Bone Cyst Formation Research Articles

Results of the osteochondral autologous transplantation for treatment of osteochondral lesions of the talus with harvesting from the ipsilateral talar articular facets.

There are few studies on the clinical outcomes of osteochondral autologous transplantation (OAT) harvesting from local talar non-weight-bearing articular facets for the treatment of osteochondral lesions of the talus (OLTs). The purpose of this study was to review the short- to midterm outcomes of our patients who were treated with OAT harvesting from ipsilateral talar articular facets for OLTs. Between December 2010 and November 2018, 24 patients were enrolled in this study. There were 16 males and eight females with an average age of 39.1years and a follow-up period of 50.9months. The clinical results were evaluated according to the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score and the visual analogue scale (VAS) score. Pre-operative plain radiographs and magnetic resonance imaging (MRI) scans, post-operative radiographs, and X-ray and computed tomography (CT) scans at the last follow-up were observed. There was a significant improvement in the AOFAS score from 61.3 ± 19.0 pre-operatively to 84.9 ± 9.2 post-operatively (P < 0.001). The VAS score improved from 6.1 ± 2.3 to 2.0 ± 1.4 at the last follow-up (P < 0.001). Twenty-one patients (87.5%) were satisfied with their clinical results. By the last follow-up CT scan, there was bone cyst formation at the donor sites in three patients, at the recipient sites in five patients and at both sites in five patients. Two patients (8.3%) underwent re-operation with arthroscopic debridement because of medial gutter hypertrophic soft tissue impingement. OAT harvesting from the ipsilateral talar articular facet showed satisfactory results. The mean post-operative VAS score and AOFAS ankle-hindfoot score improved significantly. Post-operative impingement around the osteotomy site was the main complication and reason for re-operation after the index procedure. In addition, bone cysts at the recipient and/or donor site(s) were found with a large percentage under CT. Therefore, longer follow-up is necessary to determine the long-term clinical results for this technique.

Navigation-guided nasal endoscopic surgery for acute vision loss caused by fibrous dysplasia: a case report and review of literatures

BackgroundBone fibrous dysplasia is a benign disease of bone tissue dysplasia. Vision impairment is the commonest neurological complication of craniofacial fibrous dysplasia. Most of the vision loss caused by craniofacial fibrous dysplasia is usually a gradual process. Very few present with acute visual impairment as described in our case.Case presentationWe report a patient with fibrous dysplasia presenting rapidly progressive visual loss in the left eye secondary to bone cyst formation. Transnasal endoscopic surgery guided by navigation with drainage and curettage of this bone cyst and orbital decompression resulted in progressive improvement in visual acuity that returned to normal 1 month post-operatively.ConclusionsIn cases with acute visual loss due to fibrous dysplasia, emergency surgical treatment should be considered to preserve vision. In the surgical approach, navigation-guided nasal endoscopic surgery may be preferred because of its advantages.

The Effect of Bone Marrow Stimulation for Cartilage Repair on the Subchondral Bone Plate.

PurposeTo investigate the effect of bone-marrow stimulation (BMS) on subchondral bone plate morphology and remodeling compared to untreated subchondral bone in a validated minipig model.MethodsThree Göttingen minipigs received BMS with drilling as treatment for two chondral defects in each knee. The animals were euthanized after six months. Follow-up consisted of a histological semiquantitative evaluation using a novel subchondral bone scoring system and micro computed tomography (µCT) of the BMS subchondral bone. The histological and microstructural properties of the BMS-treated subchondral bone were compared to that of the adjacent healthy subchondral bone.ResultsThe µCT analysis showed that subchondral bone treated with BMS had significantly higher connectivity density compared to adjacent untreated subchondral bone (26 1/mm3 vs. 21 1/mm3, P = 0.048). This was the only microstructural parameter showing a significant difference. The histological semiquantitative score differed significantly between the subchondral bone treated with BMS and the adjacent untreated subchondral (8.0 vs. 10 P = < 0.001). Surface irregularities were seen in 43% and bone overgrowth in 27% of the histological sections. Only sparse formation of bone cysts was detected (1%).ConclusionsBMS with drilling does not cause extensive changes to the subchondral bone microarchitecture. Furthermore, the morphology of BMS subchondral bone resembled that of untreated subchondral bone with almost no formation of bone cyst, but some surface irregularities and bone overgrowth.

