The clinical results of treating Kummell's disease with mineralized collagen modified polymethyl methacrylate.

To investigate the clinical results of treating Kummell's Disease by using mineralized collagen modified polymethyl methacrylate bone cement, 23 cases (23 vertebras) who sustained Kummell's Disease treated with mineralized collagen modified polymethyl methacrylate bone cement from July 2017 to February 2019 were reviewed retrospectively. The visual analogue scale, vertebral body height, Cobb angle, CT values pre-operation and post-operation as well as incidence of complications were observed. All the patients were successfully followed up with an average period of 11.3 months (ranging from 6 to 12 months). The patients could ambulate on the second day after the operation. The visual analogue scale scores significantly decreased from two days after the operation to the last follow-up compared with that before the operation (p < 0.05); the average vertebral height and local Cobb angle had significant recovery (p < 0.05); the CT value of the treated vertebra significantly increased compared with that before the operation (p < 0.05). Bone cement leakage occurred in one case, anterior edge leakage occurred in one case, and no clinical symptoms caused by bone cement leakage occurred. No re-fracture of the treated vertebral body or adjacent vertebral bodies were observed in the follow-ups. With good osteogenic activity and degradable absorption characteristics, mineralized collagen was compounded with the existing polymethyl methacrylate bone cement to reduce its strength in the vertebral body and enhance biocompatibility, the incidence of adjacent vertebral fractures and re-fractures within the injured vertebrae is significantly reduced, and good clinical results are obtained, which is worthy of popularization.

The study of mechanical and drug release properties of the mineralized collagen/polylactic acid scaffold by tuning the crystalline structure of polylactic acid.

Open bone fractures in clinical are not only difficult to heal but also at a high risk of infections. Annual cases of fractures which result from osteoporosis amount to approximately 9 million. The objective of this study is to load the antibiotic drug of vancomycin and tune its controlled delivery on a bone repair scaffold material of Mineralized Collagen/poly(lactic acid) (MCP) via changing the crystallinity of poly(lactic acid) to achieve inhibiting infection while repairing defects. We explored the crystallization process of the material during molding and prepared non-crystalline MCP1, MCP2, MCP3 and MCP4 by rapid freeze forming and crystalline MCP5 by tuning temperature decreasing rate. This method can control the micropore structure of the material; and the material changes from brittleness to toughness, which greatly enhances the control of mechanical properties. The drug release behavior of the material was studied for 28 days. Furthermore, the antibacterial property of the material was tested by the zone of inhibition, which shows the material good bacteriostasis. The controllable MCPs are expected to be substitutes for the treatment of infectious bone defects applying to clinical practical treatment.

Bioactive poly (methyl methacrylate) bone cement for the treatment of osteoporotic vertebral compression fractures.

Rationale: Poly (methyl methacrylate) (PMMA) bone cement is one of the most commonly used biomaterials for augmenting/stabilizing osteoporosis-induced vertebral compression fractures (OVCFs), such as percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP). However, its clinical applications are limited by its poor performance in high compressive modulus and weak bonding to bone. To address these issues, a bioactive composite bone cement was developed for the treatment of osteoporotic vertebral compression fractures, in which mineralized collagen (MC) was incorporated into the PMMA bone cement (MC-PMMA). Methods: The in vitro properties of PMMA and MC-PMMA composite bone cement were determined, including setting time, compressive modulus, adherence, proliferation, and osteogenic differentiation of rat bone mesenchymal stem cells. The in vivo properties of both cements were evaluated in an animal study (36 osteoporotic New Zealand female rabbits divided equally between the two bone cement groups; PVP at L5) and a small-scale and short-term clinical study (12 patients in each of the two bone cement groups; follow-up: 2 years). Results: In terms of value for PMMA bone cement, the handling properties of MC-PMMA bone cement were not significantly different. However, both compressive strength and compressive modulus were found to be significantly lower. In the rabbit model study, at 8 and 12 weeks post-surgery, bone regeneration was more significant in MC-PMMA bone cement (cortical bone thickness, osteoblast area, new bone area, and bone ingrowth %; each significantly higher). In the clinical study, at a follow-up of 2 years, both the Visual Analogue Score and Oswestry Disability Index were significantly reduced when MC-PMMA cement was used. Conclusions: MC-PMMA bone cement demonstrated good adaptive mechanical properties and biocompatibility and may be a promising alternative to commercial PMMA bone cements for the treatment of osteoporotic vertebral fractures in clinical settings. While the present results for MC-PMMA bone cement are encouraging, further study of this cement is needed to explore its viability as an ideal alternative for use in PVP and BKP.

