The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Monaeses aciculus

Monaeses aciculus (Simon, 1903) Mecostrabus aciculus Simon, 1903: 727, ♀. Monaeses aciculus. Song and Zhu 1997: 59, figs 35A−H, ♂. Material examined. 1 ♀, CHINA: Yunnan: Xishuangbanna, Mengla County, Menglun Town, Menglun Nature Reserve, Paramichelia baillonii plantation (about 20 years old, N21º54.772', E101º16.043', 556 m), 4−11 April 2007, G. Zheng (Searching, RZI-3-18). Distribution. China (Fujian, Hunan, Taiwan, Yunnan), Japan, Nepal, Philippines.Published as part of Tang, Guo & Li, Shuqiang, 2010, Crab spiders from Xishuangbanna, Yunnan Province, China (Araneae, Thomisidae) 2703, pp. 1-105 in Zootaxa 2703 on page 4

Thomisus eminulus Tang and Li 2010

Thomisus eminulus Tang and Li, 2010 Thomisus eminulus Tang and Li 2010: 62, figs 50A − D, 51A − B, ♂. Material examined. CHINA: Yunnan , Xishuangbanna, Mengla County, Menglun Town, Menglun Nature Reserve: 6 ♂, tropical forest, August 2007 (Fogging, Zheng_sp903–sp1237), leg. G. Zheng. 6 ♂, tropical forest, November–December 2009, leg. G. Tang and Z.Y. Yao (Tang-Yao_No.4–No.42). Distribution. China (Hainan, Yunnan).Published as part of Tang, Guo & Li, Shuqiang, 2010, Crab spiders from Xishuangbanna, Yunnan Province, China (Araneae, Thomisidae) 2703, pp. 1-105 in Zootaxa 2703 on page 9

Lysiteles minusculus Song & Chai 1990

Lysiteles minusculus Song & Chai, 1990 Figs 28–30 Type material: Holotype: ♂, China: Hubei: Xuan’en Co., 25 May 1989 (IZCAS-ar9399, examined). Other material examined. China: Hainan: 19 ♂, Qiongzhong Co., Limushan Mountains (N19º10.540', E109º44.572', alt. 630 m), 1–5 April 2009 (IZCAS, Tang _ No 006–050); 13 ♂, 7 ♀, Wuzhishan Mountains (N18º54.451', E109º40.669', alt. 724 m), 6–11 April 2009 (IZCAS, Tang _ No. 060–149); 1 ♀, Lingshui Co., Diaoluoshan Mountains, road fork (N18º41. 445', E109º52.410' alt. 620 m), 18 April 2009 (IZCAS, Tang _ No. 230); 4 ♂, 3 ♀, Changjiang Co., Bawangling Mountains (N19º8.129', E109º19.199', alt. 967 m), 23–24 April 2009 (IZCAS, Tang _ No. 279, 304) (all material leg. G. Tang). Diagnosis. This species is similar to the species: L. punctiger Ono, 2001 and L. uniprocessus Tang et al., 2008 in the general appearance, but can be separated by the details in the structures of epigynal organs. Description. Female (described for the first time): Total length 3.25. Prosoma 1.15 long, 1.00 wide; Opisthosoma 1.30 long, 1.10 wide. Prosoma light yellow. Eye measurements: AME 0.06; ALE 0.10; PME 0.04; PLE 0.08; AME–AME 0.14; AME–ALE 0.28; PME–PME 0.28; PME–PLE 0.28. MOA length 0.26 with front width 0.26 and back width 0.34. Chelicera, gnathecoxa, labium and sternum yellow. Legs yellow with sparse spines. Leg formula: II, I, IV, III; leg measurements: I: 3.00 (0.90, 1.00, 0.60, 0.50); II: 3.10 (1.00, 1.10, 0.60, 0.50); III: 2.25 (0.70, 0.90, 0.35, 0.30); IV: 2.55 (0.90, 0.95, 0.40, 0.30). Opisthosomal dorsum with 2 longitudinal grayish black stripes, venter yellow. Epigynum (Figs 29 B–C, 30 C–D). Epigynum with a pair of copulatory openings bilaterally; copulatory ducts short, invisible from dorsal view; spermathecae globular. Male: see Song & Chai (1990): 368–369. Palp (Figs. 28 B–D, 30 B–D): Palp with VTA wide, RTA sickle shaped, combined with RTA proximally; bulb flat; embolus curved, arc-shaped. Distribution. China (Hubei, Hainan). Variations. Total length: male, 2.00–2.60 (n=37); female, 2.10–2.70 (n=11). Male opisthosomal dorsum grayish brown in most of the examined specimens.Published as part of Tang, Guo & Li, Shuqiang, 2010, 2369, pp. 1-68 in Zootaxa 2369 on page 3