Anatomical Features and Pathologies in Orthopantomogram

One of the most commonly utilized plain film tomographic scans is the orthopantomogram. Dentists frequently request an OPG as a screening tool. Due to its accurate depiction of the jaws and entire dentition, it is also a powerful diagnostic instrument for determining pathology such as dental disease, cysts, maxillofacial trauma, and dental emergencies. For patients of pediatric age and adults, the examination of the masticatory normal anatomy during OPG differs. The adult tooth's radiographic anatomy, which is accessible by OPT, lacks the same level of granularity as the radiographic anatomy assessed by intraoral radiographs. Even though resolution is not as precise as intra-oral radiographs for the examination of the teeth, major alterations in the calcification of the tooth structure and alterations in the maxillary and mandibular ossifications can help identify dental disease, like caries (decay), periodontal bone resorption, abscessual lesions and cyst formation. The main anatomical characteristics of an OPG are described in this article, along with some typical pathologies that might be present. Unless a methodical technique is adopted to explore the structures present, the viewer may find the vast amount of data visible on an OPG to be overwhelming. As the mandibular plane and dentition are distorted due to straightening of the curve, the observer is presented with a broader view of these structures but requires them to be reinterpreted to enable the observer to fully appreciate the image in three dimensions.

Research progress of bone marrow edema-like lesions in knee osteoarthritis

Knee osteoarthritis-associated bone marrow edema-like lesions (KOA-BMLs) is a common MRI imaging feature, which is mainly manifested as abnormal bone marrow hyperintensity in subchondral bone on T2 imaging. The formation of KOA-BMLs may be related to the abnormality of lower limb force line and subchondral bone perfusion, and related histopathological studies showed that the remodeling of bone and bone marrow in these damaged areas was abnormally increased. In KOA patients, the size of BMLs can fluctuate or even disappear in a relatively short period of time, and was closely related to pain, subchondral bone cyst formation, and the progression of KOA. However, the current treatment methods for KOA-BMLs are limited, and there is no uniform guideline or expert consensus, mainly includingmedication, physical therapy and surgical treatment. This article reviews the research progress of the disease characteristics and treatment of KOA-BMLs in order to provide guidance for the clinical diagnosis and treatment of KOA-BMLs.

Complex approach to the conservative treatment of hallux rigidus

Introduction. Hallux rigidus (HR) is a common source of forefoot pain, which leads to progressive loss of range of motion in the first metatarsophalangeal (MTP1) joint and pathologically affects biomechanics of the whole lower limb. HR is characterized by degeneration of the articular surfaces of MTP1 joint with the formation of bone growths, cysts and erosions, osteochondral defects and loose bodies. The frequency of occurrence of HR is 1 in 40 adults older than 50 years, and this localization of osteoarthritis is the most common among all joints of the foot. The aim of this article is to improve the results of conservative treatment of HR through the use of physical rehabilitation methods, such as manual therapy, therapeutic exercises and foot orthotics.Materials and methods. This study included retrospective cases of 24 patients (28 feet), who underwent a single course of conservative treatment of HR at the European Clinic for Sports Traumatology and Orthopedics (ECSTO) of the European Medical Center (EMC) since January 2014 to December 2018. The patients’ mean age was 51 years (range, 41 to 69 years). Median time between the beginning of treatment and final examination was 26 months (interquartile range from 17 to 36 months). Patient satisfaction, VAS pain scale, AOFAS and FAAM questionnaires and MTP1 dorsiflexion were evaluated in this study.Results. According to AOFAS scale, we obtained 18% (5/28) of excellent, 78% (22/28) of good, 4% (1/28) of fair and no poor results. Median AOFAS score significantly increased from 58.5 points before treatment to 87.0 points on the final examination (p&lt;0.05). Median FAAM daily activity subscale showed 98% of functional outcome with median subjective score of 95%, median FAAM sports score was 97% and median subjective sports score rate was 90%. Patient’s satisfaction at the final examination was “excellent” in 57% (16/28), “good” in 39% (11/28), “fair” in 4% (1/28) of cases and no poor results were obtained. Median VAS pain scale decreased from 5 points before treatment to 1 point at the final examination (p&lt;0.05). Median angle of the MTP1 dorsiflexion significantly increased from 23° before treatment to 30° on the final examination (p&lt;0.05).Conclusion. Described approach of the conservative treatment of HR is an effective method of treatment of early stages of the disease with high patient satisfaction rate and functional outcome.