Minimally invasive injectable lumbar interbody fusion with mineralized collagen-modified PMMA bone cement: A new animal model.

This study was to develop a feasible and safe animal model for minimally invasive injectable lumbar interbody fusion using a novel biomaterial, mineralized collagen-polymethylmethacrylate bone cement (MC-PMMA), with unilateral pedicle screw fixation in an in vivo goat model. Eight goats (Capra aegagrus hircus) were divided into three groups: MC-PMMA, unmodified commercial-polymethylmethacrylate bone cement (UC-PMMA), and a control group (titanium cage filled with autogenous bone, TC-AB). Each group of goats was treated with minimally invasive lumbar interbody fusion at the L3/L4 and L5/L6 disc spaces (injected for MC-PMMA and UC-PMMA, implanted for TC-AB). The pedicle screws were inserted at the L3, L4, L5, and L6 vertebrae, respectively, and fixed on the left side. The characteristics of osteogenesis and bone growth were assessed at the third and the sixth month, respectively. The methods of evaluation included the survival of each animal, X-ray imaging, and 256-layer spiral computed tomography (256-CT) scanning, imaged with three-dimensional microfocus computed tomography (micro-CT), and histological analysis. The results showed that PMMA bone cement can be extruded smoothly after doping MC, the MC-PMMA integrates better with bone than the UC-PMMA, and all goats recovered after surgery without nerve damage. After 3 and 6 months, the implants were stable. New trabecular bone was observed in the TC-AB group. In the UC-PMMA group a thick fibrous capsule had formed around the implants. The MC-PMMA was observed to have perfect osteogenesis and bone ingrowth to adjacent bone surface. Minimally invasive injectable lumbar interbody fusion using MC-PMMA bone cement was shown to have profound clinical value, and the MC-PMMA showed potential application prospects.

Mineralized Collagen Modified Polymethyl Methacrylate Bone Cement for Osteoporotic Compression Vertebral Fracture at 1-Year Follow-up.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: This study aimed to compare the clinical effects and imaging features of polymethyl methacrylate (PMMA) bone cement with and without mineralized collagen (MC) in percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs). SUMMARY OF BACKGROUND DATA: PKP with PMMA is widely performed for OVCF. However, numerous complications have also been reported about the PMMA bone cement. Moreover, PMMA bone cement with and without MC have not been compared with respect to their postoperative efficacy and long-term follow-up. METHODS: From July 2016 to July 2017, 105 OVCF patients were randomly divided into two groups based on their PKP treatment: MC-PMMA group and PMMA group. Clinical operation, cement leakage, Oswestry Disability Index, visual analog scale, height of the fractured vertebrae, Cobb angle, refracture of the adjacent vertebra, recompression, and computed tomography values of the injured vertebra were compared between the two groups postoperatively and after 1-year follow-up. RESULTS: Clinical operation showed no differences between the two groups. Visual analog scale scores, Oswestry Disability Index scores, and Cobb angles showed statistically significant differences between the two groups after 1-year follow-up. The height of the vertebral body showed significant difference at 3 days postoperatively and preoperatively in each group and significant difference after 1 year between the two groups. The rate of refracture and leakage of the MC-PMMA group was lower than that of the PMMA group. The computed tomography value of the MC-PMMA group was obviously higher than that of the PMMA group after 1-year follow-up. CONCLUSION: MC-modified PMMA did not change the beneficial properties of PMMA. This new bone cement has better biocompatibility, can form a stable structure in the vertebral body, and improve the prognosis of patients by reducing pain and reoperation. LEVEL OF EVIDENCE: 3.

