Publications by authors named "Jaakko M Piitulainen"

9 Publications

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Biomaterial and implant induced ossification: in vitro and in vivo findings.

J Tissue Eng Regen Med 2020 08 8;14(8):1157-1168. Epub 2020 Jul 8.

International Clinical Research Center of St. Anne's University Hospital Brno, Brno, Czech Republic.

Material-induced ossification is suggested as a suitable approach to heal large bone defects. Fiber-reinforced composite-bioactive glasses (FRC-BGs) display properties that could enhance the ossification of calvarial defects. Here, we analyzed the healing processes of a FRC-BG implant in vivo from the perspective of material-induced ossification. Histological analysis of the implant, which was removed 5 months after insertion, showed the formation of viable, noninflammatory mesenchymal tissue with newly-formed mineralized woven bone, as well as nonmineralized connective tissue with capillaries and larger blood vessels. The presence of osteocytes was detected within the newly generated bone matrix. To expand our understanding on the osteogenic properties of FRC-BG, we cultured human adipose tissue-derived mesenchymal stromal cells (AD-MSCs) in the presence of two different BGs (45S5 and S53P4) and Al O control. AD-MSCs grew and proliferated on all the scaffolds tested, as well as secreted abundant extracellular matrix, when osteogenic differentiation was appropriately stimulated. 45S5 and S53P4 induced enhanced expression of COL2A1, COL10A1, COL5A1 collagen subunits, and pro-osteogenic genes BMP2 and BMP4. The concomitant downregulation of BMP3 was also detected. Our findings show that FRC-BG can support the vascularization of the implant and the formation of abundant connective tissue in vivo. Specifically, BG 45S5 and BG S53P4 are suited to evoke the osteogenic potential of host mesenchymal stromal cells. In conclusion, FRC-BG implant demonstrated material-induced ossification both in vitro and in vivo.
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August 2020

A large calvarial bone defect in a child: osteointegration of an implant.

World Neurosurg 2019 Jan 23. Epub 2019 Jan 23.

Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland; PO Box 23, 90029 OYS, Finland; Medical Research Center Oulu, and PEDEGO Research Unit, University of Oulu, Oulu, Finland.

Background: This is an original report describing the long-term follow-up outcome of a cranioplasty. A large calvarial bone defect of a child was reconstructed with a bioactive and biostable non-metallic implant.

Case Description: This is a case study of a young child with an infantile fibrosarcoma of occipital bone. The malignancy in an occipital bone was removed from a child of 2.5 years of age, and the defect site was reconstructed with an on-lay glass fibre-reinforced composite - bioactive glass implant. After 5 years and 7 months, the follow-up examination showed no signs of a recidive. During the follow-up period, the contour of the reconstructed area followed skull anatomical development. Computed tomography demonstrated considerably large areas (approximately 70 % of the total area) of bone on-growth to the peridural surface of the implant.

Conclusions: In the future, a synthetic cranioplasty material that is capable to integrate with cranial bone may be considered superior to cryopreserved bone grafts in younger age groups.
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January 2019

Predictors of primary autograft cranioplasty survival and resorption after craniectomy.

J Neurosurg 2018 May 1:1-8. Epub 2018 May 1.

6Department of Biomaterials Science, Institute of Dentistry, University of Turku and City of Turku, Welfare Division, Turku.

