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PubMedDate not supplied

Bone regeneration: new findings and potential clinical applications.

Bone is a biologically privileged tissue in that it has the capacity to undergo regeneration as part of a repair process. Fracture healing is the most common and recognizable form of bone regeneration, but several other examples of bone regeneration have been observed in humans, suggesting that the ability to regulate bone regeneration as a therapeutic tool should be possible. Historically, efforts at limb lengthening have led to procedures for regenerating bone, such as the method of Ilizarov. This procedure, known as distraction osteogenesis, has applications in a variety of skeletal conditions, including the restoration of large skeletal defects, the transport of bone in cases of severe trauma with bone loss, and the correction of skeletal deformities. Fibrodysplasia ossificans progressiva is an example of how an abnormal metabolic condition can be viewed as evidence for the capacity of humans to regenerate large amounts of bone if the cellular and molecular signaling events are altered. Elucidation of the cellular and molecular basis for bone regeneration in humans - particularly the role of the human genome in relation to the expression of various growth factors and cytokines, such as the bone morphogenetic proteins - offers great potential for the treatment of orthopaedic conditions. Development of specific bone morphogenetic proteins as therapeutic substances to induce bone regeneration in patients is well under way. As methods for enhancing fracture healing, distraction osteogenesis, and other procedures are refined, the development of protein- and gene-based therapies for regulating bone formation should lead to a new era of orthopaedic practice.

Bone Morphogenetic Proteins↗
PubMed2001

Bioabsorbable materials for guided bone regeneration prior to implant placement and 7-year follow-up: report of 14 cases.

BACKGROUND: The purpose of the present study was to evaluate the efficacy of a guided bone regeneration (GBR) procedure prior to implant placement and the long-term outcome of the inserted implants. METHODS: Prior to dental implant placement, GBR procedure was performed on 14 patients (mean age 48 years) using a synthetic hydroxyapatite (HA) spacer under a collagen membrane. After a mean healing period of 8 months, bone biopsies were obtained during the placement of 14 implants. The specimens were processed for histology without demineralization in order to assess bone quality and quantity of the regenerated bone. RESULTS: Both the bone density and the resorption degree of HA particles were relatively varied between samples. The different phenotypes of osteoclasts and multinucleated giant cells and the individual host response could partially explain the unpredictable results in terms of bone remodeling and biomaterial resorption. However, the presence of HA particles in the regenerated bone had no influence on the osseointegration of implants presenting a success rate of 86% after a 7-year observation period. CONCLUSIONS: These results confirm the possibility of regenerating bone by means of bioabsorbable materials, assuring at the same time the long-term success for implants inserted in regenerated sites.

Absorbable Implants↗
PubMed2005

Distraction osteogenesis may promote periodontal bone regeneration.

Distraction osteogenesis has numerous applications in the treatment of conditions affecting the dentofacial complex, from midface advancement to orthodontic tooth movement produced by transversal distraction of the periodontal ligament. The purpose of this study was to test the hypothesis that periodontium can be consistently distracted toward the tooth crown to promote periodontal bone regeneration. After the surgical production of periodontal defects in maxillary canines of 5 mongrel dogs, periodontal bone distraction was performed. Light microscopy was used for histopathological and morphometric analysis. Periodontal bone regeneration occurred in all animals. Periodontal bone regeneration in the distraction sites (Mean +/- SD: 5.45 +/- 2.01 mm) differed from that in control sites (0.008 +/- 0.67 mm; p < 0.0001). Periodontal bone distraction resulted in periodontal bone regeneration. This finding may establish periodontal bone distraction as a new treatment alternative for periodontal defects.

Alveolar Process↗
PubMed2005

Biological evaluation of chitosan nanofiber membrane for guided bone regeneration.

