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PubMed1981

Protoplast fusion in Streptomyces: conditions for efficient genetic recombination and cell regeneration.

Protoplasts from four different species of Streptomyces regenerated cells efficiently in hypertonic soft agar medium overlaid on partially dehydrated regeneration medium. The efficiencies of regeneration were strongly dependent upon the incubation temperatures for cell growth and for protoplast regeneration. Cell growth temperatures (before protoplast formation) required for efficient protoplast regeneration varied from species to species, and did not necessarily correlate with the optimum temperatures for protoplast regeneration. Under the best conditions, protoplasts from all four species were able to regenerate viable cells at nearly 100% efficiency and also formed confluent lawns of mycelia when plated in high concentrations. The temperatures for cell growth and protoplast regeneration also affected the frequencies of genetic recombinants obtained by protoplast fusion in S. fradiae, and highest recombinant frequencies were obtained under conditions which favoured efficient protoplast regeneration. With the modified procedure described, maximum frequencies of genetic recombinants were obtained by treating parental protoplasts with 40 to 60% polyethylene glycol 1000.

Agar↗
PubMed2001

A novel ATP regeneration system using polyphosphate-AMP phosphotransferase and polyphosphate kinase.

Polyphosphate-AMP phosphotransferase (PAP) and polyphosphate kinase (PPK) were used for designing a novel ATP regeneration system, named the PAP-PPK ATP regeneration system. PAP is an enzyme that catalyzes the phospho-conversion of AMP to ADP, and PPK catalyzes ATP formation from ADP. Both enzymes use inorganic polyphosphate [poly(P)] as a phosphate donor. In the PAP-PPK ATP regeneration system, ATP was continuously synthesized from AMP by the coupling reaction of PAP and PPK using poly(P). Poly(P) is a cheap material compared to acetyl phosphate, phosphoenol pyruvate and creatine phosphate, which are phosphate donors used for conventional ATP regeneration systems. To achieve efficient synthesis of ATP from AMP, an excessive amount of poly(P) should be added to the reaction solution because both PAP and PPK consume poly(P) as a phosphate donor. Using this ATP generation reaction, we constructed the PAP-PPK ATP regeneration system with acetyl-CoA synthase and succeeded in synthesizing acetyl-CoA from CoA, acetate and AMP. Since too much poly(P) may chelate MG2+ and inhibit enzyme activity, the Mg2+ concentration was optimized to 24 mM in the presence of 30 mM poly(P) in the reaction. In this reaction, ATP was regenerated 39.8 times from AMP, and 99.5% of CoA was converted to acetyl-CoA. In addition, since the PAP-PPK ATP regeneration system can regenerate GTP from GMP, it could also be used as a GTP regeneration system.

Journal Article↗
PubMed2002

[Natural regeneration of Pinus sylvestris var. mongolica plantation on sandy land].

By employing comparison analysis and field survey, the natural regeneration of Mongolian pine plantations on sandy soil was investigated. In plantation areas where regeneration can take place naturally, natural regeneration of Mongolian pine varied temporally and spatially. Natural regeneration wasn't temporally continuous; it had a close relationship with autumn precipitation in particular years. In spatial aspect, there were three regeneration types: regeneration in forest gaps, regeneration on edges of a forest, regeneration under young broadleaf forest. There was no significant difference between the growth of regeneration saplings and plantation trees.

Agriculture↗
PubMed2000

A morphometric study of optic axons regenerated in a sciatic nerve graft of adult rats.

PURPOSE: In the present study we have morphometrically examined a regeneration model in which axons normally residing in CNS have regrown and are interacting with Schwann cells from the PNS. This study will not only provide morphometric data on regenerated optic fibers but also shed light on possible factors in determining the fiber morphometry. METHODS: The optic nerves of rats aged 6 weeks were cut intra-orbitally and replaced with a autologous sciatic nerve. After a survival period of 9 months, the graft or "regenerated" nerves containing the regenerated optic axons and Schwann cells were processed for morphometric measurements. RESULTS: The mean myelinated axon diameter of regenerated nerve (1.8 +/- 0.2 micro m) was significantly (P < 0.05) greater than that of the optic nerve (0.9 +/- 0.03 micro m). However, unmyelinated regenerated optic axons had a smaller mean axon diameter (0.49 +/- 0.04 micro m) than normal myelinated optic axons. This may suggest that myelinating glial cells exert an influence on axon caliber and Schwann cells seem to have greater effect than oligodendrocytes. The mean g-ratio showing the relative myelin sheath thickness was found to be the highest in the optic nerve (0.78 +/- 0.003), least in the sciatic nerve (0.6 +/- 0.009) and intermediate in the regenerated nerve (0.68 +/- 0.01). The results indicated that Schwann cells myelinating the regenerated optic axons have produced a thinner myelin sheath. Intra-axonally, no significant difference was detected in the number of axonal microtubules and neurofilaments between the regenerated and optic nerves. Therefore the disposition of microtubules and neurofilaments into axon may be intrinsically determined. CONCLUSIONS: In this study, we have identified some of the extrinsic and intrinsic factors in determining the fiber morphometry of the regen-erated nerve. The axon-size and myelination by glial cells were determined through the external axon-glial interactions, whereas the number of axonal microtubules and neurofilaments were intrinsically determined.