OBJECTIVECraniectomy is a common neurosurgical procedure that reduces intracranial pressure, but survival necessitates cranioplasty at a later stage, after recovery from the primary insult. Complications such as infection and resorption of the autologous bone flap are common. The risk factors for complications and subsequent bone flap removal are unclear. The aim of this multicenter, retrospective study was to evaluate the factors affecting the outcome of primary autologous cranioplasty, with special emphasis on bone flap resorption.METHODSThe authors identified all patients who underwent primary autologous cranioplasty at 3 tertiary-level university hospitals between 2002 and 2015. Patients underwent follow-up until bone flap removal, death, or December 31, 2015.RESULTSThe cohort comprised 207 patients with a mean follow-up period of 3.7 years (SD 2.7 years). The overall complication rate was 39.6% (82/207), the bone flap removal rate was 19.3% (40/207), and 11 patients (5.3%) died during the follow-up period. Smoking (OR 3.23, 95% CI 1.50-6.95; p = 0.003) and age younger than 45 years (OR 2.29, 95% CI 1.07-4.89; p = 0.032) were found to independently predict subsequent autograft removal, while age younger than 30 years was found to independently predict clinically relevant bone flap resorption (OR 4.59, 95% CI 1.15-18.34; p = 0.03). The interval between craniectomy and cranioplasty was not found to predict either bone flap removal or resorption.CONCLUSIONSIn this large, multicenter cohort of patients with autologous cranioplasty, smoking and younger age predicted complications leading to bone flap removal. Very young age predicted bone flap resorption. The authors recommend that physicians extensively inform their patients of the pronounced risks of smoking before cranioplasty.
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May 2018

Cranioplasty After Severe Traumatic Brain Injury: Effects of Trauma and Patient Recovery on Cranioplasty Outcome.

Front Neurol 2018 9;9:223. Epub 2018 Apr 9.

Department of Biomaterials Science and Turku Clinical Biomaterials Centre--TCBC, Institute of Dentistry, University of Turku, Turku, Finland.

Background: In patients with severe traumatic brain injury (sTBI) treated with decompressive craniectomy (DC), factors affecting the success of later cranioplasty are poorly known.

Objective: We sought to investigate if injury- and treatment-related factors, and state of recovery could predict the risk of major complications in cranioplasty requiring implant removal, and how these complications affect the outcome.

Methods: A retrospective cohort of 40 patients with DC following sTBI and subsequent cranioplasty was studied. Non-injury-related factors were compared with a reference population of 115 patients with DC due to other conditions.

Results: Outcome assessed 1 day before cranioplasty did not predict major complications leading to implant removal. Successful cranioplasty was associated with better outcome, whereas a major complication attenuates patient recovery: in patients with favorable outcome assessed 1 year after cranioplasty, major complication rate was 7%, while in patients with unfavorable outcome the rate was 42% ( = 0.003). Of patients with traumatic subarachnoid hemorrhage (tSAH) on admission imaging 30% developed a major complication, while none of patients without tSAH had a major complication ( = 0.014). Other imaging findings, age, admission Glasgow Coma Scale, extracranial injuries, length of stay at intensive care unit, cranioplasty materials, and timing of cranioplasty were not associated with major complications.

Conclusion: A successful cranioplasty after sTBI and DC predicts favorable outcome 1 year after cranioplasty, while stage of recovery before cranioplasty does not predict cranioplasty success or failure. tSAH on admission imaging is a major risk factor for a major complication leading to implant removal.
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April 2018

Load-bearing capacity and fracture behavior of glass fiber-reinforced composite cranioplasty implants.

J Appl Biomater Funct Mater 2017 Nov 10;15(4):e356-e361. Epub 2017 Nov 10.

Department of Biomaterials Science and Turku Clinical Biomaterials Centre (TCBC), Institute of Dentistry, University of Turku, Turku - Finland.

Background: Glass fiber-reinforced composites (FRCs) have been adapted for routine clinical use in various dental restorations and are presently also used in cranial implants. The aim of this study was to measure the load-bearing capacity and failure type of glass FRC implants during static loading with and without interconnective bars and with different fixation modes.

Methods: Load-bearing capacities of 2 types of FRC implants with 4 different fixation modes were experimentally tested. The sandwich-like FRC implants were made of 2 sheets of woven FRC fabric, which consisted of silanized, woven E-glass fiber fabrics impregnated in BisGMA-TEGDMA monomer resin matrix. The space between the outer and inner surfaces was filled with glass particles. All FRC implants were tested up to a 10-mm deflection with load-bearing capacity determined at 6-mm deflection. The experimental groups were compared using nonparametric Kruskal-Wallis analysis with Steel-Dwass post hoc test.

