Reconstruction Of Bone Defects Research Articles

Engineering hypertrophic cartilage grafts from lipoaspirate for critical-sized calvarial bone defect reconstruction: An adipose tissue-based developmental engineering approach.

Developmental engineering of living implants from different cell sources capable of stimulating bone regeneration by recapitulating endochondral ossification (ECO) is a promising strategy for large bone defect reconstruction. However, the clinical translation of these cell‐based approaches is hampered by complex manufacturing procedures, poor cell differentiation potential, and limited predictive in vivo performance. We developed an adipose tissue‐based developmental engineering approach to overcome these hurdles using hypertrophic cartilaginous (HyC) constructs engineered from lipoaspirate to repair large bone defects. The engineered HyC constructs were implanted into 4‐mm calvarial defects in nude rats and compared with decellularized bone matrix (DBM) grafts. The DBM grafts induced neo‐bone formation via the recruitment of host cells, while the HyC pellets supported bone regeneration via ECO, as evidenced by the presence of remaining cartilage analog and human NuMA‐positive cells within the newly formed bone. However, the HyC pellets clearly showed superior regenerative capacity compared with that of the DBM grafts, yielding more new bone formation, higher blood vessel density, and better integration with adjacent native bone. We speculate that this effect arises from vascular endothelial growth factor and bone morphogenetic protein‐2 secretion and mineral deposition in the HyC pellets before implantation, promoting increased vascularization and bone formation upon implantation. The results of this study demonstrate that adipose‐derived HyC constructs can effectively heal large bone defects and present a translatable therapeutic option for bone defect repair.

Engineering 3D Printed Scaffolds with Tunable Hydroxyapatite.

Orthopedic and craniofacial surgical procedures require the reconstruction of bone defects caused by trauma, diseases, and tumor resection. Successful bone restoration entails the development and use of bone grafts with structural, functional, and biological features similar to native tissues. Herein, we developed three-dimensional (3D) printed fine-tuned hydroxyapatite (HA) biomimetic bone structures, which can be applied as grafts, by using calcium phosphate cement (CPC) bioink, which is composed of tetracalcium phosphate (TTCP), dicalcium phosphate anhydrous (DCPA), and a liquid [Polyvinyl butyral (PVB) dissolved in ethanol (EtOH)]. The ink was ejected through a high-resolution syringe nozzle (210 µm) at room temperature into three different concentrations (0.01, 0.1, and 0.5) mol/L of the aqueous sodium phosphate dibasic (Na2HPO4) bath that serves as a hardening accelerator for HA formation. Raman spectrometer, X-ray diffraction (XRD), and scanning electron microscopy (SEM) demonstrated the real-time HA formation in (0.01, 0.1, and 0.5) mol/L Na2HPO4 baths. Under those conditions, HA was formed at different amounts, which tuned the scaffolds’ mechanical properties, porosity, and osteoclast activity. Overall, this method may pave the way to engineer 3D bone scaffolds with controlled HA composition and pre-defined properties, which will enhance graft-host integration in various anatomic locations.

Effects of Channels and Micropores in Honeycomb Scaffolds on the Reconstruction of Segmental Bone Defects.

The reconstruction of critical-sized segmental bone defects is a key challenge in orthopedics because of its intractability despite technological advancements. To overcome this challenge, scaffolds that promote rapid bone ingrowth and subsequent bone replacement are necessary. In this study, we fabricated three types of carbonate apatite honeycomb (HC) scaffolds with uniaxial channels bridging the stumps of a host bone. These HC scaffolds possessed different channel and micropore volumes. The HC scaffolds were implanted into the defects of rabbit ulnar shafts to evaluate the effects of channels and micropores on bone reconstruction. Four weeks postoperatively, the HC scaffolds with a larger channel volume promoted bone ingrowth compared to that with a larger micropore volume. In contrast, 12 weeks postoperatively, the HC scaffolds with a larger volume of the micropores rather than the channels promoted the scaffold resorption by osteoclasts and bone formation. Thus, the channels affected bone ingrowth in the early stage, and micropores affected scaffold resorption and bone formation in the middle stage. Furthermore, 12 weeks postoperatively, the HC scaffolds with large volumes of both channels and micropores formed a significantly larger amount of new bone than that attained using HC scaffolds with either large volume of channels or micropores, thereby bridging the host bone stumps. The findings of this study provide guidance for designing the pore structure of scaffolds.

