Biodegradable materials for bone defect repair.

Compared with non-degradable materials, biodegradable biomaterials play an increasingly important role in the repairing of severe bone defects, and have attracted extensive attention from researchers. In the treatment of bone defects, scaffolds made of biodegradable materials can provide a crawling bridge for new bone tissue in the gap and a platform for cells and growth factors to play a physiological role, which will eventually be degraded and absorbed in the body and be replaced by the new bone tissue. Traditional biodegradable materials include polymers, ceramics and metals, which have been used in bone defect repairing for many years. Although these materials have more or fewer shortcomings, they are still the cornerstone of our development of a new generation of degradable materials. With the rapid development of modern science and technology, in the twenty-first century, more and more kinds of new biodegradable materials emerge in endlessly, such as new intelligent micro-nano materials and cell-based products. At the same time, there are many new fabrication technologies of improving biodegradable materials, such as modular fabrication, 3D and 4D printing, interface reinforcement and nanotechnology. This review will introduce various kinds of biodegradable materials commonly used in bone defect repairing, especially the newly emerging materials and their fabrication technology in recent years, and look forward to the future research direction, hoping to provide researchers in the field with some inspiration and reference.

Mechanical behavior of a titanium alloy scaffold mimicking trabecular structure.

BACKGROUND: Additively manufactured porous metallic structures have recently received great attention for bone implant applications. The morphological characteristics and mechanical behavior of 3D printed titanium alloy trabecular structure will affect the effects of artificial prosthesis replacement. However, the mechanical behavior of titanium alloy trabecular structure at present clinical usage still is lack of in-depth study from design to manufacture as well as from structure to mechanical function. METHODS: A unit cell of titanium alloy was designed to mimick trabecular structure. The controlled microarchitecture refers to a repeating array of unit-cells, composed of titanium alloy, which make up the scaffold structure. Five kinds of unit cell mimicking trabecular structure with different pore sizes and porosity were obtained by modifying the strut sizes of the cell and scaling the cell as a whole. The titanium alloy trabecular structure was fabricated by 3D printing based on Electron Beam Melting (EBM). The paper characterized the difference between the designs and fabrication of trabecular structures, as well as mechanical properties and the progressive collapse behavior and failure mechanism of the scaffold. RESULTS: The actual porosities of the EBM-produced bone trabeculae are lower than the designed, and the load capacity of a bearing is related to the porosity of the structure. The larger the porosity of the structure, the smaller the stiffness and the worse the load capacity is. The fracture interface of the trabecular structure under compression is at an angle of 45o with respect to the compressive axis direction, which conforms to Tresca yield criterion. The trabeculae-mimicked unit cell is anisotropy. Under quasi-static loading, loading speed has no effect on mechanical performance of bone trabecular specimens. There is no difference of the mechanical performance at various orientations and sites in metallic workspace. The elastic modulus of the scaffold decreases by 96%-93% and strength reduction 96%-91%, compared with titanium alloy dense metals structure. The apparent elastic modulus of the unit-cell-repeated scaffold is 0.39-0.618 GPa, which is close to that of natural bone and stress shielding can be reduced. CONCLUSION: We have systematically studied the structural design, fabrication and mechanical behavior of a 3D printed titanium alloy scaffold mimicking trabecula bone. This study will be benefit of the application of prostheses with proper structures and functions.

Pre-Registration Assessment of Bone-Filling Products.

The use of bone-filling material to repair bone defects and fix implanted bone grafts is a developing area in medicine. Investigators can evaluate bone-filling materials through use of several indices to make comparisons and to determine suitability for application in humans1 . However, it is quite difficult to transform their discovery into practical use, because the viability of the studied material might require examination of all aspects of properties. In addition, for a material to become a product, a complete procedure involving a declaration, registration, and approval is necessary. This article introduces the technical indices that the investigators and reporters should provide in their declaration and registration data to meet the relevant standards in China. The indices include physical and chemical properties, biocompatibility, biosecurity, pre-clinical animal model tests, sterilization and disinfection, product duration, and packaging. Full consideration of all possible indices is crucial to realize the transformation from a designed product to a commercial medical device, which requires effective interaction between clinicians and engineers.

Bone Graft Displacement After Maxillary Sinus Floor Augmentation With or Without Covering Barrier Membrane: A Retrospective Computed Tomographic Image Evaluation.