Journal Article↗
PubMed2005

[RAPD and ISSR analyses of regenerated pea Pisum sativum L. plants].

Long-term pea callus cultures of different genotypes (mutants R-9 and W-1 and cultivar Viola) were used to regenerate plants (generation R0). The regenerants displayed changes both in qualitative and in quantitative traits. The most dramatic morphological alterations and complete sterility were observed in regenerants of the cultivar Viola. To estimate the genetic differences, regenerants were compared with the original lines with the use of RAPD (random amplified polymorphic DNA) and ISSR (inter simple sequence repeat) analyses. The extent of divergence varied among regenerants and depended mostly on the original genotype. The genetic difference from the original line was no more than 1% in W-1 regenerants, 0.7-5.3% in R-9 regenerants, and 10-15% in sterile regenerants of the cultivar Viola. The genetic variation of plants regenerated from a callus culture maintained for ten years did not exceed that of plants obtained from a culture maintained for two years.

Base Sequence↗
PubMed1994

Pattern duplication by retinoic acid treatment in the regenerating limbs of Korean salamander larvae, Hynobius leechii, correlates well with the extent of dedifferentiation.

In the regenerating limbs of Korean salamanders, Hynobius leechii, retinoic acid (RA) induces duplication of skeletal structures in the proximodistal (PD) axis and often in the transverse axes. In the present study, the stage-dependent effects of RA for the duplication of limb skeletal structures at two amputation levels, the distal stylopodium and the distal zeugopodium, were studied using larval limbs of Korean salamanders. The results showed that the mean level of proximalization (MLP) by RA treatment increased during the stages of dedifferentiation and early bud formation while the MLP declined thereafter in both amputation levels. The decline of the MLP at the later stages of regeneration was due to the high frequency of hypomorphic regeneration or blocked regeneration. When the effects of RA treatment at two amputation levels were compared, the overall trends were similar but the actual timing was delayed for 2-4 days in the proximal level of amputation. Furthermore, the peak level of proximalization was achieved earlier and the peak level remained longer in the distal stylopodial level of amputation compared to the distal zeugopodial level of amputation. Since the histological observations revealed that the dedifferentiation period was also extended up to 2-4 days in the proximal level of amputation, the acid phosphatase activity during the course of regeneration was measured to look for a quantitative relationship between the enzyme activity and the states of dedifferentiation. The results show that the level and the duration of acid phosphatase activity in the upper arm regenerates are both higher and longer than those in the lower arm regenerates. Furthermore, RA treatment caused an increase in acid phosphatase activity. Thus our results suggest that the state of dedifferentiation might be closely linked to the extent of proximalization of regenerating limbs by RA treatment.

Acid Phosphatase↗
PubMed2005

Ultrastructural analysis of guided nerve regeneration using progesterone- and pregnenolone-loaded chitosan prostheses.