Clinical outcome comparison of polymethylmethacrylate bone cement with and without mineralized collagen modification for osteoporotic vertebral compression fractures.

A retrospective study of consecutive patients.The purpose of this study was to compare the clinical effect of biomimetic mineralized collagen (MC) modified polymethylmethacrylate (PMMA) bone cement and traditional PMMA bone cement for the treatment of osteoporotic vertebral compression fractures (OVCF).New fracture on adjacent level is the major postoperative complication of percutaneous vertebroplasty (PVP). The clinical incidence was 12.4% to 27.7%. The increased stiffness of the treated vertebral body caused by filling bone cement is considered as one of the main reasons.A total of 30 patients treated with traditional PMMA bone cement from June 2013 to March 2016 were selected as the traditional group, while 50 patients treated with MC modified PMMA bone cement from July 2014 to March 2016 were selected as the modified group. The 2 groups were compared by injection time of the bone cements, postoperative pain relief effects, vertebral height restoration, CT value changes of the treated vertebral bodies, and postoperative complications in the clinical observations.The surgeries were successfully completed in both groups. In the treatment of OVCF, the MC modified bone cement was able to achieve the same pain relief and vertebral height restoration effects compared to traditional bone cement during the follow-ups, although the injection time of the cement was prolonged in the operation. MC modified bone cement significantly reduced the incidence of postoperative adjacent vertebral fracture from 13.3% to 2%, and significantly increased bone density of the treated vertebral bodies.The MC modified PMMA bone cement showed good clinical outcomes and better mechanical properties than the traditional bone cements.

[Application of biomimetic mineralized collagen bone graft material in rabbits posterolateral spinal fusion].

Objective: To investigate the bone repair and regeneration ability of biomimetic mineralized collagen bone graft material and autologous bone marrow in rabbit posterolateral spinal fusion model. Methods: Twenty-seven 20-week-old male New Zealand white rabbits ï¼»weighing (5.0±0.5) kgï¼½ were used to establish the posterolateral spinal fusion model of L 5 and L 6 segments by stripping the transverse process and exposing cancellous bone with electric burr. The rabbits were randomly divided into 3 groups, 9 in each group. Groups A, B, and C were implanted 1.5 mL autologous iliac bone, 1.5 mL (30 mm×10 mm×5 mm) biomimetic mineralized collagen bone graft material, and 1.5 mL (30 mm×10 mm×5 mm) biomimetic mineralized collagen bone graft material and autologous bone marrow in each bone defect. At 4, 8, and 12 weeks after operation, the apparent hardness of the bone grafting area was observed by manipulation method, in order to evaluate bone graft fusion effects. Three animals were sacrificed in each group at each time point, the vertebral body specimens were excised and the bone defect repair and fusion were observed by X-ray films, and three-dimensional CT examination was performed to evaluate whether new bone was formed in the body. HE staining was performed at each time point to observe the formation of new bone and the repair and fusion of bone defects. Results: The manipulation test showed that bone graft fusion was not found in all groups at 4 weeks after operation; 3 (50.0%), 2 (33.3%), and 4 (66.7%) of groups A, B, and C reached bone graft fusion at 8 weeks after operation; 5 (83.3%), 4 (66.7%), and 5 (83.3%) of groups A, B, and C reached bone graft fusion at 12 weeks after operation; the fusion rate of group C was similar to that of group A, and all higher than that of group B. X-ray film observation showed that the fusion rate of group C at 8 and 12 weeks after operation was higher than that of group B, similar to group A. Three-dimensional CT observation showed that the effect of bone fusion in group C was better than that in group B, which was close to group A. HE staining observation showed that large area of mature lamellar bone coverage appeared in the bone graft area of groups A, B, and C at 12 weeks after operation, the material was completely degraded, and the marginal boundary of the host bone disappeared and tightly combined. Conclusion: Biomimetic mineralized collagen bone graft material mixed with autologous bone marrow has good osteoinduction and osteogenesis guidance. Compared with biomimetic mineralized collagen bone graft material, it has better and faster osteogenesis effect, which is close to autologous bone transplantation.