PURPOSE: Scientific publications have recently found that bone graft quality and implant survival rates were not influenced by antrostomy membrane coverage during maxillary sinus floor augmentation with a lateral approach. The aim of this study was to evaluate the stability of the bone substitute after a maxillary sinus floor augmentation procedure with or without using a covering membrane. MATERIALS AND METHODS: This retrospective study evaluated all patients who were enrolled between April 2016 and January 2017. The stability of the bone graft inside the sinus cavity as well at the level of the lateral bone window was assessed through preoperative and postoperative cone beam computed tomography images up to 6-month follow-up. The clinical postoperative morbidity was evaluated following a visual analog scale (VAS) protocol. RESULTS: Maxillary sinus floor augmentation with a lateral approach was performed in 41 patients. In 17 cases (10 women/7 men, mean age: 55.4 years), a barrier membrane was used to cover the lateral bone window (control group), and in 24 cases (13 women/11 men, mean age: 56.2 years), no membrane was used (test group). The bone graft dislodgement within the buccal mucosa at 6 months postoperative ranged from 0 to 12.2 mm (mean value: 3.8 ± 3.1 [standard deviation] mm) in the test group and from 0 to 2.3 mm (mean value: 0.5 ± 0.4 mm) in the control group. The postoperative pain and swelling complications were significantly more important for the test group (3.3 ± 1.4/4.3 ± 4.5, respectively) than for the control group (2.1 ± 0.9/2.7 ± 0.9). CONCLUSION: On the basis of this preliminary study, it appears that the use of a barrier membrane to cover the lateral bone window during maxillary sinus floor augmentation surgery with a lateral approach reduces the postoperative dislodgement of the bone graft throughout the sinus antrostomy and prevents the bone substitute particles penetrating within the buccal mucosa, which is related to postoperative morbidity.

In vivo comparative investigation of three synthetic graft materials with varying compositions processed using different methods.

PURPOSE: The aim of this study was to compare the osteoconductive potential and bone-healing pattern of biphasic calcium phosphates (BCPs) with varying compositions produced using different processing methods. MATERIALS AND METHODS: Ten male New Zealand white rabbits were used. Four circular defects with a diameter of 8 mm were made in the rabbit calvarium. Each defect was assigned to one of the following BCP groups: control; BCP1, 70% hydroxyapatite (HA)/30% ß-tricalcium phosphate (ß-TCP); BCP2, 30% HA/70% ß-TCP; and BCP3, 20% HA/80% ß-TCP. The rabbits were killed either 2 (n = 5) or 8 weeks (n = 5) before surgery. Histologic and histomorphometric analyses were conducted. RESULTS: The total amount of augmentation was significantly greater in the BCP groups than in the control group (P < .05). The amount of new bone formation did not differ significantly among the groups at either 2 or 8 weeks. The resorption of BCPs was significantly greater in the BCP3 group than in the BCP1 and BCP2 groups at 2 weeks, but the difference became insignificant compared with the BCP2 group at 8 weeks. The patterns of new bone formation and material resorption varied markedly among the BCP groups. New bone lined the residual particles in the BCP1 group, but filopodia-shaped new bone was observed in the BCP2 group, and collagen fragments were scattered inside the residual particles in the BCP3 group. Multiple cracklike lines were observed on the particles in the BCP3 group. CONCLUSION: The specific HA-ß-TCP ratios in the present study did not significantly influence new bone formation and space maintenance. The observed differences in healing patterns between the groups may be attributable to different physicochemical properties conferred upon the BCPs by the different processing methods used to produce them.

Potential lack of "standardized" processing techniques for production of allogeneic and xenogeneic bone blocks for application in humans.