Borboropactus brevidens Tang & Li 2010, sp. nov.

Borboropactus brevidens sp. nov. Figs 3–6 Type material: Holotype: ♀, China: Hainan: Lingshui Co., Diaoluoshan Mountains, Vacation Village (N18º43. 589', E109º52.026', alt. 937 m), 17 April 2009, G. Tang (IZCAS, Tang_No. 213). Paratype: 1 ♂, same data as holotype (IZCAS). Etymology. The specific epithet is taken from the Latin adjective brevidens and means short-teeth like, referring to the shape of epigynal teeth, adjective. Diagnosis. This new species is similar to B. edentatus sp. nov., but can be separated by the presence of a pair of epigynal teeth, vase-shaped epigynal median septum (calyx-shaped in B. edentatus) in the female; and the DTA arising near RTA from dorsal side of cymbium (far from RTA and near the prolateral side of cymbium in B. edentatus), embolus without basal modifications (fork-shaped in B. edentatus) in the male. Description. Female (holotype measured): Total length 6.50. Prosoma 3.30 long, 2.85 wide; Opisthosoma 3.20 long, 2.60 wide. Prosoma grayish brown, carapace covered with short white hairs. Clypeus with 2 thick setae. Eye measurements: AME 0.12; ALE 0.14; PME 0.13; PLE 0.15; AME–AME 0.12; AME–ALE 0.18; PME–PME 0.16; PME–PLE 0.30. MOA length 0.42 with front width 0.36 and back width 0.44. Chelicera, gnathecoxa, labium dark brown, chelicerae with 5 pro- and 4 retromarginal teeth, and 8 small denticles between the teeth. Sternum yellow. Femur I swollen medially, bears 3 spines. Tibiae I with 5 prolateral, 4 retrolateral thick spines, metatarsi I with 3 prolateral and 3 retrolateral spines. Leg formula: I, IV, III, II; leg measurements: legs I 10.20 (3.10, 4.40, 1.90, 0.80); II: 6.90 (2.10, 2.60, 1.40, 0.80); III: 7.20 (2.00, 2.60, 1.60, 1.00); IV: 7.70 (2.40, 2.60, 1.70, 1.00). Opithosoma grayish black, covered with short clavate hairs. Venter yellow. Epigynum (Figs 3 B–C, 6 C–D): Epigynum with a large anterior hood; median septum vase-shaped; epigynal teeth paired, arising bilaterally; copulatory ducts long, narrower than spermathecae; spermathecae twisted, convoluted; a pair of wrinkled chitinous lamellae cover the posterior part of spermathecae in the basal of vulva. Male: Total length 4.90. Prosoma 2.70 long, 2.35 wide; Opisthosoma 2.40 long, 1.80 wide. Prosoma brown, carapace with white short hairs and a longitudinal black stripe. Clypeus with 2 thick setae. Eye measurements: AME 0.10; ALE 0.14; PME 0.14; PLE 0.15; AME–AME 0.10; AME–ALE 0.10; PME–PME 0.08; PME–PLE 0.22. MOA length 0.32 with front width 0.30 and back width 0.36. Chelicera dark brown with 5 pro- and 4 retromarginal teeth; gnathecoxa, labium brown. Sternum yellow. Femur I swollen medially, bears 3 spines. Tibiae I with 5 prolateral and 4 retrolateral spines. metatarsi I with 3 prolateral and 3 retrolateral spines. Leg formula: I, IV, II, III; leg measurements: I: 9.50 (3.00, 3.80, 1.90, 0.80); II: 6.50 (2.60, 2.00, 1.30, 0.60); III: 6.00 (1.70, 2.30, 1.30, 0.70); IV 6.80 (2.20, 2.30, 1.50, 0.80). Opithosoma yellowish brown. dorsum with small yellow spots and clavate hairs. Venter yellow. Palp (Figs 5 A–D, 6 A–B). Palp with VTA, RTA and DTA; tegulum with a soft, ear-shaped apophysis; conductor membranous; embolus with a wide base and a curved apex. Distribution. China (Hainan). Only known from the type locality. Remark. Both B. brevidens and B. edentatus were collected from a high altitude of tropical forest. They are different from other members of this genus by the light body pigment, presence of an extra tibial apophysis, slightly curved distal embolus (twisted and helix-shaped in other species), and epigynal hoods that anteriorly situated and distinctly separated with median septum (connected in other species).Published as part of Tang, Guo & Li, Shuqiang, 2010, 2369, pp. 1-68 in Zootaxa 2369 on pages 8-1