Juvenile Trabecular Ossifying Fibroma (TrJOF) Orginating from Lateral Fronto-Orbital Bone with Secondary Aneurysmal Bone Cyst (ABC) Formation: Report of an Unusual Case and Literature Review

Juvenile trabeculated Ossifying Fibroma (JTrOF) is commonly arising from the maxilla and the mandibular bones, while Psammomatoid Juvenile Ossifying Fibroma (PsJOF) commonly arises in the sinonasal and calvarial bones. In our paper, we described a 12-year-old pediatric female who presented with a right fronto-orbital disfiguring swelling. She underwent total resection, peripheral osteotomy, and reconstruction. Pathology reported a TrJOF associated with Aneurysmal Bone Cyst (ABC) formation. TrJOF rarely originates from superolateral wall orbital bone, and it is exceedingly rare when it is associated with ABC formation. Pathologically, it is difficult to distinguish TrJOF from other FOLs due to similarities and overlap. The ideal treatment is total surgical excision and reconstruction. The Surgical resection is challenging as regards functional and cosmetic outcomes.

Juvenile Trabecular Ossifying Fibroma (TrJOF) Orginating from Lateral Fronto-Orbital Bone with Secondary Aneurysmal Bone Cyst (ABC) Formation: Report of an Unusual Case and Literature Review

Juvenile Trabecular Ossifying Fibroma (TrJOF) Orginating from Lateral Fronto-Orbital Bone with Secondary Aneurysmal Bone Cyst (ABC) Formation: Report of an Unusual Case and Literature Review

Cyst formation in the subchondral bone following cartilage repair.

Subchondral bone cysts represent an early postoperative sign associated with many articular cartilage repair procedures. They may be defined as an abnormal cavity within the subchondral bone in close proximity of a treated cartilage defect with a possible communication to the joint cavity in the absence of osteoarthritis. Two synergistic mechanisms of subchondral cyst formation, the theory of internal upregulation of local proinflammatory factors, and the external hydraulic theory, are proposed to explain their occurrence. This review describes subchondral bone cysts in the context of articular cartilage repair to improve investigations of these pathological changes. It summarizes their epidemiology in both preclinical and clinical settings with a focus on individual cartilage repair procedures, examines an algorithm for subchondral bone analysis, elaborates on the underlying mechanism of subchondral cyst formation, and condenses the clinical implications and perspectives on subchondral bone cyst formation in cartilage repair.

Interpreting an orthopantomogram.

An orthopantomogram (OPG) is a common radiograph used to identify thehard tissues of the oral cavity and surrounding skeletal structures. It is an extra-oral radiograph that approximates the focal trough of the mandible. Although resolution is not as detailed as intra-oral radiographs for examination of the teeth, gross changes in calcification of the dental structures, and changes in ossification of the underlying mandible and maxilla can aid in identification of dental disease such as caries (decay), periodontal bone loss, and abscess and cyst formation. This article outlines key anatomical features identifiable in an OPG and illustrates some common pathology thatmay be seen. The large amount of data visible on an OPG may appear daunting to the viewer unless a systematic approach is used to examine structures present. Distortion due to flattening of the curve of the mandible and dentition will give an overall view of these structures and requires the viewer to reinterpret these intheir mind for a three-dimensional appreciation of the image.