In the present study, the structure of two allogeneic and three xenogeneic bone blocks, which are used in dental and orthopedic surgery, were histologically analyzed. The ultimate goal was to assess whether the components postulated by the manufacturer can be identified after applying conventional histological and histochemical staining techniques. Three samples of each material, i.e. allogeneic material-1 and -2 as well as xenogeneic material-1, -2 and -3, were obtained commercially. After decalcification and standardized embedding processes, conventional histological staining was performed in order to detect inorganic matrix, cellular or organic matrix components. Allogeneic material-1 showed trabecular bone-like structures, which were free of cellular components as well as of organic matrix. The allogeneic material-2 showed trabecular bone structures, in which connective tissue and cellular remnants were embedded. Additionally, some connective tissue, which resembled fat-like tissue, was found within this material. The xenogeneic material-1 showed trabecular bone-like structures and contained organic components comparable to that demonstrated for the allogeneic material-2. The xenogeneic material-2 showed trabecular bone structures with single cells located in lacunae. The xenogeneic material-3 also showed trabecular structures. Neither cellular nor organic matrix components were found within this material. According to the data of the present study, the allogeneic material-1 and the xenogeneic material-3 were the only investigated materials for which the obtained histological data were in accordance with the manufacturers advertised information. The remaining three materials showed discrepancies-although the manufacturers of all five bone substitute materials stated that their blocks were free of organic/cellular remnants. These data are of great clinical and material science interest. It seems that even patented processing techniques are not always able to deliver reproducible materials. Although the manufacturers of all five bone blocks stated that their blocks were free of organic/cellular remnants, our histological analysis revealed that three out of five bone blocks did contain such remnants. Such specimens might be able to induce an immune response within the recipient.

One-year volume stability of human facial defects filled with a ß-tricalcium phosphate-hydroxyl apatite mixture (Atlantik).

INTRODUCTION: We investigated the applicability and 1-year stability of a ß-tricalcium phosphate-hydroxyl apatite mixture (Atlantik) for secondary reconstruction of craniofacial defects and the application of OsiriX in evaluating bone and implant volumes. METHODS: We included 6 patients (25-59 years) with craniofacial defects. A computed tomography scan was made preoperative, directly postoperative, and at least 1 year postoperative to evaluate volume changes. OsiriX was used to quantify volumes of the implanted Atlantik. Measurements were performed by 2 independent investigators and analyzed by calculating both Pearson correlation and interclass correlation coefficient. RESULTS: After 1 year, the mean volume reduction of the implanted Atlantik was 9.8%. The absolute volume reduction in 1 year was 0.38 cm (range, 0.10-0.69 cm(3)). Pearson correlation test was 0.996, with a significance level of P < 0.01, and the interclass correlation coefficient was 0.998. CONCLUSIONS: Atlantik is a stable osteoconductive material for the repair of various craniofacial defects. There is a reduction of only 10% of the augmented volume in the long term. Applying OsiriX for computed tomography image volume analysis proved to be a well-reproducible technique.

Bone products in surgery: a blueprint for standardization.

Surgical facilities often stock many types of bone and bone products to meet the needs of multiple surgeons. In this era of cost containment, product standardization is necessary for the financial well-being of health care facilities. By familiarizing themselves with bone and bone product harvesting and processing and the US Food and Drug Administration requirements for approval of these products, perioperative nurses and managers can more easily standardize the bone and tissue products stocked and reduce costs. Steps toward standardization include establishing a multidisciplinary surgical product use committee to evaluate products used in the OR, limiting the number of tissue vendors for the facility to as few as possible, completing a product inventory to identify what is currently available, and constructing charts to share with surgeons that provide the rationales for standardizing products.

Instrumented spondylodesis in degenerative spondylolisthesis with bioactive glass and autologous bone: a prospective 11-year follow-up.

A prospective long-term follow-up study of bioactive glass (BAG)-S53P4 and autogenous bone (AB) used as bone graft substitutes for posterolateral spondylodesis in treatment of degenerative spondylolisthesis during 1996 to 1998 was conducted. The surgical procedure was a standardized instrumented posterolateral fusion that used USS/VAS. BAG was implanted on the left side of the fusion bed and AB on the right side. The operative outcome was evaluated on x-rays and computed tomography scans, and a clinical examination was also performed. Seventeen patients (12 women, 5 men) participated in the 11-year follow-up. The mean Oswestry Disability Index score at the follow-up was 21 (range 0 to 52), compared with 49 (range 32 to 64) at the preoperative time. A solid bony fusion was seen on computed tomography scans on the AB side in all patients and on the BAG side in 12 patients. The fusion rate of all fusion sites (n=41) for BAG as a bone substitute was 88% at the L4/5 level and 88% at the L5/S1 level. The use of BAG as a bone graft extender can be considered as a good alternative in spinal surgery in the future.

Optimizing and evaluating the biocompatibility of fiber composites with calcium phosphate additives.