Addition of a Vascular Bundle Accelerates Bone Union in Femoral Bone Defects.

The Masquelet method has become increasingly popular for the treatment of bone defects in recent years. In this method, an induced membrane (IM) with abundant blood circulation, stem cells, and osteogenesis-promoting factors is formed by implanting bone cement during the first surgery. This IM stimulates bone formation in the bone defect after implantation of the bone graft during the second surgery. However, the Masquelet method requires two surgeries and thus a longer treatment period. In the present study, we investigated whether bone defects could be reconstructed in a single surgery by introducing a vascular bundle into the bone defect as an alternative to the IM, in addition to bone grafting. Thirty-six 12-week-old female Sprague-Dawley rats were used. After creating a 5-mm long bone defect in the femur, a mixture of autologous and artificial bone was grafted into the defect, and a saphenous arteriovenous vascular bundle was introduced. The animals were divided into three groups: the control group (bone defect only), the BG group (bone grafting only), and the BG + V group (bone grafting + vascular bundle introduction). After surgery, radiological and histological evaluations were performed to assess osteogenesis and angiogenesis in bone defects. In the BG + V group, significant bone formation was observed in the bone defect on radiological and histological evaluations, and the amount of bone formation was significantly higher than that in the other two groups. Furthermore, cortical bone continuity was observed in many specimens in the BG + V group. On histological evaluation, the number of blood vessels was also significantly higher in the BG + V group than in the other two groups. Our results suggest that the introduction of a vascular bundle in addition to bone grafting can promote bone formation in bone defects and allow for complete bone defect reconstruction in a single surgery.

Regenerative matching axial vascularisation of absorbable 3D-printed scaffold for large bone defects: A first in human series

BackgroundWe describe the first clinical series of a novel bone replacement technique based on regenerative matching axial vascularisation (RMAV). This was used in four cases: a tibial defect after treatment of osteomyelitis; a calvarial defect after trauma and failed titanium cranioplasty; a paediatric tibial defect after neoadjuvant chemotherapy and resection of Ewing sarcoma; and a paediatric mandibular deficiency resulting from congenital hemifacial microsomia. MethodAll patients underwent reconstruction with three-dimensional (3D)-printed medical-grade polycaprolactone and tricalcium phosphate (mPCL-TCP) scaffolds wrapped in vascularised free corticoperiosteal flaps. OutcomeFunctional volumes of load-sharing regenerate bone have formed in all cases after a moderate duration of follow-up. At 36 cm, case 1 remains the longest segment of load bearing bone ever successfully reconstructed. This technique offers an alternative to existing methods of large volume bone defect reconstruction that may be safe, reliable, and give predictable outcomes in challenging situations. It achieves this by using a bioresorbable scaffold to support and direct the growth of regenerate bone, driven by RMAV. ConclusionThis technique may facilitate the reconstruction of bone defects previously thought unreconstructable, reduce the risk of long-term implant-related complications and achieve these outcomes in a hostile environment. These potential benefits must now be formally tested in prospective clinical trials.

Comparison of Hydroxyapatite/Poly(lactide-co-glycolide) and Hydroxyapatite/Polyethyleneimine Composite Scaffolds in Bone Regeneration of Swine Mandibular Critical Size Defects: In Vivo Study.

Reconstruction of jaw bone defects present a significant problem because of specific aesthetic and functional requirements. Although widely used, the transplantation of standard autograft and allograft materials is still associated with significant constraints. Composite scaffolds, combining advantages of biodegradable polymers with bioceramics, have potential to overcome limitations of standard grafts. Polyethyleneimine could be an interesting novel biocompatible polymer for scaffold construction due to its biocompatibility and chemical structure. To date, there have been no in vivo studies assessing biological properties of hydroxyapatite bioceramics scaffold modified with polyethyleneimine. The aim of this study was to evaluate in vivo effects of composite scaffolds of hydroxyapatite ceramics and poly(lactide-co-glycolide) and novel polyethyleneimine on bone repair in swine’s mandibular defects, and to compare them to conventional bone allograft (BioOss). Scaffolds were prepared using the method of polymer foam template in three steps. Pigs, 3 months old, were used and defects were made in the canine, premolar, and molar area of their mandibles. Four months following the surgical procedure, the bone was analyzed using radiological, histological, and gene expression techniques. Hydroxyapatite ceramics/polyethyleneimine composite scaffold demonstrated improved biological behavior compared to conventional allograft in treatment of swine’s mandibular defects, in terms of bone density and bone tissue histological characteristics.