Bilateral chest wall mesenchymal hamartoma: Prenatal diagnosis and staged surgical resection

Mesenchymal hamartoma of the chest wall is a rare condition seen in infants. This case describes a prenatally diagnosed rapidly growing bilateral chest wall masses, suspected to be a mesenchymal hamartoma. Prenatal MRI performed at 33 weeks gestation showed large bilateral lesions with substantial mass effect in the form of pulmonary compression and displacement of the mediastinal structures necessitating delivery at our tertiary care facility at 35 weeks. At 48 hours post-birth, CTA revealed bilateral chest wall masses consistent with mesenchymal hamartoma and secondary aneurysmal bone cyst formation. The large left-sided lesion compressed the left lung and severely hindered pulmonary function, and the neonate required increasing respiratory support. The left-sided lesion was completely resected on day of life 15, and the neonate was extubated shortly after surgery. At the time of surgery the chest wall was reconstructed with alloderm, vicryl mesh and a latissimus dorsi advancement flap. A CTA at 3 months of age showed resection of the left-sided lesion with no evidence of recurrence, but significant growth in the unresected right hemithorax lesion. The right-sided lesion was resected uneventfully 8 months later. The prenatal and postnatal images showing the symptomatic lesion growth are discussed in this report.

Morphological Assessment of MACI Grafts in Patients with Revision Surgery and Total Joint Arthroplasty.

To compare the histological and immunohistochemical characteristics of matrix-assisted chondrocyte implantation (MACI) grafts between patients with revision surgery and patients with total joint arthroplasty. Biopsies of MACI grafts from patients with revision and total joint arthroplasty. The graft tissue characteristics and subchondral bone were examined by qualitative histology, ICRS (International Cartilage Repair Society) II scoring and semiquantitative immunohistochemistry using antibodies specific to type I and type II collagen. A total of 31 biopsies were available, 10 undergoing total knee arthroplasty (TKA) and 21 patients undergoing revision surgery. Patients in the clinically failed group were significantly older (46.3 years) than patients in the revision group (36.6 years) (P = 0.007). Histologically, the predominant tissue in both groups was of fibrocartilaginous nature, although a higher percentage of specimens in the revision group contained a hyaline-like repair tissue. The percentages of type I collagen (52.9% and 61.0%) and type II collagen (66.3% and 42.2%) were not significantly different between clinically failed and revised MACI, respectively. The talar dome contained the best and patella the worst repair tissue. Subchondral bone pathology was present in all clinically failed patients and consisted of bone marrow lesions, including edema, necrosis and fibrosis, intralesional osteophyte formation, subchondral bone plate elevation, intralesional osteophyte formation, subchondral bone cyst formation, or combinations thereof. MACI grafts in patients with revision and total joint arthroplasty were predominantly fibrocartilage in repair type, did not differ in composition and were histologically dissimilar to healthy cartilage. Clinically failed cases showed evidence of osteochondral unit failure, rather than merely cartilage repair tissue failure. The role of the subchondral bone in relation to pain and failure and the pathogenesis warrants further investigation.

Possible pathogenesis of calcaneal bone cysts.

Recent literature indicates that calcaneal bone cysts have different clinical features compared to long bone cysts. Yet, previous studies have mainly focused on pathogenesis of long bone cysts. In this study, the pathogenesis of calcaneal bone cysts was investigated from radiological and pathological findings. Patients comprised 18 males and 6 females diagnosed with calcaneal bone cysts at a median age ± standard deviation of 13.0 ± 3.6years. Plain radiographs, computed tomography, magnetic resonance imaging, cystography, bone scintigraphy, and pathology were reviewed. All cysts occupied the central triangular area of the bone, with six extending posteriorly and two developing anteriorly. Fifteen of 20 cases (75%) showed the expanded foramen structures at the anterior margin of the posterior facet. According to cystography, four cysts showed absence of leakage to subtalar joint. Cystic fluid caused chronic haemorrhaging in 18 cases and pathologically detected cholesterol clefts were noted in 14 cases. The location of the expanded foramen structures was consistent with the nutrient foramens of the sinus tarsi artery in the unaffected population. Hence, initial cysts may originate from the collapse of the sinus tarsi artery. Subsequent haemorrhage may extend into the central triangle area, which is biomechanically free of stress. Because of poor bone remodelling, degenerative change of the haemorrhage is prolonged. The results of this study showed that circulation collapse of the sinus tarsi artery and mechanical factors are important in the formation of calcaneal bone cysts.

Chondroblastomas presenting in adulthood: a study of 39 patients with emphasis on histological features and skeletal distribution.