Composite materials based on a polyamide fabric (aramid) and a polydymethylsiloxane (PDMS) matrix were designed for application in bone surgery. In order to increase the bioactivity, 2, 5, 10, 15, 20, and 25 vol.% of nano/micro hydroxyapatite (HA) and tricalcium phosphate (TCP) were added. We studied the effect of the additives on the biocompatibility of the composite. It appears that nano additives have a more favorable effect on mechanical properties than microparticles. 15 vol.% of nano hydroxyapatite additive is an optimum amount for final application of the composites as substitutes for bone tissue: in this case both the mechanical properties and the biological properties are optimized without distinct changes in the inner structure of the composite.

Microstructure and biomechanical characteristics of bone substitutes for trauma and orthopaedic surgery.

BACKGROUND: Many (artificial) bone substitute materials are currently available for use in orthopaedic trauma surgery. Objective data on their biological and biomechanical characteristics, which determine their clinical application, is mostly lacking. The aim of this study was to investigate structural and in vitro mechanical properties of nine bone substitute cements registered for use in orthopaedic trauma surgery in the Netherlands. METHODS: Seven calcium phosphate cements (BoneSource®, Calcibon®, ChronOS®, Eurobone®, HydroSet™, Norian SRS®, and Ostim®), one calcium sulphate cement (MIIG® X3), and one bioactive glass cement (Cortoss®) were tested. Structural characteristics were measured by micro-CT scanning. Compression strength and stiffness were determined following unconfined compression tests. RESULTS: Each bone substitute had unique characteristics. Mean total porosity ranged from 53% (Ostim®) to 0.5% (Norian SRS®). Mean pore size exceeded 100 µm only in Eurobone® and Cortoss® (162.2 ± 107.1 µm and 148.4 ± 70.6 µm, respectively). However, 230 µm pores were found in Calcibon®, Norian SRS®, HydroSet™, and MIIG® X3. Connectivity density ranged from 27/cm3 for HydroSet™ to 0.03/cm3 for Calcibon®. The ultimate compression strength was highest in Cortoss® (47.32 MPa) and lowest in Ostim® (0.24 MPa). Young's Modulus was highest in Calcibon® (790 MPa) and lowest in Ostim® (6 MPa). CONCLUSIONS: The bone substitutes tested display a wide range in structural properties and compression strength, indicating that they will be suitable for different clinical indications. The data outlined here will help surgeons to select the most suitable products currently available for specific clinical indications.

Impactability and time-dependent mechanical properties of porous titanium particles for application in impaction grafting.

AIMS: Impaction grafting with bone particles is a successful technique to restore bone stock loss during hip revision surgery. Allograft shortage is expected within the near future. This study investigates the feasibility of porous titanium particles (TiP) to replace bone particles (BoP) and to compare mechanical properties of TiP and a commercially available porous ceramic bone graft extender (CeP). Impactability and time-dependent mechanical properties (stability and stiffness during physiologic loading (0.1-2.5 MPa)) were assessed by standardized impaction and a confined compression test. Loaded samples were used for particle release analysis. FINDINGS: TiP were more impactable than BoP and created a stable, highly entangled macroporous construct. CeP were crushed during impaction, resulting in non-cohesive specimens of small ceramic particles. TiP showed very little deformation at the end of physiological loading. Impacted TiP were stiffer than BoP but more elastic than CeP. TiP generated a low volume of microparticles (0.2% of original TiP weight) with a bimodal size distribution (diameter range, 7-2000 microm). CONCLUSION: TiP are impactable and create a stable, elastic and highly entangled, macroporous layer. Further in-vitro testing and biological studies are warranted to verify whether the promising results are maintained with THA reconstructions.

Variability across ten production lots of a single demineralized bone matrix product.