Asymmetric SIS membranes specifically loaded with exosomes through the modification of engineered recombinant peptides for guide bone regeneration

Guided bone regeneration (GBR) technology is an effective method for reconstructing bone defects, and barrier membranes are widely used in this process. The objective of this study was to develop a novel asymmetric SIS (small intestinal submucosa) membrane and modify the membrane with exosomes and engineered recombinant peptides. The asymmetric SIS membrane was developed with liquid nitrogen quencher. The engineered recombinant peptides were designed by connecting collagen binding peptides with the exosomal capture peptide CP05 via linker. In vitro experiments demonstrated that the engineered recombinant peptides contributed to promoting the positive effect of exosomes on the osteogenic differentiation of BMSCs. Further mechanistic studies confirmed that the PI3K/Akt signaling pathway is critical in the exosome-induced osteogenic differentiation of BMSCs. Moreover, the asymmetric SIS membrane combining engineered recombinant peptides and exosomes could reconstruct bone defects effectively within 12 weeks. Therefore, the membrane developed in this study has the potential to repair bone defects. • The asymmetric SIS membrane was developed using liquid nitrogen quencher. • Engineered recombinant peptides were designed by connecting collagen binding peptides with CP05. • SIS–P1P2-EXO membranes could reconstruct bone defects effectively within 12 weeks.

Additive Manufacturing Technologies for Fabrication of Biomaterials for Surgical Procedures in Dentistry: A Narrative Review.

To screen and critically appraise available literature regarding additive manufacturing technologies for bone graft material fabrication in dentistry. PubMed and Scopus were searched up to May 2021. Studies reporting the additive manufacturing techniques to manufacture scaffolds for intraoral bone defect reconstruction were considered eligible. A narrative review was synthesized to discuss the techniques for bone graft material fabrication in dentistry and the biomaterials used. The databases search resulted in 933 articles. After removing duplicate articles (128 articles), the titles and abstracts of the remaining articles (805 articles) were evaluated. A total of 89 articles were included in this review. Reading these articles, 5 categories of additive manufacturing techniques were identified: material jetting, powder bed fusion, vat photopolymerization, binder jetting, and material extrusion. Additive manufacturing technologies for bone graft material fabrication in dentistry, especially 3D bioprinting approaches, have been successfully used to fabricate bone graft material with distinct compositions.

Auto-tooth bone graft material for reconstruction of bone defects in the oral region: case reports

We present some clinical cases of autogenous tooth graft - a modern method in which the extracted teeth are processed into a demineralised dentin matrix (DDM) and are then immediately transplanted into the post-extraction sockets or bone defects.

Reconstruction of a traumatic femoral bone defect using the extruded diaphyseal segment after autoclave sterilization

Joint Diseases and Related Surgery (JDRS), the official journal of the Turkish Joint Diseases Foundation, is an international, peer-reviewed, immediate open access journal. All published articles in JDRS has been free for everyone, without embargo, since 1990.

Development of Intracorporeal Differentiation of Stem Cells to Induce One-Step Mastoid Bone Reconstruction during Otitis Media Surgeries.

Mastoidectomy is a surgical procedure for the treatment of chronic otitis media. This study investigated the ability of rat stromal vascular fraction cells (rSVF) in combination with polycaprolactone (PCL) scaffolds and osteogenic differentiation-enhancing blood products to promote the regeneration of mastoid bone defect. Twenty male Sprague Dawley rats were randomly divided according to obliteration materials: (1) control, (2) PCL scaffold only, (3) rSVFs + PCL, (4) rSVFs + PCL + platelet-rich plasma, and (5) rSVFs + PCL + whole plasma (WP). At 7 months after transplantation, the rSVFs + PCL + WP group showed remarkable new bone formation in the mastoid. These results indicate that SVFs, PCL scaffolds, and blood products accelerate bone regeneration for mastoid reconstruction. Autologous SVF cells with PCL scaffolds and autologous blood products are promising composites for mastoid reconstruction which can be easily harvested after mastoidectomy. With this approach, the reconstruction of mastoid bone defects can be performed right after mastoidectomy as a one-step procedure which can offer efficiency in the clinical field.