Recently, numerous guide chambers for the treatment of injured nerves made up of different biomaterials have been designed, capable of hosting living cells or carrying neurotrophic or neuroactive substances to be directly released to the injured tissue. In this study, chitosan prostheses containing neurosteroids (progesterone and pregnenolone) were used for bridging a 10-mm gap in the rabbit facial nerve. Gas chromatography was used to quantify neurosteroid content in the prostheses prior to and after subcutaneous implantation at different periods of up to 60 days. The regeneration of the nerve fibers were evaluated at 15 and 45 days after axotomy by means of ultrastructural morphometric analysis. Different nerve fibers regenerative patterns were seen depending the groups studied and the analyzed stages. At 15 days after axotomy, the newly regenerating tissue revealed Schwann cells holding nonmyelinated nerve fiber bundles in an incipient and organized regenerative pattern. At 45 days, the regenerating tissue showed myelinated nerve fibers of different sizes, shapes, and myelin sheath thickness. Although the regeneration of the nerve fibers under neurosteroid treatment showed statistically significant differences in comparison with vehicle regenerated tissue, progesterone-loaded chitosan prostheses produced the best guided nerve regeneration response. These findings indicate that chitosan prostheses allowed regeneration of nerve fibers in their lumen, and when containing neurosteroids produced a faster guided nerve regeneration acting as a long-lasting release delivery vehicle.

Animals↗
PubMed2005

Tail regeneration and ependymal outgrowth in the adult newt, Notophthalmus viridescens, are adversely affected by experimentally produced ischemia.

Spinal axons of the adult newt will regenerate when the spinal cord is severed or when the tail is amputated. Ischemia and associated hypoxia have been correlated with poor central nervous system regeneration in mammals. To test the effects of ischemia on newt spinal cord regeneration, the spinal cord and major blood vessels of the newt tail were severed 2 cm caudal to the cloaca as a primary injury. This primary injury severely reduced circulation in the caudal direction for 7 days; by day 8, circulation was largely restored. After various periods of time after primary injury, tails were amputated 1 cm caudal to the primary injury (in the area of ischemia) and tested for regeneration. If the tail was amputated within 5 days of the primary injury, regeneration did not occur. If amputation was 7 days or longer after the primary injury, a regenerative response occurred. Histology showed that in the non-regenerating tails the spinal cord and associated ependyma, known to be important to tail regeneration, had degenerated in the rostral direction. Such degeneration was prevented when tails were first amputated and allowed to form blastemas before the primary injury. The data indicate that the first 5-7 days of blastema formation are particularly sensitive to compromised blood flow (ischemia/hypoxia). It follows that mechanisms must be present in the adult newt to reduce ischemia to a minimum and thus allow ependymal outgrowth and tail regeneration.

Amputation, Surgical↗
PubMed2005

Structural parameters of collagen nerve grafts influence peripheral nerve regeneration.

Large nerve defects require nerve grafts to allow regeneration. To avoid donor nerve problems the concept of tissue engineering was introduced into nerve surgery. However, non-neuronal grafts support axonal regeneration only to a certain extent. They lack viable Schwann cells which provide neurotrophic and neurotopic factors and guide the sprouting nerve. This experimental study used the rat sciatic nerve to bridge 2 cm nerve gaps with collagen (type I/III) tubes. The tubes were different in their physical structure (hollow versus inner collagen skeleton, different inner diameters). To improve regeneration Schwann cells were implanted. After 8 weeks the regeneration process was monitored clinically, histologically and morphometrically. Autologous nerve grafts and collagen tubes without Schwann cells served as control. In all parameters autologous nerve grafts showed best regeneration. Nerve regeneration in a noteworthy quality was also seen with hollow collagen tubes and tubes with reduced lumen, both filled with Schwann cells. The inner skeleton, however, impaired nerve regeneration independent of whether Schwann cells were added or not. This indicates that not only viable Schwann cells are an imperative prerequisite but also structural parameters determine peripheral nerve regeneration.

Animals↗
PubMed2006

Framework for optimal design of porous scaffold microstructure by computational simulation of bone regeneration.

In bone tissue engineering using a biodegradable scaffold, geometry of the porous scaffold microstructure is a key factor for controlling mechanical function of the bone-scaffold system in the regeneration process as well as after the regeneration. In this study, we propose a framework for the optimal design of the porous scaffold microstructure by three-dimensional computational simulation of bone tissue regeneration that consists of scaffold degradation and new bone formation. The rate of scaffold degradation due to hydrolysis, that leads to decrease in mechanical properties, was simply assumed to relate to the water content diffused from the surface to the bulk material. For the new bone formation on both bone and scaffold surfaces, the rate equation of trabecular surface remodeling driven by mechanical stimulation was applied. Solving these two phenomena in the same time frame, the bone regeneration process in the bone-scaffold system was predicted by computational simulation using a voxel finite element method. The change in the mechanical function of the bone-scaffold system during the regeneration process was quantitatively evaluated by measuring the change in total strain energy, and this was used for the evaluation function to optimize the scaffold microstructure that provides the desired mechanical function during and after the bone regeneration process. A case study conducted for the scaffold with a simple microstructure demonstrated that the proposed simulation method could be applied to the design of a porous scaffold microstructure. In addition, the regeneration process was found to be very complex even though the simple rate equations for scaffold regeneration and new bone formation were used because of the coupling effects of these phenomena.