BACKGROUND: Demineralized bone matrix is an osteoinductive allograft derived from processed bone that is commonly mixed with autogenous bone in fusion procedures to treat diseases of the spine. An increasing number of demineralized bone matrix-based products are commercially available for spinal fusion procedures, but osteoinductive variability has been found not only across different products but also among production lots from the same demineralized bone matrix formulation. The purpose of this study was to assess the lot-to-lot variability across a single demineralized bone matrix-based product in terms of both extracted bone morphogenetic protein (BMP) concentrations (in vitro) and fusion performance in rats (in vivo). The goal was also to determine whether the in vitro measures could sufficiently and accurately predict the in vivo fusion performance of different demineralized bone matrix-based product lots. METHODS: BMP-2 and BMP-7 were extracted from ten production lots of InterGro DBM Putty and quantified with use of ELISA (enzyme-linked immunosorbent assay). A posterolateral lumbar spinal fusion was performed on forty athymic rats with implantation of a demineralized bone matrix-based product. Fusion success was determined at eight weeks with use of radiographs and manual palpation of the segments. Logistic regression was used to determine the predictive abilities of BMPs. RESULTS: Significant lot-to-lot variability was found in terms of both BMP concentrations (22 to 110 pg of BMP-2 per milligram of product and 44 to 125 pg of BMP-7 per milligram of product) and in vivo rates of fusion (0% to 75%; p < 0.04 for all). BMP-2 and BMP-7 concentrations correlated positively with each other across lots (r = 0.77, p < 0.0001). Most notably, extracted amounts of BMP-2 and BMP-7 each predicted in a dose-dependent manner the in vivo fusion performance in rats (R(2) = 0.32, p < 0.01 for BMP-2, and R(2) = 0.22, p < 0.009 for BMP-7). CONCLUSIONS: Assays for demineralized bone matrix-extracted BMP-2 and BMP-7 levels may be feasible and sufficient for predicting spinal fusion performance of individual production lots from the same demineralized bone matrix-based product.

Calcium phosphate cement augmentation in the treatment of depressed tibial plateau fractures with open reduction and internal fixation.

OBJECTIVES: We aimed to evaluate the clinical and radiological outcomes of open reduction and internal fixation augmented with calcium phosphate cement (CPC) in the treatment of depressed tibial plateau fractures. METHODS: Twenty-eight knees of 28 patients [19 males and 9 females; mean age, 41.2 years (range 22-72 years)] who had open reduction and internal fixation combined with CPC augmentation were included in this study. Seventeen fractures were Schatzker type II, 5 were type III, 3 were type IV, 2 were type V, and 1 was type VI. CPC was used to fill the subchondral bone defects in all knees. Fixation of the fragments was done with screws in 3 knees (10%). Standard proximal tibial plates or buttress plates were used in 25 knees (90%) with an additional split fragment extending distally to achieve internal fixation. Full weight-bearing was allowed in 6.4 weeks (range 6-12 weeks) after surgery. Resorption of CPC granules was defined as the decrease in the size and density of grafting material on radiographs. Rasmussen's radiological and clinical scores were determined postoperatively. Functionality was assessed with Lysholm knee scoring system. Activity was graded with Tegner's activity scale. RESULTS: Union was achieved in all patients with a mean follow-up of 22.2 months (range 6-36 months). There were no intraoperative complications. At the latest follow-up radiographs, resorption of the graft was observed in 25 knees (89%). Rasmussen's radiologic score was excellent in 17 patients (61%), good in 9 patients (32%), and fair in 2 patients (7%). Rasmussen's clinical score was excellent in 9 patients (32%), good in 18 patients (64%), and fair in 1 patient (4%). According to the Lysholm knee score, functional results were excellent in 16 patients (57%), good in 8 patients (29%), and fair in 4 patients (14%). Twenty-two patients (78%) achieved the preoperative activity level after surgery, and there was no significant difference between the mean preoperative and postoperative Tegner scores (4.11±0.68 and 4.04±0.64, respectively, p=0.161). CONCLUSION: CPC is a safe biomaterial with many advantages in augmenting the open reduction and internal fixation of depressed tibial plateau fractures, including elimination of morbidity associated with bone graft harvesting, the unlimited supply of bone substitute, the optimum filling of irregular bone defects, and shortening of the postoperative full weight-bearing time.

Use of autologous bone graft in anterior cervical decompression: morbidity & quality of life analysis.

BACKGROUND: Autologous iliac crest graft has long been the gold standard graft material used in cervical fusion. However its harvest has significant associated morbidity, including protracted postoperative pain scores at the harvest site. Thus its continued practice warrants scrutiny, particularly now that alternatives are available. Our aims were to assess incidence and nature of complications associated with iliac crest harvest when performed in the setting of Anterior Cervical Decompression (ACD). Also, to perform a comparative analysis of patient satisfaction and quality of life scores after ACD surgeries, when performed with and without iliac graft harvest. METHODS: All patients who underwent consecutive ACD procedures, with and without the use of autologous iliac crest graft, over a 48 month period were included (n = 53). Patients were assessed clinically at a minimum of 12 months postoperatively and administered 2 validated quality of life questionnaires: the SF-36 and Cervical Spine Outcomes Questionnaires (Response rate 96%). Primary composite endpoints included incidence of bone graft donor site morbidity, pain scores, operative duration, and quality of life scores. RESULTS: Patients who underwent iliac graft harvest experienced significant peri-operative donor site specific morbidity, including a high incidence of pain at the iliac crest (90%), iliac wound infection (7%), a jejunal perforation, and longer operative duration (285 minutes vs. 238 minutes, p = 0.026). Longer term follow-up demonstrated protracted postoperative pain at the harvest site and significantly lower mental health scores on both quality of life instruments, for those patients who underwent autologous graft harvest CONCLUSION: ACD with iliac crest graft harvest is associated with significant iliac crest donor site morbidity and lower quality of life at greater than 12 months post operatively. This is now avoidable by using alternatives to autologous bone without compromising clinical or technical outcome.