BACKGROUND: Chitosan is known as a biodegradable and non-toxic natural polymer that enhances wound healing and bone formation. The aims of this study are to evaluate the biocompatibility of chitosan nanofiber membranes and to examine the effect of the chitosan nanofiber membranes on bone regeneration in rabbit calvarial defects. METHODS: In vitro cell proliferation tests using human osteosarcoma cell line MG63 and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate the expression of alkaline phosphatase (ALP), collagen, osteocalcin (OCN), and GAPDH were done on chitosan nanofiber membranes. Chitosan nanofiber membranes were implanted in subcutaneous connective tissue and observed for 2, 4, and 6 weeks in rats. Ten-millimeter diameter round cranial defects were made in rabbits and covered by chitosan nanofiber membranes for 4 weeks. Specimens were decalcified and observed by a light microscope. RESULTS: MG63 cells proliferated for 28 days on the chitosan nanofiber membranes and expressed ALP, collagen, OCN, and GAPDH at 2 weeks. Chitosan nanofiber membranes that were grafted into rat subcutaneous tissue maintained their shape and space for bone regeneration for as long as 6 weeks. No inflammation could be seen on the membrane surface or in the surrounding tissues. In the rabbit calvarial defects, new bone filled the defects and fused to the original old bone in 4 weeks. CONCLUSIONS: The biocompatibility of the chitosan nanofiber membrane was confirmed, with enhanced bone regeneration and no evidence of an inflammatory reaction. This experiment shows that the novel biodegradable chitosan nanofiber membrane may be useful as a tool for guided bone regeneration.

Analysis of Variance↗
PubMedDate not supplied

Facilitation of beta-tricalcium phosphate-induced alveolar bone regeneration by platelet-rich plasma in beagle dogs: a histologic and histomorphometric study.

PURPOSE: The effects of 2 graft materials, beta-tricalcium phosphate (Cerasorb) alone and a combination of Cerasorb and platelet-rich plasma (PRP), on the bone regeneration process were evaluated in the canine mandible. MATERIALS AND METHODS: The mandibular premolars of 12 beagle dogs were surgically removed. The extraction sockets were filled with Cerasorb on the control side and a mixture of Cerasorb and PRP on the test side. Bilateral biopsy samples were taken from the graft insertion sites at 6, 12, and 24 weeks after surgery. Sections were prepared from the undecalcified resin-embedded samples. RESULTS: Six weeks after grafting, the proliferation of cellular osteogenic mesenchyma was more abundant in the test group. The histomorphometric data revealed a significantly higher percentage of bone area in the test group (45.9%) than in the control group (30.8%) (P < .05). Twelve weeks after grafting, the test group still had some advantage over the control group in terms of bone regeneration (52.5% bone in the test group versus 49.4% in the control group, P < .05). Twenty-four weeks after grafting, bone-forming activity was nearly equal in the 2 groups, and the bone area in the 2 groups did not differ significantly (62.9% and 61.9%, respectively) (P < .05). DISCUSSION: The histomorphometric results suggested more intensive bone regeneration in the early healing phase following the topical application of PRP. CONCLUSION: The increase in bone density facilitated by grafting with a combination of Cerasorb and PRP requires thorough study in humans.

Animals↗
PubMedDate not supplied

[Effect of prolonged administration of thyrocalcitonine on mineralization of regenerating bone after fracture].

A distinct effect on all the stages of regenerating bone mineralisation was observed after daily (within the experimental period) intramuscular administration of thyrocalcitonine with prolonged action (a complex with polyvinyl pyrrolidone) into male rat at a dose 2.5 un/kg of body weight. The drug caused an inhibitory effect on metabolism within the first 10 days of the experiment. Within 2-3 weeks after the fracture the intensity of metabolic processes was increased. Contents of calcium, phosphorus, sodium and potassium were markedly increased in liquid phase of the bone rissue. The synthesis of phosphoproteins, organic non-protein phosphates and the inorganic phosphate was also increased. The data obtained suggest that thyrocalcitonine caused a stimulating effect on aerobic resynthesis of macroergic phosphate containing substances and the increase in the functional activity of osteogenic cells.

Animals↗
PubMed2004

[Healing of osseous defects by guided bone regeneration using ribose cross linked collagen membranes].

The ultimate goal of periodontal therapy has long been the complete regeneration of the periodontal attachment apparatus. Guided Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR) are two regenerative procedures which converted this goal from a dream to reality. In search of a biocompatible resorbable tissue barrier, collagen, being a natural protein and a weak antigen, has attracted much interest and became the focus of much intention during the 80's and the 90's. The understanding that cross linking of collagen with aldehyde sugars, especially ribose, produces collagen which is highly resistant to resorption in vivo led to the development of a "natural" Crossed-Linked Collagen Barrier (CB-SX). Animal and Human studies have shown that the newly developed membrane is biocompatible, remains intact in the tissues 6 months and more, and results in impressive guided tissue/bone regeneration. Spontaneous early exposure of the membrane is common but the healing potential of the resulted tissue dehiscence is favorable with no tendency for bacterial infection. The commercial version of the CB-SX is especially suitable for GBR procedures; it is highly recommended that the gingival flaps involved will properly be released, will lack tension, and be thoroughly sutured.