Animals↗
PubMed1994

Guided tissue regeneration in jawbone defects prior to implant placement.

The principle of guided tissue regeneration has been successfully applied for the regeneration of bone in various jaw defects in human. The purpose of this study was to assess the bone volume regenerated using nonresorbable membrane barriers. Nineteen patients with jaw bone defects of various sizes and configurations were included in the study. Combined split-thickness/full-thickness mucosal flaps were elevated in the area of missing bone. The size of the defects was assessed by measuring the distance from a reference line between 2 adjacent teeth (cementoenamel junctions) to the alveolar crest (a) every 2 or 3 mm. In addition, the crestal width was measured. Consequently, the surface of the triangle formed by a and the width of the crest as well as the volume between all triangles were calculated geometrically. Following the placement of Gore-Tex augmentation material as a barrier, the distance (b) to the top of the membrane from the reference line was assessed, and the maximum possible volume for bone regeneration based on (a-b) and the width of the crest was calculated. At the time of membrane removal (3-8 months later), the same measurements were performed and the percentages of regenerated bone in relation to the possible volume for regeneration determined. In 6 patients in whom the membranes had to be removed early due to an increased risk for infection between 3 and 5 months, bone regeneration varied between 0 and 60%. In 13 patients in whom membranes were left for 6-8 months, regenerated bone filled 90-100% of the possible volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

[Regeneration of vertebrate appendage: an old experimental model to study stem cells in the adult].

The application of stem cell therapy to cure degenerative diseases offers immense possibilities, but the research in this field is the subject of ethical debates raised by the question of destructive research on early human embryos. Stem cells taken in the adult constitute an alternative to human embryonic stem cells, but our knowledge on totipotent or pluripotent cells is currently insufficient. Furthermore, many questions must be solved before selection and differentiation of these cells in a given cellular type can be controlled on a routine basis. What are the molecular characteristics of an adult stem cell? What are the mechanisms involved in cell reprogramming? Which signals control stem cell replication and differentiation? Basic research activities must be carried out in order to clarify all these points. In this context, the regeneration of vertebrate appendages provides a model for this type of research. The regeneration process is defined by both the morphological and functional reconstruction of a part of a living organism, which has previously been destroyed. But why are some vertebrates able to regenerate complex structures and others apparently not? Among most vertebrates, the capacity to regenerate is limited to some tissues. It is however possible to observe the regeneration of appendages (limb, tail, fin, jaw, etc.) among several amphibians and fish. This regeneration leads to re-forming of the amputated part with a complete restoration of its shape, segmentation and function. Why is the amputation of limbs not followed by regeneration in mammals and birds: absence of stem cells, absence of recruitment signals for these cells, or absence of signal receptivity? This review constitutes a report on the current understanding of the basis of on regeneration of legs in tetrapods and of fins in fish with an emphasis in the role of the nervous system in this process.

Animals↗
PubMed2006

Guided tissue regeneration enhances bone formation in a rat model of failed osteogenesis.

BACKGROUND: Guided tissue regeneration is a technique that uses barrier materials to enhance tissue regeneration. Although previously demonstrated to be an effective way of enhancing craniofacial osteogenesis in several animal models, the ability of guided tissue regeneration to augment bone formation in the context of distraction osteogenesis is unknown. In the current study, the authors applied the principle of guided tissue regeneration to their rat mandibular distraction osteogenesis model in an attempt to enhance bone regeneration. METHODS: Twelve (n = 6 per group) adult Sprague-Dawley rats underwent routine gradual distraction (5 days' latency, 4-mm distraction over 8 days, 4 to 6 weeks of consolidation) and acute distraction (immediate lengthening to 4 mm, 6 to 8 weeks of consolidation). An additional 10 animals underwent acute distraction followed by application of bioabsorbable Gore Resolut XT membranes (acute distraction plus guided tissue regeneration). Membranes were completely wrapped around the distraction gap. Animals were killed 6 and 8 weeks postoperatively and mandibles analyzed radiographically and histologically. RESULTS: Quantitative histomorphometric analyses were performed to compare relative bone formation between all three groups. Gradual distraction mandibles achieved bony union by 6 weeks with 86 percent bone formation, which increased to 98 percent by 8 weeks. Acute distraction mandibles healed with a fibrous nonunion and only 37 percent bone formation by 8 weeks. In contrast, acute distraction plus guided tissue regeneration-treated mandibles formed significantly more bone than acute distraction mandibles by 6 weeks (57 percent) and achieved bony bridging by 8 weeks, with 88 percent new bone formation. CONCLUSION: The authors' data demonstrate that guided tissue regeneration can significantly enhance bone formation in a fibrous nonunion model of mandibular distraction osteogenesis.