Results: FRC implants underwent elastic and plastic deformation until 6-mm deflection. The loading test did not demonstrate any protrusions of glass fibers or cut fiber even at 10-mm deflection. An elastic and plastic deformation of the implant occurred until the FRC sheets were separated from each other. In the cases of the free-standing setup (no fixation) and the fixation with 6 screws, the FRC implants with 2 interconnective bars showed a significantly higher load-bearing capacity compared with the implant without interconnective bars.

Conclusions: FRC implants used in this study showed a load-bearing capacity which may provide protection for the brain after cranial bone defect reconstruction.
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November 2017

A glass fiber-reinforced composite - bioactive glass cranioplasty implant: A case study of an early development stage implant removed due to a late infection.

J Mech Behav Biomed Mater 2015 Mar 7;55:191-200. Epub 2015 Nov 7.

Department of Otorhinolaryngology - Head and Neck Surgery, Division of Surgery and Cancer Diseases, Turku University Hospital, PO Box 52, 20521 Turku, Finland; City of Turku Welfare Division, PO Box 670, 20101 Turku, Finland.

This case study describes the properties of an early development stage bioactive glass containing fiber-reinforced composite calvarial implant with histology that has been in function for two years and three months. The patient is a 33-year old woman with a history of substance abuse, who sustained a severe traumatic brain injury later unsuccessfully treated with an autologous bone flap and a custom-made porous polyethylene implant. She was thereafter treated with developmental stage glass fiber-reinforced composite - bioactive glass implant. After two years and three months, the implant was removed due to an implant site infection. The implant was analyzed histologically, mechanically, and in terms of chemistry and dissolution of bioactive glass. Mechanical integrity of the load bearing fiber-reinforced composite part of the implant was not affected by the in vivo period. Bioactive glass particles demonstrated surface layers of hydroxyapatite like mineral and dissolution, and related increase of pH was considerably less after two and three months period than that for fresh bioactive glass. There was a difference in the histology of the tissues inside the implant areas near to the margin of the implant that absorbed blood during implant installation surgery, showed fibrous tissue with blood vessels, osteoblasts, collagenous fibers with osteoid formation, and tiny clusters of more mature hard tissue. In the center of the implant, where there was less absorbed blood, only fibrous tissue was observed. This finding is in line with the combined positron emission tomography - computed tomography examination with (18F)-fluoride marker, which demonstrated activity of the mineralizing bone by osteoblasts especially at the area near to the margin of the implant 10 months after implantation. Based on these promising reactions found in the bioactive glass containing fiber-reinforced composite implant that has been implanted for two years and three months, calvarial reconstruction with the presented material appears to be a feasible method.
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March 2015

Outcomes of cranioplasty with synthetic materials and autologous bone grafts.

World Neurosurg 2015 May 11;83(5):708-14. Epub 2015 Feb 11.

Department of Neurosurgery, Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.

Objective: Using current surgical methods, cranioplasty is associated with a high complication rate. We analyzed if there are preexisting medical conditions associated with complications and compared the effect of different implant materials on the degree of complications.

Methods: A retrospective review of the medical records of all patients who underwent cranioplasty for cranial bone defects during the period 2002-2012 was conducted, and 100 consecutive cranioplasty procedures that met eligibility criteria were identified. Patients were analyzed in 4 groups, which were created based on the cranioplasty material: autograft (n = 20), bioactive fiber-reinforced composite (n = 20), hydroxyapatite (n = 31), and other synthetic materials (n = 29). Survival estimates were constructed with Kaplan-Meier curves, and the differences between categorical variable levels were determined using a log-rank test. Multiple comparisons were adjusted using a Šidák correction.