Establishment of a rabbit's model for modified Capanna technique

Massive bone allograft with an intramedullary vascularized fibula (Capanna technique) represents one of the most widely used methods for the reconstruction of massive bone defect. However, the mechanisms, healing process, and underlying influential factors were poorly understood due to the lack of suitable experimental animal models. Critical-sized defects (CSD) in bone were constructed in the proximal tibia of 24 rabbits and randomly divided into two groups. Allogeneic bone segments of the same size as CSDs were obtained from another 12 rabbits and then inactivated. In group Ⅰ, an ipsilateral pedicled vascularized fibula was dissociated and transferred into the intramedullary cavity of allograft to assemble a composite for CSD reconstruction (Capanna technique), while group Ⅱ received a reconstruction with allogeneic bone alone. Radiographic evaluation was performed every week after the operation to assess union status. All animals were sacrificed at 16th week, and the specimens were histologically analyzed. All animals survived without severe intraoperative complications. There was one rabbit (8.33%) in group Ⅰ developed a postoperative infection and died, while three rabbits (25%) had postoperative complications in group Ⅱ (two died of infection and one died of internal fixation fracture). Radiographically, the mean time to union at the allograft-host junction in group Ⅰ was 12.8±1.80 weeks, significantly shorter than in group II (>15.18±1.12 weeks; p<0.001). The grade of graft union of group Ⅰ was significantly higher than that of group Ⅱ both at 8th and 16th week (8th week: p=0.035; 16th week: p=0.033). Fully bone union at the junctions was histologically confirmed in all specimens in group Ⅰ and 66.67% (8/12) in group Ⅱ. Combined allograft and intramedullary vascularized fibula transfer in rabbit's tibia represent an ideal model that accurately simulates the Capanna technique for CSD reconstruction.

Novel approach to estimate distraction forces in distraction osteogenesis and application in the human lower leg

PurposeIn distraction osteogenesis (DO) of long bones, new bone tissue is distracted to lengthen limbs or reconstruct bone defects. However, mechanical boundary conditions in human application such as arising forces are mainly based on limited empirical data. Our aim was the numerical determination of the callus distraction force (CDF) and the total distraction force (TDF) during DO in the tibia of adults to advance the understanding of callus tissue behavior and optimize DO procedures. MethodWe implemented a mathematical model based on an animal experiment to enable the calculation of forces arising while distracting callus tissue, excluding the influence of surrounding soft tissue (muscles, skin etc.). The CDF progression for the distraction period was calculated using the implemented model and varying distraction parameters (initial gap, area, step size, time interval, length). Further, we estimated the CDF based on reported forces in humans and compared the results to our model predictions. In addition, we calculated the TDF based on our CDF predictions in combination with reported resisting forces due to soft tissue presence in human cadavers. Finally, we compared the progressions to in vivo TDF measurements for validation. ResultsDue to relaxation, a peak and resting CDF is observable for each distraction step. Our biomechanical results show a non-linear degressive increase of the resting and peak CDF at the beginning and a steady non-linear increase thereafter. The calculated resting and peak CDF in the tibial metaphysis ranged from 0.00075 to 0.0089 N and 0.22–2.6 N at the beginning as well as 20–25 N and 70–75 N at the end of distraction. The comparison to in vivo data showed the plausibility of our predictions and resulted in a 10–33% and 10–23% share of resting CDF in the total resting force for bone transport and elongation, respectively. Further, the percentage of peak CDF in total peak force was found to be 29–58% and 27–55% for bone transport and elongation, respectively. Moreover, our TDF predictions were valid based on the comparison to in vivo forces and resulted in a degressive increase from 6 to 125 N for the peak TDF and from 5 to 76 N for the resting TDF. ConclusionOur approach enables the estimation of forces arising due to the distraction of callus tissue in humans and results in plausible force progressions as well as absolute force values for the callus distraction force during DO. In combination with measurements of resisting forces due to the presence of soft tissue, the total distraction force in DO may also be evaluated. We thus propose the application of this method to approximate the behavior of mechanical callus properties during DO in humans as an alternative to in vivo measurements.