Chondroblastomas (CB) are rare bone tumours that typically arise in the epiphysis/apophysis of long bones in skeletally immature patients. We explore the clinicopathological features of CB presenting in adults. CB in patients ≥20years of age were retrieved from our institutional archives. Thirty-nine CB were identified (29 male/10 female; aged 20-54years). Twenty (51%) cases occurred in long tubular bones, 10 (26%) in small bones of the feet, five (13%) in flat bones and four (10%) in the patella. All cases showed classic cytological features of CB, and chondroid matrix was universally present. Calcification was identified in 10 cases (26%), including various combinations of serpiginous (n=7), punctate (n=6), classic chicken-wire (n=4) and psammomatous (n=2) patterns. Haemosiderin (n=19), woven bone (n=13), secondary aneurysmal bone cyst formation (n=8), foamy macrophages (n=4), hyalinised vascular spaces (n=2) and cholesterol clefts (n=2) were noted. Follow-up information (n=32, 1-452months) revealed local recurrence in three patients, all >40years of age with flat bone origin, one of which developed pulmonary metastases 132months after initial diagnosis. CB in patients >20years of age more frequently involves the short bones of the hands/feet and flat bones compared to those arising in their younger counterparts. A subset may harbour extensive serpiginous or psammomatous calcification rather than the classic chicken-wire pattern. Although the overall local recurrence rate in adulthood is approximately 10%, all three patients with recurrent disease had tumours involving flat bones, suggesting that tumours arising in these sites may behave more aggressively.

Incidences and Risk Factors for Postoperative Non-Union after Posterior Lumbar Interbody Fusion with Closed-Box Titanium Spacers.

Study DesignA retrospective, single-center clinical study with follow-up of more than 24 months.PurposeTo evaluate the union rates and relevant risk factors for non-union after posterior lumbar interbody fusion (PLIF) using porous-coated closed-box titanium spacers.Overview of LiteratureAlthough the use of a closed-box interbody spacer for PLIF could avoid potential complications associated with the harvesting of autologous bone, few studies have reported detailed follow-up of fusion progression and risk factors for non-union in the early postoperative period.MethodsPLIF using closed-box spacers without filling the autologous bone was performed in 78 (88 levels) consecutive patients. Surgical procedures included PLIF using traditional pedicle screw fixation (PLIF, n=37), PLIF using cortical bone trajectory screw fixation (CBT-PLIF, n=30), and transforaminal lumbar interbody fusion with traditional pedicle screw fixation (TLIF, n=11). Lateral dynamic radiography and computed tomography findings were investigated, and the relationship between the union status and variables that may be related to the risk of non-union was tested statistically.ResultsThe overall bone union rates at 12 and 24 months were 68.0% and 88.5%, respectively. Incidences of bone cyst formation, subsidence, and retropulsion of spacers were 33.3%, 47.4%, and 14.1%, respectively. Union rates at 24 months were 94.6% in PLIF, 80.0% in CBT-PLIF, and 90.9% in TLIF. Multivariate logistic regression analyses showed that at 12 months postoperatively, the risk factor for non-union was age >75 years (p =0.02). In contrast, no significant risk factor was observed at 24 months.ConclusionsThese findings demonstrated the efficacy of interbody closed-box spacers for PLIF without the need to fill the spacer with autologous bone. However, the risk of non-union should be considered in elderly patients, especially intra-operatively and during the early postoperative stage.

Microglia express GPNMB in the brains of Alzheimer's disease and Nasu-Hakola disease.