Absorbable Implants↗
PubMed2001

In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration.

BACKGROUND: Barrier membranes are used to prevent down-growth of the oral mucosa along the root surface and to allow alveolar bone regeneration in guided tissue regeneration. Several studies have demonstrated bone regenerates in the presence of bioabsorbable and non-resorbable membranes, but no studies have compared multiple bioabsorbable barriers to one another and to non-resorbable barriers. This study evaluated the in vitro influence of bioabsorbable and non-resorbable membranes on specific parameters of human osteoblast activity. METHODS: Human osteoblasts were cultured on bioabsorbable membranes made of collagen, hyaluronic acid, and poly DL-lactide, and the most common non-resorbable membrane which is made of expanded polytetrafluoroethylene (ePTFE). The osteoblasts were cultured in vitro for 24 hours on barrier membranes in the presence of 3H-thymidine and 3H-proline to study cell proliferation and collagen synthesis. Transforming growth factor-beta1 (TGF-beta1) secretion was evaluated in conditioned media using an ELISA kit. RESULTS: The results showed that collagen and poly DL-lactide stimulated DNA synthesis more than ePTFE and hyaluronic acid. All bioabsorbable membranes significantly increased collagen synthesis and alkaline phosphatase activity. Collagen and hyaluronic acid increased secretion of TGF-beta1, a growth factor involved in bone remodeling. CONCLUSIONS: These data suggest bioabsorbable membranes, particularly collagen and hyaluronic acid, may promote bone regeneration through their activity on osteoblasts.

Absorbable Implants↗
PubMed2001

Migration of osteoblastic cells on various guided bone regeneration membranes.

To evaluate the biological effects of guided bone regeneration (GBR) barrier materials on osteoblastic cell migration, migration of mouse osteoprogenitor cells (MC3T3-E1) was examined, in vitro, on various membranes. Eight commercially available GBR membranes - bovine type I collagen (BioMend; BM), porcine type I collagen (BioGide; BG), bovine type I atelocollagen (Tissue Guide; TG), polylactic acid (Epi-Guide; EG), co-polymer of polylactic acid and polyglycolic acid (Resolute; RL, Resolut XT; RL-XT), expanded polytetrafluoroethylene (e-PTFE; Gore Tex; GT) and co-polymer of cellulose acetate and nitrocellulose (Millipore filter; MP) - were tested. A 3x5 mm section of the membrane was fixed to the bottom of a culture dish with double-sided adhesive tape, and half of the membrane was closely covered by PARAFILM (American National Can) to leave an unexposed area for cell migration. The border between exposed and unexposed areas was marked as a baseline of cell migration. Membranes were then plated with 3 ml of cell suspension at an initial density of 1x105 cells/ml in alpha-MEM culture medium with 10% fetal bovine serum and ascorbic acid. After a 5-hour incubation, non-attached cells were completely washed out with phosphate buffered saline and the PARAFILM cover was removed. After 3 days cultivation, specimens were fixed with 10% buffered formalin and stained briefly with hematoxylin. The area of cell migration on a membrane was analyzed using a LA 500 Image Analysis System and migration area per unit length of the baseline (mm2/mm) was compared among membranes. Results demonstrated that cell migration was greater in the order: RL>RL-XT, BM, TG, MP>EG, BG. Membranes except for BG, EG and GT showed the migration rate equal to or higher than a plastic culture cover slip (Celldesk) (P<0.01) on which cells generally grow favorably. Only a small number of the cells attached to GT, and the net cell migration for the membrane could not be determined. These results indicate that GBR barrier materials per se may influence the process of bone regeneration in vivo through the effects of their presence on cell migration.

Animals↗
PubMed1999

Comparison of bioabsorbable and bioinert membranes for guided bone regeneration around non-submerged implants. An experimental study in the mongrel dog.