Integrating 3D Printing and Biomimetic Mineralization for Personalized Enhanced Osteogenesis, Angiogenesis, and Osteointegration.

Titanium (Ti) alloy implants can repair bone defects at load-bearing sites. However, they mechanically mismatch with the natural bone and lack customized adaption with the irregularly major-sized load-bearing bone defects, resulting in the failure of implant fixation. Mineralized collagen (MC), a building block in bone, can induce angiogenesis and osteogenesis, and 3D printing technology can be employed to prepare scaffolds with an overall shape customized to the bone defect. Hence, we induced the formation of MC, made of hydroxyapatite (HAp) nanocrystals and collagen fibers, in 3D-printed porous Ti6Al4V (PT) scaffolds through in situ biomimetic mineralization. The resultant MC/PT scaffolds exhibited a bone-like Young's modulus and were customized to the anatomical contour of actual bone defects of rabbit model. We found that the biocompatibility and osteogenic differentiation are best when the mass ratio between HAp nanocrystals and collagen fibers is 1 in MC. We then implanted the MC/PT scaffolds into the customized radius defect rabbit model and found that the MC/PT scaffolds significantly improved the vascularized bone tissue formation and integration between new bone and the implants. Therefore, a combination of 3D printing and biomimetic mineralization could lead to customized 3D PT scaffolds for enhanced angiogenesis, osteogenesis, and osteointegration. Such scaffolds represent novel patient-specific implants for precisely repairing irregular major-sized load-bearing bone defects.

Comparison of human mesenchymal stem cells proliferation and differentiation on poly(methyl methacrylate) bone cements with and without mineralized collagen incorporation.

Poly(methyl methacrylate) bone cement is widely used in vertebroplasty, joint replacement surgery, and other orthopaedic surgeries, while it also exposed many problems on mechanical property and biocompatibility. Better performance in mechanical match and bone integration is highly desirable. Recently, there reported that incorporation of mineralized collagen into poly(methyl methacrylate) showed positive results in mechanical property and osteointegration ability in vivo. In the present study, we focused on the comparison of osteogenic behavior between mineralized collagen incorporated in poly(methyl methacrylate) and poly(methyl methacrylate). Human marrow mesenchymal stem cells are used in this experiment. Adhesion and proliferation were used to characterize biocompatibility. Activity of alkaline phosphatase was used to assess the differentiation of human marrow mesenchymal stem cells into osteoblasts. Real-time PCR was performed to detect the expression of osteoblast-related markers at messenger RNA level. The results show that osteogenic differentiation on mineralized collagen incorporated in poly(methyl methacrylate) bone cement is more than two times higher than that of poly(methyl methacrylate) after culturing for 21 days. Thus, important mechanism on mineralized collagen incorporation increasing the osteogenetic ability of poly(methyl methacrylate) bone cement may be understood in this concern.

Test in canine extraction site preservations by using mineralized collagen plug with or without membrane.