Electrospun and 3D printed polymeric materials for one-stage critical-size long bone defect regeneration inspired by the Masquelet technique: Recent Advances

Critical-size long bone defects represent one of the major causes of fracture non-union and remain a significant challenge in orthopaedic surgery. Two-stage procedures such as a Masquelet technique demonstrate high level of success however their main disadvantage is the need for a second surgery, which is required to remove the non-resorbable cement spacer and to place the bone graft into the biological chamber formed by the ‘induced membrane’. Recent research efforts have therefore been dedicated towards the design, fabrication and testing of resorbable implants that could mimic the biological functions of the cement spacer and the induced membrane. Amongst the various manufacturing techniques used to fabricate these implants, three-dimensional (3D) printing and electrospinning methods have gained a significant momentum due their high-level controllability, scalable processing and relatively low cost. This review aims to present recent advances in the evaluation of electrospun and 3D printed polymeric materials for critical-size, long bone defect reconstruction, emphasizing both their beneficial properties and current limitations. Furthermore, we present and discuss current state-of-the art techniques required for characterisation of the materials’ physical, mechanical and biological characteristics. These represent the essential first steps towards the development of personalised implants for single-surgery, large defect reconstruction in weight-bearing bones.

Prefabrication technique by preserving a muscular pedicle from masseter muscle as an in vivo bioreactor for reconstruction of mandibular critical-sized bone defects in canine models.

In vivo bioreactors serve as regenerative niches that improve vascularization and regeneration of bone grafts. This study has evaluated the masseter muscle as a natural bioreactor for βTCP or PCL/βTCP scaffolds, in terms of bone regeneration. The effect of pedicle preservation, along with sole, or MSC- or rhBMP2-combined application of scaffolds, has also been studied. Twenty-four mongrel dogs were randomly placed in six groups, including βTCP, βTCP/rhBMP2, βTCP/MSCs, PCL/βTCP, PCL/βTCP/rhBMP2, and PCL/βTCP/MSCs. During the first surgery, the scaffolds were implanted into the masseter muscle for being prefabricated. After 2months, each group was divided into two subgroups prior to mandibular bone defect reconstruction; one with a preserved vascularized pedicle and one without. After 12 weeks, animals were euthanized, and new bone formation was evaluated using histological analysis. Histological analysis showed that all β-TCP scaffold groups had resulted in significantly greater rates of new bone formation, either with a pedicle surgical approach or non-pedicle surgical approach, comparing to their parallel groups of βTCP/PCL scaffolds (p ≤ .05). Pedicled β-TCP scaffold groups that were treated with either rhBMP2 (48.443% ± 0.250%) or MSCs (46.577% ± 0.601%) demonstrated the highest rates of new bone formation (p ≤ .05). Therefore, masseter muscle can be used as a local in vivo bioreactor with potential clinical advantages in reconstruction of human mandibular defects. In addition, scaffold composition, pedicle preservation, and treatment with MSCs or rhBMP2, influence new bone formation and scaffold degradation rates in the prefabrication technique.

Bio-3D printing of scaffold-free osteogenic and chondrogenic constructs using rat adipose-derived stromal cells.