The aim of this clinical investigation was to evaluate the effect of guided bone regeneration around non-submerged implants using different barrier membranes. Five adult mongrel dogs were used in this investigation. After having all premolars extracted and implant osteotomies performed in the regions of the former premolars, buccal bone defects were created. Subsequently, 3 implants were placed and the defects treated with 1 of the following 3 modalities: a) guided bone regeneration using an expanded polytetrafluoroethylene membrane, b) guided bone regeneration using a bioabsorbable membrane made from a synthetic copolymer of glycolide and lactide and c) no membrane application. Following implant and membrane placement, the mucoperiosteal flaps were repositioned and tightly sutured around the neck of the implants allowing for a non-submerged healing. After a healing period of 6 months, the animals were sacrificed and the specimens processed for histologic evaluation. The clinical pre-treatment defects between the different treatment groups were not statistically different (bioinert membrane group: 4.9 mm; control group: 4.8 mm; bioabsorbable membrane group: 4.5 mm). The remaining histological defects after 6 months of healing amounted to approximately 2.5 mm in the bioinert membrane group, 5.7 mm in the control group and 6.0 mm in the bioabsorbable membrane group. A significant difference was observed between the bioinert membrane group and the other 2 groups. The mineralized bone-to-implant contact in the bioinert membrane group was 51.5%, in the control group 46.3% and in the bioabsorbable membrane group 37.5%. The values between the bioinert membrane group and the bioabsorbable membrane group were statistically different. The results of this study indicate that bone regeneration with bioinert e-PTFE membranes around non-submerged implants is possible. The utilized absorbable polyglycolic/polylactid membrane did not show any bone regenerative effect and the results did not differ from the control group without membrane application.

Absorbable Implants↗
PubMed1998

Evaluation of a diphenylphosphorylazide-crosslinked collagen membrane for guided bone regeneration in mandibular defects in rats.

In the present study, the potential of a diphenylphosphorylazide-crosslinked type I bovine collagen membrane was evaluated in the healing of mandibular bone defects applying the biological concept of guided bone regeneration. The experiment was carried out on 25 Wistar rats. After exposing the mandibular ramus bilaterally, 5 mm diameter full-thickness circular bone defects were surgically created. While the defect on one side was covered by the membrane (experimental), the defect on the other side was left uncovered (control) before closure of the overlying soft tissues. The rats were sacrificed in groups of 5 after 7, 15, 30, 90, and 180 days of healing. Although at early stages of healing similar amounts of bone formation were observed in the experimental and control defects, after 1 month of healing, most of the experimental defects were completely closed with new bone, while in the control defects, only limited amounts of new bone were observed at the rims and in the lingual aspect of the lesions. In the 90- and 180-day animals, all experimental defects were completely closed, while in the control defects, no statistically significant increase in bone regeneration was observed. The increase in percentage of bone regeneration in the experimental defects was statistically significant between the 15-day specimens as compared with the 7-day specimens (P < 0.01) and likewise between 30-day and 15-day specimens (P < 0.001). It can be concluded that a DPPA-crosslinked collagen membrane yields biocompatibility, ad hoc mechanical hindrance, and handling characteristics suitable for guided bone regeneration applications in this experimental model.

Alveolar Bone Loss↗
PubMed1991

[Histomorphometry of bone regenerate in limb lenghthening by the Ilizarov's technique].

Eleven biopsies of bone regenerate during bone lengthening following the Ilizarov technique were studied. They concerned 10 patients with a mean age of 13.5 years. The length of the biopsied regenerate was between 14 and 90 mm, and the delay after the initial procedure was 23 to 502 days. The aim of this study was to get informations on the histology of the regenerate, to quantify osseous data and to propose a surgical strategy. These data were obtained by analyze of non decalcified bone, biopsies were included in a methylmetacrylate block. Measure of the mineralisation speed was determined after a double intake of tetracycline. The bony trabeculations were formed very early, as soon as the third week. They were placed like a thread, that means in an anastomotic system which can quickly become resistant. But is was necessary to keep a lengthening speed under 1 mm per day 0.7 to 0.8 mm per day seems to be the best speed in adolescents. The ossification was of membranous type, without cartilaginous stage. Osteoblastic and osteoclastic activities were extremely rich, even after one year or after the bone healing. The main point was the maturity of the regenerate acquired as soon as the 4th month.