Borboropactus hainanus Song 1993

Borboropactus hainanus Song, 1993 Figs 11–14 Borboropactus hainanus Song, 1993: 89, figs. 1a–c (male only, female mismatched and lost). Type material. Holotype: ♂, China: Hainan: Changjiang Co., Bawangling Mountains, 15 May 1990, M.B. Gu (IZCAS-Ar9362, examined). Other material examined. China: Hainan: 4 ♂, 1 ♀, Wuzhishan mountainside (N18º53.840', E109º41.514', alt. 1210 m), 8 April 2009 (IZCAS, Tang _ No. 109); 1 ♂, 2 ♀, Lingshui Co., Diaoluoshan Mountains, road fork (N18º41. 445', E109º52.410' alt. 620 m), 18 April 2009 (IZCAS, Tang _ No. 231); 1 ♂, Bawangling Mountains, Changjiang Co., Dong-Er Station (N19º9.908', E109º17.53', alt. 1007 m), 22 April 2009 (IZCAS, Tang _ No. 270); 1 ♂, Ledong Co., Jianfengling Mountains, Mingfeng Valley (E18º74.425', N109º84.269', alt. 977 m), 27 April 2009 (IZCAS, Tang _ No. 349) (all material leg. G. Tang). Diagnosis. This species is similar to B. cinerascens (Doleschall, 1859) (judged from the figures of Benjamin et al. 2008), but can be separated by the flat or slightly concaved dorsal cymbium (convex in B. cinerascens) and flat, not posteriorly folded bulb (with a fold posteriorly in B. cinerascens). Description. Male: See Song, 1993. Palp (Figs 12 A–D, 14 A–B). Palp with a short RTA; the dorsal cymbium slightly concave, with trim scopulae; tegulum with a ear-shaped median apophysis; embolus twisted, helix-shaped distally; conductor translucent. Female (IZCAS, Tang_No. 82, described for the first time): Total length 9.10. Prosoma 4.50 long, 4.00 wide; Opisthosoma 4.90 long, 3.50 wide. Body flat with clavate hairs. Prosoma blackish brown, 2 clavate hairs mounted between AME. Clypeus with clavate hairs. Eye measurements: AME 0.14; ALE 0.18; PME 0.16; PLE 0.16; AME–AME 0.20; AME–ALE 0.16; PME–PME 0.26; PME–PLE 0.42. MOA length 0.56 with front width 0.48 and back width 0.56. Chelicera, gnathecoxa, labium brown, chelicerae with 4 pro- and 5 retromarginal teeth including a vestige tooth, with about 8 small denticles between teeth. Sternum yellowish brown. Femur I swollen medially, bears 3 short spines with large base. Tibiae I with 5 prolateral, 4 retrolateral thick spines, metatarsi I with 3 prolateral and 3 retrolateral spines. Leg formula: I, IV, III, II; leg measurements: I: 13.00 (4.30, 5.60, 2.10, 1.00); II: 7.60 (2.60, 2.80, 1.40, 0.80); III: 8.30 (2.60, 3.00, 1.80, 0.90); IV: 8.60 (3.20, 2.80, 1.80, 0.80). Opithosoma grayish black with black spots. Dorsum with clavate hairs. Epigynum (Figs 13 C–D, 14 C–D). Epigynum with an anteriorly situated hood; median septum long, connected with hood; epigynal teeth paired, short, arising bilaterally; copulatory ducts thick, twisted; spermathecae convoluted, narrower than copulatory ducts; a pair of wrinkled chitinous lamellae covered the posterior part of spermathecae. Distribution. China (Hainan, Yunnan). Variations. Total length: male 6.00–6.80 (n=8); female: 8.20–9.50 (n=3). Remark. The male of this species was first described by Song (1993). The female was then described by Song (1994), but unfortunately it was not correctly matched. The female specimen (Song 1994) was not found in IZCAS collection now. We identified B. hainanus with both sexes from a large sample of specimens collected from Hainan.Published as part of Tang, Guo & Li, Shuqiang, 2010, 2369, pp. 1-68 in Zootaxa 2369 on pages 16-1