Animals↗
PubMed1998

Effect of allogeneic freeze-dried demineralized bone matrix on regeneration of alveolar bone and periodontal attachment in dogs.

This split-mouth study was designed to evaluate regeneration of alveolar bone and periodontal attachment following implantation of allogeneic, freeze-dried, demineralized bone matrix (DBM). Buccal fenestration defects (6x4 mm) were created on the maxillary canine teeth in 6 beagle dogs. DBM was implanted into one randomly selected defect in each animal. The contralateral defect served as surgical control. Tissue blocks were harvested following a 4-week healing interval and prepared for histometric analysis. DBM was discernible in all implanted defects with limited evidence of bone metabolic activity. The DBM particles appeared invested within a dense connective tissue, often in close contact to the instrumented root. Fenestration defect height averaged 3.8+/-0.1 and 3.7+/-0.3 mm, total bone regeneration 0.9+/-0.9 and 0.4+/-1.2 mm, and total cementum regeneration 2.3+/-1.5 and 0.6+/-0.7 mm for DBM and control defects, respectively. Differences with regards to cementum regeneration were statistically significant (p=0.03). In summary, the results of this study suggest that DBM implants may enhance cementum regeneration in this defect model, and that they have no apparent effect on alveolar bone regeneration. Enhanced cementum regeneration may be possibly be explained by provisions for guided tissue regeneration from the implant suppressing a significant influence of the gingival connective tissue on the healing process. Moreover, a 4-week healing interval appears insufficient for turnover of DBM.

Alveolar Bone Loss↗
PubMed2004

Prognostic factors for alveolar regeneration: osteogenic potential of resident bone.

OBJECTIVES: There is a limited understanding of the role of resident bone in periodontal regeneration. The objective of this study was to evaluate the influence of the resident alveolar bone on bone regeneration in conjunction with guided tissue regeneration (GTR) in the presence or the absence of cell occlusivity. METHODS: Critical-size, 6-mm, supra-alveolar periodontal defects were created in six young adult Beagle dogs. Space-providing, occlusive or porous expanded polytetrafluaroethylene devices were implanted to provide for GTR. Treatments were alternated between left and right jaw quadrants in subsequent animals. The gingival flaps were advanced for primary intention healing. The animals were euthanized at week 8 postsurgery. The histometric analysis assessed regeneration of alveolar bone relative to space-provision by the GTR device and width of the alveolar crest at the base of the defect. RESULTS: There were no significant differences in mean alveolar regeneration between sites receiving the porous GTR device with a narrow versus a wide alveolar ridge after adjusting for wound area (2.22 versus 2.50 mm, respectively; p=0.36). In contrast, analysis using sites receiving the occlusive GTR device revealed significantly greater bone regeneration at sites with a wide compared with a narrow alveolar ridge (3.34 versus 2.53 mm, respectively; p=0.02). Regression analysis showed a significant relationship (p< or =0.05) between space-provision and bone regeneration for all groups except for sites with a wide alveolar ridge receiving the occlusive GTR device (p=0.5). CONCLUSIONS: The resident alveolar bone may significantly influence the magnitude of alveolar bone regeneration. The relative presence of cells from the gingival connective tissue may attenuate this effect.

Alveolar Bone Loss↗
PubMed2004

Prognostic factors for alveolar regeneration: bone formation at teeth and titanium implants.