Adolescent↗
PubMed1999

[Guided bone regeneration by using biodegradable co-polymer membranes in rabbits].

OBJECTIVE: To repair long bone segmental defects using biodegradable poly epsilon-caprolactone (PCL) and polylactic acid(PLA) co-polymer membranes, and explore its role and mechanism in guided bone regeneration (GBR). METHODS: Rabbit radial segmental defects (1.2 cm in length, retain the periosteum) were created in this study, 24 animals were divided into 2 groups. The membranes were used to enclose the defects in experimental group, and no treatment in control group. After 3, 6, and 12 weeks of operation, X-ray, gross and histological examinations were observed. RESULTS: The bone regeneration of experimental group was better than that of control group. Three weeks after operation, obvious external callus along the membrane were found in experimental group, and bony linking composed of external callus bridge were found in 6 weeks after operation. After 12 weeks of operation, callus bridge outside the membrane and bony reunion inside the membrane were achieved in experimental group. While in control group, typical nonunion was observed after 6 weeks of operation. CONCLUSION: Guided bone regeneration can be achieved by using biodegradable membrane. The defects are repaired by the means of outside membrane callus and relatively late inside membrane callus. The membrane can prevent the ingrowth of fibrous tissue into defect area, thus nonunion are avoid, and keep a high concentration of nutritive elements, also serve as a frame for osteocyte growth to enhance bone healing.

Absorbable Implants↗
PubMed2004

Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration.

This study analyzed the effect of the platelet count in platelet-rich plasma (PRP) on bone regeneration in vivo. Twenty male New Zealand white rabbits were used. PRP was produced using the Platelet Concentrate Collection System (PCCS) (3i, Miami, FL, USA). After inducing ketamine-xylazine anaesthesia, a self-tapping titanium screw (Branemark MK III TiUnite, 3.75 x 7 mm) was inserted in each distal femur; the femurs were randomized so that one side was treated with PRP while the other (control) was not. Intravital fluorochrome staining was performed on days 1, 7 (1.5 ml of 2% doxycycline/kg bodyweight), 14 (6% xylenol orange, 1.5 ml/kg), and 21 (1% calcein green, 5 ml/kg). Animals were euthanized on day 28 (n = 20). Specimens were prepared for histomorphological evaluation according to Donath and Breuner [J. Oral Pathol. 11 (1982) 318]. Comparing the bone regeneration (fluorochrome staining) in the 4-week implants (n = 19), the only significant difference (sign test, P = 0.004) was seen with intermediate platelet concentrations (n = 9,503,000-1,729,000 platelets/microl PRP). There were no differences in the bone/implant contact rates between the test and the control side among the three groups. The platelet concentration required for a positive PRP effect on bone regeneration seems to span a very limited range. Advantageous biological effects seem to occur when PRP with a platelet concentration of approximately 1,000,000/microl is used. At lower concentrations, the effect is suboptimal, while higher concentrations might have a paradoxically inhibitory effect. On the other hand, the effect of this type of platelet concentrate was not beneficial to accelerate the osseointegration of enosseous dental implants.

Animals↗
PubMed1998

The effect of a deproteinized bovine bone mineral on bone regeneration around titanium dental implants.