Endocultivation: 3D printed customized porous scaffolds for heterotopic bone induction.

The aim of this study was to evaluate the ability of computer assisted designed (CAD) synthetic hydroxyapatite and tricalciumphosphate blocks to serve as precise scaffolds for intramuscular bone induction in a rat model. A central channel to allow for vessel pedicle or nerve integration was added. Natural bovine hydroxyapatite blocks served as controls to evaluate and compare biocompatibility of the new matrices. Individually designed 3D-printed rounded and porous hydroxyapatite (HA) and tricalcium phosphate (TCP) blocks were placed in pouches in the Musculus latissimus dorsi in 12 Lewis rats bilaterally. Bovine hydroxyapatite blocks with and without a central channel served as controls. Simultaneously, 200 microg rhBMP-2 in 1 ml sodium chloride was injected on both sides. For 8 weeks, bone generation was monitored by computer tomography and fluorescence labeling. The increase rates of bone density in CT examinations were higher in the HA groups (184-220 HU 8 weeks after implantation) compared to the TCP group (18 HU; p<0.0001). Microradiography and fluorescence microscopy 8 weeks after implantation showed new bone formation for all materials tested. For all scaffolds, toluidine staining revealed vital bone directly on the scaffold materials but also in the gaps between. It can be concluded from our data that the specially shaped hydroxyapatite and tricalcium phosphate blocks tested against the bovine hydroxyapatite blocks showed good biocompatibility and osteoinductivity in vivo. Further studies should explore if the stability of the individually designed blocks is sufficient to cultivate larger replacements without an external matrix for support.

Comparative performance of three ceramic bone graft substitutes.

BACKGROUND CONTEXT: A number of different synthetic calcium-based bone graft substitutes (BGS) are currently available for clinical use. There is, however, a lack of comparative performance data regarding the relative efficacy of these materials when placed in an osseous defect site. PURPOSE: To compare the rate, quality, and extent of osseous healing in a standard rabbit defect model for three commercially available BGS materials by measuring early bone formation and completion of defect healing and to identify whether rapid scaffold resorption stimulated or impaired bone healing. STUDY DESIGN: Osteochondral defects, 4.8 mm in diameter and 6 to 7 mm deep, were made through the articular surface into the subchondral bone of the femoral condyle of New Zealand White rabbits and filled with cylindrical pellets of one of three commercially available BGS materials: dense calcium sulfate (DCaS), ultraporous tricalcium phosphate (beta-TCP), and porous silicated calcium phosphate (Si-CaP). The repair response was examined at 1, 3, 6, and 12 weeks after surgery (n=4 per BGS per time point). METHOD: Qualitative histological and quantitative histomorphometric (% new bone, % bone graft substitute, capillary index, and mineral apposition rates) analysis. RESULTS: Rapid resorption of D-CaS, primarily through dissolution, elicited a mild inflammatory response that left the defect site empty before significant quantities of new bone were formed. Both beta-TCP and Si-CaP scaffolds supported early bone apposition (<1 week). However, beta-TCP degradation products subsequently provoked an inflammatory response that impaired and reversed bone apposition within the defect site. The Si-CaP scaffolds appeared to be more stable and supported further bone apposition, with the development of an adaptive bone-scaffold composite; cell-mediated resorption of scaffold and new bone were observed in response to local load and contributed to the production of a functional repair within the defect site. CONCLUSIONS: Rapid BGS resorption impaired the regenerative ability of local bone via three pathways: 1) insufficient persistence of an osteoconductive scaffold to encourage bone apposition, 2) destabilization of early bony apposition through scaffold disintegration, and 3) stimulation of an inflammatory response by elevated levels of particulate degradation products. This had a significant impact on the ultimate rate of healing. D-CaS did not stimulate early bone apposition, but bone repair was more advanced in D-CaS-treated defects at 12 weeks as compared with those treated with beta-TCP, despite the beta-TCP supporting direct bone apposition at 1 week. Si-CaP appeared to provide a more stable osteoconductive scaffold, which supported faster angiogenesis and bone apposition throughout the defect site, with the development of a functionally adaptive trabecular structure through resorption/remodelling of both scaffold and new bone. There was rapid formation of mineralized tissue at week 1 within the center of the defect and complete infiltration with dense, predominantly mature bone by weeks 3 to 6. The progressive remodeling of bone ingrowth and scaffold to reflect the distribution of local host tissue, combined with histological evidence of targeted osteoclastic resorption of both scaffold and bone, suggest that bone adaptation within the scaffold could be in response to Wolff's law. Although this model may not directly translate to a spinal fusion model and the products may vary according to the environment, these results suggest that, in patients in whom bone regeneration may be compromised, the degradation observed with some resorbable bone grafts may contribute to the decoupling of bone regeneration and resorbtion within the graft site, which may ultimately lead to incomplete bone repair.