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein first identified in low-metastatic human melanoma cell lines as a regulator of tumor growth. GPNMB is widely expressed in various tissues, where it is involved in cell differentiation, migration, inflammation/anti-inflammation, tissue regeneration, and neuroprotection. GPNMB is identified in microglia of adult rat brains, neurons and astrocytes of GPNMB transgenic (Tg) mouse brains, and motor neurons of amyotrophic lateral sclerosis (ALS) patients. Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of either TYROBP (DAP12) or TREM2. TREM2 and DAP12 constitute a receptor/adaptor signaling complex expressed exclusively on osteoclasts, dendritic cells, macrophages, and microglia. Pathologically, the brains of NHD patients exhibit leukoencephalopathy, astrogliosis, accumulation of axonal spheroids, and remarkable activation of microglia predominantly in the white matter of frontal and temporal lobes and the basal ganglia. At present, molecular mechanisms responsible for development of leukoencephaolpathy in NHD brains remain totally unknown. Recent evidence indicates that disease-associated microglia (DAM) that cluster around amyloid plaques express high levels of GPNMB in Alzheimer's disease (AD) brains. Because microglia act as a key regulator of leukoencephalopathy in NHD brains, it is proposed that GPNMB expressed on microglia might play a protective role in progression of leukoencephalopathy possibly via active phagocytosis of myelin debris. In the present study using immunohistochemistry, we have attempted to clarify the expression of GPNMB in NHD brains, compared with AD brains. We found that microglia accumulating in the white matter express an intense GPNMB immunoreactivity in both NHD and AD brains, suggesting that the accumulation of GPNMB-immunoreactive microglia is a general phenomenon in neurodegenerative brains.

Radiological Outcomes of Posterior Lumbar Interbody Fusion Using a Titanium-coated PEEK Cage.

INTRODUCTION Titanium (Ti) coated polyether ether ketone (PEEK) interbody cages (IBCs) have been introduced to overcome any disadvantages. The purpose of this study was to investigate the radiological outcomes of lumbar interbody fusion (LIF) surgery using the Ti-coated PEEK IBC with a minimum of 1-year of follow-up. METHODS A total of 26 intervertebral spaces in consecutive 21 patients who underwent posterior/transforaminal LIF using the Ti-coated PEEK IBC were evaluated. Rates of bone union, screw loosening, cage subsidence and bone cyst formation around the endplate were evaluated on computed tomography scans acquired at least 1 year postoperatively. RESULTS AND DISCUSSION At the 1-year follow-up, bone fusion was achieved in 23 (88.4%) of 26 intervertebral spaces. Cagesubsidence was found in 5 intervertebral spaces ; however,bone fusion was achieved in all these spaces. Bone cysts formed in 4 intervertebral spaces and 4 of 94 screws were found to be loosened. Three of the loosened screws were found in vertebral bodies adjacent to intervertebral spaces with nonunion. However, there was no association between these events. Although more scientific evidence is required to determine the advantages of Ti-coated PEEK IBCs, we believe the clinical outcomes achieved were favorable at the 1 year minimum follow-up. J. Med. Invest. 66 : 119-122, February, 2019.

Pleural effusion caused by polyostotic fibrous dysplasia involving the ribs, the sternum and the thoracic spine associated with multiple cystic degenerations – a case report

Introduction. Fibrous dysplasia is a noninherited benign skeletal disorder associated with abnormal bone development. Single bone involvement, the monostotic form, accounts for 70 ? 80% of cases, while the polyostotic form, with multiple bone involvement, accounts for 20 ? 30% of cases. Cystic degeneration and occasional aneurysmal bone cyst formation may be found in fibrous dysplasia lesions, particularly in the costal lesions. Case Report. A 51-year-old man presented with acute shortness of breath after sustaining simple chest wall injury. Chest computed tomography showed multiple massive osteolytic rib lesions, as well as a massive left-sided pleural effusion with compression atelectasis of the lung parenchyma. Osteolytic lesions of the anterior 2nd and 7th thoracic vertebral body were found, along with a well defined osteolytic lesion in the body of the sternum. Video-assisted thoracoscopy of the left pleural space was performed and frozen sections, collected using endoscopic biopsy forceps of the cystic wall and solid parts of the tumors, were sent for ex tempore histopathological analysis. Results showed fibrous dysplasia with suspected malignancy. Talc pleurodesis was performed based on the obtained results. At present, the patient is asymptomatic with his daily routine uninterrupted by his medical condition. Conclusion. Treatment of pleural effusion caused by a cyst rupture of unresectable degenerated polyostotic fibrous dysplasia of the ribs represents a surgical challenge. Surgical drainage of the cysts followed by chemical pleurodesis seems to be a reasonable solution in cases where pulmonary functions are impacted by combined effects of pleural effusion and cystic compression.

Enhanced Skull Bone Regeneration by Sustained Release of BMP-2 in Interpenetrating Composite Hydrogels.

