a pale yellow crystalline flavonoid pigment found in old fustic and osage orange trees) has recently been reported, and the combined use of bone morphogenetic protein-9 (BMP9) and leptin might improve fracture healing. Inhibition with methyl-piperidino-pyrazole of estrogen receptor alpha signaling delays bone regeneration. Smoking causes a chondrogenic disorder, aberrant activity of the skeleton’s stem and progenitor cells, and an intense initial inflammatory response. Smoking cessation 4 weeks before surgery is therefore highly recommended. The delay in fracture consolidation in diabetic animals is related to BMP6 deficiency (35 kDa). The combination of bioceramics and expanded autologous human mesenchymal stem cells from bone marrow is a new and encouraging alternative for treating recalcitrant nonunions. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bone Healing)
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