OBJECTIVES: There is a limited understanding of the effect of defect characteristics on alveolar bone healing. The objectives of this study were to assess the effect of alveolar bone width and space provision on bone regeneration at teeth and titanium implants, and to test the hypothesis that the regenerative potentials at teeth and implants are not significantly different. METHODS: Critical size, 5-6-mm, supra-alveolar, periodontal defects were surgically created in 10 young adult dogs. Similarly, critical size, 5-mm, supra-alveolar, peri-implant defects were created in four dogs. A space-providing expanded polytetrafluoroethylene device was implanted for guided tissue regeneration/guided bone regeneration. The animals were euthanized at 8 weeks postsurgery. Histometric analysis assessed alveolar bone regeneration (height) relative to space provision by the device and the width of the alveolar crest at the base of the defect. Statistical analysis used the linear mixed models. RESULTS: A significant correlation was found between bone width and wound area (r=0.55892, p<0.0001). Generally, bone width and wound area had statistically significant effects on the extent of bone regeneration (p<0.0005 and p<0.0001, respectively). Bone regeneration was linearly correlated with the bone width at periodontal (p<0.001) and implant (p=0.04) sites, and with the wound area at periodontal (p<0.0001) and implant (p=0.03) sites. The relationships of bone regeneration with these two variables were not significantly different between teeth and implants (bone width: p=0.83; wound area: p=0.09). When adjusted for wound area, bone regeneration was significantly greater at periodontal than at implant sites (p=0.047). CONCLUSIONS: The horizontal dimension of the alveolar bone influences space provision. Space provision and horizontal dimension of the alveolar bone appear to be important determinants of bone regeneration at teeth and implants. The extent of alveolar bone formation at implant sites is limited compared with that at periodontal sites.

Alveolar Bone Loss↗
PubMed2006

Porcine sheath proteins show periodontal ligament regeneration activity.

The purpose of this study was to identify the periodontal regeneration factors of enamel protein extracts that induce cementum and bone regeneration in vivo. Cementum regeneration, one aspect of periodontal ligament regeneration, was examined using a buccal dehiscence model of dogs. Enamel matrix protein fractions were prepared from developing porcine incisors. Cementum-regeneration activity was found to reside in a protein aggregate composed of amelogenins and sheath proteins extracted from newly formed secretory enamel. Cementum-regeneration activity was not observed in protein fractions containing only amelogenin or its derivatives. The sheath proteins were purified to homogeneity and tested for alkaline phosphatase (ALP)-inducing activity on human periodontal ligament (HPDL) cells. The induction of ALP was observed following application of the 17-kDa sheath protein but not of the lower-molecular-weight sheath proteins. Although transforming growth factor-beta1 also shows ALP-inducing activity, contamination with growth factors was excluded because synthetic peptides (based on the sheath protein's sequence) also showed ALP-inducing activity. The 17-kDa sheath protein showed both cytodifferentiation and cementum-regeneration activity, but it is unclear whether its cementum-regeneration activity is derived from its ALP-inducing activity on HPDL cells.

Alkaline Phosphatase↗
PubMed1997

Overview of clinical trials on periodontal regeneration.

Periodontal regeneration means healing after periodontal surgery that results in the restoration of the tooth-supporting tissues; namely, cementum, alveolar bone, and periodontal ligament. The response of the periodontium to conventional periodontal flap surgery is primarily repair. Regenerative flap procedures involve modifications intended to alter variables in the normal wound healing response to shift the outcome from repair to regeneration. Technical manipulations, devices, pharmacological agents, and biologicals have been used to obtain regeneration. Evaluation of periodontal therapy is done by clinical and histological assessments. Human clinical trials depend on probing, re-entry, and radiographic measurements which cannot distinguish between periodontal repair and regeneration. Histological studies are difficult in humans because they require the retrieval of tissue blocks containing the teeth and their surrounding tissues, and for this reason these studies have largely been done in animal models; however, the use of animal models creates problems of interpretation when applying the information to the human. There are other fundamental problems related to assessment of new methods of periodontal regeneration. Ideally, periodontal regeneration is attempted after resolving the periodontitis that produced the loss of periodontal support. Does the type of periodontal disease affect the outcome? If it does, then separate clinical trials would be indicated to manage defects produced by different diseases. Furthermore, certain types of periodontal defects apparently respond better than others (for example, intrabony defects versus suprabony defects). Does each type of defect require a separate trial? Do subjects respond differently and, if so, how should this be factored into selection of the study population and sample size? There appear to be more questions than answers concerning the design of clinical trials for periodontal regeneration. This is not surprising since regeneration has been possible for only a few years, is apparently unpredictable, and the origin and nature of the new tissue are poorly understood. These factors make it important that the design of clinical trials be openly and thoroughly discussed so that practical solutions are forthcoming.

Animals↗