Lysiteles furcatus Tang & Li 2010, sp. nov.

Lysiteles furcatus sp. nov. Figs 23–25 Type material: Holotype: ♂, China: Hainan: Lingshui Co., Diaoluoshan Mountains, Vacation Village (N18º43. 589', E109º52.026', alt. 937 m), 17 April 2009, G. Tang (IZCAS, Tang_No. 214). Paratypes: 1 ♂, 3 ♀, same data as holotype; China: Hainan: 1 ♀, Ledong Co., Jianfengling Mountains, Mingfeng Valley (E18º74.425', N109º84.269', alt. 977 m), 27 April 2009 (IZCAS, Tang _ No. 349); 4 ♀, Ledong Co., Jianfengling Mountains, Botanical Garden (N18º73.794', E108º85.847', alt. 905 m), 28 April 2009 (IZCAS, Tang _ No. 362) (all material leg. G. Tang). Etymology. The specific epithet is taken from the Latin adjective furcatus, and means fork-shaped, referring to the embolus with an apophysis basally and looked fork-shaped in the lateral view. Diagnosis. This new species can easily be separated from other congeneric species by the fork-shaped embolus. Description. Male (holotype measured): Total length 3.20. Prosoma 1.60 long, 1.45 wide; Opisthosoma 1.70 long, 1.20 wide. Prosoma yellow with sparse setae, carapace with a pair of longitudinal light gray stripes bilaterally. Eye measurements: AME 0.09; ALE 0.14; PME 0.05; PLE 0.13; AME–AME 0.14; AME–ALE 0.14; PME–PME 0.22; PME–PLE 0.31. MOA length 0.36 with front width 0.32 and back width 0.32. Chelicera blackish brown, gnathecoxa and labium brown, sternum yellow. Legs yellow with sparse spines. Leg formula: II, I, IV, III; leg measurements: I: 5.50 (1.50, 1.90, 1.20, 0.90); II: 6.00 (1.70, 2.20, 1.30, 0.80); III: 3.80 (1.20, 1.40, 0.70, 0.50); IV: 4.00 (1.30, 1.40, 0.80, 0.50). Opithosomal dorsum with 3 pairs of grayish black stripes, venter light yellow. Palp (Figs 23 B–D, 25 A–B). Palpal VTA large, digitiform; RTA stout, with 3 small distal apophyses; embolus with a fork-shaped apophysis proximally. Female (measurements of one paratype): general appearance similar as male. Total length 4.00. Prosoma 1.60 long, 1.50 wide; Opisthosoma 2.40 long, 2.30 wide. Eye measurements: AME 0.10; ALE 0.15; PME 0.05; PLE 0.14; AME–AME 0.14; AME–ALE 0.14; PME–PME 0.24; PME–PLE 0.30. MOA length 0.36 with front width 0.35 and back width 0.34. Leg formula: II, I, IV, III; leg measurements: I: 4.80 (1.50, 1.70, 1.00, 0.60); II: 4.90 (1.50, 1.80, 1.00, 0.60); III: 3.20 (1.30, 1.00, 0.50, 0.40); IV: 3.50 (1.30, 1.20, 0.60, 0.40). Epigynum (Figs 24 B–E, 25 C–D). Epigynum with a hood situated anteriorly; atrium round; copulatory openings posteriorly situated; copulatory ducts short; spermathecae oval. Distribution. China (Hainan). Variations. Total length: male, 3.20–3.40 (n=2); female, 3.30–4.00 (n=8).Published as part of Tang, Guo & Li, Shuqiang, 2010, 2369, pp. 1-68 in Zootaxa 2369 on pages 31-3