The aim of this study was to discuss the feasibility of porous mineralized collagen plug and bilayer mineralized collagen-guided bone regeneration membrane in site preservation in extraction sockets. The third mandibular premolars on both sides were extracted from four dogs, thus there were 16 alveolar sockets in all dogs and were randomly assigned into three groups. Group A had six alveolar sockets, and groups B and C had five alveolar sockets, respectively. Each alveolar socket of group A was immediately implanted with a porous mineralized collagen plug and covered with a bilayer mineralized collagen-guided bone regeneration membrane after tooth extraction. Alveolar sockets of group B were implanted with porous mineralized collagen plug only, and group C was set as blank control without any implantation. The healing effects of the extraction sockets were evaluated by gross observation, morphological measurements, and X-ray micro-computed tomography after twelve weeks. Twelve weeks after operation, both groups A and B had more amount of new bone formation compared with group C; in terms of the degree of alveolar bone height, group A was lower than groups B and C with significant differences; the bone mineral density in the region of interest and bone remodeling degree in group A were higher than those of groups B and C. As a result, porous mineralized collagen plug could induce the regeneration of new bone in extraction socket, and combined use of porous mineralized collagen plug and bilayer mineralized collagen guided bone regeneration membrane could further reduce the absorption of alveolar ridge and preserve the socket site.

Clinical evaluations of mineralized collagen in the extraction sites preservation.

The purpose of this study was to explore the different effects between biomimetic mineralized collagen (MC) and ordinary physically blended hydroxyapatite/collagen (HA/Col) composite in evaluating new bone formation and regenerated bone height in human extraction sockets. Thirty-four patients who cannot retain teeth caused by trauma or decay were randomly selected from Department of Stomatology of Dongzhimen Hospital from December 2013 to December 2014. The patients were randomly divided into two groups. After the operation of tooth extraction, 17 patients were implanted with biomimetic MC (MC group), and other 17 patients were implanted with ordinary physically blended nHA/Col composite (nHA/Col group). X-ray positioning projection by auto-photographing was taken to test the distance between the lowest position and the neighboring CEJm-CEJd immediately, 1 month and 3 months after the operation. The height of new bone formation of the MC group was significantly higher than the nHA/Col group. Biomimetic MC showed better clinical outcomes in the bone formation for extraction site preservation and would have broad application prospect in the field of oral and maxillofacial surgeries.

Influence of Nano-HA Coated Bone Collagen to Acrylic (Polymethylmethacrylate) Bone Cement on Mechanical Properties and Bioactivity.

OBJECTIVE: This research investigated the mechanical properties and bioactivity of polymethylmethacrylate (PMMA) bone cement after addition of the nano-hydroxyapatite(HA) coated bone collagen (mineralized collagen, MC). MATERIALS & METHODS: The MC in different proportions were added to the PMMA bone cement to detect the compressive strength, compression modulus, coagulation properties and biosafety. The MC-PMMA was embedded into rabbits and co-cultured with MG 63 cells to exam bone tissue compatibility and gene expression of osteogenesis. RESULTS: 15.0%(wt) impregnated MC-PMMA significantly lowered compressive modulus while little affected compressive strength and solidification. MC-PMMA bone cement was biologically safe and indicated excellent bone tissue compatibility. The bone-cement interface crosslinking was significantly higher in MC-PMMA than control after 6 months implantation in the femur of rabbits. The genes of osteogenesis exhibited significantly higher expression level in MC-PMMA. CONCLUSIONS: MC-PMMA presented perfect mechanical properties, good biosafety and excellent biocompatibility with bone tissues, which has profoundly clinical values.

An improved biofunction of titanium for keratoprosthesis by hydroxyapatite-coating.