Direct administration of bone morphogenetic protein-2 (BMP-2) for bone regeneration could cause various clinical side effects such as osteoclast activation, inflammation, adipogenesis, and bone cyst formation. In this study, thiolated gelatin/poly(ethylene glycol) diacrylate (PEGDA) interpenetrating (IPN) composite hydrogels were developed for guided skull bone regeneration. To promote bone regeneration, either polycation-based coacervates (Coa) or gelatin microparticles (GMPs) were incorporated within IPN gels as BMP-2 carriers. Both BMP-2 loaded Coa and BMP-2 loaded GMPs showed significantly enhanced in vitro alkaline phosphate (ALP) activity of human mesenchymal stem cells (hMSCs) than non-BMP-2 treated control. Moreover, BMP-2 loaded GMPs group exhibited statistically increased ALP activity compared to both bolus BMP-2 administration and BMP-2 loaded Coa group, indicating that our carriers could protect and maintain biological activity of cargo BMP-2. Sustained release kinetics of BMP-2 from IPN composite hydrogels could be controlled by different formulations. For in vivo bone regeneration, various IPN gel formulations (i.e., (1) control, (2) only hydrogel, (3) hydrogel with bolus BMP-2, (4) hydrogel with BMP-2-loaded Coa, and (5) hydrogel with BMP-2-loaded GMPs) were bilaterally implanted into 5 mm-sized rat calvarial defects. After 4 weeks, micro-CT and histological analysis were performed to evaluate new bone formation. Significantly higher scores for bony bridging and union were observed in BMP-2-loaded Coa and BMP-2-loaded GMP groups as compared to other formulations. In addition, rats treated with BMP-2-loaded GMPs showed a significantly higher ratio of bone volume/total volume and lower trabecular separation scores than others. Finally, rats treated with either Coa or GMP groups exhibited a significant increase in bone formation area, as assessed via histomorphometric analysis. Taken together, it could be concluded that Coa and GMPs were effective carriers to maintain the bioactivity of cargo BMP-2 during its sustained release. Consequently, our IPN composite hydrogel system that combines such BMP-2 carriers could effectively promote skull bone regeneration.

Histological Evaluation of Early-Phase Changes in the Osteochondral Unit After Microfracture in a Full-Thickness Cartilage Defect Rat Model

Background: The microfracture (MF) technique is an established surgical treatment for cartilage injury. However, the early-phase histological changes in full-thickness cartilage defects (FTCDs) after MF and the concomitant changes in the subchondral bone are still unknown. Purpose: To determine the early-phase histological changes in FTCD associated with subchondral bone remodeling after MF in rat model. Study Design: Controlled laboratory study. Methods: Rats were subjected to FTCD, followed by MF at the trochlear groove. For histological analysis, experiment and untreated control rats were sacrificed at 0, 1, 3, 7, 14, 28, and 56 days postoperatively (n = 6 knees per time point). Cartilage healing response was evaluated with the Pineda score. Osteoclast activity was evaluated by counting and locating the number of tartrate-resistant acid phosphatase (TRAP)–positive cells in the subchondral bone. MF hole diameter and bone mineral density in the subchondral bone were measured sequentially in 3 rats (n = 6 knees) by 3-dimensional μ–computed tomography. Results: Pineda score showed no difference in cartilage response from day 0 to day 3 but a significant improvement from day 7 to day 56. Although the MF holes were filled with blood clots in all specimens, the defect sites were not. The number of TRAP-positive cells peaked at day 3, mostly accumulating around the deeper zone of the MF holes. Over time, the number of TRAP-positive cells decreased to preoperative levels, localizing around the aperture of the MF holes where there was active remodeling of the osteochondral unit. The MF hole diameter was largest at day 14, and most holes disappeared by day 28. Bone mineral density was also highest at day 14 and decreased to preoperative levels by day 56. Conclusion: Histological changes in the FTCD after MF were derived from endochondral ossification within the deeper zone of the MF holes. Clinical Relevance: The absence of healing by blood clot in the FTCD should be noted by surgeons performing MF, and indications for MF should be carefully considered not only for maximizing the postoperative clinical outcome but also minimizing potential complications, such as formation of subchondral bone cysts or intralesional osteophytes.