The aim of the present experiment was to test the effect of a deproteinized bovine bone mineral (Bio-Oss) on guided bone regeneration (GBR) in dehiscence defects around implants. The first 2 molars and all premolars were extracted on both sides of the mandibles of 3 monkeys (Macaca fascicularis). Three months later, 2 titanium plasma-coated cylindrical implants were placed in all quadrants of each monkey. During the surgical procedure, standardized dehiscence defects were produced buccally and lingually, measuring 2.5 mm in width and 3 mm in height. Four different experimental situations were created: 2 sites in each monkey were covered with an ePTFE membrane (M), 2 were filled with the graft material (DBBM), 2 were filled with the graft material and also covered with a membrane (M + DBBM), and 2 control sites were neither grafted nor covered (C). The flaps were sutured to allow for primary healing. Linear measurements of bone height and width were calculated on histological specimens obtained 6 months following surgery. In addition, values for bone density and for surface fraction of graft to new bone contact were measured. Vertical bone growth along the implant surface of 100% (SD 0%) for M + DBBM, 91% (SD 9%) for M, 52% (SD 24%) for DBBM, and 42% (SD 35%) for C was measured. The width of the regenerated bone 1.5 mm above the bottom of the original defect, i.e. at the 50% mark of the vertical extension of the defect, in relation to the width at the bottom of the defect amounted to 97% (SD 2%) for M + DBBM, 85% (SD 9%) for M, 42% (SD 41%) for DBBM, and 23% (SD 31%) for C. Assessment of bone density within the confinement of the regenerated bone resulted in an increase of 30% (SD 11%) for M + DBBM, 45% (SD 20%) for M, 33% (SD 20%) for DBBM, and 22% (SD 23%) for C. The values for graft to new bone contact within this compartment amounted to 80% (SD 15%) for M + DBBM and 89% (SD 14%) for DBBM. In conclusion, Bio-Oss exhibited osteoconductive properties and hence can be recommended for GBR procedures in dehiscence defects with respect to vertical and horizontal growth of bone.

Animals↗
PubMed1998

Incomplete bone regeneration of rabbit calvarial defects using different membranes.

The present study describes the use of a degradable and a non-degradable material for guided bone regeneration. Forty rabbits were divided into 5 groups. Bicortical defects 15 mm in diameter were prepared in rabbit calvaria. A titanium microplate was placed over the defect to prevent collapse of the membrane. The calvarial defects of 2 groups were covered by an outer expanded polytetrafluoroethylene (ePTFE) membrane respectively by a Polyglactin 910 membrane. Bicortical ePTFE membranes or Polyglactin 910 membranes were used in 2 other groups. The defects were not covered by membranes in the control group. Undecalcified sections were prepared for histologic evaluation after an observation period of 8 weeks. Complete bone healing of the defects was not observed in any of the specimens. The Polyglactin 910 material lacks physical strength, resulting in collapse of the membrane and brain tissue herniation into the defects. Subsequently, bone regeneration was impaired. The cellular reactions due to degradation of the material were minor and did not interfere with bone healing. Defects covered bicortically by ePTFE membranes revealed the largest amount of regenerated bone. The ePTFE membrane induced a severe cellular reaction, but no inhibition of bone regeneration was noted.

Animals↗
PubMed2005

Bone regeneration in a rat cranial defect with delivery of PEI-condensed plasmid DNA encoding for bone morphogenetic protein-4 (BMP-4).

Gene therapy approaches to bone tissue engineering have been widely explored. While localized delivery of plasmid DNA encoding for osteogenic factors is attractive for promoting bone regeneration, the low transfection efficiency inherent with plasmid delivery may limit this approach. We hypothesized that this limitation could be overcome by condensing plasmid DNA with nonviral vectors such as poly(ethylenimine) (PEI), and delivering the plasmid DNA in a sustained and localized manner from poly(lactic-co-glycolic acid) (PLGA) scaffolds. To address this possibility, scaffolds delivering plasmid DNA encoding for bone morphogenetic protein-4 (BMP-4) were implanted into a cranial critical-sized defect for time periods up to 15 weeks. The control conditions included no scaffold (defect left empty), blank scaffolds (no delivered DNA), and scaffolds encapsulating plasmid DNA (non-condensed). Histological and microcomputed tomography analysis of the defect sites over time demonstrated that bone regeneration was significant at the defect edges and within the defect site when scaffolds encapsulating condensed DNA were placed in the defect. In contrast, bone formation was mainly confined to the defect edges within scaffolds encapsulating plasmid DNA, and when blank scaffolds were used to fill the defect. Histomorphometric analysis revealed a significant increase in total bone formation (at least 4.5-fold) within scaffolds incorporating condensed DNA, relative to blank scaffolds and scaffolds incorporating uncondensed DNA at each time point. In addition, there was a significant increase both in osteoid and mineralized tissue density within scaffolds incorporating condensed DNA, when compared with blank scaffolds and scaffolds incorporating uncondensed DNA, suggesting that delivery of condensed DNA led to more complete mineralized tissue regeneration within the defect area. This study demonstrated that the scaffold delivery system encapsulating PEI-condensed DNA encoding for BMP-4 was capable of enhancing bone formation and may find applications in other tissue types.

Animals↗