Boliscus tuberculatus

Boliscus tuberculatus (Simon, 1886) Corynethrix tuberculata Simon, 1886: 146, ♀. Boliscus tuberculatus. Ono 1984: 66, figs 1−8, ♂; Song and Zhu 1997: 175, figs 123A−H, ♂. Material examined. CHINA: Yunnan: Xishuangbanna, Mengla County, Menglun Town, Menglun Nature Reserve, leg. G. Zheng: 1 ♀, Paramichelia baillonii plantation (about 20 years old, N21º54.200', E101º16.923', 608 m), 1−15 June 2007 (trunk-traps RZII-5-10, Zheng _sp35). 2 ♀, Secondary tropical seasonal moist forest (N21º54.718', E101º16.940', 645 m), 27 July 2007 (Fogging-JSI, Zheng _sp1112); 1 ♀, Primary tropical seasonal rain forest (N21º57.445', E101º12.997', 744 m), 30 July 2007 (Fogging-GBII, Zheng _sp714); 1 ♀, Secondary tropical montane evergreen broad-leaved forest (N21º54.813', E101º12.634', 876 m), 5 August 2007 (Fogging-CBIV, Zheng _sp1285); 1 ♀, Secondary tropical montane evergreen broad-leaved forest (N21º57.784', E101º11.947', 895 m), 6 August 2007 (Fogging-CBI, Zheng _sp1236); leg. G. Tang and Z.Y. Yao: 1 ♀, Lvshilin Forest Park (N21º54.614', E101º16.890', 640 m), 14 November 2009 (Tang-Yao _ No. 7); 1 ♀, Lvshilin Forest Park (N21º54.609´, E101º17.090´, 643 m), 17 November 2009 (Tang-Yao _ No. 13). Distribution. China (Hainan, Yunnan), Japan, Myanmar.Published as part of Tang, Guo & Li, Shuqiang, 2010, Crab spiders from Xishuangbanna, Yunnan Province, China (Araneae, Thomisidae) 2703, pp. 1-105 in Zootaxa 2703 on page

Epidius ganxiensis

Epidius ganxiensis (Yin, Peng and Kim, 1999) Philodromus ganxiensis Yin et al., 1999: 356, figs 2A–G, ♂. Epidius ganxiensis. Tang et al. 2009: 44, figs 3A−J, ♂. Material examined. 1 ♀, CHINA: Yunnan , Xishuangbanna, Mengla County, Menglun Town, Menglun Nature Reserve, Secondary tropical seasonal moist forest (N21º54.607'; E101º17.005', 633 m), 28 July 2007, G. Zheng (Fogging-JSIII, Zheng_sp914). Distribution. China (Hunan, Yunnan).Published as part of Tang, Guo & Li, Shuqiang, 2010, Crab spiders from Xishuangbanna, Yunnan Province, China (Araneae, Thomisidae) 2703, pp. 1-105 in Zootaxa 2703 on page 1