Although autogenous bone implantation is considered to be the gold standard for the reconstruction of bone defects, this approach remains challenging when treating extensive bone defects (EBDs). Therefore, artificial materials (AMs) such as artificial bone and scaffolds are often used for treating EBDs. Nevertheless, complications such as material failure, foreign body reaction, and infection are common. To overcome these issues, we aimed to develop a new treatment for an EBD using scaffold-free adipose-derived stromal cells (ADSCs) to fabricate chondrogenic/osteogenic-induced constructs without AMs. ADSCs were obtained from the subcutaneous adipose tissue of 8-week-old female Wistar rats (n = 3) and assessed to determine their potential for multilineage differentiation into adipocytes (Oil Red O staining), chondrocytes (hematoxylin and eosin, Alcian blue, and Safranin O staining), and osteoblasts (Alizarin red and von Kossa staining). Spheroids (n = 320), each containing 3.0 × 104 ADSCs, were then used to fabricate scaffold-free cell constructs using a bio-3D printer with a needle array. The spheroids and constructs were stimulated with induction medium to induce chondrogenic and osteogenic differentiation. The induced cartilage- and bone-like constructs were finally evaluated using micro-computed tomography (μCT) and histological analysis. The collected ADSCs were capable of trilineage differentiation, and were successfully used to produce scaffold-free constructs. The fabricated constructs (n = 3) exhibited equivalent strength (load, 195.3 ± 6.1 mN; strength, 39.1 ± 1.2 kPa; and stiffness, 0.09 ± 0.01 N/mm) to that of soft tissues such as the muscles in the uninduced condition. In chondrogenic induction experiments, Alcian blue and Safranin O staining confirmed the differentiation of the constructs into cartilage, and cartilage tissue-like structures were produced. In the osteogenic induction experiment, Alizarin Red and von Kossa staining showed calcium salt deposition, and μCT images confirmed the same calcification level as that of the cortical bone. Scaffold-free constructs consisting of ADSCs without an AM were fabricated, and cartilage- and bone-like tissues were successfully generated, demonstrating their potential for bone reconstruction.

BMP2-Mediated Silica Deposition: An Effective Strategy for Bone Mineralization.

The combined use of an osteogenic factor, such as bone morphogenetic protein 2 (BMP2), with a bone scaffold was quite functional for the reconstruction of bone defects. Although many studies using BMP2 have been done, there is still a need to develop an efficient way to apply BMP2 in the bone scaffold. Here, we reported an interesting fact that BMP2 has a silica deposition ability in the presence of silicic acid and proposed that such an ability of BMP2 can effectively immobilize and transport itself by a kind of coprecipitation of BMP2 with a silica matrix. The presence of BMP2 in the resulting silica was proved by SEM and EDS and was visualized by FITC-labeled BMP2. The delivery efficacy of BMP2 of silica-entrapped BMP2 on osteoblast differentiation and mineralization using MC3T3 E1 preosteoblast cells was evaluated in vitro. The coprecipitated BMP2 with silica exhibited osteogenesis at a low concentration that was insufficient to give an osteoinductive signal as the free form. Expectedly, the silica-entrapped BMP2 exhibited thermal stability over free BMP2. When applied to bone graft substitution, e.g., hydroxyapatite granules (HA), silica-entrapped BMP 2 laden HA (BMP2@Si/HA) showed sustained BMP2 release, whereas free BMP2 adsorbed HA by a simple dipping method (BMP2/HA) displayed a burst release of BMP2 at an initial time. In the rat critical-size calvarial defect model, BMP2@Si/HA showed better bone regeneration than BMP2/HA by about 10%. The BMP2/silica hybrid deposited on a carrier surface via BMP2-mediated silica precipitation demonstrated an increase in the loading efficiency, a decrease in the burst release of BMP2, and an increase in bone regeneration. Taken together, the coprecipitated BMP2 with a silica matrix has the advantages of not only being able to immobilize BMP2 efficiently without compromising its function but also serving as a stable carrier for BMP2 delivery.

Case Report: Large bone defect reconstruction in lower extremities with ipsilateral transposition fibular graft with combined inlay and onlay technique using plate and screw fixation (fibula pro tibia technique)

Introduction: Management of large bone defect is a challenging problem. Hahns, in 1884, introduced the first use of fibula pro tibia to bridge a large defect of the tibia due to chronic osteomyelitis. In this case, we did a transposition of the ipsilateral fibular with inlay and onlay technique using a locking plate and screw into the defect of the tibia. Case presentation: A 20-year-old male came to our emergency department at RSUD Dr. Saiful Anwar, Malang, Indonesia with an open fracture grade III B of his left lower leg. We found a large defect of the tibia approximately 7.5 cm after regular wound care for ten months. Then, we performed ipsilateral transposition fibular graft with combined inlay and onlay technique using a locking plate and screw fixation. No infections occurred and there was progressive callus formation with extending ossification along the periosteal tissue in the four-month postoperative evaluation. There was no leg length discrepancy, and the union sign showed that the patient could achieve full range of movement (ROM) and walk with crutches without pain with a Lower Extremity Functional Scale (LEFS) score of 62. Discussion: Contralateral fibula graft carries a high risk of endangering the unaffected limb. The ipsilateral fibula can be utilized to replace the missing segment with minimal morbidity. The purpose of combining ipsilateral fibular transport with the inlay and onlay technique is to minimalize the gap defect between fracture fragments, therefore enhancing the union rate of the bone. Conclusion: The fibula pro tibia technique can be used as an alternative treatment option for large gap bone defects in lower extremities with minimal complication.