Results: During a median follow-up time of 14 months (interquartile range 3-39 months), 32 of 100 patients (32.0%) developed at least 1 complication. A minor complication occurred in 13 patients (13.0%), whereas 19 patients (19.0%) developed a major complication, which required reoperation or removal of the implant. In the autograft subgroup, 40.0% of patients required removal of the cranioplasty. The 3-year survival of the autograft subgroup was lower compared with other subgroups of synthetic materials. In hydroxyapatite and bioactive fiber-reinforced composite groups, fewer complications were observed compared with the autograft group.

Conclusions: Based on these results, synthetic materials for cranial bone defect reconstruction exhibit more promising outcomes compared with autograft. There were differences in survival rates among synthetic materials.
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May 2015

Paediatric cranial defect reconstruction using bioactive fibre-reinforced composite implant: early outcomes.

Acta Neurochir (Wien) 2015 Apr 10;157(4):681-7. Epub 2015 Feb 10.

Division of Surgery and Cancer Diseases, Department of Otorhinolaryngology - Head and Neck Surgery, Turku University Hospital, PO Box 52, 20521, Turku, Finland,

Background: In children, approximately half of cryopreserved allograft bone flaps fail due to infection and resorption. Synthetic materials offer a solution for allograft bone flap resorption. Fibre-reinforced composite with a bioactive glass particulate filling is a new synthetic material for bone reconstruction. Bioactive glass is capable of chemically bonding with bone and is osteoinductive, osteoconductive and bacteriostatic. Fibre-reinforced composite allows for fabricating thin (0.8 mm) margins for implant, which are designed as onlays on the existing bone. Bioactive glass is dissolved over time, whereas the fibre-reinforced composite serves as a biostable part of the implant, and these have been tested in preclinical and adult clinical trials. In this study, we tested the safety and other required properties of this composite material in large skull bone reconstruction with children.

Method: Eight cranioplasties were performed on seven patients, aged 2.5-16 years and having large (>16 cm(2)) skull bone defects. The implant used in this study was a patient-specific, glass-fibre-reinforced composite, which contained a bioactive glass particulate compound, S53P4.

Results: During follow-up (average 35.1 months), one minor complication was observed and three patients needed revision surgery. Two surgical site infections were observed. After treatment of complications, a good functional and cosmetic outcome was observed in all patients. The implants had an onlay design and fitted the defect well. In clinical and imaging examinations, the implants were in the original position with no signs of implant migration, degradation or mechanical breakage.

Conclusions: Here, we found that early cranioplasty outcomes with the fibre-reinforced composite implant were promising. However, a longer follow-up time and a larger group of patients are needed to draw firmer conclusions regarding the long-term benefits of the proposed novel biomaterial and implant design. The glass-fibre-reinforced composite implant incorporated by particles of bioactive glass may offer an original, non-metallic and bioactive alternative for reconstruction of large skull bone defects in a paediatric population.
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April 2015

Craniofacial bone reconstruction with bioactive fiber-reinforced composite implant.

Head Neck 2014 May 1;36(5):722-8. Epub 2013 Aug 1.

Department of Otorhinolaryngology - Head and Neck Surgery, Turku University Hospital, Turku, Finland.

Background: A novel, bioactive, fiber-reinforced composite implant is a solution to address the shortcomings in craniofacial bone reconstruction. A longitudinal clinical investigation with a follow-up time of 4 years was conducted.

Methods: A cranial bone reconstruction with the implant was performed on 12 patients. In these patients, the reasons for craniotomies resulting in craniofacial bone defects were traumatic and spontaneous intracranial bleeding as well as infections to the primary reconstruction material. The implant material consisted of a supporting fiber-reinforced framework, porous inner layers, and a bioactive glass (BG; S53P4) filling. The framework and the porous layers were made of a bisphenol-a-glycidyl methacrylate and triethyleneglycoldi-methacrylate (pBisGMA-pTEGDMA) resin matrix, which was reinforced with silanized E-glass.

Results: In clinical examinations and skull X-rays, the implants were in original positions providing the expected functional and aesthetic outcome at all time points.

Conclusion: The implants functioned appropriately, which would provide a potential solution for craniofacial bone reconstruction in the future.
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May 2014