Extensive H(+) release by bone substitutes affects biocompatibility in vitro testing.

Bone substitutes are widespread in orthopedic and trauma surgery to restore critical bony defects and/or promote local bone healing. Cell culture systems have been used for many years to screen biomaterials for their toxicity and biocompatibility. This study applies a human bone marrow cell culture system to evaluate the toxic in vitro effects of soluble components of different bone substitutes, which are already in clinical use. Different specimens of tricalcium phosphates (TCP) (Vitoss, Cerasorb), nondecalcified bovine bone (Lubboc), demineralized human bone matrices (DBM) (Grafton Flex/Putty), and collagen I/III matrix (ACI-Maix) were tested in Dulbecco's modified Eagle's medium (DMEM) and MesenCult culture solution and compared with a biomaterial-free cell culture. Biocompatibility parameters were cell viability evaluated by phase-contrast microscopy and laser flow cytometry, morphology, and the local H(+) release by bone substitutes. There were significant differences (p < 0.05) between the tested biomaterials and culture solutions. Collagen I/III, non-demineralized bovine bone, and TCP materials showed advantages for cell survival over other tested biomaterials (average values of vital cells/mL MesenCult/DMEM: Collagen I/III: 1090/1083; Vitoss: 893/483; Cerasorb: 471/523; Lubboc: 815/410; Grafton Putty: 61/44; Grafton Flex: 149/57). Especially the DBM materials lead to a significant decrease of pH, which is considered to be a major factor for cell death. DMEM culture solution supports cell survival for those bone substitutes that induce an alkaline reaction, whereas MesenCult media promotes cell vitality in biomaterials, which leads to an acidification of culture solution.

[Experimental study of the biocompatible and osteoinductive behavior of the hydroxyapatite/ultra-high molecular weight polyethtlene composite].

OBJECTIVE: To compare the biocompatibility and osteoinductive behavior of HA (hydroxyapatite) and HA/UHMWPE (ultra-high molecular weight polyethtlene) composite in orbital implantation. METHODS: Osteoectomy of the upper orbital rim was perform on 24 adult New Zealand rabbits. The animals were randomly divided into 4 groups with 6 of each. The HA, HA/UHMWPE composite or UHMWPE (10 mm x 10 mm x 3 mm in size) was implanted to the upper orbital defect of the animal in respective group. Animals were sacrificed at 1, 4, 8, 12 weeks. Histopathologic sections of the implants were evaluated and compared with light and transmission electron microscopy study. RESULTS: During the experimental period of 12 weeks, there was no implant extrusion or displacement. In the groups of HA and HA/UHMWPE composite, vascular ingrowth and fibroblasts were observed shortly and osteocytes were seen at 8 weeks. Calcium deposition of the implants showed a laminar fashion at 12 weeks. In the group of UHMWPE, fibrous membranes were seen around the implant at 1 week. Transmission electron microscopy study showed that in the HA and HA/UHMWPE groups, fibroblasts and vascular ingrowth could be seen, but osteocytes were not observed. CONCLUSION: HA/UHMWPE composite demonstrated biocompatibility and osteoinductive property. It would be a good substitute for bone, particularly for orbital bone.