Titanium framework keratoprosthesis has been commonly used in the severe corneal blindness, but the tissue melting occurred frequently around titanium. Since hydroxyapatite has been approved to possess a good tissue integration characteristic, nanostructured hydroxyapatite was coated on the surface of titanium through the aerosol deposition method. In this study, nanostructured hydroxyapatite coating was characterized by X-ray diffraction, scanning electron microscopy, atomic force microscopy, and auger electronic spectrometer. Biological evaluations were performed with rabbit cornea fibroblast in vitro and an animal model in vivo. The outcomes showed the coating had a grain-like surface topography and a good atomic mixed area with substrate. The rabbit cornea fibroblasts appeared a good adhesion on the surface of nanostructured hydroxyapatite in vitro. In the animal model, nanostructured hydroxyapatite-titanium implants were stably retained in the rabbit cornea, and by contrast, the corneal stroma became thinner anterior to the implants in the control. Therefore, our findings proved that nanostructured hydroxyapatite-titanium could not only provide an improved bond for substrate but also enhance the tissue integration with implants in host. As a promising material, nanostructured hydroxyapatite-titanium-based keratoprosthesis prepared by the aerosol deposition method could be utilized for the corneal blindness treatment.

The mineralized collagen for the reconstruction of intra-articular calcaneal fractures with trabecular defects.

BACKGROUND: In cases of severe subversion of the morphology of calcaneal fractures with trabecular defects, bone graft is often necessary to provide a mechanical buttress. The mineralized collagen (MC) is a novel bone substitute that is developed by biomimetic synthesis strategy that mimics the extracellular matrix (ECM) of natural bone in structure and chemical composition. It can avoid donor site morbidity and complications associated with harvesting autologous bone graft. OBJECTIVE: In this study, we conducted a retrospective matched-pair analysis to assess the clinical and radiological performances of MC as a bone graft substitute in intra-articular calcaneal fractures with trabecular defects. METHODS: 24 pairs of intra-articular calcaneal fractures with trabecular defects were treated with open reduction, internal fixation, and grafting either with MC or autograft. Patient demographics, medical history, and CT fracture classification were matched. Fractures were monitored 6 weeks, 12 weeks, 6 months, and 1 year postoperatively for healing and postoperative complications and results were analyzed. RESULTS: All patients had follow-up at a minimum of 12 months after surgery with a mean follow-up time of 17 months. All fractures were healed; there were no significant differences in the meantime to union and clinical between the two groups. The radiographic evaluation confirmed that a significant improvement in the mean Böhler's angle, Gissane's angle and the calcaneus height was observed in all patients in both treatment groups. A total of 29% (7/24) of patients suffered from harvest-site morbidity at 12 months in the autograft group. In contrast, all patients were free from postoperative local complications in the iliac region and no patient developed adverse reactions attributable to MC in the MC group. CONCLUSION: These results justify and favor the use of MC as a good autograft alternative in displaced intra-articular calcaneal fractures with trabecular defects.

A modified double-emulsion method for the preparation of daunorubicin-loaded polymeric nanoparticle with enhanced in vitro anti-tumor activity.

The encapsulation of hydrophilic drug in polymeric nanoparticles with high loading remains a challenge due to the rapid penetration of the drug to the external aqueous phase. In order to improve the encapsulation efficiency of daunorubicin (DNR) in poly(D,L-lactic-co-glycolic acid (PLGA) and poly(D,L-lactic acid) (PDLLA) nanoparticles, we fabricated a series of DNR-loaded nanoparticles using a modified double-emulsion solvent evaporation/diffusion method, which introduced a partially water-soluble organic solvent into the particle formation. The influence of various preparation parameters was investigated systematically, such as the ratio of organic solvent, the type of surfactant, the type of polymers and the molecular weight. Results showed that regular spherical PLGA nanoparticles with diameters of 200-300 nm could be produced with a remarkably high DNR encapsulation efficiency (>80%) and loading (6.5% (w/w)). Upon encapsulation, the sustained release of DNR could be controlled over 2 weeks. The results of FT-IR and DSC analysis indicated that the encapsulated DNR in polymeric nanoparticles was inclusion, not absorption. Furthermore, optimized DNR/PLGA nanoparticles showed a significant enhancement of cellular uptake, higher cytotoxicity against HL-60 cells compared with free DNR. These results were potentially useful for the nanoparticle formulation of hydrophilic chemotherapeutic drugs that require efficient delivery to cancer cells as well as sustained release at the specific site.