Three-dimensional printing of clinical scale and personalized calcium phosphate scaffolds for alveolar bone reconstruction

ObjectiveAlveolar bone defects can be highly variable in their morphology and, as the defect size increases, they become more challenging to treat with currently available therapeutics and biomaterials. This investigation sought to devise a protocol for fabricating customized clinical scale and patient-specific, bioceramic scaffolds for reconstruction of large alveolar bone defects. MethodsTwo types of calcium phosphate (CaP)-based bioceramic scaffolds (alginate/β-TCP and hydroxyapatite/α-TCP, hereafter referred to as hybrid CaP and Osteoink™, respectively) were designed, 3D printed, and their biocompatibility with alveolar bone marrow stem cells and mechanical properties were determined. Following scaffold optimization, a workflow was developed to use cone beam computed tomographic (CBCT) imaging to design and 3D print, defect-specific bioceramic scaffolds for clinical-scale bone defects. ResultsOsteoink™ scaffolds had the highest compressive strength when compared to hybrid CaP with different infill orientation. In cell culture medium, hybrid CaP degradation resulted in decreased pH (6.3) and toxicity to stem cells; however, OsteoInk™ scaffolds maintained a stable pH (7.2) in culture and passed the ISO standard for cytotoxicity. Finally, a clinically feasible laboratory workflow was developed and evaluated using CBCT imaging to engineer customized and defect-specific CaP scaffolds using OsteoInk™. It was determined that printed scaffolds had a high degree of accuracy to fit the respective clinical defects for which they were designed (0.27 mm morphological deviation of printed scaffolds from digital design). SignificanceFrom patient to patient, large alveolar bone defects are difficult to treat due to high variability in their complex morphologies and architecture. Our findings shows that Osteoink™ is a biocompatible material for 3D printing of clinically acceptable, patient-specific scaffolds with precision-fit for use in alveolar bone reconstructive procedures. Collectively, emerging digital technologies including CBCT imaging, 3D surgical planning, and (bio)printing can be integrated to address this unmet clinical challenge.

Algorithm of surgical treatment of large bone defects of long tubular bones by vascularized bone grafting

The purpose of this study was to develop a clinical classification of large defects of long tubular bones of the extremities and protocols for surgical treatment by vascularized bone grafting.Material and methods. The results of treatment of 51 patients with large defects of the long tubular bones of the upper and lower extremities were analyzed. In 25 cases, along with bone defects, there were significant defects of the soft tissues of the limb with trophic and scar changes. In order to replace the bone defect vascularized grafts were used: bone-muscular fibular, bone-cutaneous fibular, bone-cutaneous iliac, bone-cutaneous radial, bone-cutaneous tibial, and combined bone-cutaneous fibular with an allograft from the tibia. The results of treatment of patients were evaluated according to the clinical criteria of R. Johner, O. Wruhs (1983), proposed for the lower limb. The DASH questionnaire was use to evaluate the results of treatment for upper limb defects.The results and discussion. The classification is based on 4 variable criteria: the size, anatomical localization of the bone defect, the size of the soft tissue defect and the shortening of the damaged limb segment. The size and anatomical location of the defect in the long tubular bone is important in choosing a bone flap. Based on the anatomical localization of the bone defect, soft tissue damage and limb shortening, the patients were classified into 4 types. The first 3 types were divided into 2 subtypes, depending on the size of bone damage and soft tissues defect of the limb. Based on the proposed classification, we have developed protocols for microsurgical reconstruction of large bone defects of the extremities for each subtype of bone defect.Conclusion. The application of the developed clinical classification of large bone defects of long tubular bones and protocols for their surgical treatment by vascularized bone grafting made it possible to restore limb function in 96% of cases.